BACKGROUND Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P = 0.29), with an absolute difference of 5 percentage points (95% CI, −3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P = 0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P = 0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute–National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.)

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Summary:Treatment options for persons with leukemia relapsing after allogeneic transplantation are limited. We analyzed the outcome of 279 patients with acute and chronic leukemia, who relapsed after HLA-identical sibling transplantation and received a second allogeneic transplant. The influence of potential risk factors on treatment-related mortality (TRM), relapse, treatment failure (relapse or death) and overall survival after second transplantation were assessed using proportional-hazards regression. The cumulative incidences (95% confidence interval) of relapse and TRM at 5 years were 42 (36-48)% and 30 (24-36)%, respectively. The 5-year probabilities of both overall and leukemia-free survival were 28 (23-34)%. In multivariate analyses, risks of treatment failure and mortality were lower in younger patients (p20 years) and patients who relapsed after 6 months from first transplantation. Risks of relapse were lower in patients who relapsed after 6 months from first transplantation and in complete remission prior to second transplantation. Risks of relapse were higher after reduced-intensity conditioning regimens. Any potential advantage of using a different matched related donor for a second transplantation is not supported by these data. Although age, disease status and conditioning regimen are important, duration of remission after first transplantation appear to be the most important determinant of outcome.

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Approximately 20,000 hematopoietic cell transplantation (HCT) procedures are performed in the United States annually. With advances in transplantation technology and supportive care practices, HCT has become safer and patient survival continues to improve over time. Indications for HCT continue to evolve as research refines the role for HCT in established indications and identifies emerging indications where HCT may be beneficial. The American Society for Blood and Marrow Transplantation (ASBMT) established a multi-stakeholder task force consisting of transplant experts, payer representatives and a patient advocate to provide guidance on ‘routine’ indications for HCT. This white paper presents the recommendations from the Task Force. Indications for HCT were categorized as (1) Standard of care, where indication for HCT is well defined and supported by evidence, (2) Standard of care, clinical evidence available, where large clinical trials and observational studies are not available but HCT has been shown to be effective therapy, (3) Standard of care, rare indication, for rare diseases where HCT has demonstrated effectiveness but large clinical trials and observational studies are not feasible, (4) Developmental, for diseases where pre-clinical and/or early phase clinical studies show HCT to be a promising treatment option, and (5) Not generally recommended, where available evidence does not support the routine use of HCT. The ASBMT will periodically review these guidelines and will update them as new evidence becomes available.

Although reduced intensity (RIC) and nonmyeloablative (NMA) conditioning regimens have been used for over a decade, their relative efficacy versus myeloablative (MA) approaches to allogeneic hematopoietic cell transplantation (HCT) in patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) is unknown. We compared disease status, donor, graft and recipient characteristics with outcomes of 3731 MA with 1448 RIC/NMA procedures performed at 217 centers between 1997 and 2004. Five year univariate probabilities and multivariate relative risk (RR) outcomes of relapse, transplant related mortality (TRM), disease free survival (DFS) and overall survival (OS) are reported. Adjusted OS at 5 years was 34%, 33%, and 26% for MA, RIC and NMA transplants, respectively. NMA conditioning resulted in inferior DFS and OS but there was no difference in DFS and OS between RIC and MA regimens. Late TRM negates early decreases in toxicity with RIC and NMA regimens. Our data suggest higher regimen intensity may contribute to optimal survival in patients with AML/MDS, suggesting roles for both regimen intensity and graft vs. leukemia in these diseases. Prospective studies comparing regimens are needed to confirm this finding and determine the optimal approach to patients who are eligible for either MA or RIC/NMA conditioning.

We analyzed the outcome of 692 patients with severe aplastic anemia (SAA) receiving transplants from HLA-matched siblings. A total of 134 grafts were peripheral blood progenitor cell (PBPC) grafts, and 558 were bone marrow (BM) grafts. Rates of hematopoietic recovery and grades 2 to 4 chronic graft-versushost disease (GVHD) were similar after PBPC and BM transplantations regardless of age at transplantation. In patients older than 20 years, chronic GVHD and overall mortality rates were similar after PBPC and BM transplantations. In patients younger than 20 years, rates of chronic GVHD (relative risk [RR] 2.82; P ‫؍‬ .002) and overall mortality (RR 2.04; P ‫؍‬ .024) were higher after transplantation of PBPCs than after transplantation of BM. In younger patients, the 5-year probabilities of overall survival were 73% and 85% after PBPC and BM transplantations, respectively. Corresponding probabilities for older patients were 52% and 64%. These data indicate that BM grafts are preferred to PBPC grafts in young patients undergoing HLAmatched sibling donor transplantation for SAA. IntroductionTransplantation of bone marrow (BM) from an HLA-matched sibling donor is an effective treatment for severe aplastic anemia (SAA) with long-term survival in excess of 80% and graft failure rates of approximately 10%. [1][2][3][4][5][6][7] Unpublished data (January 2007) from the European Group for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR) suggest approximately 60% of HLA-matched sibling donor transplantations for SAA now use peripheral blood progenitor cell (PBPC) grafts. A similar switch to PBPC over BM grafts is reported in leukemia transplantations. [8][9][10] The higher rate of chronic graft-versus-host disease (GVHD) may be offset by lower relapse rates in some settings. In contrast, there is no perceived benefit of chronic GVHD for SAA. Further, few data on PBPCs for SAA are reported. [11][12][13][14][15] In a preliminary analysis from our group, PBPC grafts appeared to contribute to higher mortality. 16 Here, we report chronic GVHD and long-term overall survival rates in 134 PBPC recipients and 558 BM recipients of HLA-matched sibling donor transplants for SAA. Patients, materials, and methods PatientsData on patients undergoing their first PBPC and BM HLA-matched sibling transplantation from 1995 to 2003 were obtained from the EBMT and the Statistical Center of the CIBMTR at the Medical College of Wisconsin. Only patients who received transplants at centers that provided a minimum of 12 months of follow-up on all their surviving patients were included. The Institutional Review Board of the Medical College of Wisconsin approved this study. Informed consent was obtained in accordance with the Declaration of Helsinki. Statistical methodsThe probabilities of hematopoietic recovery (neutrophil count Ն 0.5 ϫ 10 9 /L for 3 consecutive days and platelet count Ն 20 ϫ 10 9 /L for 7 days, unsupported) and acute and chronic GVHD were calculated using the cum...

Although transplant practices have changed over the last decades there is no information on trends in incidence and outcome of cGVHD over time. This study utilized the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe the time trends for cGVHD incidence, non-relapse mortality, and the risk factors for cGVHD. The 12-year period was divided into three intervals: 1995-1999, 2000-2003, 2004-2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndrome. In the multivariate analysis, the incidence of cGVHD was shown to be increased in more recent years (odds ratio= 1.19, p<0.0001) and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, non-relapse mortality has decreased over time, but at 5-years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.