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Find video protocols related to scientific articles indexed in Pubmed.
Impact of chronic graft-versus-host disease on late relapse and survival on 7489 patients after myeloablative allogeneic hematopoietic cell transplantation for leukemia.
Clin. Cancer Res.
PUBLISHED: 10-29-2014
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Purpose: Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year post-transplant at the time when acute GVHD is still active. Experimental design: The current study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7489 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) who were leukemia-free at12 months after myeloablative allogeneic HCT. Results: Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on relapse was present only in patients with CML (RR: 0.47, 95% CI: 0.37-0.59, P <0.0001). cGVHD was significantly associated with higher risk of treatment related mortality, (RR: 2.43, 95% CI: 2.09-2.82, P <0.0001) and inferior overall survival (RR: 1.56, 95% CI: 1.41-1.73, P <0.0001) for all diseases. In patients with CML all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse. Conclusions: These results indicate that clinically relevant anti-leukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL or MDS. Chronic GVHD in patients who are one year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival.
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XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells.
Oncotarget
PUBLISHED: 06-23-2014
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Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML blasts, differentiation-based therapies are a promising therapeutic approach. Based on public available gene expression profiles, a myeloid-specific differentiation-associated gene expression pattern was defined as the therapeutic target. A XIAP inhibitor (Dequalinium chloride, DQA) was identified in an in silico screening searching for small molecules that induce similar gene expression regulation. Treatment with DQA, similarly to Embelin (another XIAP inhibitor), induced cytotoxicity and differentiation in AML. XIAP inhibition differentially impaired cell viability of the most primitive AML blasts and reduced clonogenic capacity of AML cells, sparing healthy mature blood and hematopoietic stem cells. Taken together, these results suggest that XIAP constitutes a potential target for AML treatment and support the evaluation of XIAP inhibitors in clinical trials.
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Noninvasive characterization of the healthy human manubrium using diffuse optical spectroscopies.
Physiol Meas
PUBLISHED: 06-05-2014
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The abnormal, uncontrolled production of blood cells in the bone marrow causes hematological malignancies which are common and tend to have a poor prognosis. These types of cancers may alter the hemodynamics of bone marrow. Therefore, noninvasive methods that measure the hemodynamics in the bone marrow have a potential impact on the earlier diagnosis, more accurate prognosis, and in treatment monitoring. In adults, the manubrium is one of the few sites of bone marrow that is rich in hematopoietic tissue and is also relatively superficial and accessible. To this end we have combined time resolved spectroscopy and diffuse correlation spectroscopy to evaluate the feasibility of the noninvasive measurement of the hemodynamics properties of the healthy manubrium in 32 subjects. The distribution of the optical properties (absorption and scattering) and physiological properties (hemoglobin concentration, oxygen saturation and blood flow index) of this tissue are presented as the first step toward investigating its pathology.
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Timing of CMV-specific effector memory T cells predicts viral replication and survival after allogeneic hematopoietic stem cell transplantation.
Transpl. Int.
PUBLISHED: 04-09-2014
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The aim of this study was to characterize timing, kinetic, and magnitude of CMV-specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV-specific T-cell response was measured in blood, while CMV viral load and chimerism were determined by real-time PCR. Patients that reconstituted CMV-specific T-cell response within 6 weeks after Allo-SCT showed a more robust immune response (CD8(+) : 0.7 cells/?l vs. 0.3/?l; P-value = 0.01), less incidence of CMV replication (33% vs. 89.5%; P-value = 0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P-value = 0.04), and better overall survival (72%; CI: 0.53-0.96 vs. 42% CI: 0.24-0.71; P-value = 0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant-related mortality than nonviremic patients after 1 year (33% CI: 0.15-0.52 vs. 0% CI: 0.05-0.34; P-value = 0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV-positive serostatus (P-value = 0.02) and acquiring CMV-specific T-cell response after 6 weeks post-transplantation (P-value = 0.009). In conclusion, timing of acquiring a positive CMV-specific T-cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival.
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Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry.
