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Find video protocols related to scientific articles indexed in Pubmed.
Long-term Survival and Late Effects among 1-year Survivors of Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Acute Leukemia and Myelodysplastic Syndromes.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-19-2014
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We analyzed the outcomes of patients who survived disease-free for 1-year or more following second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant following disease relapse; among these 325 survived relapse-free at 1-year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplant in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least one year were 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status prior to second HCT was significantly associated with higher risk for overall mortality (HR 1.71 for patients with disease not in complete remission prior to second HCT, P<0.01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults following second transplant. Chronic GVHD was the leading cause of non-relapse mortality followed by organ failure and infection. The cumulative incidence of developing at least one of the studied late effects at 10-years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence 22%) and cataracts (20%), and in adults were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease-free for at least 1-year, many can be expected to survive long term. However, they continue to be at risk for relapse and non-relapse morbidity and mortality. Novel approaches are needed to minimize relapse risk and long-term transplant morbidity in this population.
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[Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation].
Rinsho Ketsueki
PUBLISHED: 07-01-2014
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Advances in hematopoietic cell transplantation (HCT) technology and supportive care techniques have led to improvements in long-term survival after HCT. Emerging indications for transplantation, introduction of newer graft sources (eg, umbilical cord blood) and transplantation of older patients using less intense conditioning regimens have also contributed to an increase in the number of HCT survivors. These survivors are at risk for developing late complications secondary to pre-, peri-, and posttransplantation exposures and risk factors. Guidelines for screening and preventive practices for HCT survivors were published in 2006. An international group of transplantation experts was convened in 2011 to review contemporary literature and update the recommendations while considering the changing practice of transplantation and international applicability of these guidelines. This review provides the updated recommendations for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT.
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Second solid cancers after allogeneic hematopoietic cell transplantation using reduced-intensity conditioning.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-12-2014
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We examined risk of second solid cancers after allogeneic hematopoietic cell transplantation (AHCT) using reduced-intensity/nonmyeloablative conditioning (RIC/NMC). RIC/NMC recipients with leukemia/myelodysplastic syndrome (MDS) (n = 2833) and lymphoma (n = 1436) between 1995 and 2006 were included. In addition, RIC/NMC recipients 40 to 60 years of age (n = 2138) were compared with patients of the same age receiving myeloablative conditioning (MAC, n = 6428). The cumulative incidence of solid cancers was 3.35% at 10 years. There was no increase in overall cancer risk compared with the general population (leukemia/MDS: standardized incidence ratio [SIR] .99, P = 1.00; lymphoma: SIR .92, P = .75). However, risks were significantly increased in leukemia/MDS patients for cancers of lip (SIR 14.28), tonsil (SIR 8.66), oropharynx (SIR 46.70), bone (SIR 23.53), soft tissue (SIR 12.92), and vulva (SIR 18.55) and skin melanoma (SIR 3.04). Lymphoma patients had significantly higher risks of oropharyngeal cancer (SIR 67.35) and skin melanoma (SIR 3.52). Among RIC/NMC recipients, age >50 years was the only independent risk factor for solid cancers (hazard ratio [HR] 3.02, P < .001). Among patients ages 40 to 60 years, when adjusted for other factors, there was no difference in cancer risks between RIC/NMC and MAC in leukemia/MDS patients (HR .98, P = .905). In lymphoma patients, risks were lower after RIC/NMC (HR .51, P = .047). In conclusion, the overall risks of second solid cancers in RIC/NMC recipients are similar to the general population, although there is an increased risk of cancer at some sites. Studies with longer follow-up are needed to realize the complete risks of solid cancers after RIC/NMC AHCT.
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Cyclosporine in Combination with Mycophenolate Mofetil versus Methotrexate for Graft versus Host Disease Prevention in Myeloablative HLA-identical Sibling Donor Allogeneic Hematopoietic Cell Transplantation.
Am. J. Hematol.
PUBLISHED: 06-03-2014
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Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (HCT) despite current prophylaxis. Methotrexate (MTX) with a calcineurin inhibitor (CNI) is the current standard, however, has several toxicities. Mycophenolate mofetil (MMF) is frequently used in reduced-intensity HCT, but data in myeloablative transplants is limited. We thus retrospectively identified 241 patients who underwent myeloablative HCT from an HLA-identical sibling donor; 174 patients received cyclosporine (CSA) + MMF and 67 received CSA +MTX. Patients receiving MMF+CSA had rapid neutrophil (median 11 versus 19 days with MTX+CSA), and platelet recovery (median 19 versus 25 days), lower incidence of severe mucositis by OMAS (19% versus 53%), and shorter length of hospital stay (median 25 versus 36 days) (p<0.001 for all comparisons). There were no significant differences in incidence of grade 2-4 (MMF+CSA 37% versus MTX+CSA 39%) or 3-4 acute GVHD (17% versus 12%), chronic GVHD (46% versus 56%), relapse (28% versus 27%), non-relapse mortality (20% versus 27%) or overall survival (47% versus 44%) (p=NS for all). However, in multivariable analysis, the use of MMF+CSA was associated with an increased risk of severe grade 3-4 acute GVHD (HR 2.92, 95% CI 1.2-7.15, p=0.019). There were no differences between the two regimens in multivariable analyses for other survival outcomes. This analysis demonstrates that the use of MMF in myeloablative sibling donor transplantation is well tolerated. However, there may be an increased risk of severe GVHD with MMF+CSA compared to MTX+CSA. Further studies evaluating optimal dosing strategies are needed.
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Hospital Length of Stay in the First 100 Days after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia in Remission: Comparison among Alternative Graft Sources.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-27-2014
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Several studies have shown comparable survival outcomes with different graft sources, but the relative resource needs of hematopoietic cell transplantation (HCT) by graft source have not been well studied. We compared total hospital length of stay in the first 100 days after HCT in 1577 patients with acute leukemia in remission who underwent HCT with an umbilical cord blood (UCB), matched unrelated donor (MUD), or mismatched unrelated donor (MMUD) graft between 2008 and 2011. To ensure a relatively homogenous study population, the analysis was limited to patients with acute myelogenous leukemia and acute lymphoblastic leukemia in first or second complete remission who underwent HCT in the United States. To account for early deaths, we compared the number of days alive and out of the hospital in the first 100 days post-transplantation. For children who received myeloablative conditioning, the median time alive and out of the hospital in the first 100 days was 50 days for single UCB recipients, 54 days for double UCB recipients, and 60 days for MUD bone marrow (BM) recipients. In multivariate analysis, use of UCB was significantly associated with fewer days alive and out of the hospital compared with MUD BM. For adults who received myeloablative conditioning, the median time alive and out of the hospital in first 100 days was 52 days for single UCB recipients, 55 days for double UCB recipients, 69 days for MUD BM recipients, 75 days for MUD peripheral blood stem cell (PBSC) recipients, 63 days for MMUD BM recipients, and 67 days for MMUD PBSC recipients. In multivariate analysis, UCB and MMUD BM recipients had fewer days alive and out of the hospital compared with recipients of other graft sources. For adults who received a reduced-intensity preparative regimen, the median time alive and out of the hospital during the first 100 days was 65 days for single UCB recipients, 63 days for double UCB recipients, 79 days for MUD PBSC recipients, and 79 days for MMUD PBSC recipients. Similar to the other 2 groups, receipt of UCB was associated with a fewer days alive and out of the hospital. In conclusion, length of stay in the first 100 days post-transplantation varies by graft source and is longer for UCB HCT recipients. These data provide insight into the resource needs of patients who undergo HCT with these various graft sources.
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Peripheral blood progenitor cell mobilization for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-30-2014
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Peripheral blood progenitor cell mobilization practices vary significantly among institutions. Effective mobilization regimens include growth factor alone, chemotherapy and growth factor combined, and, more recently, incorporation of plerixafor with either approach. Many institutions have developed algorithms to improve stem cell mobilization success rates and cost-effectiveness. However, an optimal stem cell mobilization regimen has not been defined. Practical guidelines are needed to address important clinical questions, including which growth factor is optimal, what chemotherapy and dose is most effective, and when to initiate leukapheresis. We present recommendations, based on a comprehensive review of the literature, from the American Society of Blood and Marrow Transplantation.
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Exercise and stress management training prior to hematopoietic cell transplantation: Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0902.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-29-2014
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Studies show that engaging patients in exercise and/or stress management techniques during hematopoietic cell transplantation (HCT) improves quality of life. The Blood and Marrow Transplant Clinical Trials Network tested the efficacy of training patients to engage in self-directed exercise and stress management during HCT. The study randomized 711 patients at 21 centers to receive 1 of 4 training interventions before HCT: a self-directed exercise program, a self-administered stress management program, both, or neither. Participants completed self-reported assessments at enrollment and up to 180 days after HCT. Randomization was stratified by center and transplant type. There were no differences in the primary endpoints of the Physical Component Summary and Mental Component Summary scales of the Medical Outcomes Study Short Form 36 at day +100 among the groups, based on an intention-to-treat analysis. There also were no differences in overall survival, days of hospitalization through day +100 post-HCT, or in other patient-reported outcomes, including treatment-related distress, sleep quality, pain, and nausea. Patients randomized to training in stress management reported more use of those techniques, but patients randomized to training in exercise did not report more physical activity. Although other studies have reported efficacy of more intensive interventions, brief training in an easy-to-disseminate format for either self-directed exercise or stress management was not effective in our trial.
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Lower risk for serious adverse events and no increased risk for cancer after PBSC vs BM donation.
