JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Dextramer reagents are effective tools for quantifying CMV antigen-specific T cells from peripheral blood samples.
Cytometry B Clin Cytom
PUBLISHED: 04-04-2014
Show Abstract
Hide Abstract
The enumeration of antigen-specific T cells is increasingly relevant in clinical and research settings. This information is useful for evaluating immune responses to treatment, monitoring the efficacy of anticancer vaccines, and for detecting self-reactive T cells in autoimmune disorders. Quantifying antigen-specific T cells can be accomplished via IFN? ELISpot assay, the measurement of intracellular cytokine production by flow cytometry, or by lymphocyte proliferation assays in response to antigen. While robust, these technologies are labor-intensive and can take several days to obtain results. New technology has led to more powerful tools for quickly and accurately measuring antigen-specific T cells by flow cytometry via fluorescently-labeled TCR-specific multimers. In this study, we evaluated the use of an assay based on Dextramer reagents for enumerating cytomegalovirus (CMV) antigen-specific T cells (CASTs). Assay performance characteristics were assessed by establishing Dextramers' sensitivity (median?=?0.4; range?=?0.1-1.4 CASTs ?l(-1) ), determining their specificity (100%), evaluating assay robustness with different leukocyte sources and assay reproducibility via interlaboratory and interinstrument investigations. Furthermore, the levels of CASTs in 95 peripheral blood samples from 62 unique blood and marrow transplants recipients correlated well between Dextramers and Tetramers (R(2) ?=?0.9042). © 2014 International Clinical Cytometry Society.
Related JoVE Video
Dextramer reagents are effective tools for quantifying CMV antigen-specific T cells from peripheral blood samples.
Cytometry B Clin Cytom
PUBLISHED: 04-04-2014
Show Abstract
Hide Abstract
The enumeration of antigen-specific T cells is increasingly relevant in clinical and research settings. This information is useful for evaluating immune responses to treatment, monitoring the efficacy of anti-cancer vaccines, and for detecting self-reactive T cells in autoimmune disorders. Quantifying antigen-specific T cells can be accomplished via IFN? ELISpot assay, the measurement of intracellular cytokine production by flow cytometry, or by lymphocyte proliferation assays in response to antigen. While robust, these technologies are labor-intensive and can take several days to obtain results. New technology has led to more powerful tools for quickly and accurately measuring antigen-specific T cells by flow cytometry via fluorescently-labeled TCR-specific multimers. In this study, we evaluated the use of an assay based on Dextramer reagents for enumerating cytomegalovirus (CMV) antigen-specific T cells (CASTs). Assay performance characteristics were assessed by establishing Dextramers' sensitivity (median = 0.4; range = 0.1 - 1.4 CASTs µL(-1) ), determining their specificity (100%), evaluating assay robustness with different leukocyte sources and assay reproducibility via inter-laboratory and inter-instrument investigations. Furthermore, the levels of CASTs in 95 peripheral blood samples from 62 unique BMT recipients correlated well between Dextramers and Tetramers (R(2) = 0.9042). © 2014 Clinical Cytometry Society.
Related JoVE Video
Early versus late preemptive allogeneic hematopoietic cell transplantation for relapsed or refractory acute myeloid leukemia.
Biol. Blood Marrow Transplant.
