Hematopoietic cell transplantation (HCT) is an established curative treatment for a number of malignant and non-malignant diseases involving the hematopoietic system and some solid tumors. In this report, we provide information about the number of HCT procedures performed in the United States (US) in 2015 and analyze trends and outcomes of HCT as reported to the Center for International Blood and Marrow Transplant Research® (CIBMTR®). We show that the numbers of HCT performed annually continue to increase, the indications for HCT, preferred donor sources and GVHD prophylaxis continue to evolve. We report on general overall survival by indication, disease status at transplant and by transplant type. This report demonstrates a current perspective on transplant activity in the US with focus on recent trends in alternative donors and contemporary transplant practices.

Hematopoietic cell transplantation (HCT) is a well-established treatment to control and/or cure many malignant and nonmalignant diseases involving the hematopoietic system and some solid tumors. We report information about HCT procedures performed in the United States in 2018 and analyze trends and outcomes of HCT as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Overall, compared with 2017, the number of allogeneic HCTs performed in the United States increased by 1%, and the number of autologous HCTs decreased by 5%. Key findings are fewer autologous HCTs performed for non-Hodgkin lymphoma and increasing numbers of haploidentical HCTs, nearly all of which use post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis. There is a continuing increase in HCT in adults age >70 years, particularly for acute myelogenous leukemia and myelodysplastic syndromes. Survival rates by disease, disease stage, donor type, and age are presented. This report, prepared annually by the CIBMTR, provides a snapshot of current transplant activity in the United States.

There are limited data to guide the choice of high-dose therapy (HDT) regimen prior to autologous hematopoietic cell transplantation (AHCT) for patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL). We studied 4,917 patients (NHL n=3,905; HL n=1,012) who underwent AHCT from 1995-2008 using the most common HDT platforms: BEAM (n=1730), CBV (n=1853), BuCy (n=789), and TBI-containing (n=545). CBV was divided into CBVhigh and CBVlow based on BCNU dose. We analyzed the impact of regimen on development of idiopathic pulmonary syndrome (IPS), transplant-related mortality (TRM), progression free and overall survival (PFS and OS). The 1-year incidence of IPS was 3-6% and was highest in recipients of CBVhigh (HR 1.9) and TBI (HR 2.0) compared to BEAM. 1-year TRM was 4-8% and was similar between regimens. Among patients with NHL, there was a significant interaction between histology, HDT regimen, and outcome. Compared to BEAM, CBVlow (HR 0.63) was associated with lower mortality in follicular lymphoma (p<0.001), and CBVhigh (HR1.44) with higher mortality in diffuse large B-cell lymphoma (p=0.001). For patients with HL, CBVhigh (HR1.54), CBVlow (HR1.53), BuCy (HR1.77) and TBI (HR 3.39) were associated with higher mortality compared to BEAM (p<0.001). The impact of specific AHCT regimen on post transplant survival is different depending on histology; therefore, further studies are required to define the best regimen for specific diseases.

In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥70 years with hematologic malignancies across the United States. Adults ≥70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥70 years underwent HCT across 103 transplant centers. The number and proportion of allografts performed in this population rose markedly over the past decade, accounting for 0.1% of transplants in 2000 to 3.85% (N = 298) in 2013. Acute myeloid leukemia and myelodysplastic syndromes represented the most common disease indications. Two-year OS and PFS significantly improved over time (OS: 26% [95% confidence interval (CI), 21% to 33%] in 2000-2007 to 39% [95% CI, 35% to 42%] in 2008-2013, < .001; PFS: 22% [16% to 28%] in 2000-2007 to 32% [95% CI, 29% to 36%] in 2008-2013, = .003). Two-year TRM ranged from 33% to 35% and was unchanged over time ( = .54). Multivariable analysis of OS in the modern era of 2008-2013 revealed higher comorbidity by HCT comorbidity index ≥3 (hazard ratio [HR], 1.27; = .006), umbilical cord blood graft (HR, 1.97; = .0002), and myeloablative conditioning (HR, 1.61; = .0002) as adverse factors. Over the past decade, utilization and survival after allogeneic transplant have increased in patients ≥70 years. Select adults ≥70 years with hematologic malignancies should be considered for transplant.