Blood
PUBLISHED: 04-15-2014
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We compared serious early and late events experienced by 2726 bone marrow (BM) and 6768 peripheral blood stem cell (PBSC) donors who underwent collection of PBSC or BM between 2004 and 2009 as part of a prospective study through the National Marrow Donor Program. Standardized FDA definitions for serious adverse events (SAEs) were used, and all events were reviewed by an independent physician panel. BM donors had an increased risk for SAEs (2.38% for BM vs 0.56% for PBSC; odds ratio [OR], 4.13; P < .001), and women were twice as likely to experience an SAE (OR for men, 0.50; P = .005). Restricting the analysis to life-threatening, unexpected, or chronic/disabling events, BM donors maintained an increased risk for SAEs (0.99% for BM vs 0.31% for PBSC; OR, 3.20; P < .001). Notably, the incidence of cancer, autoimmune illness, and thrombosis after donation was similar in BM vs PBSC donors. In addition, cancer incidence in PBSC donors was less than that reported in the general population (Surveillance, Epidemiology, and End Results Program database). In conclusion, SAEs after donation are rare but more often occurred in BM donors and women. In addition, there was no evidence of increased risk for cancer, autoimmune illness, and stroke in donors receiving granulocyte colony-stimulating factor during this period of observation.
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Synergistic Effect of Major Histocompatibility Complex Class I-Related Chain A and Human Leukocyte Antigen-DPB1 Mismatches in Association with Acute Graft-versus-Host Disease after Unrelated Donor Hematopoietic Stem Cell Transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-10-2014
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The clinical relevance of mismatches at the MHC class I-related chain A (MICA) in hematopoietic stem cell transplantation (HSCT) remains unclear. We investigated the association of MICA donor/recipient mismatch and whether there is an interaction between these and HLA-DPB1 mismatch on clinical outcomes after unrelated donor HSCT. Our study included 227 patients who underwent unrelated donor allogeneic HSCT at our institution between 2000 and 2010. Among these, 177 (78%) received HSCT from a 10/10 HLA-matched donor. MICA genotyping was performed using commercially available kits. In univariable analysis, the risk of grade II to IV acute graft-versus-host disease (GVHD) was greater for patients with MICA mismatch (hazard ratio [HR], 1.73; P = .02) than for those with HLA-DPB1 mismatch (HR, 1.62; P = .07). When MICA and HLA-DPB1 were assessed simultaneously, patients mismatched at both loci had the greatest risk (HR, 2.51; P < .01) and those mismatched at only 1 locus had somewhat greater risk (HR, 1.53; P = .12) than patients matched at both loci; this remained significant in multivariable analysis. The 100-day incidence was 66%, 45%, and 31%, respectively (P = .03). Results were similar for grade III and IV acute GVHD, with 100-day incidence 34%, 16%, and 8% (P = .01). These results are clinically pertinent to donor selection strategies and indicate that patients with mismatch at both MICA and HLA-DPB1 are at increased risk for acute GVHD.
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Variation in medicaid coverage for hematopoietic cell transplantation.
J Oncol Pract
PUBLISHED: 04-08-2014
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Variation in Medicaid policies among states may lead to differences in coverage for complex treatments. This article uses hematopoietic cell transplantation (HCT), an established treatment for patients with hematologic cancers, as a case study to highlight state variation in Medicaid coverage of complex oncology treatments.
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Iron overload in allogeneic hematopoietic cell transplantation outcome: a meta-analysis.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-01-2014
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An elevated ferritin level before allogeneic hematopoietic cell transplantation (HCT) is an adverse prognostic factor for overall survival (OS) and nonrelapse mortality. Because ferritin is an imperfect surrogate of iron stores, the prognostic role of iron overload remains unclear. We conducted a patient-level meta-analysis of 4 studies that used magnetic resonance imaging to estimate pre-HCT liver iron content (LIC). An elevated LIC was not associated with a significant increase in mortality: the hazard ratio (HR) for mortality associated with LIC > 7 mg/g dry weight (primary endpoint) was 1.4 (P = .18). In contrast, ferritin >1000 ng/mL was a significant prognostic factor (HR for mortality, 1.7; P = .036). There was, however, no significant association between ferritin > 2500 and mortality. This meta-analysis suggests that iron overload, as assessed by LIC, is not a strong prognostic factor for OS in a general adult HCT population. Our data also suggest that ferritin is an inadequate surrogate for iron overload in HCT.
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Survival improvements in adolescents and young adults after myeloablative allogeneic transplantation for acute lymphoblastic leukemia.
Biol. Blood Marrow Transplant.
PUBLISHED: 02-25-2014
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Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children.
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Challenges and potential solutions for recruitment and retention of hematopoietic cell transplantation physicians: the National Marrow Donor Program's System Capacity Initiative Physician Workforce Group report.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-27-2014
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Hematopoietic cell transplantation (HCT) remains the only known curative therapy for many patients with hematologic, metabolic, and immunologic disorders. Furthermore, the use of HCT has increased with the emergence of HCT as a viable therapeutic option for older patients, those with significant comorbidities, and, with the demonstrated clinical effectiveness of alternative allogeneic donor sources, for those patients without a suitable sibling donor. The National Marrow Donor Program (NMDP) estimates that by 2020, it will facilitate 10,000 transplantations per year, double the number in 2010. To understand the needs of the HCT infrastructure to facilitate this number of transplantations, the NMDP organized the System Capacity Initiative 2020, centered on 6 working groups representing a diverse group of stakeholders. The Physician Workforce Group was tasked with addressing issues relating to recruitment and retention of transplantation physicians. We report here the results of our efforts and future initiatives.
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Conditioning chemotherapy dose adjustment in obese patients: a review and position statement by the American Society for Blood and Marrow Transplantation practice guideline committee.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-21-2014
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Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for patients with malignant and nonmalignant disease states. This article reviews the current published literature on the dosing of pharmacologic agents used for HCT preparative regimens with specific focus on the obese patient population. The review found that dose adjustments for obesity have, to date, been based empirically or extrapolated from published data in the nontransplantation patient population. As a result, the Committee determined that clear standards or dosing guidelines are unable to be made for the obese population because Level I and II evidence are unavailable at this time. Instead, the Committee provides a current published literature review to serve as a platform for conditioning agent dose selection in the setting of obesity. A necessary goal should be to encourage future prospective trials in this patient population because further information is needed to enhance our knowledge of the pharmacokinetics and pharmacodynamics of conditioning agents in the setting of obesity.
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Evaluation of peripheral blood stem cell quality in products transported by traditional courier or commercial overnight shipping services.
Transfusion
PUBLISHED: 01-03-2014
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Peripheral blood stem cell (PBSC) products have traditionally been transported from the collection center to a transplant center using validated volunteer courier-based procedures. Evolving airline service strategies and security policies have complicated this model of product transport. This study was designed to evaluate the feasibility of transporting PBSC products using commercial overnight shipping services, while maintaining product quality, compared to courier-transported products.
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Avascular necrosis of bone after allogeneic hematopoietic cell transplantation in children and adolescents.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-02-2014
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We conducted a nested case-control study within a cohort of 6244 patients to assess risk factors for avascular necrosis (AVN) of bone in children and adolescents after allogeneic transplantation. Eligible patients were ?21 years of age, received their first allogeneic transplant between 1990 and 2008 in the United States, and had survived ? 6 months from transplantation. Overall, 160 patients with AVN and 478 control subjects matched by year of transplant, length of follow-up and transplant center were identified. Patients and control subjects were confirmed via central review of radiology, pathology, and/or surgical procedure reports. Median time from transplant to diagnosis of AVN was 14 months. On conditional logistic regression, increasing age at transplant (?5 years), female gender, and chronic graft-versus-host disease (GVHD) were significantly associated with increased risks of AVN. Compared with patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with nonmalignant diseases and those who had received reduced-intensity conditioning regimens for malignant diseases. Children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to myeloablative conditioning regimens and immunosuppression after hematopoietic cell transplantation for the treatment of GVHD. More research is needed to determine whether screening strategies specifically for patients at high risk for developing AVN with early interventions may mitigate the morbidity associated with this complication.
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Osteoporosis after stem cell transplantation.
Curr Osteoporos Rep
PUBLISHED: 11-09-2013
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With long-term survival for recipients of autologous and allogeneic hematopoietic cell transplantation (HCT) increasing, the recognition of late complications such as decreased bone mineral density leading to osteoporosis (OP) has also increased. With an incidence that is reported to affect as many 50 % of allo HCT recipients, studies continue to mount supporting the need and success in treatment of this HCT complication. In this review, we highlight the major pathological mechanisms behind the development of OP, its diagnosis, and the literature supporting consensus treatment recommendations while noting areas of uncertainty that need further research.
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Prevalence of hematopoietic cell transplant survivors in the United States.
Biol. Blood Marrow Transplant.
PUBLISHED: 07-01-2013
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Advances in hematopoietic cell transplantation (HCT) have led to an increasing number of transplant survivors. To adequately support their healthcare needs, there is a need to know the prevalence of HCT survivors. We used data on 170,628 recipients of autologous and allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research from 1968 to 2009 to estimate the current and future number of HCT survivors in the United States. Stacked cohort simulation models were used to estimate the number of HCT survivors in the United States in 2009 and to make projections for HCT survivors by the year 2030. There were 108,900 (range, 100,500 to 115,200) HCT survivors in the United States in 2009. This included 67,000 autologous HCT and 41,900 allogeneic HCT survivors. The number of HCT survivors is estimated to increase by 2.5 times by the year 2020 (242,000 survivors) and 5 times by the year 2030 (502,000 survivors). By 2030, the age at transplant will be < 18 years for 14% of all survivors (n = 64,000), 18 to 59 years for 61% survivors (n = 276,000), and 60 years and older for 25% of survivors (n = 113,000). In coming decades, a large number of individuals will be HCT survivors. Transplant center providers, hematologists, oncologists, primary care physicians, and other specialty providers will need to be familiar with the unique and complex health issues faced by this population.
