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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., (Copyright © 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only known curative therapy for chronic myelogenous leukemia (CML). Failure, because of relapse or nonrelapse mortality (NRM), generally occurs within 3 years of transplantation, but large studies with long-term follow-up are limited. We present mature results in 335 patients with CML who underwent allogeneic bone marrow transplantation (BMT) from HLA-identical siblings following busulfan and cyclophosphamide (BU/Cy2). Two hundred twenty-nine were in chronic phase (CP) and 106 in accelerated or blastic phase at transplantation. Median follow-up exceeded 14 years. The estimated probability of 18-year leukemia-free survival (LFS) for CP patients was 55.6% and for those beyond CP, 10.5%. Of 182 patients who survived leukemia-free at 3 years, the estimated probability of LFS at 18 years was 61.9%. Late relapse (P = .039) and late NRM (P = .008) occurred at higher rates in patients beyond CP at transplantation. There was no plateau in LFS.

The ability to predict clinical outcomes is essential to accurate medical decision analysis. Many accepted bone marrow transplant related prognostic variables are derived from data that is over 20-years old and may or may not be applicable to current medical practice. This report reviews both older data concerning bone marrow transplantation prognostic factors as well as more current reports. In addition to pretransplant variables, this review examines easily measured post-transplant variables that may affect prognosis, as well as data concerning the cellular component of the infused graft in both allogeneic and autologous transplantation.

Reports have shown a worse outcome for donor-recipient pairs mismatched for ABO blood groups in bone marrow transplantation (BMT). These studies, however, included small and heterogeneous study populations, and not all considered bidirectional ABO incompatibility separately. Because the issue remains controversial, we analyzed the effect of ABO mismatch on the overall survival, transplant-related mortality, and occurrence of acute and chronic graft-versus-host disease (GVHD) in a large homogenous group of patients undergoing allogeneic BMT. A total of 3103 patients with early-stage leukemia who underwent transplantation between 1990 and 1998 with bone marrow from an HLA-identical sibling and who were reported to the Center for International Blood and Marrow Transplant Research were studied. The median follow-up was 54 months. A total of 2108 (67.9%) donor-recipient pairs were ABO identical, 451 (14.5%) had a minor mismatch, 430 (13.9%) had a major mismatch, and 114 (3.7%) had a bidirectional ABO mismatch. The groups did not differ significantly in patient or donor characteristics except for more female-to-male sex mismatch in the bidirectional ABO mismatch group (P = .017). In multivariate models of overall survival, transplant-related mortality, and grade II to IV acute GVHD, there were no significant differences among the 4 groups. Bidirectional ABO mismatch was associated with a significantly higher risk of grade III or IV acute GVHD (hazard ratio, 1.869; 95% confidence interval, 1.192-2.93; P = .006). Patients with major ABO mismatch received red blood cell transfusions (P = .001) for a longer timer after transplantation and had a slightly slower neutrophil recovery (P < .001). There was no evidence of a substantial effect of ABO blood group incompatibility on the outcome of conventional BMT among patients with leukemia.

Bone marrow transplantation (BMT) can cure myelodysplastic syndrome (MDS), although transplantation carries significant risks of morbidity and mortality. Because the optimal timing of HLA-matched BMT for MDS is unknown, we constructed a Markov model to examine 3 transplantation strategies for newly diagnosed MDS: transplantation at diagnosis, transplantation at leukemic progression, and transplantation at an interval from diagnosis but prior to leukemic progression. Analyses using individual patient risk-assessment data from transplantation and nontransplantation registries were performed for all 4 International Prognostic Scoring System (IPSS) risk groups with adjustments for quality of life (QoL). For low and intermediate-1 IPSS groups, delayed transplantation maximized overall survival. Transplantation prior to leukemic transformation was associated with a greater number of life years than transplantation at the time of leukemic progression. In a cohort of patients under the age of 40 years, an even more marked survival advantage for delayed transplantation was noted. For intermediate-2 and high IPSS groups, transplantation at diagnosis maximized overall survival. No changes in the optimal transplantation strategies were noted when QoL adjustments were incorporated. For low- and intermediate-1-risk MDS, delayed BMT is associated with maximal life expectancy, whereas immediate transplantation for intermediate-2- and high-risk disease is associated with maximal life expectancy.

