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.

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.

Hematopoietic stem cell transplantation (SCT) is routinely offered to suitable candidates with high-risk or advanced acute lymphoblastic leukemia (ALL). In this report, we update our experience with SCT in patients with ALL with a novel conditioning regimen. A total of 44 patients with high-risk or advanced (greater than first complete remission) ALL in remission underwent SCT after myeloablative conditioning with fludarabine + busulfan + total body irradiation. The median follow-up of surviving patients was 4.3 years (range, 1.0-9.0 years). The cohort consists of 32 patients with high-risk disease (median age, 40 years; range, 19-64 years) and 12 patients with advanced disease (median age, 25 years; range, 19-65 years) who underwent SCT: 25 with a related donor (21 fully matched) and 19 with an unrelated donor (16 fully matched). The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 53.2%, and that of grade III-IV acute GVHD was 20.6%. The incidence of chronic GVHD was 55%. The 100-day nonrelapse mortality was 13.6%. Five-year progression-free survival was 56.7%, and 5-year overall survival was 66.0%. Nine patients (20%) died in remission, 6 (14%) died after relapse, and 2 survived after a second SCT for relapsed disease. Outcomes were inferior in older patients with comorbidities compared with other patients.

It remains unknown why rabbit antithymocyte globulin (ATG; Thymoglobulin) has not affected relapse after hematopoietic cell transplantation (HCT) in randomized studies. We hypothesized that high pre-HCT ATG area under the curve (AUC) would be associated with a low incidence of relapse, whereas high post-HCT AUC would be associated with a high incidence of relapse. We measured serum levels of ATG capable of binding to mononuclear cells (MNCs), lymphocytes, T cells, CD4 T cells, or CD33 cells. We estimated pre- and post-HCT AUCs in 152 adult recipients of myeloablative conditioning and blood stem cells. High pre-HCT AUCs of MNC- and CD33 cell–binding ATG were associated with a low incidence of relapse and high relapse-free survival (RFS). There was a trend toward an association of high post-HCT AUC of lymphocyte-binding ATG with a high incidence of relapse and low RFS. High pre-HCT AUCs were also associated with faster engraftment and had no impact on graft-versus-host disease (GVHD) or fatal infections. High post-HCT AUCs were associated with a low risk of GVHD, seemed associated with an increased risk of fatal infections, and had no impact on engraftment. In conclusion, pre-HCT AUC seems to have a positive, whereas post-HCT AUC seems to have a negative, impact on relapse.

We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)–HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched unrelated (MUD) HR, 4.50 [95% CI, 2.24-9.03]; mismatched unrelated HR, 5.13 [95% CI, 1.44-18.31]; P < .001). This difference in OS aligns with lower graft failure with MSD (haploidentical HR, 6.11 [95% CI, 2.98-12.54]; matched unrelated HR, 2.33 [95% CI, 1.20-4.51]; mismatched unrelated HR, 1.82 [95% CI, 0.58-5.72]). There was no significant difference in OS among haploidentical, MUD, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months after HCT, relapse, disease-free survival, or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. Although MSD-HCTs were superior, there is no significant difference in HCT outcomes from haploidentical and MUDs. These results establish haploidentical HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.