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Association of iron overload with allogeneic hematopoietic cell transplantation outcomes: a prospective cohort study using R2-MRI-measured liver iron content.
Blood
PUBLISHED: 06-18-2013
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Using liver magnetic resonance imaging (R2-MRI) to quantify liver iron content (LIC), we conducted a prospective cohort study to determine the association between iron overload and adult allogeneic hematopoietic cell transplantation (HCT) outcomes. Patients received pretransplant ferritin measurements; patients with ferritin >500 ng/mL underwent R2-MRI. Patients were defined as no iron overload (N = 28) and iron overload (LIC >1.8 mg/g; N = 60). Median LIC in the iron-overload group was 4.3 mg/g (range, 1.9-25.4). There was no difference in the 1-year probability of overall survival, nonrelapse mortality, relapse, acute or chronic graft-versus-host disease, organ failure, infections, or hepatic veno-occlusive disease between groups. We also found no difference in the cumulative incidence of a composite end point of nonrelapse mortality, any infection, organ failure, or hepatic veno-occlusive disease (1-year cumulative incidence, 71% vs 80%; P = .44). In multivariate analyses, iron-overload status did not impact risks of overall mortality (relative risk = 2.3; 95% confidence interval, 0.9-5.9; P = .08). In conclusion, we found no association between pretransplant iron overload and allogeneic HCT outcomes. Future studies in this population should use LIC to define iron overload instead of ferritin.
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Importance of Donor Ethnicity/Race Matching in Unrelated Adult and Cord Blood Allogeneic Hematopoietic Cell Transplantation.
Leuk. Lymphoma
PUBLISHED: 06-12-2013
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Donor race matching (both recipients and donors belonging to the same race) might be a factor in outcomes of donor allogeneic hematopoietic cell transplantation (alloHCT). A total of 858 patients who underwent umbilical cord blood (UCB) (475 patients: 202 double UCB and 273 single UCB) or unrelated donor (URD) (383 patients) alloHCT between January 1995 to December 2010 were studied. Most patients were Caucasian (87%), followed by Asians (4%), African Americans (3%), Hispanics (3%), mixed race (3%), and American Indians (<1%). Caucasians comprised 88% of the donor grafts; Caucasians are the most common race of the donor grafts for all races except for Asians. As a result, donor race matching was significantly higher in Caucasian recipients than ethnic minorities (95% vs. 47%, p<0.01). Donor race matching did not affect non-relapse mortality, relapse, acute or chronic graft-versus-host disease or overall survival. Acknowledging the limitations of this study (mainly, self-reported race information and small number of ethnic minorities), at present, there is no data supporting that donor race should be considered a factor in donor selection.
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Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors.
J. Clin. Oncol.
PUBLISHED: 05-28-2013
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Over the past four decades, allogeneic hematopoietic cell transplantation (alloHCT) has evolved as a curative modality for patients with hematologic diseases. This study describes changes in use, technique, and survival in a population-based cohort.
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Barriers to hematopoietic cell transplantation clinical trial participation of african american and black youth with sickle cell disease and their parents.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 04-25-2013
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African Americans and Blacks have low participation rates in clinical trials and reduced access to aggressive medical therapies. Hematopoietic cell transplantation (HCT) is a high-risk but potentially curative therapy for sickle cell disease (SCD), a disorder predominantly seen in African Americans. We conducted focus groups to better understand participation barriers to HCT clinical trials for SCD. Nine focus groups of youth with SCD (n=10) and parents (n=41) were conducted at 3 sites representing the Midwest, South Atlantic, and West South Central US. Main barriers to clinical trial participation included gaps in knowledge about SCD, limited access to SCD/HCT trial information, and mistrust of medical professionals. For education about SCD/HCT trials, participants highly preferred one-on-one interactions with medical professionals and electronic media as a supplement. Providers can engage with sickle cell camps to provide information on SCD/HCT clinical trials to youth and local health fairs for parents/families. Youth reported learning about SCD through computer games; investigators may find this medium useful for clinical trial/HCT education. African Americans affected by SCD face unique barriers to clinical trial participation and have unmet HCT clinical studies education needs. Greater recognition of these barriers will allow targeted interventions in this community to increase their access to HCT.
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Trends in use of and survival after autologous hematopoietic cell transplantation in North America, 1995-2005: significant improvement in survival for lymphoma and myeloma during a period of increasing recipient age.
Biol. Blood Marrow Transplant.
PUBLISHED: 03-29-2013
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Autologous hematopoietic cell transplantation (auto-HCT) is performed to treat relapsed and recurrent malignant disorders and as part of initial therapy for selected malignancies. This study evaluated changes in use, techniques, and survival in a population-based cohort of 68,404 patients who underwent first auto-HCT in a US or Canadian center between 1994 and 2005 and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The mean annual number of auto-HCTs performed was highest during 1996-1999 (6948), and decreased subsequently 2000-2003 (4783), owing mainly to fewer auto-HCTs done to treat breast cancer. However, the mean annual number of auto-HCTs increased from 5278 annually in 1994-1995 to 5459 annually in 2004-2005, reflecting increased use for multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Despite an increase in the median recipient age from 44 to 53 years, there has been a significant improvement in overall survival (OS) from 1994 to 2005 in patients with chemotherapy-sensitive relapsed non-Hodgkin lymphoma (day +100 OS, from 85% to 96%; 1-year OS, from 68% to 80%; P < .001) and chemotherapy-sensitive multiple myeloma (day +100 OS, from 96% to 98%; 1-year OS, from 83% to 92%; P < .001). This improvement in OS was most pronounced in middle-aged (>40 years) and older (>60 years) individuals.
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Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 10-21-2011
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Advances in hematopoietic cell transplantation (HCT) technology and supportive care techniques have led to improvements in long-term survival after HCT. Emerging indications for transplantation, introduction of newer graft sources (eg, umbilical cord blood) and transplantation of older patients using less intense conditioning regimens have also contributed to an increase in the number of HCT survivors. These survivors are at risk for developing late complications secondary to pre-, peri-, and posttransplantation exposures and risk factors. Guidelines for screening and preventive practices for HCT survivors were published in 2006. An international group of transplantation experts was convened in 2011 to review contemporary literature and update the recommendations while considering the changing practice of transplantation and international applicability of these guidelines. This review provides the updated recommendations for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT.
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Relationship of race/ethnicity and survival after single umbilical cord blood transplantation for adults and children with leukemia and myelodysplastic syndromes.
Biol. Blood Marrow Transplant.
PUBLISHED: 09-15-2011
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The relationship of race/ethnicity with outcomes of umbilical cord blood transplantation (UCBT) is not well known. We analyzed the association between race/ethnicity and outcomes of unrelated single UCBT for leukemia and myelodysplastic syndromes. Our retrospective cohort study consisted of 885 adults and children (612 whites, 145 blacks, and 128 Hispanics) who received unrelated single UCBT for leukemia and myelodysplastic syndromes between 1995 and 2006 and were reported to the Center for International Blood and Marrow Transplant Research. A 5-6/6 HLA-matched unit with a total nucleated cell count infused of ?2.5 × 10(7)/kg was given to 40% white and 42% Hispanic, but only 21% black patients. Overall survival at 2 years was 44% for whites, 34% for blacks, and 46% for Hispanics (P = .008). In multivariate analysis adjusting for patient, disease, and treatment factors (including HLA match and cell dose), blacks had inferior overall survival (relative risk of death, 1.31; P = .02), whereas overall survival of Hispanics was similar (relative risk, 1.03; P = .81) to that of whites. For all patients, younger age, early-stage disease, use of units with higher cell dose, and performance status ?80 were independent predictors of improved survival. Black patients and white patients infused with well-matched cords had comparable survival; similarly, black and white patients receiving units with adequate cell dose had similar survival. These results suggest that blacks have inferior survival to whites after single UCBT, but outcomes are improved when units with a higher cell dose are used.
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Outcomes of allogeneic hematopoietic cell transplantation for adolescent and young adults compared with children and older adults with acute myeloid leukemia.
Biol. Blood Marrow Transplant.
PUBLISHED: 09-13-2011
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Adolescents and young adults (AYAs) with cancer have not experienced improvements in survival to the same extent as children and older adults. We compared outcomes among children (<15 years), AYAs (15-40 years) and older adults (>40 years) receiving allogeneic hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML). Our cohort consisted of 900 children, 2,708 AYA, and 2,728 older adult recipients of HLA-identical sibling or unrelated donor (URD) transplantation using myeloablative or reduced-intensity/nonmyeloablative conditioning. Outcomes were assessed over three time periods (1980-1988, 1989-1997, 1998-2005) for siblings and two time periods (1989-1997, 1998-2005) for URD HCT. Analyses were stratified by donor type. Results showed overall survival for AYAs using either siblings or URD improved over time. Although children had better and older adults had worse survival compared with AYAs, improvements in survival for AYAs did not lag behind those for children and older adults. After sibling donor HCT, 5-year adjusted survival for the three time periods was 40%, 48%, and 53% for children, 35%, 41%, and 42% for AYAs, and 22%, 30%, and 34% for older adults. Among URD HCT recipients, 5-year adjusted survival for the two time periods was 38% and 37% for children, 24% and 28% for AYAs, and 19% and 23% for older adults. Improvements in survival occurred because of a reduction in risk of treatment-related mortality. The risk of relapse did not change over time. Improvements in survival among AYAs undergoing allogeneic HCT for AML have paralleled those among children and older adults.