Several single-institution pilot studies have suggested that augmented preparative regimens, including those containing total body irradiation combined with an autologous bone marrow transplantation, are superior to standard regimens for the treatment of relapsed or refractory Hodgkin disease. On the basis of these data, we undertook, in the cooperative group setting, a phase II trial of augmented preparative regimens for patients experiencing treatment failure with conventional chemotherapy. Eighty-one patients with either sensitive or refractory (induction failures or chemoresistant) relapse received etoposide (60 mg/kg), cyclophosphamide (100 mg/kg), and either total body irradiation (12 Gy) or, if previously irradiated, carmustine (15 mg/kg), followed by an autologous bone marrow transplantation. Progression-free (PFS) and overall (OS) survival were estimated, and a Cox regression model was used to assess potential prognostic variables. The 5-year PFS and OS for the 74 eligible patients treated at 20 Southwest Oncology Group centers were 41% (95% confidence interval [CI], 29%-53%) and 54% (95% CI, 43%-65%), respectively, despite a median remission after initial chemotherapy of only 6 months. The 3-year OS for those whose induction therapy failed was 72% (95% CI, 52%-93%). There was 1 (1.4%) early treatment-related death, 2 late deaths due to lung toxicity, and only 1 death due to myelodysplasia. There were no differences in PFS or OS on the basis of regimen or chemosensitivity. A Cox prognostic factor analysis determined that >2 prior regimens, relapse in a radiated field, and extranodal disease were adverse prognostic factors. Among the 46 patients who received prior radiotherapy, the 5-year OS was 38% (95% CI, 14%-61%) for patients with 2 or 3 adverse factors, versus 60% (95% CI, 42%-78%) for those with 0 factors or 1 adverse factor. Augmented preparative regimens seem promising for the treatment of relapsed or refractory Hodgkin disease, without an increase in regimen-related mortality. A poor-prognosis group was identified that should be treated with novel therapies.

We studied the association between CD34 cell dose and transplant outcomes in 359 bone marrow (BM) and 511 peripheral blood stem cell (PBSC) transplant recipients from human leucocyte antigen (HLA)-identical siblings, reported to the International Bone Marrow Transplant Registry (IBMTR). Transplants for leukaemia were performed between 1995 and 1998. Patients were divided into those receiving below or above the median CD34+ dose, for BM (3 x 106/kg) and PBSC (6 x 106/kg) grafts respectively. Cox proportional hazards regression was used to adjust for baseline patient-, disease- and transplant-related characteristics. Analysis of the BM recipients showed that high CD34 cell dose was associated with lower transplant-related mortality [relative risk (RR) = 0.60, P = 0.033] and treatment failure (inverse of leukaemia-free survival, RR = 0.69, P = 0.032). Among PBSC recipients, high CD34 dose was associated with faster recovery of neutrophils to > 0.5 x 109/l (RR = 1.38, P < 0.001) and platelets to > 20 x 109/l (RR = 1.34, P = 0.003), lower risk of relapse (RR = 0.62, P = 0.029) and treatment failure (RR = 0.74, P = 0.03). We conclude that higher CD34 cell doses decrease treatment failure in recipients of HLA-identical sibling BM and PBSC transplants.

Lymphoblastic lymphoma (LBL) is a rare, clinically aggressive neoplasm of the young that frequently involves the bone marrow (BM) and/or central nervous system. Because LBL is similar to acute lymphoblastic leukemia, some centers prefer allogeneic hematopoietic stem cell (SC) transplantation to autologous SC transplantation. We retrospectively analyzed outcomes for patients who underwent autologous (auto, n = 128) or HLA-identical sibling (allo, n = 76) SC transplantations from 1989 to 1998 and were reported to International Bone Marrow Transplant Registry (IBMTR) or Autologous Blood and Marrow Transplant Registry (ABMTR). Allo stem cell transplant (SCT) recipients had higher treatment-related mortality (TRM) at 6 months (18% versus 3%, P =.002), and this disadvantage persisted at 1 and 5 years. Early relapse rates after alloSC transplantation and autoSC transplantation were similar, but significantly lower relapse rates were observed in alloSCT recipients at 1 and 5 years (32% versus 46%, P =.05; and 34% versus 56%, P =.004, respectively). No differences were noted in lymphoma-free survival rates between alloSC transplantations and autoSC transplantations (5-year rates 36% versus 39%, P =.82). AutoSCT recipients had higher overall survival at 6 months (75% versus 59%, P =.01), but survival did not significantly differ between the 2 groups at 1 and 5 years (60% versus 49%, P =.09; 44% versus 39%, P =.47, respectively). Multivariate analyses to account for confounding factors confirmed these results. Independent of SCT type, BM involvement at the time of transplantation and disease status more advanced than first complete remission were associated with inferior outcomes. In summary, alloSC transplantation for LBL is associated with fewer relapses than with autoSC transplantation, but higher TRM offsets any potential survival benefit.

