Posttransplant Cyclophosphamide Allows Allogeneic Stem-Cell Transplantation across Donor Types for Nonmalignant Hematologic Diseases.

We compared posttransplant cyclophosphamide (PTCY)-based regimens with historical regimens with calcineurin inhibitor/methotrexate (CNI/MTX) for allogeneic stem-cell transplant (alloSCT) in nonmalignant hematologic disorders. In a single-center retrospective study, we reviewed acquired severe aplastic anemia (SAA) (N=18) and Diamond-Blackfan anemia (DBA) (N=1) patients who had alloSCT from 2011 to 2024. Graft-versus-host disease (GVHD) prophylaxis was CNI/MTX or PTCY, mycophenolate mofetil, and tacrolimus (PTCY cohort). Primary endpoints: overall survival (OS) and graft failure-free survival (FFS). The CNI/MTX cohort (N=14) with SAA had fludarabine (FLU)/CY/ATG (thymoglobulin)/total body irradiation (TBI) (N=11) or CY/ATG (N=3) alloSCT. Mean age: 29.1 years (18-58). All patients had failed horse ATG and cyclosporine and then had alloSCT at a median of 319 days (37-4962) from diagnosis. Donors were matched unrelated (MUD) (N=7), matched related (MRD) (N=6), and mismatched unrelated (N=1). Graft source was bone marrow (BM) (N=12) and peripheral blood stem cell (PBSC) (N=2). One patient had grade 2 skin acute (a)GVHD. None had chronic (c)GVHD. There was primary graft failure (N=6), mixed chimerism (N=4), and 100% donor chimerism (N=4). Four patients with primary graft failure had salvage second transplants at a median of 103 days (35-322) after the first transplant. Five patients with primary graft failure died at a median 6 months (0.89 – 9.3) from first transplant. The PTCY cohort (N=5) had FLU/CY/ATG/TBI 4Gy alloSCT for SAA (N=4) and DBA (N=1). Mean age: 33.8 years (21-48). Three SAA patients had upfront transplant at a median of 118 days (105-143) from diagnosis. The DBA patient had a MUD PBSC transplant at age 35. A SAA patient relapsed 2 years after immunosuppressive therapy (horse ATG, cyclosporine, eltrombopag) and had haploidentical BM alloSCT 804 days from diagnosis. Donors were MRD (N=1), MUD (N=2), syngeneic (N=1), and haploidentical (N=1). Graft source: PBSC (N=3) in MRD, MUD, and syngeneic alloSCT, and BM (N=2) in haploidentical and MUD alloSCT. Donor chimerism was 100% (N=3) and mixed chimerism (N=2). All patients became transfusion independent. None had a/c GVHD or graft failure. There was no difference in the age, comorbidity index, donor type, or graft source between the CNI/MTX and PTCY cohorts. Two-year OS rate was 64.3% vs. 100% and 2-year FFS rate was 57.1% vs. 100% for CNI/MTX vs. PTCY cohorts. Despite a trend to better graft failure-free survival with PTCY, the OS and FFS time distributions found no significant differences between the two cohorts (P= .15 and .09, respectively). Uniform conditioning with FLU/CY/ATG/TBI 4Gy alloSCT and PTCY GVHD prophylaxis is effective in adults with SAA or DBA across donor types (MRD, syngeneic, MUD, haploidentical) and should be prospectively compared with historical regimens.