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The National Marrow Donor Programs Symposium on Hematopoietic Cell Transplantation in 2020: a health care resource and infrastructure assessment.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-19-2011
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Hematopoietic cell transplantation (HCT) is the only known curative therapy for many patients with life-threatening hematologic and oncologic diseases. It is estimated that the National Marrow Donor Program(®) (NMDP) will facilitate 10,000 transplants by 2015, double the current number. To better understand the existing personnel and center infrastructure for HCT in the country and to address system capacity challenges to the future growth of HCT, the NMDP convened a diverse group of stakeholders and thought leaders representing HCT physicians, physician assistants, nurse practitioners, nurses, pharmacists, other healthcare providers, HCT program directors, hospital administrators, payors, and professional organizations. Working groups were formed to identify: capacity issues because of shortages in human resources, structural constraints, and patient access barriers including diversity and healthcare disparity challenges; recommendations to address challenges; and stakeholders to engage. This report details the deliberations and recommendations of a national symposium, "Hematopoietic Cell Transplantation in 2020: A Health Care Resource and Infrastructure Assessment," held in September 2010.
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Abandonment of high-dose chemotherapy/hematopoietic cell transplants for breast cancer following negative trial results.
Health Serv Res
PUBLISHED: 07-25-2011
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In 1999, three randomized controlled trials concluded that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDC/HCT) is no better than conventional chemotherapy for women with breast cancer. This study documents the impact of the trials on use of HDC/HCT and describes how hospitals reacted to the trials.
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Trends in allogeneic stem cell transplantation for multiple myeloma: a CIBMTR analysis.
Blood
PUBLISHED: 06-20-2011
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Allogeneic hematopoietic cell transplantation in multiple myeloma is limited by prior reports of high treatment-related mortality. We analyzed outcomes after allogeneic hematopoietic cell transplantation for multiple myeloma in 1207 recipients in 3 cohorts based on the year of transplantation: 1989-1994 (n = 343), 1995-2000 (n = 376), and 2001-2005 (n = 488). The most recent cohort was significantly older (53% > 50 years) and had more recipients after prior autotransplantation. Use of unrelated donors, reduced-intensity conditioning and the blood cell grafts increased over time. Rates of acute graft-versus-host (GVHD) were similar, but chronic GVHD rates were highest in the most recent cohort. Overall survival (OS) at 1-year increased over time, reflecting a decrease in treatment-related mortality, but 5-year relapse rates increased from 39% (95% confidence interval [CI], 33%-44%) in 1989-1994 to 58% (95% CI, 51%-64%; P < .001) in the 2001-2005 cohort. Projected 5-year progression-free survival and OS are 14% (95% CI, 9%-20%) and 29% (95% CI, 23%-35%), respectively, in the latest cohort. Increasing age, longer interval from diagnosis to transplantation, and unrelated donor grafts adversely affected OS in multivariate analysis. Survival at 5 years for subjects with none, 1, 2, or 3 of these risk factors were 41% (range, 36%-47%), 32% (range, 27%-37%), 25% (range, 19%-31%), and 3% (range, 0%-11%), respectively (P < .0001).
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Sensitivity of changes in chronic graft-versus-host disease activity to changes in patient-reported quality of life: results from the Chronic Graft-versus-Host Disease Consortium.
Haematologica
PUBLISHED: 06-17-2011
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The 2005 National Institute of Health Chronic Graft-versus-Host Disease Consensus Conference recommended collection of patient-reported outcomes in clinical trials on chronic graft-versus-host disease. We assessed whether changes in chronic graft-versus-host disease severity, determined using National Institute of Health criteria, clinicians assessment or patients self-evaluation, correlated with patient-reported quality of life as measured by the Short Form-36 and Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) instruments.
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Secondary cancers following allogeneic haematopoietic cell transplantation in adults.
Br. J. Haematol.
PUBLISHED: 05-26-2011
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Secondary cancers that arise in allogeneic haematopoietic-cell transplant recipients, possibly as a result of treatment exposures, are a relatively rare complication of transplantation. However, they can be associated with significant morbidity and mortality. Secondary cancers include post-transplant lymphoproliferative disorders, new solid cancers and donor-derived haematological malignancies. This review describes the epidemiology, risk factors and screening recommendations for secondary cancers among adult allogeneic haematopoietic-cell transplant recipients. Constructing a patient-specific risk profile based on known exposures and risk-factors is the key to developing appropriate screening and preventative strategies for secondary cancers after allogeneic transplantation.
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Easy-to-read informed consent forms for hematopoietic cell transplantation clinical trials.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-09-2011
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Informed consent is essential to ethical research and is requisite to participation in clinical research. Yet most hematopoietic cell transplantation (HCT) informed consent forms (ICFs) are written at reading levels that are above the ability of the average person in the United States (U.S.). The recent development of ICF templates by the National Cancer Institute, National Institutes of Health, and the National Heart Blood and Lung Institute have not resulted in increased patient comprehension of information. Barriers to creating Easy-to-Read ICFs that meet U.S. federal requirements and pass institutional review board (IRB) review are the result of multiple interconnected factors. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) formed an ad hoc review team to address concerns regarding the overall readability and length of ICFs used for BMT CTN trials. This paper summarizes recommendations of the review team for the development and formatting of Easy-to-Read ICFs for HCT multicenter clinical trials, the most novel of which is the use of a 2-column format. These recommendations intend to guide the ICF writing process, simplify local IRB review of the ICF, enhance patient comprehension, and improve patient satisfaction. The BMT CTN plans to evaluate the impact of the Easy-to-Read format compared with the traditional format on the informed consent process.
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Long-term survival and late deaths after allogeneic hematopoietic cell transplantation.
J. Clin. Oncol.
PUBLISHED: 04-04-2011
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Allogeneic hematopoietic cell transplantation (HCT) is curative but is associated with life-threatening complications. Most deaths occur within the first 2 years after transplantation. In this report, we examine long-term survival in 2-year survivors in the largest cohort ever studied.
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Financial conflicts of interest in economic analyses in oncology.
Am. J. Clin. Oncol.
PUBLISHED: 03-29-2011
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Financial conflicts of interest can influence biomedical research. Using data from the American Society of Hematology and the American Society of Clinical Oncology annual meetings, we evaluated the frequency and influence of financial conflicts of interest on economic analyses in oncology.
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Late-onset noninfectious pulmonary complications in adult allogeneic hematopoietic cell transplant recipients.
Transplantation
PUBLISHED: 03-16-2011
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Late-onset noninfectious pulmonary complications (LONIPCs) after allogeneic hematopoietic cell transplantation (HCT) contribute to posttransplant mortality, morbidity, and decreased quality of life. The effect of newer HCT approaches including reduced intensity and umbilical cord on the incidence and outcome of LONIPC has not been studied. We hereby present a study evaluating the incidence, risk factors, and outcomes of LONIPC in a recent cohort of allogeneic HCT recipients.
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To cry or not to cry: physicians and emotions at the bedside.
Minn Med
PUBLISHED: 03-04-2011
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Whether it is appropriate for physicians to display their emotions in front of a patient is a question that has no easy answer. Some physicians may consider it an expression of empathy, while others caution against doing so. This article describes the findings of a survey of blood and marrow transplant physicians who were asked whether it is OK to cry in front of patients.
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Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by NIH criteria: report on baseline data from the Chronic GVHD Consortium.
Blood
PUBLISHED: 02-25-2011
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Quality of life (QOL) after hematopoietic cell transplantation (HCT) is compromised by chronic GVHD. In a prospectively assembled multicenter cohort of adults with chronic GVHD (n = 298), we examined the relationship between chronic GVHD severity defined by National Institutes of Health (NIH) criteria and QOL as measured by the SF-36 and FACT-BMT instruments at time of enrollment. Chronic GVHD severity was independently associated with QOL, adjusting for age. Compared with population normative data, SF-36 scores were more than a SD (10 points) lower on average for the summary physical component score (PCS) and role-physical subscale, and significantly lower (with magnitude 4-10 points) for several other subscales. Patients with moderate and severe cGVHD had PCS scores comparable with scores reported for systemic sclerosis, systemic lupus erythematosus, and multiple sclerosis, and greater impairment compared with common chronic conditions including diabetes, hypertension, and chronic lung disease. Moderate to severe cGVHD as defined by NIH criteria is associated with significant compromise in multiple QOL domains, with PCS scores in the range of other systemic autoimmune diseases. Compromised QOL provides a functional assessment of the effects of chronic GVHD, and may be measured in cGVHD clinical studies using either the SF-36 or the FACT-BMT.
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Hematopoietic cell transplantation comorbidity index predicts transplantation outcomes in pediatric patients.