PUBLISHED: 03-20-2014
Show Abstract
Hide Abstract
Many patients with relapsed or refractory acute myeloid leukemia (AML) do not receive allogeneic hematopoietic cell transplantation (alloHCT) because they are unable to achieve a complete remission (CR) after reinduction chemotherapy. Starting in January 2003, we prospectively assigned patients with AML with high-risk clinical features to preemptive alloHCT (p-alloHCT) as soon as possible after reinduction chemotherapy. High-risk clinical features were associated with poor response to chemotherapy: primary induction failure, second or greater relapse, and first CR interval <6 months. We hypothesized that any residual disease would be maximally reduced at the time of transplant, resulting in the best milieu and most lead time for developing a graft-versus-leukemia effect and in improved long-term overall survival (OS) without excess toxicity. This analysis studied the effect of transplant timing on p-alloHCT in 30 patients with high-risk clinical features of 156 consecutive AML patients referred for alloHCT. We compared early p-alloHCT within 4 weeks of reinduction chemotherapy before count recovery with late p-alloHCT 4 weeks after reinduction chemotherapy with count recovery. OS and progression-free survival (PFS) at 2 years were not significantly different for early versus late p-alloHCT (OS 23% versus 33%, respectively, P > .1; PFS 18% versus 22%, respectively, P > .1). Day 100 and 1-year transplant-related mortality were similar (33.3% versus 22.2%, P > .1; 44.4% versus 42.9%, P > .1, respectively). Preemptive alloHCT allowed 30 patients to be transplanted who would normally not receive alloHCT. Clinical outcomes for early p-alloHCT are similar to those for late p-alloHCT without excess toxicity. Early p-alloHCT is a feasible alternative to late p-alloHCT for maximizing therapy of AML that is poorly responsive to induction chemotherapy.
Related JoVE Video
Bone health history in breast cancer patients on aromatase inhibitors.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
A cross-sectional study was performed to assess bone health history among aromatase inhibitor (AI) users before breast cancer (BC) diagnosis, which may impact fracture risk after AI therapy and choice of initial hormonal therapy. A total of 2,157 invasive BC patients initially treated with an AI were identified from a prospective cohort study at Kaiser Permanente Northern California (KPNC). Data on demographic and lifestyle factors were obtained from in-person interviews, and bone health history and clinical data from KPNC clinical databases. The prevalence of osteoporosis and fractures in postmenopausal AI users was assessed, compared with 325 postmenopausal TAM users. The associations of bone health history with demographic and lifestyle factors in AI users were also examined. Among all initial AI users, 11.2% had a prior history of osteoporosis, 16.3% had a prior history of any fracture, and 4.6% had a prior history of major fracture. Postmenopausal women who were taking TAM as their initial hormonal therapy had significantly higher prevalence of prior osteoporosis than postmenopausal AI users (21.5% vs. 11.8%, p<0.0001). Among initial AI users, the associations of history of osteoporosis and fracture in BC patients with demographic and lifestyle factors were, in general, consistent with those known in healthy older women. This study is one of the first to characterize AI users and risk factors for bone morbidity before BC diagnosis. In the future, this study will examine lifestyle, molecular, and genetic risk factors for AI-induced fractures.
Related JoVE Video
Fludarabine and cyclophosphamide provides a nonmyeloablative alternative conditioning regimen with low transplant-related mortality and control of high risk disease.
Leuk Res Rep
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Non-myeloablative allogeneic transplant (NMAT) has a curative potential for patients who are not myeloablative allogeneic transplant (MAT) candidates. We report a phase II trial of a NMAT regimen with cyclophosphamide and fludarabine in 40 patients; 21 of whom had a prior MAT. Day +100 and 1-year transplant-related mortality (TRM) post-NMAT were 13% and 34%, respectively. Day +100 and 1-year Overall/Progression-Free Survival (OS/PFS) were 80%/65% and 43%/25%, respectively. OS was higher in patients with KPS?90 and lower in recipient/donor CMV+/- vs. other combinations. FluCy has low TRM and is curative in about 20% of high-risk patients.
Related JoVE Video
Strategies for induction, autologous hematopoietic stem cell transplantation, consolidation, and maintenance for transplantation-eligible multiple myeloma patients.
Hematology Am Soc Hematol Educ Program
PUBLISHED: 12-10-2013
Show Abstract
Hide Abstract
There have been major advances in the past decade in the continuum of therapy for transplantation-eligible multiple myeloma patients. For patients requiring therapy, recommended induction treatment consists of triple drug regimens followed by the collection of hematopoietic stem cells. The question of early versus delayed transplantation is under investigation and may identify patients for whom early transplantation is optimal therapy and those for whom it may be delayed. For transplantation-eligible patients, high-dose melphalan remains the standard regimen. After transplantation, consolidation can be considered for patients with less than a complete remission. Maintenance therapy with bortezomib or lenalidomide (or both in very-high-risk patients) is a reasonable option for long-term disease control and improvement in overall survival. Incorporation of new agents into the continuum of multiple myeloma care should result in improved outcomes and long-term disease control.