• In combination with cyclophosphamide, intravenous busulfan is associated with better leukemia-free and overall survival in AML than TBI.Cyclophosphamide combined with total body irradiation (Cy/TBI) or busulfan (BuCy) are the most widely used myeloablative conditioning regimens for allotransplants. Recent data regarding their comparative effectiveness are lacking. We analyzed data from the Center for International Blood and Marrow Transplant Research for 1230 subjects receiving a first hematopoietic cell transplant from a human leukocyte antigen-matched sibling or from an unrelated donor during the years 2000 to 2006 for acute myeloid leukemia (AML) in first complete remission (CR) after conditioning with Cy/TBI or oral or intravenous (IV) BuCy. Multivariate analysis showed significantly less nonrelapse mortality (relative risk [RR] 5 0.58; 95% confidence interval [CI]: 0.39-0.86; P 5 .007), and relapse after, but not before, 1 year posttransplant (RR 5 0.23; 95% CI: 0.08-0.65; P 5 .006), and better leukemia-free survival (RR 5 0.70; 95% CI: 0.55-0.88; P 5 .003) and survival (RR 5 0.68; 95% CI: 0.52-0.88; P 5 .003) in persons receiving IV, but not oral, Bu compared with TBI. In combination with Cy, IV Bu is associated with superior outcomes compared with TBI in patients with AML in first

Prospective validation of the hematopoietic cell transplantation-comorbidity index (HCT-CI) using contemporary patients treated with HCT across the Unites States is necessary to confirm its widespread applicability. We performed a prospective observational study including all patients (8115 recipients of allogeneic and 11,652 recipients of autologous HCT) who underwent first HCT that was reported to the CIBMTR between 2007 and 2009. In proportional hazards models, increased HCT-CI scores were independently associated with increases in hazard ratios for NRM (p<0.0001) and overall mortality (p<0.0001) among recipients of allogeneic HCT. HCT-CI Scores of ≥3 were uniformly associated with higher risks for outcomes in both allogeneic and autologous HCT, and all subgroups regardless of diagnoses, age, and conditioning intensity. Recipients of allogeneic HCT with scores of 1–2 who were aged <18 or were treated with lower intensity conditioning regimens had similar outcomes compared to those with score 0. Higher risks for overall mortality, but not for NRM, were observed among recipients of autologous HCT with scores of 1–2 versus 0. Our results confirm the validity the HCT-CI in both allogeneic and autologous HCT. The index should be used as a valid standard-of-care health measure in counseling patients for HCT, in clinical trial design, and in adjusting outcome analyses.

• Compared with TBI, IV-BU resulted in superior survival with no increased risk for relapse or TRM.• The results support the use of myeloablative IV-BU vs TBIbased conditioning regimens for treatment of myeloid malignancies.We conducted a prospective cohort study testing the noninferiority of survival of ablative intravenous busulfan (IV-BU) vs ablative total body irradiation (TBI)-based regimens in myeloid malignancies. A total of 1483 patients undergoing transplantation for myeloid malignancies (IV-BU, N 5 1025; TBI, N 5 458) were enrolled. Cohorts were similar with respect to age, gender, race, performance score, disease, and disease stage at transplantation. Most patients had acute myeloid leukemia (68% IV-BU, 78% TBI). Grafts were primarily peripheral blood (77%) from HLA-matched siblings (40%) or well-matched unrelated donors (48%). Two-year probabilities of survival (95% confidence interval [CI]), were 56% (95% CI, 53%-60%) and 48% (95% CI, 43%-54%, P 5 .019) for IV-BU (relative risk, 0.82; 95% CI, 0.68-0.98, P 5 .03) and TBI, respectively. Corresponding incidences of transplantrelated mortality (TRM) were 18% (95% CI, 16%-21%) and 19% (95% CI, 15%-23%, P 5 .75) and disease progression were 34% (95% CI, 31%-37%) and 39% (95% CI, 34%-44%, P 5 .08).The incidence of hepatic veno-occlusive disease (VOD) was 5% for IV-BU and 1% with TBI (P < .001). There were no differences in progression-free survival and graft-versus-host disease. Compared with TBI, IV-BU resulted in superior survival with no increased risk for relapse or TRM. These results support the use of myeloablative IV-BU vs TBI-based conditioning regimens for treatment of myeloid malignancies. (Blood. 2013;122(24):3871-3878)

Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs. 7.3%; P<0.001). A 4-fold increase of PGF was observed in myeloproliferative disorders compared to acute leukemia (P<0.001). Other risk factors for PGF included recipient age below 30, HLA-mismatch, male recipients of female donor grafts, ABO-incompatibility, busulfan/cyclophosphamide conditioning, and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 108/kg were associated with PGF (OR 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post-transplant may provide the rationale for an early request for additional hematopoietic stem cells.