Haematologica
PUBLISHED: 01-31-2014
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Paroxysmal nocturnal hemoglobinuria is a rare, acquired disease associated with hemolytic anemia, bone marrow failure, thrombosis, and, frequently, poor quality of life. The International PNH Registry is a worldwide, observational, non-interventional study collecting safety, effectiveness, and quality-of-life data from patients with a confirmed paroxysmal nocturnal hemoglobinuria diagnosis or detectable paroxysmal nocturnal hemoglobinuria clone, irrespective of treatment. In addition to evaluating the long-term safety and effectiveness of eculizumab in a global population, the registry aims to improve diagnosis, optimize patient management and outcomes, and enhance the understanding of the natural history of paroxysmal nocturnal hemoglobinuria. Here we report the characteristics of the first 1610 patients enrolled. Median disease duration was 4.6 years. Median granulocyte paroxysmal nocturnal hemoglobinuria clone size was 68.1% (range 0.01-100%). Overall, 16% of patients had a history of thrombotic events and 14% a history of impaired renal function. Therapies included anticoagulation (31%), immunosuppression (19%), and eculizumab (25%). Frequently reported symptoms included fatigue (80%), dyspnea (64%), hemoglobinuria (62%), abdominal pain (44%), and chest pain (33%). Patients suffered from poor quality of life; 23% of patients had been hospitalized due to paroxysmal nocturnal hemoglobinuria-related complications and 17% stated that paroxysmal nocturnal hemoglobinuria was the reason they were not working or were working less. This international registry will provide an ongoing, valuable resource to further the clinical understanding of paroxysmal nocturnal hemoglobinuria.
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Gene and miRNA expression profiles of hematopoietic progenitor cells vary depending on their origin.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-21-2014
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Hematopoietic progenitor cells (HPCs) from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood (G-PB), bone marrow (BM), or umbilical cord blood (CB) have differing biological properties and differing kinetics of engraftment post-transplantation, which might be explained, at least in part, by differing gene and miRNA expression patterns. To assess the differences in gene and miRNA expression, we analyzed whole genome expression profiles as well as the expression of 384 miRNAs in CD34(+) cells isolated from 18 healthy individuals (6 individuals per subtype of HPC source). We identified 43 genes and 36 miRNAs differentially expressed in the various CD34(+) cell sources. We observed that CD34(+) cells from CB and BM showed similar gene and miRNA expression profiles, whereas CD34(+) cells from G-PB had a very different expression pattern. Remarkably, 20 of the differentially expressed genes are targets of the differentially expressed miRNAs. Of note, the majority of genes differentially expressed in CD34(+) cells from G-PB are involved in cell cycle regulation, promoting the process of proliferation, survival, hematopoiesis, and cell signaling, and are targets of overexpressed and underexpressed miRNAs in CD34(+) cells from the same source. These data suggest significant differences in gene and miRNA expression among the various HPC sources used in transplantation. We hypothesize that the differentially expressed genes and miRNAs involved in cell cycle and proliferation might explain the differing kinetics of engraftment observed after transplantation of hematopoietic stem cells obtained from these different sources.
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The Granulocyte colony-stimulating factor produces long-term changes on gene and miRNA expression profiles in CD34+ cells from healthy donors.
Haematologica
PUBLISHED: 09-20-2013
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The Granulocyte-colony stimulating factor is the most commonly used cytokine for the mobilization of hematopoietic progenitor cells from healthy donors for the allogeneic stem cell transplantation. Although the administration of this cytokine is considered safe, the knowledge about its long-term effects, especially in hematopoietic progenitor cells, is limited. With this background, the aim of our study was to analyze whether or not the Granulocyte-colony stimulating factor might induce changes on gene and miRNA expression profiles in hematopoietic progenitor cells from healthy donors, and to determine whether or not these changes persist at the long-term. For this purpose, we analyzed the whole genome expression profile and the expression of 384 miRNAs in CD34+ cells isolated from peripheral blood of 6 healthy donors, before the mobilization and at 5, 30 and 365 days post-mobilization with the Granulocyte-colony stimulating factor. Six miRNAs were differentially expressed at all time points analyzed after mobilization treatment as compared to samples obtained before exposure to the drug. In addition, 2424 genes were also differentially expressed for at least 1 year post-mobilization. Of interest, 109 of these genes are targets of the differentially expressed miRNAs also identified in this study. These data strongly suggest that the Granulocyte-colony stimulating factor modifies gene and miRNA expression profiles in hematopoietic progenitor cells from healthy donors. Remarkably, some changes are observed from early time-points and persist at least 1 year after exposure to the drug. This effect on hematopoietic progenitor cells has not been previously reported.