Related JoVE Video
Prevalence of hematopoietic cell transplant survivors in the United States.
Biol. Blood Marrow Transplant.
PUBLISHED: 07-01-2013
Show Abstract
Hide Abstract
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.
Related JoVE Video
Unrelated donor allogeneic hematopoietic cell transplantation is underused as a curative therapy in eligible patients from the United States.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-18-2013
Show Abstract
Hide Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) is a curative therapy for hematologic disorders including acute lymphoblastic and myeloid leukemia, chronic lymphocytic and myeloid leukemia, Hodgkins and non-Hodgkin lymphoma, multiple myeloma, and myelodysplastic syndrome. To determine the utilization of alloHCT from unrelated donors (URDs) in the United States, we calculated the number of patients diagnosed with hematologic disorders age 20 to 74 years based on 2004 to 2008 Surveillance, Epidemiology and End Results and 2007 US Census data, estimated the percentage of patients who would be eligible for URD alloHCT after discounting the mortality rate during induction therapy and the rate of severe comorbidities, and compared these with the actual 2007 alloHCTs facilitated by the National Marrow Donor Program. We found that the number of URD alloHCT as a percentage of the estimated potential transplantations ranged from 11% for multiple myeloma to 54% for chronic myeloid leukemia, with an average percentage of 26% for all the disorders considered. In an analysis stratified by age groups (20 to 44, 45 to 64, and 65 to 74 years), the utilization of URD alloHCT was higher in younger patients than in older patients for all disorders. Of acute lymphoblastic and myeloid leukemia patients, approximately 66% underwent URD alloHCT later in the course of their disease (in second or greater complete remission). URD alloHCT is likely underused for potentially curable hematologic disorders, particularly in older patients. Understanding the reasons for low use of alloHCT may lead to strategies to expand the use of this curative therapy for more patients with hematologic disorders.
Related JoVE Video
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
Show Abstract
Hide Abstract
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.
Related JoVE Video
Simplified validated prognostic model for progression-free survival after autologous transplantation for hodgkin lymphoma.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-20-2013
Show Abstract
Hide Abstract
Hodgkin lymphoma (HL) prognostic models based on factors measured at time of autologous hematopoietic cell transplantation (AHCT) are limited by small sample sizes. Models based on information at diagnosis are often not uniformly collected or available at transplantation. We propose an easily implementable prognostic model for progression-free survival (PFS) post-AHCT based on factors available at transplantation in a large international cohort of HL patients. The outcomes of 728 AHCT recipients for relapsed/refractory HL were studied. Patients were randomly selected for model development (n = 337) and validation (n = 391). The multivariate model identified 4 major adverse risk factors at the time of AHCT with the following relative weights: Karnofsky performance score <90 and chemotherapy resistance at AHCT were each assigned 1 point, whereas at least 3 chemotherapy regimens pre-AHCT and extranodal disease at AHCT were each assigned 2 points. Based on the total score summed for the 4 adverse risk factors, 3 risk groups were identified: low (score = 0), intermediate (score = 1 to 3), or high (score = 4 to 6). The 4-year PFS for the low- (n = 176), intermediate- (n = 261), and high- (n = 283) risk groups were 71% (95% confidence interval [CI], 63% to 78%), 60% (95% CI, 53% to 66%), and 42% (95% CI, 36% to 49%), respectively. The prognostic model was validated in an independent cohort. The Center for International Blood and Marrow Transplant Research model is based on factors easily available at the time of AHCT and discriminates patients with favorable post-AHCT outcomes as well as an intermediate-risk group. This model should assist in the prospective evaluation of alternative treatment strategies.
Related JoVE Video
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
Show Abstract
Hide Abstract
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.
