Posttransplant cyclophosphamide vs cyclosporin A and methotrexate as GVHD prophylaxis in matched sibling transplantation

Blood Adv. 2019 Nov 12;3(21):3351-3359. doi: 10.1182/bloodadvances.2019000236.

Abstract

Posttransplant cyclophosphamide (PTCy) effectively prevents graft-versus-host disease (GVHD) after HLA-haploidentical hematopoietic stem cell transplantation (HSCT). The use of PTCy in HLA-identical HSCT is less explored. We conducted a retrospective study of 107 consecutive patients undergoing an HLA-identical sibling (10/10) HSCT in 2 centers in Spain, 50 with GVHD prophylaxis with methotrexate-cyclosporin A (MTX-CsA) and 57 using a PTCy-based regimen with additional immunosuppression. Graft source was unmanipulated mobilized peripheral blood stem cells (PBSC) in most patients (97 patients, 91%). Cumulative incidences of grade II to IV and III to IV acute GVHD at 100 days were lower in the PTCy group (22.6% vs 52.2%, P = .0015; 8.8% vs 24.4%, P = .016), without statistically significant differences in the 2-year cumulative incidence of chronic moderate to severe GVHD (16.7% vs 26%, P = .306). At 2 years, no statistically significant differences were observed in OS (78% vs 56%, P = .088), EFS (62.5% vs 48%, P = .054), relapse (28% vs 27%, P = .47), and NRM (8.8% vs 24%, P = .054). The composite endpoint of GVHD and relapse-free survival (GRFS) was favorable for the PTCy group (24% vs 48%, P = .011), PTCy being the sole independent factor identified in the multivariate analysis for this endpoint. In this study, PTCy combination with additional immunosuppression using mostly PBSCs grafts showed a reduction of acute GVHD rate and an impact on GRFS, with safety results comparable with those obtained with MTX-CsA. Further prospective studies are needed to confirm these observations..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Cell Count
  • Cyclophosphamide / administration & dosage*
  • Cyclosporine / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / methods
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Male
  • Middle Aged
  • Recurrence
  • Severity of Illness Index
  • Siblings*
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Cyclophosphamide