Haploidentical peripheral stem cell transplantation for young patients with severe aplastic anemia using post-transplant cyclophosphamide and methotrexate

Abstract Background Severe aplastic anemia (SAA) is a serious bone marrow failure disorder that is often cured with hematopoietic stem cell transplantation. Absence of a matched related donor is common, and thus, novel approaches are needed to safely expand the donor pool to include alternative donors, especially haploidentical related donors for SAA. Objectives This study aimed to explore a novel transplant approach for patients with AA without an available HLA-identical sibling nor matched unrelated donor. The strategy is haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) using a conditioning regimen with cyclophosphamide, busulphan, plus fludarabine (CBF) and a graft-versus-host disease (GVHD) prophylactic regimen with post-transplant cyclophosphamide (PTCy), low-dose methotrexate (LD-MTX), and calcineurin inhibitors. Study Design This prospectively designed non-randomized study included 29 patients with SAA who received haplo-PBSCT between November 2017 and May 2020. This trial was registered at www.chictr.org.cn as # ChiCTR17012896. Results The median age and time to neutrophil recovery were 17 (14–30) years and 13 (13–15) days, respectively. There was one primary graft failure (GF) in the group using PTCy at 50 mg/kg and no GF in the group using PTCy at 100 mg/kg. The median follow-up was 736 days (95% confidence interval [CI], 512–879). The estimated one-year overall survival and disease-free survival were 91.7% ± 5.7% and 89.7% ± 5.7% respectively. Among 27 patients, only one developed grade II acute GVHD. There were four cases of limited and mild chronic GVHD, involving only the skin or/and oral mucosa. Conclusions Haplo-PBSCT followed CBF with PTCy and LD-MTX represents a novel approach for safely expanding the donor pool to include alternative donors for young patients with SAA patients.