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There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P < .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

We investigated the impact of the number of induction/consolidation cycles on outcomes of 3113 adult AML patients who received allogeneic hematopoietic cell transplantation (allo-HCT) between 2008 and 2019. Patients received allo-HCT using myeloablative (MAC) or reduced-intensity (RIC) conditioning in first complete remission (CR) or with primary induction failure (PIF). Patients who received MAC allo-HCT in CR after 1 induction cycle had 1.3-fold better overall survival (OS) than 2 cycles to CR and 1.47-fold better than ≥3 cycles. OS after CR in 2 or ≥3 cycles was similar. Relapse risk was 1.65-fold greater in patients receiving ≥3 cycles to achieve CR. After RIC allo-HCT, the number of induction cycles to CR did not affect OS. Compared to CR in 1 cycle, relapse risk was 1.24-1.41-fold greater in patients receiving 2 or ≥3 cycles. For patients receiving only 1 cycle to CR, consolidation therapy prior to MAC allo-HCT was associated with improved OS vs. no consolidation therapy. Detectable MRD at the time of MAC allo-HCT did not impact outcomes while detectable MRD preceding RIC allo-HCT was associated with an increased risk of relapse. For allo-HCT in PIF, OS was significantly worse than allo-HCT in CR after 1-3 cycles.

IntroductionEndogenous granulocyte-macrophage colony-stimulating factor (GM-CSF), identified by its ability to support differentiation of hematopoietic cells into several types of myeloid cells, is now known to support maturation and maintain the metabolic capacity of mononuclear phagocytes including monocytes, macrophages, and dendritic cells. These cells sense and attack potential pathogens, present antigens to adaptive immune cells, and recruit other immune cells. Recombinant human (rhu) GM-CSF (e.g., sargramostim [glycosylated, yeast-derived rhu GM-CSF]) has immune modulating properties and can restore the normal function of mononuclear phagocytes rendered dysfunctional by deficient or insufficient endogenous GM-CSF.MethodsWe reviewed the emerging biologic and cellular effects of GM-CSF. Experts in clinical disease areas caused by deficient or insufficient endogenous GM-CSF examined the role of GM-CSF in mononuclear phagocyte disorders including autoimmune pulmonary alveolar proteinosis (aPAP), diverse infections (including COVID-19), wound healing, and anti-cancer immune checkpoint inhibitor therapy.ResultsWe discuss emerging data for GM-CSF biology including the positive effects on mitochondrial function and cell metabolism, augmentation of phagocytosis and efferocytosis, and immune cell modulation. We further address how giving exogenous rhu GM-CSF may control or treat mononuclear phagocyte dysfunction disorders caused or exacerbated by GM-CSF deficiency or insufficiency. We discuss how rhu GM-CSF may augment the anti-cancer effects of immune checkpoint inhibitor immunotherapy as well as ameliorate immune-related adverse events.DiscussionWe identify research gaps, opportunities, and the concept that rhu GM-CSF, by supporting and restoring the metabolic capacity and function of mononuclear phagocytes, can have significant therapeutic effects. rhu GM-CSF (e.g., sargramostim) might ameliorate multiple diseases of GM-CSF deficiency or insufficiency and address a high unmet medical need.

Adult hematopoietic stem cell transplantation (HSCT) recipients are at a high risk of adverse outcomes after COVID-19. Although children have had better outcomes after COVID-19 compared to adults, data on risk factors and outcomes of COVID-19 among pediatric HSCT recipients are lacking. We describe outcomes of HSCT recipients who were ≤21 years of age at COVID-19 diagnosis and were reported to the Center for International Blood and Marrow Transplant Research between March 27, 2020, and May 7, 2021. The primary outcome was overall survival after COVID-19 diagnosis. We determined risk factors of COVID-19 as a secondary outcome in a subset of allogeneic HSCT recipients. A total of 167 pediatric HSCT recipients (135 allogeneic; 32 autologous HSCT recipients) were included. Median time from HSCT to COVID-19 was 15 months (interquartile range [IQR] 7-45) for allogeneic HSCT recipients and 16 months (IQR 6-59) for autologous HSCT recipients. Median follow-up from COVID-19 diagnosis was 53 days (range 1-270) and 37 days (1-179) for allogeneic and autologous HSCT recipients, respectively. Although COVID-19 was mild in 87% (n = 146/167), 10% (n = 16/167) of patients required supplemental oxygen or mechanical ventilation. The 45-day overall survival was 95% (95% confidence interval [CI], 90-99) and 90% (74-99) for allogeneic and autologous HSCT recipients, respectively. Cox regression analysis showed that patients with a hematopoietic cell transplant comorbidity index (HCT-CI) score of 1-2 were more likely to be diagnosed with COVID-19 (hazard ratio 1.95; 95% CI, 1.03-3.69, P = .042) compared to those with an HCT-CI of 0. Pediatric and early adolescent and young adult HSCT recipients with pre-HSCT comorbidities were more likely to be diagnosed with COVID-19. Overall mortality, albeit higher than the reported general population estimates, was lower when compared with previously published data focusing on adult HSCT recipients.

