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To develop a prognostic model for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) for myelofibrosis (MF). We examined 623 patients undergoing allo-HCT between 2000 - 2016 in the USA (CIBMTR cohort). A Cox multivariable model was used to identify factors prognostic of mortality. A weighted score using these factors was assigned to patients transplanted in Europe (EBMT cohort) (n = 623). Age above 50 (hazard ratio [HR], 1.39; 95% confidence interval [CI], 0.98 -1.96), and HLA matched unrelated donor (HR, 1.29; 95% CI, 0.98-1.7) were associated with increased hazard of death and were assigned 1 point. Hemoglobin lower than 100g/L at time of transplant (HR, 1.63; 95% CI, 1.2- 2.19), and a mismatched unrelated donor (HR, 1.78; 95% CI, 1.25- 2.52), were assigned 2 points. The 3-year overall survival (OS) in patients with a low (1-2 points), intermediate (3-4 points) and high score (5 points) were 69% (95% CI, 61% -76 %), 51 % (95% CI, 46% -56.4 %), and 34% (95% CI, 21% - 49%), respectively (P. < 0.001). Increasing score was predictive of increased transplant related mortality (TRM) (P .0017) but not for relapse (P. 0.12). The derived score was predictive for OS (P. < 0.001) and TRM (P. 0.002) but not relapse (P. 17) in the EBMT cohort as well. The proposed system was prognostic of survival in two large cohorts, CIBMTR and EBMT, and can easily be applied by clinicians consulting patients with MF on transplant outcomes.

Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1− myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation–based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.

A common method to prevent graft-versus-host disease after allogeneic hematopoietic cell transplantation (HCT) from an HLA-mismatched unrelated donor (MMUD) is tacrolimus, methotrexate, and antithymocyte globulin (ATG). The use of posttransplant cyclophosphamide (PTCy) showed promise in a prospective trial for MMUD HCT. We compared 1-year graft-versus-host disease–free, relapse-free survival (GRFS) in 128 recipients of prophylaxis based on tacrolimus/methotrexate/ATG (ATG group, n = 46) vs PTCy, mycophenolate mofetil, and tacrolimus or sirolimus (PTCy group, n = 82) after MMUD HCT. Patients receiving HCT from a MMUD mismatched at ≥1 locus among HLA-A, HLA-B, HLA-C, and HLA-DRB1 were included. The 2 groups were well matched for HCT indication, high-risk disease, and HCT comorbidity index, whereas more patients on PTCy received bone marrow (50% vs 26%; P = .01) and >1 locus HLA-mismatched (30.5% vs 2.2%; P = .001) grafts. The 1-year GRFS was 16% (95% confidence interval (CI): 8%-31%) vs 54% (95% CI: 44%-66%; P < .001) in the ATG and PTCy groups, respectively. The multivariable adjusted hazard ratio for GRFS was 0.34 (95% CI: 0.21-0.55; P < .001) with the use of PTCy. The 1-year overall survival in the ATG group was 45% (95% CI: 32%-62%) vs 75% (95% CI: 66%-85%) in the PTCy group (P < .001). Relapse incidence was similar. One-year nonrelapse mortality was greater after ATG-based prophylaxis: 38% (95% CI: 23%-52%) vs 16% (95 CI: 9%-25%), P < .001. In summary, PTCy-based prophylaxis resulted in superior GRFS and overall survival in recipients of MMUD.

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