Pb2190: hla-haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide after reduced-intensity conditioning

Background: Allogeneic peripheral blood stem cell transplantation (PBSCT) is a potentially curative treatment for patients with hematological malignancies. However, the availability of HLA-matched, related or unrelated donors is always in question. Haploidentical related donors are alternative donor options for patients who lack an HLA-matched donor but are in urgent need of transplantation. However, haploidentical PBSCT (haploPBSCT) poses significant challenges because of the HLA mismatch, which often increases the risk of graft-versus-host disease (GVHD) and non-relapse mortality (NRM). A recent study led by a group at Johns Hopkins pioneered the use of post-transplant cyclophosphamide (PTCY) in the haploPBSCT setting. In the haploPBSCT, the use of PTCY in combination with tacrolimus and mycophenolate mofetil (MMF) have been found to lower the rates of acute and chronic GVHD, as well as NRM. Aims: We conducted this prospective study to further evaluate the safety and efficacy of PTCy-haploPBSCT. Methods: Eleven patients diagnosed with hematologic disease (AML, ALL, MDS, and aplastic anemia; 4, 1, 4, and 2, respectively) were enrolled in this study. The median age was 44 (range, 24 to 65). The conditioning regimen consisted of fludarabine (150 mg/m2), busulfan (6.4 mg/kg), and total body irradiation (TBI, 3Gy). High-dose cyclophosphamide (50 mg/kg/day on days 3 and 5), cyclosporine, and MMF were used for GVHD prophylaxis. The median numbers of CD34+ cells of PBSCs were 11.6 × 106 /kg (range, 6.1–24.9 × 106 /kg). Results: Overall survival (OS) and relapse-free survival (RFS) at 1-year were 79% and 69%, respectively. Two patients relapsed. One patient was AML and another relapsed with RAEB. Neutrophil engraftment was achieved in 91% of patients with a median of 14 days (range, 13–15 days). The cumulative incidence rates of grades I–IV and III-IV acute GVHD at 100 days were 36% and 9%, respectively. The cumulative incidence rates of mild and moderate chronic GVHD at 1-year were 9% and 18%, respectively. No patients developed severe chronic GVHD. The cumulative incidence rates of NRM, relapse and GVHD-free/RFS at 1-year were 21%, 31% and 62%, respectively. Summary/Conclusion: Our results indicate that PTCy-haploPBSCT is a valid and safe strategy for preventing severe acute and chronic GVHD. In addition, it may also provide better clinical outcomes in long-term disease control. However, our study suggests that relapse still remains as a major cause of treatment failure. Therefore, there is a need for a modified conditioning regimen that can enhance anti-leukemic effects in aggressive diseases such as acute leukemia.