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis in recipients of haploidentical and fully matched transplantations is on the increase. Published studies have reported an increased incidence of cytomegalovirus (CMV) infection with the use of PTCy. Limited data exist on the incidence and outcomes of infection with non-CMV herpesviruses (NCHV) in this setting. The aim of this study was to evaluate the cumulative incidence of NCHV infections and the association of NCHV infections with transplantation-specific outcomes in recipients of haploidentical transplantation with PTCy (HaploCy), matched sibling donor transplantation with PTCy (SibCy), and matched sibling donor transplantation with calcineurin inhibitor-based prophylaxis (SibCNI). We hypothesized that, like CMV infection, HaploCy recipients of also will have a higher risk of NCHV infections. Using the Center for International Blood and Marrow Transplantation Research database, we analyzed 2765 patients (HaploCy, n = 757; SibCNI, n = 1605; SibCy, n = 403) who had undergone their first hematopoietic stem cell transplantation (HCT) between 2012 and 2017 for acute myelogenous leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. The cumulative incidence of NCHV at 6 months post-NCT was 13.9% (99% confidence interval], 10.8% to 17.3%) in the HaploCy group, 10.7% (99% CI, 7.1% to 15%) in the SibCy group, and 5.7% (99% CI, 4.3% to 7.3%) in the Sib CNI group (P < .001). This was due primarily to a higher frequency of human herpesvirus 6 viremia reported in patients receiving PTCy. The incidence of Epstein-Barr viremia was low in all groups, and no cases of post-transplantation lymphoproliferative disorder were seen in either PTCy group. The incidence of NCHV organ disease was low in all 3 cohorts. The development of NCHV infection was associated with increased treatment-related mortality, particularly in the HaploCy group. There was no association with the development of GVHD, relapse, or disease-free survival. Patients in PTCy cohorts who did not develop NCHV infection had lower rates of cGVHD. This study demonstrates that the use of PTCy is associated with an increased risk of NCHV infection. The development of NCHV infection was associated with increased nonrelapse mortality, especially in the HaploCy group. Prospective trials should consider viral surveillance strategies in conjunction with assessment of immune reconstitution for a better understanding of the clinical relevance of viral reactivation in different HCT settings.

Young adult (YA) survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk for late psychosocial challenges, including the inability to return to work post-HCT. Work-related outcomes in this population remain understudied, however. We conducted this study to assess the post-HCT work status of survivors of allogeneic HCT who underwent HCT as YAs and to analyze the patient-, disease-, and HCT-related factors associated with their work status at 1 year post-HCT. Using Center for International Blood and Marrow Transplant Research data, we evaluated the post-HCT work status (full-time, part-time work, unemployed, or medical disability) of 1365 YA HCT survivors who underwent HCT between 2008 and 2015. Percentages of work status categories were reported at 4 time points: 6 months, 1 year, 2 years, and 3 years post-HCT. Percentages of post-HCT work status categories at the 1-year time point were also described in relation to survivors' pre-HCT work status categories. Factors associated with 1-year post-HCT work status (full-time or part-time work) were examined using logistic regression. From 6 months to 3 years post-HCT, the percentage of survivors working full-time increased from 18.3% to 50.7% and the percentage working part-time increased from 6.9% to 10.5%. Of patients in full-time work pre-HCT, 50% were unemployed or on medical disability at 1 year post-HCT. Female sex (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.40 to 0.77), HCT Comorbidity Index score ≥3 (OR, 0.57; 95% CI, 0.39 to 0.82), pre-HCT unemployment (OR, 0.37; 95% CI, 0.24 to 0.56), medical disability (OR, 0.44; 95% CI, 0.28 to 0.70), development of grade III-IV acute graft-versus-host disease (OR, 0.52; 95% CI, 0.34 to 0.80), and relapse within 1 year post-HCT (OR, 0.34; 95% CI, 0.21 to 0.56) were associated with a lower likelihood of employment at 1 year post-HCT. Compared with myeloablative conditioning (MAC) with total body irradiation (TBI), MAC without TBI (OR, 1.71; 95% CI, 1.16 to 2.53) was associated with a greater likelihood of employment at 1 year post-HCT. Graduate school-level education (OR, 2.47; 95% CI, 1.49 to 4.10) was also associated with a greater likelihood of employment at 1 year post-HCT. Although the work status among YA HCT survivors continued to improve over time, a substantial subset became or remained unemployed or on medical disability. These findings underscore the need for effective interventions to support return to work in this population.