Related JoVE Video
Risk factors for acute GVHD and survival after hematopoietic cell transplantation.
Blood
PUBLISHED: 10-18-2011
Show Abstract
Hide Abstract
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.
Related JoVE Video
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
Show Abstract
Hide Abstract
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.
Related JoVE Video
Role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia: update of the 2005 evidence-based review.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-17-2011
Show Abstract
Hide Abstract
Clinical research published since the first evidence-based review on the role of hematopoietic stem cell transplantation (SCT) in the treatment of pediatric acute lymphoblastic leukemia (ALL) is presented and critically evaluated in this update. Treatment recommendations are provided by an expert panel. Allogeneic SCT is recommended for children who: are in second complete remission (CR2) after experiencing an early marrow relapse for precursor-B ALL; experienced primary induction failure, but subsequently achieved a CR1; have T-lineage ALL in CR2; or have ALL in third or greater remission. Although the 2005 pediatric ALL evidence-based review (EBR) recommended allogeneic SCT for children with Philadelphia chromosome positive (Ph+) ALL in CR1, preliminary tyrosine kinase inhibitor (TKI) data demonstrate that early outcomes are comparable for allogeneic SCT and chemotherapy + imatinib. Based on the evidence, autologous SCT is not recommended for ALL in CR1. Allogeneic SCT is not recommended for: T-lineage ALL in CR1; mixed-lineage leukemia (MLL)+ ALL when it is the sole adverse risk factor; isolated central nervous system (CNS) relapse in precursor-B ALL. Based on expert opinion, allogeneic SCT may be considered for hypodiploid ALL and persistent minimal residual disease [corrected] (MRD) positivity in ALL in CR1 or greater, although these are areas that need further study. Treatment recommendations pertaining to various transplantation techniques are also provided, as are areas of needed future research.
Related JoVE Video
Common genetic variants are associated with accelerated bone mineral density loss after hematopoietic cell transplantation.
PLoS ONE
PUBLISHED: 05-19-2011
Show Abstract
Hide Abstract
Bone mineral density (BMD) loss commonly occurs after hematopoietic cell transplantation (HCT). Hypothesizing that genetic variants may influence post-HCT BMD loss, we conducted a prospective study to examine the associations of single nucleotide polymorphisms (SNP) in bone metabolism pathways and acute BMD loss after HCT.
Related JoVE Video
The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukemia: update of the 2006 evidence-based review.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-17-2011
Show Abstract
Hide Abstract
Clinical research published since the first evidence-based review on the role of hematopoietic stem cell transplantation (SCT) in the treatment of acute lymphoblastic leukemia (ALL) in adults is presented and critically evaluated in this update. Treatment recommendations changed or modified based on new evidence include: (1) myeloablative allogeneic SCT is an appropriate treatment for adult (<35 years) ALL in first complete remission for all disease risk groups; and (2) reduced-intensity conditioning may produce similar outcomes to myeloablative regimens. Treatment recommendations unchanged or strengthened by new evidence include: (1) allogeneic SCT is recommended over chemotherapy for ALL in second complete remission or greater; (2) allogeneic is superior to autologous SCT; and (3) there are similar survival outcomes after related and unrelated allogeneic SCT. New treatment recommendations based on new evidence include: (1) in the absence of a suitable allogeneic donor, autologous SCT may be an appropriate therapy, but results in a high relapse rate; (2) it is appropriate to consider cord blood transplantation for patients with no HLA well-matched donor; and (3) imatinib therapy before and/or after SCT (for Ph+ ALL) yields significantly superior survival outcomes. Areas of needed research in the treatment of adult ALL with SCT were identified and presented in the review.
