A Modified Post-Transplant Cyclophosphamide Regimen, for Unmanipulated Haploidentical Marrow Transplantation, in Acute Myeloid Leukemia: A Multicenter Study

Abstract

We report a modified post-transplant cyclophosphamide (PT-CY) regimen, for unmanipulated haploidentical marrow transplants, in 150 patients with acute myeloid leukemia (AML). All patients received a myeloablative regimen, cyclosporine A (CsA) on day 0, mycophenolate on day +1, and PT-CY 50 mg/kg on days +3 and +5. The median age was 51 (range, 17-74) years, 51 (34%) patients had active disease at transplant, and the median follow-up of surviving patients 903 (range, 150-1955) days. The cumulative incidence (CI) of engraftment, acute graft-versus-host disease (GVHD) grade II to IV, and moderate/severe chronic GVHD was 92%, 17%, and 15%, respectively. The 4-year CI of transplant-related mortality (TRM) and relapse was 20% and 24%, respectively. Four-year survival for remission patients was 72% (74% versus 67% for <60 or ≥60 years of age) and 26% for advanced patients (17% versus 41% for <60 or ≥60 years of age). In a multivariate analysis, active disease at transplant was the only negative predictor of survival, TRM and relapse. The original PT-CY regimen can be modified with CsA on day 0, still providing protection against GVHD, low toxicity, and encouraging low relapse incidence in AML patients, also over 60 years of age.

A prospective observational study of immune reconstitution following transplantation with post‐transplant reduced‐dose cyclophosphamide from HLA ‐haploidentical donors

“…We speculated that the double doses of 50 mg/kg of PT/Cy could increase the Tregs‐to‐Tcon ratio by more effectively eradicating alloreactive T cells. Indeed, the incidence of acute GVHD was high compared to that in patients receiving the original dose of PT/Cy . Nevertheless, the incidence of chronic GVHD was very low, suggesting that the two doses of 25 mg/kg PT/Cy were sufficient to regulate chronic GVHD.…”

“…Many prospective studies of PT/Cy‐haplo have demonstrated its safety profile and efficacy, irrespective of whether the type of graft used was bone marrow (BM) or peripheral blood (PB) . The use of PT/Cy‐haplo has become widespread globally, and it is becoming a platform technique for unmanipulated HLA‐haploidentical hematopoietic cell transplantation.…”

Different risk factors of acute and chronic graft-versus-host disease with conventional prophylaxis and posttransplantation cyclophosphamide in matched related and unrelated donor transplantations

“…Contrary to this data, the European Registry Study defi ned recipient age, use of PBSC and combination prophylaxis as the risk factors [20]. Th e diff erences might be due to diff erent PTCy schedule (day +3, +5), use of cyclosporine instead of tacrolimus, duration of immunosuppression [29]. Th e absence of diff erences between PBSC and BM is explained by single-agent PTCy prophylaxis in the matched bone marrow group and combination with tacrolimus and MMF in the PBSC group, which alleviated the diff erences.…”

Impacts of post-transplantation cyclophosphamide treatment after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

“…Owing to the success of cyclophosphamide after transplantation tolerance in the setting of haplo-HCT, this regime has been extended to the patients who underwent allogeneic HSCT from HLA-matched donors. Acute GvHD is a challenge that must be managed, and its incidence can be reduced using the utility of one or more immunosuppressive agents 21 . In this perspective, we recommend the use of cyclophosphamide and cyclosporine as prophylactic agents for GvHD.…”

“…In a recent study, Chiusolo et al . suggested that post-transplant cyclophosphamide regimen provided protection against GVHD, low toxicity, and encouraging low relapse incidence in AML patients who received unmanipulated haploidentical marrow transplants along with a myeloablative regimen 21 . Bacigalupo et al .…”