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Self-renewing human bone marrow mesenspheres promote hematopoietic stem cell expansion.
Cell Rep
PUBLISHED: 02-28-2013
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Strategies for expanding hematopoietic stem cells (HSCs) include coculture with cells that recapitulate their natural microenvironment, such as bone marrow stromal stem/progenitor cells (BMSCs). Plastic-adherent BMSCs may be insufficient to preserve primitive HSCs. Here, we describe a method of isolating and culturing human BMSCs as nonadherent mesenchymal spheres. Human mesenspheres were derived from CD45- CD31- CD71- CD146+ CD105+ nestin+ cells but could also be simply grown from fetal and adult BM CD45--enriched cells. Human mesenspheres robustly differentiated into mesenchymal lineages. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased self-renewal, they promoted enhanced expansion of cord blood CD34+ cells through secreted soluble factors. Expanded HSCs were serially transplantable in immunodeficient mice and significantly increased long-term human hematopoietic engraftment. These results pave the way for culture techniques that preserve the self-renewal of human BMSCs and their ability to support functional HSCs.
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Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria.
Br. J. Haematol.
PUBLISHED: 01-17-2013
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Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival.
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Impact of global and gene-specific DNA methylation pattern in relapsed multiple myeloma patients treated with bortezomib.
Leuk. Res.
PUBLISHED: 01-16-2013
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We studied seventy-five patients with relapsed MM treated with bortezomib-based regimens. DNA was isolated from bone marrow samples at the time of relapse. Global methylation was determined by ELISA, and CpG island DNA methylation profile of 30 genes by a DNA methylation PCR system. Patients with more than 3.95% of total DNA methylated achieved better overall survival (OS) (p=0.004). A relatively low methylation percentage (<1.07%) of NFKB1 was also associated with longer OS after bortezomib treatment (p=0.015). The combination of highly methylated global genome with low NFKB1 methylation status defined a specific subset of patients with better prognosis.
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Risk factors for acute GVHD and survival after hematopoietic cell transplantation.
Blood
PUBLISHED: 10-18-2011
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Risk factors for acute GVHD (AGVHD), overall survival, and transplant-related mortality were evaluated in adults receiving allogeneic hematopoietic cell transplants (1999-2005) from HLA-identical sibling donors (SDs; n = 3191) or unrelated donors (URDs; n = 2370) and reported to the Center for International Blood and Marrow Transplant Research, Minneapolis, MN. To understand the impact of transplant regimen on AGVHD risk, 6 treatment categories were evaluated: (1) myeloablative conditioning (MA) with total body irradiation (TBI) + PBSCs, (2) MA + TBI + BM, (3) MA + nonTBI + PBSCs, (4) MA + nonTBI + BM, (5) reduced intensity conditioning (RIC) + PBSCs, and (6) RIC + BM. The cumulative incidences of grades B-D AGVHD were 39% (95% confidence interval [CI], 37%-41%) in the SD cohort and 59% (95% CI, 57%-61%) in the URD cohort. Patients receiving SD transplants with MA + nonTBI + BM and RIC + PBSCs had significantly lower risks of grades B-D AGVHD than patients in other treatment categories. Those receiving URD transplants with MA + TBI + BM, MA + nonTBI + BM, RIC + BM, or RIC + PBSCs had lower risks of grades B-D AGVHD than those in other treatment categories. The 5-year probabilities of survival were 46% (95% CI, 44%-49%) with SD transplants and 33% (95% CI, 31%-35%) with URD transplants. Conditioning intensity, TBI and graft source have a combined effect on risk of AGVHD that must be considered in deciding on a treatment strategy for individual patients.
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Risk factors associated with increased nonrelapse mortality and with poor overall survival in children with chronic graft-versus-host disease.