Related JoVE Video
The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of diffuse large B cell lymphoma: update of the 2001 evidence-based review.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-20-2010
Show Abstract
Hide Abstract
Clinical research published since the 2001 evidence-based review on the role of hematopoietic stem cell transplantation (SCT) in the treatment of diffuse large B cell lymphoma (DLBCL) in adults is presented and critically evaluated in this update. Treatment recommendations that remain unchanged from the original review include: (1) autologous SCT as salvage therapy is recommended for patients with chemosensitive relapsed DLBCL; and (2) autologous SCT is not recommended for patients who achieve a partial response to an abbreviated induction regimen. New treatment recommendations based on new published data include: (1) autologous SCT as first-line therapy is not recommended for any IPI group; (2) planned tandem or multiple sequential autologous SCT is not recommended; (3) peripheral blood is the standard stem cell source for autologous SCT; (4) age is not a contraindication for autologous SCT, although outcomes in older adults are not as good as in younger adults. There are insufficient data to make recommendations on the routine use of rituximab maintenance after autologous SCT, autologous versus allogeneic SCT, fewer versus more cycles of induction therapy prior to autologous SCT, or the use of reduced intensity versus myeloablative conditioning regimens. Areas of needed research in the treatment of DLBCL with SCT were identified and are presented in the review.
Related JoVE Video
Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome.
J. Clin. Oncol.
PUBLISHED: 03-08-2010
Show Abstract
Hide Abstract
PURPOSE Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). PATIENTS AND METHODS We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS). RESULTS Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and > or = 65 years had 2-year survival rates as follows: 44% (95% CI, 37% to 52%), 50% (95% CI, 41% to 59%), 34% (95% CI, 25% to 43%), and 36% (95% CI, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% CI, 35% to 49%), 35% (95% CI, 27% to 43%), 45% (95% CI, 36% to 54%), and 38% (95% CI, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P > .3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. CONCLUSION With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.
Related JoVE Video
Obesity does not preclude safe and effective myeloablative hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) in adults.
Biol. Blood Marrow Transplant.
PUBLISHED: 02-16-2010
Show Abstract
Hide Abstract
The incidence of excessive adiposity is increasing worldwide, and is associated with numerous adverse health outcomes. We compared outcomes by body mass index (BMI) for adult patients with acute myelogenous leukemia (AML) who underwent autologous (auto, n = 373), related donor (RD, n = 2041), or unrelated donor (URD, n = 1801) allogeneic myeloablative hematopoietic cell transplantation (HCT) using bone marrow or peripheral blood stem cells reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2004. Four weight groups by BMI (kg/m(2)) were defined: underweight <18 kg/m(2); normal 18-25 kg/m(2); overweight >25-30 kg/m(2); and obese >30 kg/m(2). Multivariable analysis referenced to the normal weight group showed an increased risk of death for underweight patients in the RD group (relative risk [RR], 1.92; 95% confidence interval [CI], 1.28-2.89; P = .002), but not in the URD group. There were no other differences in outcomes among the other weight groups within the other HCT groups. Overweight and obese patients enjoyed a modest decrease in relapse incidence, although this did not translate into a survival benefit. Small numbers of patients limit the ability to better characterize the adverse outcomes seen in the underweight RD but not the underweight URD allogeneic HCT patients. Obesity alone should not be considered a barrier to HCT.
Related JoVE Video
The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of follicular lymphoma: an evidence-based review.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-14-2010
Show Abstract
Hide Abstract
Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in the therapy of follicular non-Hodgkin lymphoma in adults is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations reached unanimously by a panel of follicular lymphoma experts are: (1) autologous SCT is recommended as salvage therapy based on pre-rituximab data, with a significant improvement in overall survival (OS) and progression-free (PFS) survival; (2) autologous SCT is not recommended as first-line treatment for most patients because of no significant improvement in OS; (3) autologous SCT is recommended for transformed follicular lymphoma patients; (4) reduced intensity conditioning before allogeneic SCT appears to be an acceptable alternative to myeloablative regimens; (5) an HLA-matched unrelated donor appears to be as effective an HLA-matched related donor for reduced intensity conditioning allogeneic SCT. There are insufficient data to make a recommendation on the use of autologous SCT after rituximab-based salvage therapy. Eleven areas of needed research in the treatment of follicular lymphoma with SCT were identified and are presented in the review.