Blood
PUBLISHED: 01-12-2011
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Quantifying the risk of hematopoietic cell transplantation (HCT)-related mortality for pediatric patients is challenging. The HCT-specific comorbidity index (HCT-CI) has been confirmed as a useful tool in adults, but has not yet been validated in children. We conducted a retrospective cohort study of 252 pediatric patients undergoing their first allogeneic HCT between January 2008 and May 2009. Pretransplantation comorbidities were scored prospectively using the HCT-CI. Median age at transplantation was 6 years (range, 0.1-20) and median follow-up was 343 days (range, 110-624). HCT-CI scores were distributed as follows: 0, n=139; 1-2, n=52; and 3+, n=61. The 1-year cumulative incidence of nonrelapse mortality (NRM) increased (10%, 14%, and 28%, respectively; P<.01) and overall survival (OS) decreased (88%, 67%, and 62%, respectively; P<.01) with increasing HCT-CI score. Multivariate analysis showed that compared with score 0, those with scores of 1-2 and 3+ had relative risks of NRM of 1.5 (95% confidence interval, 0.5-4.3, P=.48) and 4.5 (95% confidence interval, 1.7-12.1, P<.01), respectively. These results indicate that the HCT-CI score predicts NRM and OS in pediatric patients undergoing HCT and is a useful tool to assess risk, guide counseling in the pretransplantation setting, and devise innovative therapies for the highest risk groups.
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Allogeneic transplant physician and center capacity in the United States.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-06-2011
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Shortage of manpower and center capacity is expected to be a major challenge to the anticipated future growth in the utilization of allogeneic hematopoietic cell transplantation (HCT) in the United States. Using data from the National Marrow Donor Programs Transplant Center Network Renewal Survey, we describe transplant center and transplant physician capacity in the United States from 2005 to 2009. Over this 5-year period, the number of allogeneic transplants increased by 30%, bed capacity increased by 17%, and physician full-time equivalents increased by 26%. The number of related donor HCT increased by 15% and unrelated donor HCT increased by 45%. In addition to large centers, small- and medium-sized centers also made a major contribution to overall national transplant volumes for both related and unrelated donor HCT. Increase in utilization of unrelated donor HCT occurred in centers irrespective of their size. The majority of transplant centers were performing more transplantations using existing physician and bed capacity. Our study provides important descriptions of allogeneic transplant activity and capacity of U.S. centers, and our data will assist policy makers plan for the projected growth in the use of transplantation.
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Late complications in blood and marrow transplant survivors.
Minn Med
PUBLISHED: 12-15-2010
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Hematopoietic stem-cell transplantation is a potentially curative therapy for many high-risk hematologic malignancies and other life-threatening disorders. Advances in transplantation over the last four decades have resulted in an increasing number of long-term survivors who may be at risk for developing late infections, noninfectious complications, and secondary cancers. Awareness on the part of primary care physicians of the risk factors and screening recommendations for late complications can lead to their early diagnosis and treatment.
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Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning.
Blood
PUBLISHED: 10-06-2010
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Risks of secondary solid cancers among allogeneic hematopoietic cell transplant (HCT) recipients who receive conditioning without total body irradiation are not well known. We evaluated the incidence and risk factors for solid cancers after HCT using high-dose busulfan-cyclophosphamide conditioning in 4318 recipients of first allogeneic HCT for acute myeloid leukemia in first complete remission (N = 1742) and chronic myeloid leukemia in first chronic phase (N = 2576). Our cohort represented 22 041 person-years at risk. Sixty-six solid cancers were reported at a median of 6 years after HCT. The cumulative-incidence of solid cancers at 5 and 10 years after HCT was 0.6% and 1.2% among acute myeloid leukemia and 0.9% and 2.4% among chronic myeloid leukemia patients. In comparison to general population incidence rates, HCT recipients had 1.4× higher than expected rate of invasive solid cancers (95% confidence interval, 1.08-1.79, P = .01). Significantly elevated risks were observed for tumors of the oral cavity, esophagus, lung, soft tissue, and brain. Chronic graft-versus-host disease was an independent risk factor for all solid cancers, and especially cancers of the oral cavity. Recipients of allogeneic HCT using busulfan-cyclophosphamide conditioning are at risk for developing solid cancers. Their incidence continues to increase with time, and lifelong cancer surveillance is warranted in this population.
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Reduced-intensity conditioning followed by related allografts in hematologic malignancies: long-term outcomes most successful in indolent and aggressive non-Hodgkin lymphomas.
Biol. Blood Marrow Transplant.
PUBLISHED: 09-03-2010
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Reduced-intensity conditioning (RIC) extends the curative potential of allogeneic hematopoietic cell transplantation (HCT) to patients with hematologic malignancies unable to withstand myeloablative conditioning. We prospectively analyzed the outcomes of 123 patients (median age, 57 years; range, 23-70 years) with hematologic malignancies treated with a uniform RIC regimen of cyclophosphamide, fludarabine, and total-body irradiation (200 cGy) with or without antithymocyte globulin followed by related donor allogeneic HCT at the University of Minnesota between 2002 and 2008. The cohort included 45 patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), 27 with aggressive non-Hodgkin lymphoma (NHL), 8 with indolent NHL, 10 with Hodgkin lymphoma (HL), 10 with myeloma, and 23 with acute lymphocytic leukemia, chronic myelogenous leukemia, other leukemias, or myeloproliferative disorders. The probability of 4-year overall survival was 73% for patients with indolent NHL, 58% for those with aggressive NHL, 67% for those with HL, 30% for those with AML/MDS, and only 10% for those with myeloma. Corresponding outcomes for relapse in these patients were 0%, 32%, 50%, 33%, and 38%, and those for progression-free survival were 73%, 45%, 27%, 27%, and 10%. The incidence of treatment-related mortality was 14% at day +100 and 22% at 1 year. The incidence of grade II-IV acute graft-versus-host disease was 38% at day +100, and that of chronic graft-versus-host disease was 50% at 2 years. Multivariate analysis revealed superior overall survival and progression-free survival in patients with both indolent and aggressive NHL compared with those with AML/MDS, HL, or myeloma. Worse 1-year treatment-related mortality was observed in patients with a Hematopoietic Cell Transplantation Comorbidity Index score ? 3 and in cytomegalovirus-seropositive recipients. These results suggest that (1) RIC conditioning was well tolerated by an older, heavily pretreated population; (2) patients with indolent and aggressive NHL respond well to RIC conditioning, highlighting the importance of the graft-versus-lymphoma effect; and (3) additional peri-transplantation manipulations are needed to improve outcomes for patients with AML/MDS or myeloma receiving RIC conditioning before HCT.
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Access to hematopoietic stem cell transplantation: effect of race and sex.
Cancer
PUBLISHED: 06-22-2010
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The purpose of the current study was to determine whether the use of hematopoietic stem cell transplantation (HCT) to treat leukemia, lymphoma, or multiple myeloma (MM) differs by race and sex.
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Pregnancy after hematopoietic cell transplantation: a report from the late effects working committee of the Center for International Blood and Marrow Transplant Research (CIBMTR).
Biol. Blood Marrow Transplant.
PUBLISHED: 05-11-2010
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Preservation of fertility after hematopoietic cell transplantation (HCT) can have a significant influence on the quality of life of transplant survivors. We describe 178 pregnancies in HCT recipients that were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 2002 and 2007. There were 83 pregnancies in female HCT recipients and 95 pregnancies in female partners of male HCT recipients. Indications for transplantation included hematologic and other malignancies (N = 99) and nonmalignant disorders (N = 79, of which 75 patients had severe aplastic anemia). The cohort included recipients of autologous HCT (20 women, 13 men), myeloablative (MA) allogeneic HCT (12 women, 50 men), and nonmyeloablative allogeneic HCT (2 women, 2 men). Age at HCT was <20 years for 50% of women and 19% of men. Conditioning regimens included total body irradiation (TBI) in 16% of women and 19% of men; doses were MA in 10% of women and in 16% of men. Live births were reported in 86% of pregnancies in partners of male transplant patients and 85% of pregnancies in female transplant patients, with most pregnancies occurring 5 to 10 years after HCT. We conclude that some HCT recipients can retain fertility, including patients who have received TBI and/or MA conditioning. Young patients undergoing HCT should be counseled both before and after HCT about potential loss of fertility, methods for preserving fertility, and planning for future pregnancy. Fertility and outcomes of pregnancy after HCT need prospective evaluation in large transplant cohorts.
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Conflict of interest in economic analyses of aromatase inhibitors in breast cancer: a systematic review.
Breast Cancer Res. Treat.
PUBLISHED: 03-18-2010
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To determine whether authors conducting economic analyses of aromatase inhibitors in breast cancer are less likely to reach unfavorable conclusions if the economic study is sponsored by the manufacturer of the drug. Articles reporting the economic analyses of aromatase inhibitors in breast cancer were selected from PubMed in May 2009. Information was collected on the types of analysis, the qualitative conclusion, the quantitative results, and the funding sources. Fishers exact test was conducted to compare the frequency of unfavorable conclusions based on study sponsorship. Thirty-two eligible articles were identified. Twenty-six were funded by pharmaceutical companies, and 4 were funded by non-pharmaceutical companies. Two studies did not report a funding source. Twenty-one studies evaluated aromatase inhibitors in the adjuvant setting, while 11 studies examined their use in advanced breast cancer. Twenty-two studies evaluated one type aromatase inhibitor, while 10 compared multiple types of aromatase inhibitors. Only one of the 26 (4%) pharmaceutical company-sponsored studies reported unfavorable cost-effectiveness of an aromatase inhibitor, which was a competitors product, whereas two of four (50%) non-pharmaceutical company-sponsored studies concluded aromatase inhibitors are not cost-effective in certain clinical scenarios (P < 0.05). Seven pharmaceutical company-sponsored studies conducted a comparison among several aromatase inhibitors; all 7 studies reported favorable conclusions for the sponsoring companys products. The majority of economic analyses of aromatase inhibitors in breast cancer are sponsored by pharmaceuticals. Economic evaluations of aromatase inhibitors in breast cancer that are funded by a pharmaceutical company are less likely to reach unfavorable conclusions about the sponsors product.