Blood
PUBLISHED: 08-30-2011
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There is a paucity of information regarding the factors that affect nonrelapse mortality (NRM) and overall survival among children that develop chronic graft-versus-host disease (cGVHD). We performed multivariate analyses using data from the Center for International Blood and Marrow Transplant Research to identify risk factors for NRM and survival in 1117 pediatric subjects with leukemia or myelodysplastic syndrome, transplanted from related donors, unrelated donors (URD), or unrelated cord blood between 1995 and 2004. We identified 4 variables associated with higher NRM: HLA partially matched or mismatched URD, peripheral blood cell graft, Karnofsky/Lansky score < 80 at cGVHD diagnosis, and platelets < 100 × 10(9)/L at cGVHD diagnosis. Factors associated with significantly worse survival were: age > 10 years, transplantation from HLA partially matched or mismatched URD, advanced disease at transplantation, Karnofsky/Lansky < 80; and platelets < 100 × 10(9)/L. Cumulative incidence of discontinuation of systemic immune suppression at 1, 3, and 5 years after diagnosis of cGVHD were 22% (20%-25%), 34% (31%-37%), and 37% (34%-40%), respectively. This is the largest study elucidating variables affecting outcome after diagnosis of cGVHD in pediatric allograft recipients. These variables may be useful for risk stratification, development of future clinical trials, and family counseling in children with cGVHD.
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Chronic GVHD risk score: a Center for International Blood and Marrow Transplant Research analysis.
Blood
PUBLISHED: 04-14-2011
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Several risk factors are associated with increased mortality in patients with chronic graft-versus-host disease (cGVHD), but there is considerable variability in the reported factors. Therefore, we evaluated patient, transplantation, and cGVHD characteristics to develop a risk score in 5343 patients with cGVHD. Ten variables were identified as being significant in multivariate analysis of overall survival and nonrelapse mortality (NRM): age, prior acute GVHD, time from transplantation to cGVHD, donor type, disease status at transplantation, GVHD prophylaxis, gender mismatch, serum bilirubin, Karnofsky score, and platelet count. These 10 variables were used to build a cGVHD risk score, and 6 risk groups (RGs) were identified. The 5-year NRM was 5% (1%-9%) in RG1, 20% (19%-23%) in RG2, 33% (29%-37%) in RG3, 43% (40%-46%) in RG4, 63% (53%-74%) in RG5, and 72% (59%-85%) in RG6. The 5-year overall survival was highest at 91% (95% confidence interval [CI]:85%-97%) in RG1, followed by 67% (65%-69%) in RG2, 51% (46%-55%) in RG3, 40% (37%-43%) in RG4, 21% (12%-30%) in RG5, and 4% (0%-9%) in RG6 (all P < .01). This analysis demonstrates the usefulness of data from a large registry to develop risk-score categories for major transplantation outcomes. Validation of this cGVHD risk score is needed in a different population to ensure its broad applicability.
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Genomic polymorphisms of the innate immune system and allogeneic stem cell transplantation.
Expert Rev Hematol
PUBLISHED: 11-19-2010
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Allogeneic stem cell transplantation (allo-HSCT) is largely employed for treating patients affected by many hematological disorders, but despite the considerable improvement in the treatment of its complications, graft-versus-host disease and infections remain important causes of morbidity and mortality. Innate immunity is crucial in the immune defense against infections after allo-HSCT, and in the biological reactions leading to graft-versus-host disease. Thus, the innate immune system plays an important role in allo-HSCT clinical outcome. It is known now that cytokine gene polymorphisms greatly influence the outcome of allo-HSCT. In addition, genetic variability of some pattern-recognition receptors and antimicrobial peptides represent a promising field to be researched for allo-HSCT impact. Furthermore, more recent work suggests the importance of genetic variability between donor and recipient in the killer cell immunoglobulin-like receptors of the natural killer cells on the allo-HSCT outcome. This article discusses the main cytokines and innate immune gene polymorphisms influencing allo-HSCT outcome, presents new innate immune genes with promising expectations and points at the importance of genetic variability in natural killer cells in allo-HSCT outcome.
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Impact of constitutional polymorphisms in VCAM1 and CD44 on CD34+ cell collection yield after administration of granulocyte colony-stimulating factor to healthy donors.
Haematologica
PUBLISHED: 09-17-2010
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Background The number of CD34(+) cells mobilized from bone marrow to peripheral blood after administration of granulocyte colony-stimulating factor varies greatly among healthy donors. This fact might be explained, at least in part, by constitutional differences in genes involved in the interactions tethering CD34(+) cells to the bone marrow.