The authors inadvertently included grant numbers OT3HL147741 & U24CA233032, which are grant-specific. This was an oversight on the authors’ part as these grants did not support the research in this publication.

Community respiratory viral infections (CRVIs) are associated with pulmonary function impairment, alloimmune lung syndromes and inferior survival in human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplant (HCT) recipients. Although the incidence of viral infections in HLA-haploidentical HCT recipients who receive post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is reportedly increased, there are insufficient data describing the incidence of CRVIs and the impact of donor source and PTCy on transplant outcomes. Analysing patients receiving their first HCT between 2012 and 2017 for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndromes, we describe comparative outcomes between matched sibling transplants receiving either calcineurin-based GVHD prophylaxis (SibCNI, N = 1605) or PTCy (SibCy, N = 403), and related haploidentical transplants receiving PTCy (HaploCy, N = 757). The incidence of CRVIs was higher for patients receiving PTCy, regardless of donor type. Patients in the HaploCy cohort who developed a CRVI by day +180 had both a higher risk of treatment-related mortality [hazard ratio (HR) 2⋅14, 99% confidence interval (CI) 1⋅13-4⋅07; P = 0⋅002] and inferior 2-year overall survival (HR 1⋅65, 99% CI 1⋅11-2⋅43; P = 0⋅001) compared to SibCNI with no CRVI. This finding justifies further research into long-term antiviral immune recovery, as well as development of preventive and treatment strategies to improve long-term outcomes in such patients.

BackgroundThe association of community factors and outcomes after hematopoietic cell transplantation (HCT) has not been comprehensively described. Using the County Health Rankings and Roadmaps (CHRR) and the Center for International Blood and Marrow Transplant Research (CIBMTR), this study evaluated the impact of community health status on allogeneic HCT outcomes.MethodsThis study included 18,544 adult allogeneic HCT recipients reported to the CIBMTR by 170 US centers in 2014-2016. Sociodemographic, environmental, and community indicators were derived from the CHRR, an aggregate community risk score was created, and scores were assigned to each patient (patient community risk score [PCS]) and transplant center (center community risk score [CCS]). Higher scores indicated less healthy communities. The impact of PCS and CCS on patient outcomes after allogeneic HCT was studied.ResultsThe median age was 55 years (range, 18-83 years). The median PCS was -0.21 (range, -1.37 to 2.10; standard deviation [SD], 0.42), and the median CCS was -0.13 (range, -1.04 to 0.96; SD, 0.40). In multivariable analyses, a higher PCS was associated with inferior survival (hazard ratio [HR] per 1 SD increase, 1.04; 99% CI, 1.00-1.08; P = .0089). Among hematologic malignancies, a tendency toward inferior survival was observed with a higher PCS (HR, 1.04; 99% CI, 1.00-1.08; P = .0102); a higher PCS was associated with higher nonrelapse mortality (NRM; HR, 1.08; 99% CI, 1.02-1.15; P = .0004). CCS was not significantly associated with survival, relapse, or NRM.ConclusionsPatients residing in counties with a worse community health status have inferior survival as a result of an increased risk of NRM after allogeneic HCT. There was no association between the community health status of the transplant center location and allogeneic HCT outcomes.

Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR], .74; 95% confidence interval [CI], .62 to .88; P < .001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P < .001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P = .001). In the high/very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR, .83; 95% CI, .68 to 1.00; P = .051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P = .002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/very-high risk DRI group.

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.

Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.

Donor lymphocyte infusion has been used in the management of relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. It can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions in a subset of patients. With the increased use of haploidentical hematopoietic cell transplantation, there is renewed interest in the use of donor lymphocytes to either treat or prevent disease relapse post transplant. Published retrospective and small prospective studies have shown encouraging results with therapeutic donor lymphocyte infusion in different haploidentical transplantation platforms. In this consensus paper, finalized on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize the available evidence on the use of donor lymphocyte infusion from haploidentical donor, and provide recommendations on its therapeutic, pre-emptive and prophylactic use in clinical practice.

BackgroundWe examined the impact of vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) on outcomes of allogeneic hematopoietic cell transplantation (HCT) utilizing the Center for International Blood and Marrow Transplant Research database.MethodsAdult and pediatric patients (N = 7128) who underwent first HCT for acute leukemia or myelodysplastic syndrome from 2008 through 2012 were analyzed as 3 groups-VRE BSI, non-VRE BSI, without BSI-according to BSI status at 100 days (D100) after allogeneic HCT. Multivariable models examined the effect of VRE BSI for overall survival (OS) and nonrelapse mortality (NRM) at 1 year.ResultsOf 7128 patients, 258 (3.2%) had VRE BSI, 2398 (33.6%) had non-VRE BSI, and 4472 (63%) had no BSI. The median time to VRE BSI and non-VRE BSI were D11 and D15, respectively. Compared with non-VRE BSI patients, VRE BSI patients were older, had advanced-stage acute leukemia, and received umbilical cord blood (UCB) allografts. In multivariable models, VRE BSI was associated with lower OS (relative risk [RR], 2.9;(99% confidence interval [CI], 2.2-3.7) and increased NRM (RR, 4.7; 99% CI, 3.6-6.2) (P < .0001) for both. Other predictors for worse OS and increased NRM were non-VRE BSI, older age, advanced disease stage, UCB allograft, - mismatch, comorbidity index ≥3, and cytomegalovirus seropositivity (P < .001 for all variables).ConclusionsVRE BSI is associated with lowest OS and highest NRM compared with patients without BSI or non-VRE BSI. Novel interventions that address the pathophysiology of VRE BSI have the potential of improving survival after HCT.

Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n = 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P = .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P < .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged >30 years after HLA-matched sibling (HR, 2.74; P < .001) or unrelated donor (HR, 1.98; P = .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.

Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT-comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range,

Limited data exist on characteristics of central nervous system viruses (CNS-V) in allogeneic hematopoietic stem cell transplant (HCT) recipients. Between 2007 and 2015, the Center for International Blood and Marrow Transplant Research (CIBMTR) received information on 27,532 patients undergoing HCT. Of these, centers reported 165 HCT recipients with CNS-V detected in cerebrospinal fluid within 6 months after HCT. CNS viruses predominantly included human herpes virus 6 (HHV-6) (73%), followed by Epstein-Barr Virus (10%), cytomegalovirus (3%), varicella zoster virus (3%), herpes simplex virus (3%) and Adenovirus (3%). Median time of viral detection in CNS was 31 days after HCT; and viral detection was earlier in patients with CNS HHV-6. Concurrent viremia occurred in 52% of patients. Cord blood transplant recipients (CBT) accounted for the majority (53%) of patients with CNS-V. Myeloablative conditioning (65%), use of fludarabine (63%), or use of anti-thymocyte globulin (61%) were also predominant. Overall survival from the time of detection of CNS-V was 50% at 6 months and 30% at 5 years. Infections were the leading cause of death (32%). In summary, CBT recipients predominated in the population with CNS-V. Outcomes after CNS-V were poor with significant mortality seen in the first 6 months.

