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.

Posttransplant cyclophosphamide (PTCy) is a promising graft-versus-host disease (GVHD) prophylaxis in haploidentical and matched unrelated donor hematopoietic stem cell transplantation (HSCT), but its role in matched sibling donor (MSD) transplants remains unclear. We conducted a retrospective study of 413 MSD-HSCT patients receiving peripheral blood stem cell (PBSC) grafts from January 2010 to January 2023. Patients were categorized into 4 groups: group I (calcineurin inhibitor [CNI] + methotrexate [MTX] or mycophenolate mofetil [MMF]), group II (CNI + MTX or MMF + antithymocyte globulin [ATG]), group III (PTCy + ATG + CNI), and group IV (PTCy + CNI + MMF). PTCy was associated with a significant reduction in grade 2- 4 and grade 3-4 acute GVHD and moderate-to-severe chronic GVHD compared with CNI + MTX (or MMF)–containing regimens. PTCy did not increase relapse risk; PTCy reduced nonrelapse mortality, leading to improved GVHD-free/relapse-free survival (GRFS; Hazard Ratio, 0.4; P < .001). PTCy was also associated with improved overall survival. Bloodstream infections were increased with PTCy. The addition of ATG to PTCy did not further improve GRFS and was associated with a higher incidence of clinically significant cytomegalovirus (csCMV) and Epstein-Barr virus (csEBV) reactivation and a numerical increase in NRM. PTCy significantly appeared to improve GRFS in the MSD setting using PBSC grafts. The addition of ATG to PTCy increases csCMV and csEBV reactivation without further improving GRFS. Prospective trials and PTCy dose optimization are warranted.

For AML, older age, advanced disease and increased hematopoietic cell transplant comorbidity index (HCT-CI) are associated with worse prognosis following allogeneic hematopoietic cell transplantation (HCT). This single-center retrospective study investigated the influence of pre-transplant characteristics on outcomes of 387 patients undergoing allogeneic HCT for AML in CR1 and CR2. The multivariable analysis model for overall survival (OS) included age (hazard ratio (HR)=2.24 for ages 31–64 years and HR=3.23 for age ⩾65 years compared with age ⩽30 years, P=0.003), remission status (HR=1.49 for CR2 compared with CR1, P=0.005) and HCT-CI score (HR=1.47 for ⩾3 compared with <3, P=0.005). Transplant year was significantly associated with OS (P=0.001) but this did not influence the model. A weighted score was developed with age ⩽30, CR1 and HCT-CI score <3 receiving 0 points each, and CR2 and HCT-CI score ⩾3 receiving 1 point each. Ages 31–64 received 2 points, age ⩾65 received 3 points. Scores were grouped as follows: scores 0–1 (low risk, n=36), score 2 (intermediate–low risk, n=147), score 3 (intermediate–high risk, n=141) and scores 4–5 (high risk, n=63) with 3-year OS of 71%, 55%, 42% and 29% for scores 0–1, 2, 3 and 4–5, respectively (P<0.0001). The score predicted nonrelapse mortality (P=0.03) but not cumulative incidence of relapse (P=0.18). This model should be validated for the pre-HCT assessment of AML patients in CR1 and CR2.