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Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria.
Am. J. Hematol.
PUBLISHED: 07-27-2010
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Paroxysmal nocturnal hemoglobinuria (PNH) is a debilitating and life-threatening disease in which lysis of PNH red blood cells frequently manifests with chronic hemolysis, anemia, and thrombosis. Renal damage in PNH is associated with chronic hemosiderosis and/or microvascular thrombosis. We determined the incidence of renal dysfunction or damage, defined by stages of chronic kidney disease (CKD), in a large cohort of PNH patients and evaluated the safety and efficacy of the complement inhibitor eculizumab in altering its progression. Renal dysfunction or damage was observed in 65% of the study population at baseline with 21% of patients with later stage CKD or kidney failure (glomerular filtration rate [GFR]
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Comparison of outcomes after transplantation of G-CSF-stimulated bone marrow grafts versus bone marrow or peripheral blood grafts from HLA-matched sibling donors for patients with severe aplastic anemia.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-18-2010
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We compared outcomes of patients with severe aplastic anemia (SAA) who received granulocyte-colony stimulating factor (G-CSF)-stimulated bone marrow (G-BM) (n = 78), unstimulated bone marrow (BM) (n = 547), or peripheral blood progenitor cells (PBPC) (n = 134) from an HLA-matched sibling. Transplantations occurred in 1997 to 2003. Rates of neutrophil and platelet recovery were not different among the 3 treatment groups. Grade 2-4 acute graft-versus-host disease (aGVHD) (relative risk [RR] = 0.82, P = .539), grade 3-4 aGVHD (RR = 0.74, P = .535), and chronic GVHD (cGVHD) (RR = 1.56, P = .229) were similar after G-BM and BM transplants. Grade 2-4 aGVHD (RR = 2.37, P = .012) but not grade 3-4 aGVHD (RR = 1.66, P = .323) and cGVHD (RR = 5.09, P < .001) were higher after PBPC transplants compared to G-BM. Grade 2-4 (RR = 2.90, P < .001), grade 3-4 (RR = 2.24, P = .009) aGVHD and cGVHD (RR = 3.26, P < .001) were higher after PBPC transplants compared to BM. Mortality risks were lower after transplantation of BM compared to G-BM (RR = 0.63, P = .05). These data suggest no advantage to using G-BM and the observed higher rates of aGVHD and cGVHD in PBPC recipients warrants cautious use of this graft source for SAA. Taken together, BM is the preferred graft for HLA-matched sibling transplants for SAA.
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Differences in cytomegalovirus plasma viral loads measured in allogeneic hematopoietic stem cell transplant recipients using two commercial real-time PCR assays.
J. Clin. Virol.
PUBLISHED: 03-12-2010
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Quantitative detection of cytomegalovirus (CMV) DNAemia by real-time PCR is currently the primary choice for the surveillance of active CMV infection in allogeneic stem cell transplant (Allo-SCT) recipients. Nevertheless, no universally accepted standards for CMV viral load quantitation are available, this being critical when clinical studies involving various participant centers that use different assays are planned.
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Severe events in donors after allogeneic hematopoietic stem cell donation.
Haematologica
PUBLISHED: 02-13-2009
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The risk for donors of allogeneic hematopoietic stem cells transplants is generally considered negligible. Scattered reports of severe complications and a recent controversy on hematopoietic malignancies after granulocyte colony-stimulating factor administration have challenged this opinion.
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Hematopoietic stem cell transplantation in Europe. Differences between Eastern and Western countries.
Hematology
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Hemopoietic stem cell transplantation (HSCT) is increasingly used worldwide. The geographical distribution of this procedure is not homogenous within a particular continent. We have previously reviewed these differences in the use of bone marrow transplant in Europe, and in two reports we emphasized the economical reasons explaining these differences. The increasing demand for this high cost procedure represents a challenge for health care institutions. While patients need an optimal therapy, public health is confronted with limited resources. Information on changes in HSCT technology and on factors associated with its utilization might be of help. Insights into mechanisms of HSCT use are essential for rational decision making.
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HLA DR15 antigen status does not impact graft-versus-host disease or survival in HLA-matched sibling transplantation for hematologic malignancies.
Biol. Blood Marrow Transplant.
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The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.