Posttransplant Cyclophosphamide for Prevention of Graft-versus-Host Disease: results of the prospective randomized HOVON-96 trial

Annoek E C Broers*, Cornelis N de Jong, Katerina Bakunina, Mette D Hazenberg, Marinus van Marwijk Kooy, Marco de Groot, Michel van Gelder, Jürgen Kuball, Bronno van der Holt, Ellen Meijer, Jan J Cornelissen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Graft versus host disease (GVHD) is the most important complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). We performed a prospective randomized, multicenter, phase III trial to study whether posttransplant cyclophosphamide (PT-Cy) combined with a short course of cyclosporine A (CsA) would result in a reduction of severe GVHD and improvement of GVHD-free, relapse free survival (GRFS) as compared to the combination of CsA and mycophenolic acid (MPA) after non-myeloablative (NMA) matched related and unrelated peripheral blood alloHSCT. Between October 2013 and June 2018, 160 patients diagnosed with a high-risk hematological malignancy and having a matched related or at least 8 out of 8 HLA matched unrelated donor were randomized and allocated in a 1:2 ratio to CsA/MPA or PT-Cy/CsA. A total of 151 patients was transplanted (52 versus 99 patients). The cumulative incidence of grade II-IV acute GVHD at six months was 48% in recipients of CsA/MPA versus 30% following PT-Cy/CsA (Hazard ratio (HR): 0.48, 95% confidence interval (CI): 0.29-0.82, p=0.007). The two-year cumulative incidence of chronic extensive GVHD was 48% versus 16% (HR: 0.36, 95%CI: 0.21-0.64, p<0.001). The one-year estimate of GRFS was 21% (11%-32%) versus 45% (35%-55%), p<0.001. With a median follow-up of 56.4 months, relapse incidence, progression-free and overall survival were not significantly different between the two treatment arms. PT-Cy combined with a short course of CsA after NMA matched alloHSCT significantly improves GRFS due to a significant reduction in severe acute and chronic GVHD. The trial was registered as number NL2128 in the Dutch trial registry (www.trialregister.nl).

Original languageEnglish
Pages (from-to)3378-3385
Number of pages8
JournalBlood advances
Volume6
Issue number11
Early online date10 Feb 2022
DOIs
Publication statusPublished - 14 Jun 2022

Keywords

  • BONE-MARROW-TRANSPLANTATION
  • CLINICAL-TRIALS
  • CONSENSUS DEVELOPMENT PROJECT
  • GVHD PROPHYLAXIS
  • HEMATOLOGICAL MALIGNANCIES
  • HEMATOPOIETIC-CELL TRANSPLANTATION
  • MYCOPHENOLATE-MOFETIL
  • QUALITY-OF-LIFE
  • TOTAL-BODY IRRADIATION
  • UNRELATED DONORS

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