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 language | English |
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Pages (from-to) | 3378-3385 |
Number of pages | 8 |
Journal | Blood advances |
Volume | 6 |
Issue number | 11 |
Early online date | 10 Feb 2022 |
DOIs | |
Publication status | Published - 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