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Relapse and late mortality in 5-year survivors of myeloablative allogeneic hematopoietic cell transplantation for chronic myeloid leukemia in first chronic phase.
J. Clin. Oncol.
PUBLISHED: 03-08-2010
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PURPOSE Allogeneic hematopoietic cell transplantation (HCT) is curative therapy for chronic myeloid leukemia (CML), but its long-term outcomes are not well described. We studied the long-term outcomes of CML patients in first chronic phase who receive an allogeneic HCT. PATIENTS AND METHODS Our study included 2,444 patients who received myeloablative HCT for CML in first chronic phase between 1978 and 1998 and survived in continuous complete remission for at least 5 years (median follow-up, 11 years; range, 5 to 25 years). Donor sources were human leukocyte antigen-matched siblings in 1,692 patients, unrelated donors in 639 patients, and other related donors in 113 patients. RESULTS Overall survival rates at 15 years were 88% (95% CI, 86% to 90%) for sibling HCT and 87% (95% CI, 83% to 90%) for unrelated donor HCT. Corresponding cumulative incidences of relapse were 8% (95% CI, 7% to 10%) and 2% (95% CI, 1% to 4%), respectively. The latest relapse was reported 18 years post-HCT. In multivariable analyses, history of chronic graft-versus-host disease increased risks of late overall mortality and nonrelapse mortality but reduced risks of relapse. In comparison with age-, race-, and sex-adjusted normal populations, the mortality of HCT recipients was significantly higher until 14 years post-HCT; thereafter, mortality rates were similar to those of the general population (relative mortality ratio at 15 years, 2.3; 95% CI, 0 to 4.9). CONCLUSION Recipients of allogeneic HCT for CML in first chronic phase who remain in remission for at least 5 years have favorable subsequent long-term survival, and their mortality rates eventually approach those of the general population.
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A prospective study of iron overload management in allogeneic hematopoietic cell transplantation survivors.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-07-2010
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We report the results of a single-center, prospective evaluation for iron overload and subsequent treatment in 147 adult allogeneic hematopoietic cell transplantation (HCT) recipients who survived beyond 1 year after transplantation. Patients were screened by serum ferritin level; those with ferritin >1000 ng/mL underwent liver R2 magnetic resonance imaging to estimate liver iron concentration (LIC; normal < or =1.8 mg/g). Patients with significant iron overload (defined as LIC > or =5 mg/g), based on physician and patient preference, were offered observation only, phlebotomy, or enrollment in a pilot study of deferasirox. Sixteen patients had significant iron overload. Their median age was 51 years (range, 29-64 years), and they had survived a median of 21 months (range, 12-114 months). All 16 patients were transfusion-independent at study enrollment. Five patients received no treatment (median LIC, 6.4 mg/g; range, 5.1-28.3 mg/g), 8 underwent phlebotomy (median LIC, 13.1 mg/g; range, 7.8-43.0 mg/g), and 3 received daily deferasirox 20 mg/kg/day orally for 6 months (LIC, 6.3, 9.0, and 19.9 mg/g). Two patients had abnormal liver function tests, and 1 patient each had cirrhosis and unexplained congestive heart failure; all 4 of these patients underwent phlebotomy. Follow-up serum ferritin concentrations decreased spontaneously in 4 patients in the observation-only arm. Phlebotomy was generally well tolerated. Deferasirox also was well tolerated and led to decreased LIC after 6 months of therapy in all 3 patients. Phlebotomy is feasible in the majority of allogeneic HCT recipients who have survived for > or =1 year after HCT and have significant iron overload. Although the number of subjects is small, deferasirox may be a safe and effective alternative for allogeneic HCT survivors with iron overload who cannot undergo phlebotomy.
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Corticosteroid dose as a risk factor for avascular necrosis of the bone after hematopoietic cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-04-2010
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Exposure to corticosteroids increases the risks of avascular necrosis (AVN) of the bone after hematopoietic cell transplantation (HCT). However, whether this effect is dependent on the dose of corticosteroids is not well known. We conducted a case-controlled study, which included 74 recipients of autologous or allogeneic HCT with AVN and 147 controls without AVN that were matched by age, sex, and year of HCT to cases. Cases with AVN included 8 autologous HCT recipients, 58 myeloablative allogeneic HCT recipients, and 8 recipients of non-myeloablative allogeneic HCT. Corticosteroid exposure was expressed as cumulative doses of prednisone. Cases received higher cumulative doses of prednisone than controls, and among allogeneic HCT recipients, cases were more likely to have developed acute and chronic graft-versus-host disease (aGVHD, cGVHD). Cumulative dose of prednisone was an independent risk factor for AVN. Compared to no corticosteroid exposure, exposure to <3870 mg cumulative dose of prednisone was associated with 4.0 (95% confidence intervals, 1.5-11.2) times higher risk, 3870-9735 mg with 5.6 (2.1-15.2) times higher risk and >9735 with 8.6 (3.2-23.5) times higher risk of AVN. Exposure to higher doses of corticosteroids increases the risk of AVN in HCT recipients.
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Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations in acute promyelocytic leukemia: a systematic review.
Leuk. Res.
PUBLISHED: 01-01-2010
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The fms-like tyrosine kinase 3 (FLT3) gene aberrations, internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations, are frequent in acute promyelocytic leukemia (APL). To evaluate their prognostic significance, we performed a systematic review and meta-analysis. Eleven studies covering a total of 1063 subjects were included in this review. Incidence of ITD and TKD mutations was 12-38% and 2-20%, respectively. In 9 of 11 studies, ITD was associated with high WBC count at the time of diagnosis, which is a known prognostic indicator in APL. Patients with ITD had inferior 3-year overall survival compared to patients without ITD (risk ratio 1.42, 95% CI: 1.04-1.95). Similarly, ITD was also associated with adverse 3-year disease-free survival (risk ratio 1.48, 95% CI: 1.02-2.15). There were only two studies that evaluated the association of TKD mutation in APL; both showed a trend towards worse survival in patients with mutated TKD. In conclusion, FLT3 ITD is associated with high WBC at diagnosis in patients with APL. Although the available literature is limited to observational studies, our systematic review suggests that FLT3 mutations, especially ITD, can adversely affect overall survival and disease-free survival in APL.
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Access to hematopoietic cell transplantation in the United States.
Biol. Blood Marrow Transplant.
PUBLISHED: 11-02-2009
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Hematopoietic cell transplantation (HCT) is a highly specialized and resource-intense medical procedure that can be associated with disparities in access to transplantation. Barriers to access to HCT are multifactorial, complex, and interrelated. Our current knowledge of specific barriers that prevent access to HCT is very limited. As the utilization of HCT increases, it is imperative that underserved populations receive the benefit of this life-saving procedure. We review the prevailing literature on access to HCT and describe research priorities for eliminating disparities in transplantation. Better understanding of these complex barriers will minimize inequities, inform health policy, guide development of interventions targeted to eliminate disparities, and continue the expansion of HCT in the future.
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Outcomes of hematologic malignancies after unrelated donor hematopoietic cell transplantation according to place of residence.
Biol. Blood Marrow Transplant.
PUBLISHED: 10-05-2009
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Studies suggest that patients who live in rural areas may have worse clinical outcomes compared with patients living in urban areas. We studied whether place of residence (rural versus urban) is associated with clinical outcomes of patients with leukemia or myelodysplastic syndrome (MDS) who received an unrelated donor hematopoietic cell transplantation (HCT). Patients residential ZIP code at the time of transplant was used to determine rural or urban designation based on the Rural Urban Commuting Codes. The study included 6140 patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 121 U.S. HCT centers: 1179 (19%) came from rural areas, whereas 4961 (81%) came from urban areas. Rural and urban patients were similar in patient-, disease-, and transplant-related characteristics aside from household income and distance traveled to the HCT center. After adjusting for income and other significant patient, disease, and transplant-related variables, the risk of overall mortality between patients residing in rural and urban areas were not statistically significant (relative risk 1.01, 95% confidence intervals 0.93-1.10, P = .74). Similar outcomes were noted for treatment-related mortality (TRM), disease-free survival (DFS), and relapse. Patients income, derived from the U.S. Census and based on their residential ZIP code, was independently associated with outcomes. In summary, our study showed no differences in the clinical outcomes of patients from rural or urban areas after unrelated donor HCT.
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Race and outcomes of autologous hematopoietic cell transplantation for multiple myeloma.
Biol. Blood Marrow Transplant.
PUBLISHED: 09-11-2009
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Blacks are twice as likely to develop and die from multiple myeloma (MM), and are less likely to receive an autologous hematopoietic-cell transplant (AHCT) for MM compared to Whites. The influence of race on outcomes of AHCT for MM is not well described. We compared the probability of overall survival (OS), progression-free survival (PFS), disease progression, and nonrelapse mortality (NRM) among Black (N=303) and White (N=1892) recipients of AHCT for MM, who were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2005. The Black cohort was more likely to be female, and had better Karnofsky performance scores, but lower hemoglobin and albumin levels at diagnosis. Black recipients were younger and more likely to be transplanted later in their disease course. Disease stage and treatment characteristics prior to AHCT were similar between the 2 groups. Black and White recipients had similar probabilities of 5-year OS (52% versus 47%, P=.19) and PFS (19% versus 21%, P=.64) as well as cumulative incidences of disease progression (72% versus 72%, P=.97) and NRM (9% versus 8%, P=.52). In multivariate analyses, race was not associated with any of these endpoints. Black recipients of AHCT for MM have similar outcomes compared to Whites, suggesting that the reasons underlying lower rates of AHCT in Blacks need to be studied further to ensure equal access to effective therapy.
