Timing of Post-Transplantation Cyclophosphamide Administration in Haploidentical Transplantation: A Comparative Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation: Biology of Blood and Marrow Transplantation

A. Ruggeri, M. Labopin, G. Battipaglia, P. Chiusolo, J. Tischer, J.L. Diez-Martin, B. Bruno, L. Castagna, I.S. Moiseev, A. Vitek, M. Rovira, F. Ciceri, A. Bacigalupo, A. Nagler, M. Mohty

Research output: Contribution to journalArticlepeer-review

Abstract

The timing of immunosuppressive therapy used in combination with post-transplantation cyclophosphamide (PTCY) in haploidentical hematopoietic stem cell transplant (haplo-HSCT) is not standardized. We evaluated the schedules of immunosuppression therapy after haplo-HSCT in 509 patients with acute leukemia receiving PTCY on days +3 and +4 along with tacrolimus (group 1; n = 215), with cyclosporine A (CSA) and mycophenolate mofetil (MMF) from day +5 (group 2; n = 170), or CSA + MMF from day 0 or 1 with PTCY on days +3 and +5 (group 3; n = 124). Compared with the other 2 groups, patients in group 3 were younger (median age, 46 years; P = .02) and more often received bone marrow (77%; P < .01) and a regimen containing thiotepa, fludarabine, and busulfan (84%; P< .01). At 2 years, overall survival was 44% was in group 1, 48% in group 2, and 59% in group 3 (P= .15); leukemia-free survival (LFS) was 43%, 46%, and 53% (P= .05); and refined graft-versus-host disease-free, relapse-free survival (rGRFS) was 33%, 39%, and 36% (P = .02). The incidence of grade II-IV acute GVHD was 25% in group 1, 39% in group 2, and 18% in group 3 (P< .01); incidence of chronic GVHD was 25%, 21%, and 24% (P= .50); relapse incidence was 36%, 37%, and 26% (P= .02); and nonrelapse mortality was 26%, 20%, and 21% (P= .35). On multivariate analysis, early start of immunosuppression therapy at day +1 followed by PTCY was associated with a better LFS (hazard ratio [HR],. 58; P= .02) and improved rGRFS (HR,. 62; P = .02). In this study, the timing of immunosuppression influenced the outcomes of haplo-HSCT with PTCY. An early start of CSA + MMF with PTCY administered on days +3 and +5 improves LFS and rGRFS. © 2020 American Society for Transplantation and Cellular Therapy
Original languageEnglish
Pages (from-to)1915-1922
Number of pages8
JournalBiol. Blood Marrow Transplant.
Volume26
Issue number10
DOIs
Publication statusPublished - 2020

Keywords

  • Acute leukemia
  • Cyclophosphamide
  • Haploidentical transplant
  • busulfan
  • cyclophosphamide
  • cyclosporine
  • fludarabine
  • mycophenolate mofetil
  • tacrolimus
  • thiotepa
  • acute graft versus host disease
  • acute leukemia
  • acute lymphoblastic leukemia
  • acute myeloid leukemia
  • adolescent
  • adult
  • aged
  • Article
  • bone marrow transplantation
  • cancer free survival
  • chronic graft versus host disease
  • early intervention
  • female
  • haploidentical transplantation
  • hematopoietic stem cell transplantation
  • human
  • immunosuppressive treatment
  • major clinical study
  • male
  • mortality rate
  • overall survival
  • recurrence free survival
  • retrospective study
  • survival rate

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