HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide after Busulfan-Containing Reduced-Intensity Conditioning

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-SCT) using post-transplant cyclophosphamide (PTCy) is increasingly performed. We conducted a multicenter phase II study to evaluate the safety and efficacy of PTCy-based HLA-haploidentical peripheral blood stem cell transplantation (PTCy-haploPBSCT) after busulfan-containing reduced-intensity conditioning. Thirty-one patients were enrolled; 61% patients were not in remission and 42% patients had a history of prior allo-SCT. Neutrophil engraftment was achieved in 87% patients with a median of 19 days. The cumulative incidence of grades II to IV and III to IV acute graft-versus-host disease (GVHD) and chronic GVHD at 1 year were 23%, 3%, and 15%, respectively. No patients developed severe chronic GVHD. Day 100 nonrelapse mortality (NRM) rate was 19.4%. Overall survival, relapse, and disease-free survival rates were 45%, 45%, and 34%, respectively, at 1 year. Subgroup analysis showed that patients who had a history of prior allo-SCT had lower engraftment, higher NRM, and lower overall survival than those not receiving a prior allo-SCT. Our results suggest that PTCy-haploPBSCT after busulfan-containing reduced-intensity conditioning achieved low incidences of acute and chronic GVHD and NRM and stable donor engraftment and low NRM, particularly in patients without a history of prior allo-SCT.

Post‐transplantation cyclophosphamide versus conventional graft‐versus‐host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation

“…In contrast to the rates of GVHD observed in haploidentical HCT recipients receiving PTCy (Luznik et al , ; Bacigalupo et al , ; Ciurea et al , ; Sugita et al , ), we found higher than expected rates of GVHD in our study. The burden of alloreactive T cells is much higher in the major histocompatibility complex (MHC)‐mismatched setting and it is pertinent to assume that a greater degree of mismatch at major HLA antigens will result in a more profound T cell proliferation and more efficient clonal deletion by post‐transplant cyclophosphamide.…”

Influence of FLT3‐ITD and NPM1 status on allogeneic hematopoietic cell transplant outcomes in patients with cytogenetically normal AML

“…16 Furthermore, only 26 (20%) of our patients received post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis; use of PTCy has previously been associated with lower rates of GVHD and NRM. 17 Shortcomings of our study include the single-center setting and small sample size, particularly in the NPM1 + /FLT3-ITD − subgroup, which limited our statistical power. Another weakness is related to the fact that we reported FLT3-ITD status dichotomously, as negative or positive, without reference to the actual allelic ratio.…”

Haploidentical bone marrow and stem cell transplantation: experience with post-transplantation cyclophosphamide

“…38 Sugita et al 39 recently reported outcomes of 31 patients who received haploidentical PBSC grafts also after RIC conditioning. The NRM in that study was 23%, but this can be partially explained by the rate of graft failure which was 13%, 39 likely due to the inclusion of poor-risk patients including 13 patients who had prior alloBMT. Despite the inclusion of challenging patient population OS, relapse, and disease-free survival rates were 45%, 45%, and 34%, respectively, at 1 year.…”