We evaluated transplant-related mortality (TRM), leukaemia relapse, leukaemia-free survival (LFS) and overall survival (OS) in patients receiving busulphan and cyclophosphamide (BuCy) or cyclophosphamide and total body irradiation (CyTBI) prior to allogeneic bone marrow transplantation (BMT) for acute myelogenous leukaemia (AML) in first remission. Outcomes of 381 human leucocyte antigen (HLA)-matched sibling transplants using BuCy were compared with 200 transplants using CyTBI performed between 1988 and 1996. The incidence of hepatic veno-occlusive disease was higher with BuCy (13%) than with CyTBI (6%) (P = 0.009). Risks of acute and chronic GVHD were similar. In multivariate analysis, relapse risk was higher in the BuCy group [relative risk (RR) = 1.72; 95% confidence interval (CI), 1.05-2.81; P = 0.031]. Eleven of 373 evaluable patients in the BuCy group had a central nervous system relapse in contrast to none of 194 evaluable patients in the CyTBI group (P = 0.016). There were no differences in TRM, LFS and OS. CyTBI conditioning may lower relapse risk but produces comparable TRM, LFS and OS to BuCy for HLA-matched sibling transplantation in first remission AML.

Although donation of bone marrow (BM) or peripheral blood stem cells (PBSCs) from children to family members undergoing allogeneic transplantation are well-established procedures, studies detailing levels of pain, symptoms, and long-term recovery are lacking. To address this lack, we prospectively enrolled 294 donors age 20% of females and males age 13 to 17 years do not return to baseline pain levels by 1 year after BM donation. Studies aimed at decreasing symptoms and improving recovery in older children are warranted.

The long-term follow-up is presented for 317 patients with acute myeloid leukaemia who underwent human leucocyte antigen-identical sibling marrow transplants between 1984 and 1995 following preparation with busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. Among the 142 (45%) who were alive and leukaemia-free 3 years following transplantation, the leukaemia-free survival at 15 years was 72·8%. The cumulative incidence of late (>3 years beyond transplant) non-relapse mortality at 15 years was 12·9% and of late relapse was 16·5%. None of the variables considered (including age, disease stage, and graft- versus-host disease) were predictive of late failure. [ABSTRACT FROM AUTHOR]

We previously reported a risk score that predicted mortality in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (HCT) between 1995 and 2004 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We sought to validate this risk score in an independent CIBMTR cohort of 1128 patients with CGVHD who underwent transplantation between 2005 and 2007 using the same inclusion criteria and risk score calculations. According to the sum of the overall risk score (range, 1 to 12), patients were assigned to 4 risk groups (RGs): RG1 (0 to 2), RG2 (3 to 6), RG3 (7 to 8), and RG4 (9 to 10). RG3 and RG4 were combined, as RG4 accounted for only 1% of the total cohort. Cumulative incidences of nonrelapse mortality (NRM) and probability of overall survival were significantly different between each RG (all P < .01). NRM and overall survival at 5 years after CGVHD for each RG were 17% and 72% in RG1, 26% and 53% in RG2, and 44% and 25% in RG3, respectively (all P < .01). Our study validates the prognostic value of the CIBMTR CGVHD RGs for overall survival and NRM in a contemporary transplantation population. The CIBMTR CGVHD RGs can be used to predict major outcomes, tailor treatment planning, and enroll patients in clinical trials. [ABSTRACT FROM AUTHOR]

The poor prognosis of patients with prolymphocytic leukemia (PLL) has led some clinicians to recommend allogeneic hematopoietic cell transplant (HCT). However, the data to support this approach is limited to case-reports and small case series. We reviewed the database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to determine outcomes after allotransplant for patients with PLL. We identified 47 patients with a median age of 54 years (range: 30-75 years). With a median follow-up of 13 months, progression-free survival (PFS) was 33% (95% confidence interval [CI] 20%-47%) at 1 year. The most common cause of death was relapse or progression in 49%. The cumulative incidence of treatment-related mortality (TRM) at 1-year posttransplant was 28%. The small patient population prohibited prognostic factor analysis, but these data support consideration of allotransplant for PLL. Further study of a larger population of patients is needed to determine which patients are more likely to benefit. [Copyright &y& Elsevier]

Abstract: To compare the clinical outcomes of older (age ≥55 years) non-Hodgkin lymphoma (NHL) patients with younger NHL patients (<55 years) receiving autologous hematopoietic cell transplantation (HCT) while adjusting for patient-, disease-, and treatment-related variables, we compared autologous HCT outcomes in 805 NHL patients aged ≥55 years to 1949 NHL patients <55 years during the years 1990–2000 using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). In multivariate analysis, older patients with aggressive histologies were 1.86 times (95% confidence interval [CI] 1.43-2.43, P < .001) more likely than younger patients to experience treatment-related mortality (TRM). Relative death risks were 1.33 times (CI 1.04-1.71, P = .024) and 1.50 times (CI 1.33-16.9, P < .001) higher in older compared to younger patients with follicular grade I/II and aggressive histologies, respectively. Autologous HCT in older NHL patients is feasible, but most disease-related outcomes are statistically inferior to younger patients. Studies addressing supportive care particular to older patients, who are most likely to benefit from this approach, are recommended. [Copyright &y& Elsevier]