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Long-term survival and late relapse in 2-year survivors of autologous haematopoietic cell transplantation for Hodgkin and non-Hodgkin lymphoma.
Br. J. Haematol.
PUBLISHED: 07-01-2009
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This study described long-term outcomes of autologous haematopoietic-cell transplantation (HCT) for advanced Hodgkin (HL) and non-Hodgkin lymphoma (NHL). The study included recipients of autologous HCT for HL (N = 407) and NHL (N = 960) from 1990-98 who were in continuous complete remission for at least 2 years post-HCT. Median follow-up was 104 months for HL and 107 months for NHL. Overall survival at 10-years was 77% (72-82%) for HL, 78% (73-82%) for diffuse large-cell NHL, 77% (71-83%) for follicular NHL, 85% (75-93%) for lymphoblastic/Burkitt NHL, 52% (37-67%) for mantle-cell NHL and 77% (67-85%) for other NHL. On multivariate analysis, mantle-cell NHL had the highest relative-risk for late mortality [2.87 (1.70-4.87)], while the risks of death for other histologies were comparable. Relapse was the most common cause of death. Relative mortality compared to age, race and gender adjusted normal population remained significantly elevated and was 14.8 (6.3-23.3) for HL and 5.9 (3.6-8.2) for NHL at 10-years post-HCT. Recipients of autologous HCT for HL and NHL who remain in remission for at least 2-years have favourable subsequent long-term survival but remain at risk for late relapse. Compared to the general population, mortality rates continue to remain elevated at 10-years post-transplantation.
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Race and socioeconomic status influence outcomes of unrelated donor hematopoietic cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-20-2009
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Success of hematopoietic cell transplantation (HCT) can vary by race, but the impact of socioeconomic status (SES) is not known. To evaluate the role of race and SES, we studied 6207 unrelated-donor myeloablative (MA) HCT recipients transplanted between 1995 and 2004 for acute or chronic leukemia or myelodysplastic syndrome (MDS). Patients were reported by transplant center to be White (n = 5253), African American (n = 368), Asian/Pacific-Islander (n = 141), or Hispanic (n = 445). Patient income was estimated from residential zip code at time of HCT. Cox regression analysis adjusting for other significant factors showed that African American (but not Asian or Hispanic) recipients had worse overall survival (OS) (relative-risk [RR] 1.47; 95% confidence interval [CI] 1.29-1.68, P < .001) compared to Whites. Treatment-related mortality (TRM) was higher in African Americans (RR 1.56; 95% CI 1.34-1.83, P < .001) and in Hispanics (RR 1.30; 95% CI 1.11-1.51, P = .001). Across all racial groups, patients with median incomes in the lowest quartile (<$34,700) had worse OS (RR 1.15; 95% CI 1.04-1.26, P = .005) and higher risks of TRM (RR 1.21; 1.07-1.36, P = .002). Inferior outcomes among African Americans are not fully explained by transplant-related factors or SES. Potential other mechanisms such as genetic polymorphisms that have an impact on drug metabolism or unmeasured comorbidities, socioeconomic factors, and health behaviors may be important. Low SES, regardless of race, has a negative impact on unrelated donor HCT outcomes.
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The National Marrow Donor Programs symposium on patient advocacy in cellular transplantation therapy: addressing barriers to hematopoietic cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-13-2009
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Although hematopoietic cell transplantation (HCT) is an effective treatment option for patients with life-threatening blood, immune system, or genetic disorders, many barriers besides a lack of suitably matched donors exist and can have an adverse impact on access and outcomes of HCT. In 2008, the National Marrow Donor Program, through its Office of Patient Advocacy, convened a diverse group of experts and transplantation survivors to identify persistent patient barriers throughout the transplantation process and to make recommendations for programs and initiatives to address these barriers, including new research opportunities. This group included transplantation physicians and other health care providers, relevant subject experts, and representatives from transplantation centers and patient advocacy organizations. Working groups were formed to identify patient barriers to HCT and to recommend and prioritize initiatives as they relate to the pretransplantation period, the early posttransplantation period, long-term survivorship, financial issues, and special populations. This report summarizes the symposiums deliberations and recommendations to address persistent patient barriers throughout the transplantation process.
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Hypertension and diabetes mellitus in adult and pediatric survivors of allogeneic hematopoietic cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 03-02-2009
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Hypertension and diabetes are frequent early complications of allogeneic hematopoietic cell transplantation (HCT); however, their long-term outcomes are not well known. We conducted a retrospective cohort study to describe the risk factors and natural history of post-HCT hypertension and diabetes in 180 consecutive adult (n = 106) and pediatric (n = 74) allogeneic HCT recipients from 2003-2005 who had survived for 1 year post-HCT. The pediatric patients were less likely than the adult patients to have pre-HCT hypertension and diabetes, smoking history, or high-risk disease and more likely to receive myeloablative (MA) conditioning. All patients were followed until at least 2 years post-HCT; of these 1-year survivors, 156 (87%) were alive at 2 years. Acute or chronic graft-versus-host disease (aGVHD, cGVHD) occurred in 118 (66%) patients; of these, 24% received cyclosporine (CsA) for >12 months and 47% received prednisone for >12 months. Within 2 years post-HCT, 126 (70%) had hypertension and 54 (30%) had diabetes. Rates were similar for the adult recipients (hypertension, 68%; diabetes, 30%) and the pediatric recipients (hypertension, 73%; diabetes, 30%). At 2 years post-HCT, in the patients with hypertension, hypertension had not resolved in 34%, and among patients with diabetes, diabetes had not resolved in 32%. On multivariate analyses, exposure to CsA increased the risk of developing hypertension post-HCT (relative risk, 1.6; 95% confidence interval [CI], 1.1-2.5; P = .03), but did not affect its persistence at 2 years. Exposure to high-dose corticosteroids (cumulative prednisone dose of > 0.25 mg/kg/day) increased the likelihood of developing diabetes (relative risk, 3.6; 95% CI, 1.7-7.5; P < .01) and for having persistent diabetes at 2 years post-HCT (relative risk, 4.1; 95% CI, 1.0-18.2; P = .05). Hypertension and diabetes are frequent early complications of allogeneic HCT, but subsequently resolve in a large proportion of recipients in the first 2 years after transplantation. Continued monitoring and treatment of hypertension and diabetes is necessary in allogeneic HCT survivors, especially in those exposed to high doses of corticosteroids.
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Promising progression-free survival for patients low and intermediate grade lymphoid malignancies after nonmyeloablative umbilical cord blood transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-27-2009
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Nonmyeloablative hematopoietic cell transplantation (HCT) has been used to treat patients with advanced or high-risk lymphoid malignancies. We studied 65 patients (median age 46 years) receiving an umbilical cord blood (UCB) graft after a single conditioning regimen consisting of cyclophosphamide (50 mg/kg) on day -6, fludarabine (40 mg/m(2)) daily on days -6 to -2, as well as a single fraction of total-body irradiation (TBI) (200 cGy) along with cyclosporine mycophenolate mofetil immunosuppression. Median time to neutrophil and platelet recovery was 7.5 days (range: 0-32) and 46 days (range: 8-111), respectively. Cumulative incidences of grade II-IV, grade III-IV acute, and chronic graft-versus-host disease (aGVHD, cGVHD) were 57% (95% confidence interval [CI]: 43%-70%), 25% (95% CI: 14%-35%), and 19% (95% CI: 9%-29%), respectively. Transplant-related mortality at 3 years was 15% (95% CI: 5%-26%). Median follow-up was 23 months. The progression free-survival (PFS), current PFS and overall survival (OS) were 34% (95% CI: 21%-47%), 49% (95% CI: 36%-62%), and 55% (95% CI: 42%-70%) at 3 years. Based on our data, we conclude that a nonmyeloablative conditioning regimen followed by UCB transplantation is an effective treatment for patients with advanced lymphoid malignancies who lack a suitable sibling donor.
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Costs of hematopoietic cell transplantation: comparison of umbilical cord blood and matched related donor transplantation and the impact of posttransplant complications.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-14-2009
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Allogeneic hematopoietic cell transplantation (HCT) is a complex and costly procedure. Unrelated umbilical cord blood (UCB) is an alternative graft source for patients without matched related donors (MRD); however, costs of UCB HCT have not been described. We compared the costs of HCT within the first 100 days among recipients of MRD (myeloablative = 67, nonmyeloablative = 54) or UCB (myeloablative = 63, nonmyeloablative = 110) HCT. Cost and hospitalization data were obtained from the institutional accounting department. The 100-day probabilities of overall survival (OS) and cumulative incidence of treatment-related mortality (TRM) were comparable among 4 transplant types; however, neutrophil recovery was delayed and graft failure was more likely in UCB recipients. The median cost per day survived (excluding costs of graft acquisition) was $1016 for myeloablative MRD, $2082 for myeloablative UCB, $612 for nonmyeloablative MRD, and $1156 for nonmyeloablative UCB recipients, respectively (P < .001). In multivariate analysis, adjusting for important patient, disease, and HCT-related characteristics, as well as major post-HCT complications, factors associated with higher costs within the first 100 days were myeloablative UCB HCT (relative risk 1.3 [95% confidence intervals, 1.1-1.5] versus myeloablative MRD HCT), graft failure (1.8 [1.7-1.9]), need for dialysis (1.3 [1.1-1.5]) or mechanical ventilation (1.3 [1.2-1.4]) and total hospital stay in the highest tertile (>48 days; 2.1 [1.9-2.3]). The median cost per day survived for patients with graft failure was $6976 (versus $1105 for no graft failure), dialysis was $4764 (versus $1102 for no dialysis), and $5099 for mechanical ventilation (versus $977 for no mechanical ventilation). Within the first 100 days, the absolute costs of myeloablative and nonmyeloablative UCB are higher than myeloablative and nonmyeloablative MRD transplantation. These costs are primarily driven by severe posttransplant complications, graft failure, and prolonged inpatient stay. Strategies to enhance engraftment will decrease the costs of UCB transplantation.