We analyzed CIBMTR data to evaluate the incidence of non-relapse mortality (NRM) and association with overall survival (OS) for bacterial blood stream infections (BSIs) occurring within 100 days of alloHCT in 2 different phases: pre-/peri-engraftment (BSI very early phase, BSI-VEP) and BSI post-engraftment (BSI occurring between 2 weeks after engraftment and day 100, late early phase, BSI-LEP). Of the 7128 alloHCT patients, 2656 (37%) had ≥1 BSI by day 100. BSI-VEP, BSI-LEP, and BSI-Both constituted 56% (n = 1492), 31% (n = 824), and 13% (n = 340) of total BSI, respectively. Starting in 2009, we observed a gradual decline in BSI incidence through 2012 (61-48%). Patients with BSI-VEP were more likely to receive a myeloablative conditioning (MAC) regimen with total body irradiation (TBI). NRM was significantly higher in patients with any BSI (RR 1.82 95% CI 1.63-2.04 for BSI-VEP, RR 2.46, 95% CI 2.05-2.96 for BSI-LEP, and RR 2.29, 95% CI 1.87-2.81 for BSI-Both) compared with those without BSI. OS was significantly lower in patients with any BSI compared with patients without BSI (RR 1.36, 95% CI 1.26-1.47 for BSI-VEP; RR 1.83, 95% CI 1.58-2.12 for BSI-LEP: RR 1.66, 95% CI 1.43-1.94 for BSI-Both). BSIs within day 100 after alloHCT are common and remain a risk factor for mortality.

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.

The revised International Staging System (R-ISS) combines ISS with genetic markers and lactate dehydrogenase and can prognosticate newly diagnosed multiple myeloma (MM). Early relapse (

Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation-related toxicities, we conducted a prospective observational trial of 11,942 related and unrelated donors aged 18-60 years. Bone marrow (BM) was collected at 37 transplant and 78 National Marrow Donor Program centers, and peripheral blood stem cells (PBSC) were collected at 42 transplant and 87 unrelated donor centers in North America. Possible presence of medical comorbidities was verified prior to donation, and standardized pain and toxicity measures were assessed pre-donation, peri-donation, and one year following. Multivariate analyses showed similar experiences for BM collection in related and unrelated donors; however, related stem cell donors had increased risk of moderate [odds ratios (ORs) 1.42; P

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34+ level before apheresis compared with younger RDs (age > 60, 59 × 106/L; age 41 to 60, 81 × 106/L; age 18 to 40, 121 × 106/L; P < .001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P < .001) and higher collection volumes (52% versus 32% > 24 L, P < .001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia

Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m2. Dose adjustment was defined as a reduction in standard dosing ≥20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) who received carmustine, etoposide, cytarabine, and melphalan conditioning. Chemotherapy dose was adjusted in 1324 patients (78%) with MM and 608 patients (78%) with lymphoma. Age, sex, BMI, race, performance score, comorbidity index, and disease features (stage at diagnosis, disease status, and time to transplant) were similar between dose groups. In multivariate analyses for MM, adjusting for melphalan dose and for center effect had no impact on overall survival (P = .894) and treatment-related mortality (TRM) (P = .62), progression (P = .12), and progression-free survival (PFS; P = .178). In multivariate analyses for lymphoma, adjusting chemotherapy doses did not affect survival (P = .176), TRM (P = .802), relapse (P = .633), or PFS (P = .812). No center effect was observed in lymphoma. This study demonstrates that adjusting chemotherapy dose before autoHCT in obese patients with MM and lymphoma does not influence mortality. These results do not support adjusting chemotherapy dose in this population.

The Revised International Staging System (R-ISS) and the International Myeloma Working Group 2014 (IMWG 2014) are newer staging systems used to prognosticate multiple myeloma (MM) outcomes. We hypothesized that these would provide better prognostic differentiation for newly diagnosed multiple myeloma (MM) compared with ISS. We analyzed the Center for International Blood and Marrow Transplant Research database from 2008 to 2014 to compare the 3 systems (N = 628) among newly diagnosed MM patients undergoing upfront autologous hematopoietic cell transplantation (AHCT). The median follow-up of survivors was 48 (range, 3 to 99) months. The R-ISS provided the greatest differentiation between survival curves for each stage (for overall survival [OS], the differentiation was 1.74 using the R-ISS, 1.58 using ISS, and 1.60 using the IMWG 2014) . Univariate analyses at 3 years for OS showed R-ISS I at 88% (95% confidence interval [CI], 83% to 93%), II at 75% (95% CI, 70% to 80%), and III at 56% (95% CI, 3% to 69%; P < .001). An integrated Brier score function demonstrated the R-ISS had the best prediction for PFS, though all systems had similar prediction for OS. Among available systems, the R-ISS is the most optimal among available prognostic tools for newly diagnosed MM undergoing AHCT. We recommend that serum lactate dehydrogenase and cytogenetic data be performed on every MM patient at diagnosis to allow accurate prognostication.