Related JoVE Video
Accelerated bone mineral density loss occurs with similar incidence and severity, but with different risk factors, after autologous versus allogeneic hematopoietic cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-13-2010
Show Abstract
Hide Abstract
Bone mineral density (BMD) loss occurs commonly in patients after allogeneic hematopoietic cell transplantation (HCT), primarily because of steroid use, but little is known about BMD change post-autologous HCT. In a prospective study of 206 consecutive first HCT patients, we measured acute BMD change at the lumbar spine and dual femur between baseline and day +100, and evaluated risk factors for bone loss. Accelerated BMD loss in this 4-month period occurred after both autologous and allogeneic HCT with similar severity (median, 0.03 g/cm(2) versus 0.03 g/cm(2) at the spine; 0.03 g/cm(2) versus 0.05 g/cm(2) at the femur, respectively). This is equivalent to 7 to 17 years worth of bone loss by aging. Risk factors for BMD loss were different between autologous and allogeneic HCT patients: lymphoma was associated with greater bone loss after autologous HCT than myeloma, whereas higher steroid dose was the most significant risk factor after allogeneic HCT. Multivariable risk models explained 11% to 30% of the variation in HCT-related BMD change. Surprisingly, BMD loss post-autologous HCT occurred with similar incidence and severity to allogeneic HCT, even in the absence of steroid use. Evaluation of clinical strategies to prevent and reverse HCT-related BMD loss is necessary in both autologous and allogeneic HCT patients.
Related JoVE Video
A deletion polymorphism in glutathione-S-transferase mu (GSTM1) and/or theta (GSTT1) is associated with an increased risk of toxicity after autologous blood and marrow transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-05-2010
Show Abstract
Hide Abstract
Toxicity after blood and marrow transplantation (BMT) has interindividual variability that may be explained by common genetic polymorphisms in critical pathways. The glutathione-S-transferase (GST) isoenzymes detoxify the reactive oxygen species generated by chemotherapy agents and radiation. We investigated whether deletion polymorphisms in 2 GST genes (GSTM1 and GSTT1) were associated with toxicity after autologous or allogeneic BMT. The study population was selected from 699 consecutive BMT patients from 2 centers in Buffalo, NY, and Moscow, Russia, of whom 321 (203 autologous, 118 allogeneic BMT) had available banked samples and amplifiable DNA. Fifty percent of patients were homozygous null for GSTM1, which did not vary by center; however, the GSTT1 homozygous null deletion polymorphism occurred more frequently in patients treated in Moscow (38% versus 18%, P < .001). Overall grade 2-4 regimen-related toxicity occurred in 56%, with nearly 1 in 5 patients having 2 or more organ systems affected. Among autologous BMT patients, a deletion polymorphism in 1 or both genes was significantly associated with increased occurrence of overall toxicity (71% versus 56%, P = .034) and mucositis (74% versus 55%, P = .006). GSTM1 and/or GSTT1 deletion polymorphisms were not associated with toxicity after allogeneic BMT. Future studies may allow for individualized genetic risk stratification.
Related JoVE Video
Outcomes of hematologic malignancies after unrelated donor hematopoietic cell transplantation according to place of residence.
Biol. Blood Marrow Transplant.
PUBLISHED: 10-05-2009
Show Abstract
Hide Abstract
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.
Related JoVE Video
Outcome of transplantation for myelofibrosis.
Biol. Blood Marrow Transplant.