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Hematopoietic cell transplantation in 2020: summary of year 2 recommendations of the National Marrow Donor Programs System Capacity Initiative.
Biol. Blood Marrow Transplant.
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The National Marrow Donor Program, in partnership with the American Society for Blood and Marrow Transplantation, sponsored and organized a series of symposia to identify complex issues affecting the delivery of hematopoietic cell transplantation (HCT) and to collaboratively develop options for solutions. "Hematopoietic Cell Transplantation in 2020: A System Capacity Initiative" used a deliberative process model to engage professional organizations, experts, transplant centers, and stakeholders in a national collaborative effort. Year 2 efforts emphasized data analysis and identification of innovative ideas to increase HCT system efficiency, address future capacity requirements, and ensure adequate reimbursement for HCT programs to meet the projected need for HCT. This report highlights the deliberations and recommendations of Year 2 and the associated symposium held in September 2011.
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Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation.
Rev Bras Hematol Hemoter
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Advances in hematopoietic cell transplantation (HCT) technology and supportive care techniques have led to improvements in long-term survival after HCT. Emerging indications for transplantation, introduction of newer graft sources (e.g. umbilical cord blood) and transplantation of older patients using less intense conditioning regimens have also contributed to an increase in the number of HCT survivors. These survivors are at risk for developing late complications secondary to pre-, periand post-transplant exposures and risk-factors. Guidelines for screening and preventive practices for HCT survivors were published in 2006. An international group of transplant experts was convened in 2011 to review contemporary literature and update the recommendations while considering the changing practice of transplantation and international applicability of these guidelines. This review provides the updated recommendations for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT.
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Late effects in hematopoietic cell transplant recipients with acquired severe aplastic anemia: a report from the late effects working committee of the center for international blood and marrow transplant research.
Biol. Blood Marrow Transplant.
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With improvements in hematopoietic cell transplant (HCT) outcomes for severe aplastic anemia (SAA), there is a growing population of SAA survivors after HCT. However, there is a paucity of information regarding late effects that occur after HCT in SAA survivors. This study describes the malignant and nonmalignant late effects in survivors with SAA after HCT. A descriptive analysis was conducted of 1718 patients post-HCT for acquired SAA between 1995 and 2006 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The prevalence and cumulative incidence estimates of late effects are reported for 1-year HCT survivors with SAA. Of the HCT recipients, 1176 (68.5%) and 542 (31.5%) patients underwent a matched sibling donor (MSD) or unrelated donor (URD) HCT, respectively. The median age at the time of HCT was 20 years. The median interval from diagnosis to transplantation was 3 months for MSD HCT and 14 months for URD HCT. The median follow-up was 70 months and 67 months for MSD and URD HCT survivors, respectively. Overall survival at 1 year, 2 years, and 5 years for the entire cohort was 76% (95% confidence interval [CI]: 74-78), 73% (95% CI: 71-75), and 70% (95% CI: 68-72). Among 1-year survivors of MSD HCT, 6% had 1 late effect and 1% had multiple late effects. For 1-year survivors of URD HCT, 13% had 1 late effect and 2% had multiple late effects. Among survivors of MSD HCT, the cumulative incidence estimates of developing late effects were all <3% and did not increase over time. In contrast, for recipients of URD HCT, the cumulative incidence of developing several late effects exceeded 3% by 5 years: gonadal dysfunction 10.5% (95% CI: 7.3-14.3), growth disturbance 7.2% (95% CI: 4.4-10.7), avascular necrosis 6.3% (95% CI: 3.6-9.7), hypothyroidism 5.5% (95% CI: 2.8-9.0), and cataracts 5.1% (95% CI: 2.9-8.0). Our results indicated that all patients undergoing HCT for SAA remain at risk for late effects, must be counseled about, and should be monitored for late effects for the remainder of their lives.
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Patient Satisfaction with Physician Discussions of Treatment Impact on Fertility, Menopause and Sexual Health among Pre-menopausal Women with Cancer.
J Cancer
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Pre-menopausal women with cancer are at risk of therapy-associated infertility, premature menopause, and sexual dysfunction. However, it is unknown whether oncologists adequately address these risks during treatment planning. We conducted a study to evaluate physician-patient discussions addressing the impact of cancer treatment and actual treatment effects on fertility, menopause status, and general sexual health.
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Costs and cost-effectiveness of hematopoietic cell transplantation.
Biol. Blood Marrow Transplant.
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Interest is growing in economic and comparative effectiveness analyses, with increasing emphasis on optimizing healthcare resources and costs. Limited information is available on the economic aspects of hematopoietic cell transplantation (HCT). We review contemporary literature on the costs and cost-effectiveness of HCT in the United States and worldwide. Published studies confirm the high costs associated with HCT, although the reported costs are highly variable, related to the differing methodologies used across studies. We examine the challenges in reviewing costs and cost-effectiveness across studies specific to HCT and highlight factors identified as associated with higher costs of HCT. We also discuss opportunities for future research in this area.
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Long-term survival and late deaths after hematopoietic cell transplantation for primary immunodeficiency diseases and inborn errors of metabolism.
Biol. Blood Marrow Transplant.
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It is uncertain whether late mortality rates after hematopoietic cell transplantation for severe combined immunodeficiency (SCID), non-SCID primary immunodeficiency diseases (non-SCID PIDD), and inborn errors of metabolism (IEM) return to rates observed in the general population, matched for age, sex, and nationality. We studied patients with SCID (n = 201), non-SCID PIDD (n = 405), and IEM (n = 348) who survived for at least 2 years after transplantation with normal T cell function (SCID) or >95% donor chimerism (non-SCID PIDD and IEM). Importantly, mortality rate was significantly higher in these patients compared with the general population for several years after transplantation. The rate decreased toward the normal rate in patients with SCID and non-SCID PIDD beyond 6 years after transplantation, but not in patients with IEM. Active chronic graft-versus-host disease at 2 years was associated with increased risk of late mortality for all diseases (hazard ratio [HR], 1.87; P = .05). In addition, late mortality was higher in patients with non-SCID PIDD who received T cell-depleted grafts (HR 4.16; P = .007) and in patients with IEM who received unrelated donor grafts (HR, 2.72; P = .03) or mismatched related donor grafts (HR, 3.76; P = .01). The finding of higher mortality rates in these long-term survivors for many years after transplantation confirms the need for long-term surveillance.
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A prognostic index for survival among mechanically ventilated hematopoietic cell transplant recipients.
Biol. Blood Marrow Transplant.
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The prognosis of recipients of allogeneic hematopoietic cell transplantation (HCT) who require mechanical ventilation (MV) has historically been poor. Of 883 adults undergoing allogeneic HCT at the University of Minnesota between 1998 and 2009, 179 (20%) required MV before day 100 posttransplantation. We evaluated the outcomes of these patients to develop a prognostic index to predict the 100-day post-MV overall survival (OS) based on factors present at the time of MV. The 179 patients were divided at random into a training set (n = 119) and a validation set (n = 60). The 100-day postventilation OS was 17% for the total population. Multivariate Cox regression on the training set identified creatinine <2 mg/dL and platelet count >20 × 10(9)/L as significant predictors of better OS. Recursive partitioning classified patients with these good prognostic criteria into class A (n = 76); all other patients were classified as class B (n = 103). Among class A patients, 100-day OS was 29% in the training set and 30% in the validation set. Corresponding OS in class B patients was 5% and 15%, respectively. This prognostic index should help guide physicians in counseling HCT patients and their families regarding the use of MV and potential outcomes.
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Bone loss and avascular necrosis of bone after hematopoietic cell transplantation.
Semin. Hematol.
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Advances in transplantation technology and supportive care measures have resulted in significant decrease in early mortality resulting in continued growth in the number of long-term hematopoietic cell transplantation (HCT) survivors. The intensity of chemotherapy and total body irradiation regimen used pretransplantation to eradicate the primary disease can lead to organ toxicities, including significant bone complications after HCT. Bone loss is frequent in HCT recipients and results from impaired bone mineralization through disturbances of calcium and vitamin D homeostasis, osteoblast and osteoclast dysfunction, and deficiencies in growth or gonadal hormone secretion. Exposure to glucocorticoids and calcineurin inhibitors for prevention and treatment of graft-versus-host disease (GVHD) represents one of the major causes for the increased risk of osteoporosis and avascular necrosis of bone (AVN) in recipients of allogeneic HCT. In this article we review the incidence, pathogenesis, and risk factors for osteoporosis and AVN after allogeneic HCT and discuss general guidelines for their treatment and monitoring based on the limited available reports.
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