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

Abstract

Post-transplant cyclophosphamide has become a promising medical option after allogeneic HSCT. In this study we aimed to evaluate the efficacy of cyclophosphamide and cyclosporine combination in acute and chronic graft-versus-host disease (GvHD) prophylaxis in acute myeloid leukemia (AML) cases scheduled for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Retrospective analysis of data from 40 cases who underwent allogeneic HSCT under GvHD prophylaxis with cyclophosphamide and cyclosporine combination between April 2016 and August 2017 was made. Cyclophosphamide was given at daily doses of 50 mg/kg on post-transplant 3rd and 4th days, and cyclosporine was applied at daily doses of 3 mg/kg/day starting from the 5th post-transplant day. Cyclosporine dose was tapered beginning from the 45th postoperative day and completely discontinued on the 90th post-transplant day. Mean age was 38.25 ± 15.25 years. Posttransplant median follow-up was six months (6–17 months). Post-transplant, the number of deaths and mortality rates related and unrelated to transplantation were 5 (12.5%), and 2 (5%), respectively. Acute GvHD was diagnosed in 7 cases (17.5%), and relapse was noted in 9 cases (22.5%). Myeloablative or reduced intensity conditioning was performed in 22 (55%) and 18 (45%) patients, respectively. The distribution of the donors was as follows: match-related (n = 26; 65%), match-unrelated (n = 9, 22.5%) and haploidentical donors (n = 5; 12.5%). There was no statistically significant correlation between the transplant-related and unrelated mortality and parameters under investigation.Cyclophosphamide use appears to be a highly effective and promising strategy for acute GvHD prophylaxis in non-haploidentical allogeneic HSCT cases. Identification of the impact of cyclophosphamide use on the development of chronic GvHD needs further investigation.

Cyclophosphamide arrhythmogenicitytesting using human-induced pluripotent stem cell-derived cardiomyocytes

“…CP is an anti-cancer drug that is used in the treatment of rheumatoid arthritis, lupus erythematosus, multiple sclerosis, neuroblastoma, and other types of cancer and it is also used in transplantology 25 . Unfortunately, its action is often associated with cardiovascular side effects such as atrioventricular block, tachyarrhythmias, heart failure, and myocarditis when taken in high doses (i.e., 100-200 mg/kg) [1][2][3][4][5][6] .…”

The Graft-Versus-Leukemia Effect in AML

“…Improved reconstitution of T cell subsets and a concomitant reduction in infectious complications was also observed in the T cell replete group (85). Following its success in haploidentical allo-SCT, post-transplant cyclophosphamide has been demonstrated to provide effective GvHD prophylaxis and a good safety profile in the HLA-matched related and unrelated donor settings (86).…”

Post-transplantation cyclophosphamide as graft versus host disease prophylaxis in patients with acute leukemia received fully matched allogeneic HSCT or haplo-identical HSCT

“…Therefore, strategies to prevent this complication without affecting thr beneficial graft-versus-tumor (GvT) effects are required. [14][15][16] With the use of PT-Cy in allogeneic HLA-matched bone marrow transplant and the haploidentical setting, significant improvement in the prevention of GVHD has been made. Our study was conducted on 80 patients with acute leukemia received either fully matched allogeneic HSCT or Haplo-identical HSCT.…”

“…13 Hemorrhagic cystitis was graded as: grade 0 = none; grade I = microscopic hematuria with urinary symptoms; grade II = macroscopic hematuria; grade III = macroscopic hematuria with clots and grade IV = macroscopic hematuria with intervention for clot evacuation and/or urinary retention. 14…”