PUBLISHED: 07-10-2009
Show Abstract
Hide Abstract
Myelofibrosis is a myeloproliferative disorder incurable with conventional strategies. Several small series have reported long-term disease-free survival (DSF) after allogeneic hematopoietic cell transplantation (HCT). In this study, we analyze the outcomes of 289 patients receiving allogeneic transplantation for primary myelofibrosis between 1989 and 2002, from the database of the Center for International Bone Marrow Transplant Research (CIBMTR). The median age was 47 years (range: 18-73 years). Donors were HLA identical siblings in 162 patients, unrelated individuals in 101 patients, and HLA nonidentical family members in 26 patients. Patients were treated with a variety of conditioning regimens and graft-versus-host disease (GVHD) prophylaxis regimens. Splenectomy was performed in 65 patients prior to transplantation. The 100-day treatment-related mortality was 18% for HLA identical sibling transplants, 35% for unrelated transplants, and 19% for transplants from alternative related donors. Corresponding 5-year overall survival (OS) rates were 37%, 30%, and 40%, respectively. DFS rates were 33%, 27%, and 22%, respectively. DFS for patients receiving reduced-intensity transplants was comparable: 39% for HLA identical sibling donors and 17% for unrelated donors at 3 years. In this large retrospective series, allogeneic transplantation for myelofibrosis resulted in long-term relapse-free survival (RFS) in about one-third of patients.
Related JoVE Video
Race and socioeconomic status influence outcomes of unrelated donor hematopoietic cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-20-2009
Show Abstract
Hide Abstract
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.
Related JoVE Video
The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation.
Blood
PUBLISHED: 05-02-2009
Show Abstract
Hide Abstract
Do some patients benefit from an unrelated donor (URD) transplant because of a stronger graft-versus-leukemia (GVL) effect? We analyzed 4099 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) undergoing a myeloablative allogeneic hematopoietic cell transplantation (HCT) from an URD (8/8 human leukocyte antigen [HLA]-matched, n=941) or HLA-identical sibling donor (n=3158) between 1995 and 2004 reported to the CIBMTR. In the Cox regression model, acute and chronic GVHD were added as time-dependent variables. In multivariate analysis, URD transplant recipients had a higher risk for transplantation-related mortality (TRM; relative risk [RR], 2.76; P< .001) and relapse (RR, 1.50; P< .002) in patients with AML, but not ALL or CML. Chronic GVHD was associated with a lower relapse risk in all diagnoses. Leukemia-free survival (LFS) was decreased in patients with AML without acute GVHD receiving a URD transplant (RR, 2.02; P< .001) but was comparable to those receiving HLA-identical sibling transplants in patients with ALL and CML. In patients without GVHD, multivariate analysis showed similar risk of relapse but decreased LFS for URD transplants for all 3 diagnoses. In conclusion, risk of relapse was the same (ALL, CML) or worse (AML) in URD transplant recipients compared with HLA-identical sibling transplant recipients, suggesting a similar GVL effect.
Related JoVE Video
The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of myelodysplastic syndromes: an evidence-based review.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-27-2009
Show Abstract
Hide Abstract
Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in the therapy of myelodysplastic syndromes (MDS) in adults is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented in Table 3, and were reached unanimously by a panel of MDS experts. The identified priority areas of needed future research in MDS include: (1) the benefit of using alternative donor sources (eg, cord blood; haploidentical family donors) for patients without matched sibling or unrelated donors; (2) the role and appropriate timing of allogeneic SCT in combination with hypomethylating and immunomodulatory treatment regimens; (3) randomized trials comparing the safety and efficacy of various novel agents for treating MDS; and (4) the influence of the various MDS treatment modalities on patient-reported quality-of-life outcomes.
Related JoVE Video
A comparison of measured creatinine clearance versus calculated glomerular filtration rate for assessment of renal function before autologous and allogeneic BMT.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-22-2009
Show Abstract
Hide Abstract
Common blood and marrow transplantation (BMT) eligibility criteria include a minimum glomerular filtration rate (GFR) that may vary by regimen intensity. GFR is often estimated by measurement of creatinine clearance in a 24-hour urine collection (24-hr CrCl), an inconvenient and error-prone method that overestimates GFR. The study objectives were to determine which of 6 GFR calculations: Cockroft-Gault (CG), modified CG (mCG), Modification of Diet in Renal Disease 1 (MDRD1), MDRD2, Jelliffe, and Wright, consistently underestimated measured 24-hr CrCl pre-BMT. We retrospectively analyzed 98 consecutive allogeneic (n = 48) or autologous (n = 50) adult BMT patients from January 2006 to April 2007. All 6 formulas were significantly (P < .001) correlated with 24-hr CrCl with R = 0.64 (Wright), 0.63 (CG), 0.61 (mCG), 0.61 (Jelliffe), 0.54 (MDRD2), and 0.50 (MDRD1). When compared to the measured 24-hr CrCl, MDRD2 consistently underestimated it in the highest proportion of patients (66%, P < .001), compared with MDRD1 (65%, P < .001), Jelliffe (61%, P = NS), mCG (55%, P = NS), Wright (34%, P < .001), and CG (34%, P = .001). Measured 24-hr CrCl, pre-BMT serum Cr, and all 6 equations were not predictive of renal regimen-related toxicity (RRT) post-BMT. The Wright and CG formulas are closest to, but overestimate 24-hr CrCl in 66% of patients. In comparison, MDRD2 consistently underestimates 24-hr CrCl in 66%. Although MDRD2 is the most conservative formula, all 6 formulas gave reasonable estimates of GFR and any of the 6 equations can replace the measured 24-hr CrCl. Larger analyses and transplantation of patients with GFR <50 mL/min may better define subgroups at risk for renal RRT.
Related JoVE Video
Seeing whats out of sight: wireless capsule endoscopys unique ability to visualize and accurately assess the severity of gastrointestinal graft-versus-host-disease.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-21-2009
Show Abstract
Hide Abstract
Early recognition of gastrointestinal graft-versus-host disease (GI GVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT) is vital to initiation of therapy. However, the most common location, the small bowel (SB), is difficult to access with upper and lower endoscopy (UGE/LGE). Wireless capsule endoscopy (WCE) is a noninvasive technology allowing complete SB evaluation. The capsule location can also be tracked to identify motility derangements. From August 2006 to July 2007, 11 alloHSCT patients with GI symptoms underwent WCE, and visual grading was performed. UGE and LGE with biopsies were done when clinically indicated. All patients had evidence of probable acute GVHD (aGVHD) on WCE. WCE revealed lesions of greater severity than those seen by UGE or LGE in most patients. WCE demonstrated that 45% of patients had delayed gastric transit time. WCE is an excellent, noninvasive method for assessing GI GVHD, with the ability to more accurately assess the severity of GVHD, evaluate clinical symptoms, and follow response to treatment.
Related JoVE Video
Transplantation for autoimmune diseases in north and South America: a report of the Center for International Blood and Marrow Transplant Research.
Biol. Blood Marrow Transplant.
Show Abstract
Hide Abstract
Hematopoietic cell transplantation (HCT) is an emerging therapy for patients with severe autoimmune diseases (AID). We report data on 368 patients with AID who underwent HCT in 64 North and South American transplantation centers reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2009. Most of the HCTs involved autologous grafts (n = 339); allogeneic HCT (n = 29) was done mostly in children. The most common indications for HCT were multiple sclerosis, systemic sclerosis, and systemic lupus erythematosus. The median age at transplantation was 38 years for autologous HCT and 25 years for allogeneic HCT. The corresponding times from diagnosis to HCT were 35 months and 24 months. Three-year overall survival after autologous HCT was 86% (95% confidence interval [CI], 81%-91%). Median follow-up of survivors was 31 months (range, 1-144 months). The most common causes of death were AID progression, infections, and organ failure. On multivariate analysis, the risk of death was higher in patients at centers that performed fewer than 5 autologous HCTs (relative risk, 3.5; 95% CI, 1.1-11.1; P = .03) and those that performed 5 to 15 autologous HCTs for AID during the study period (relative risk, 4.2; 95% CI, 1.5-11.7; P = .006) compared with patients at centers that performed more than 15 autologous HCTs for AID during the study period. AID is an emerging indication for HCT in the region. Collaboration of hematologists and other disease specialists with an outcomes database is important to promote optimal patient selection, analysis of the impact of prognostic variables and long-term outcomes, and development of clinical trials.
Related JoVE Video
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.
Show Abstract
Hide Abstract
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.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.