TY - JOUR
T1 - Posttransplant Cyclophosphamide for Prevention of Graft-versus-Host Disease
T2 - results of the prospective randomized HOVON-96 trial
AU - Broers, Annoek E C
AU - de Jong, Cornelis N
AU - Bakunina, Katerina
AU - Hazenberg, Mette D
AU - van Marwijk Kooy, Marinus
AU - de Groot, Marco
AU - van Gelder, Michel
AU - Kuball, Jürgen
AU - van der Holt, Bronno
AU - Meijer, Ellen
AU - Cornelissen, Jan J
N1 - Funding Information:
The authors thank all local data managers and the HOVON Data Center trial team for trial management and central data management; the members of the Data and Safety Monitoring Board: J.H.F. Falkenburg (Leiden, The Netherlands), N. Kroger € (Hamburg, Germany), and A. Benner (Heidelberg, Germany) for their contribution to the conduct of the study; and all collaborators and patients who participated in the study. Supported by the Dutch Cancer Society (grant 2008-4331) and Novartis.
Publisher Copyright:
© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
PY - 2022/6/14
Y1 - 2022/6/14
N2 - Graft-versus-host disease (GVHD) is the most important complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). We performed a prospective randomized, multicenter, phase 3 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 with the combination of CsA and mycophenolic acid (MPA) after nonmyeloablative (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 were transplanted (52 vs 99 patients, respectively). The cumulative incidence of grade 2 to 4 acute GVHD at 6 months was 48% in recipients of CsA/MPA vs 30% following PT-Cy/CsA (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.82; P 5 .007). The 2-year cumulative incidence of extensive chronic GVHD was 48% vs 16% (HR, 0.36; 95% CI, 0.21-0.64; P, .001). The 1-year estimate of GRFS was 21% (11% to 32%) vs 45% (35% to 55%), P, .001. With a median follow-up of 56.4 months, relapse incidence, progression-free survival, and overall survival were not significantly different between the 2 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.
AB - Graft-versus-host disease (GVHD) is the most important complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). We performed a prospective randomized, multicenter, phase 3 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 with the combination of CsA and mycophenolic acid (MPA) after nonmyeloablative (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 were transplanted (52 vs 99 patients, respectively). The cumulative incidence of grade 2 to 4 acute GVHD at 6 months was 48% in recipients of CsA/MPA vs 30% following PT-Cy/CsA (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.82; P 5 .007). The 2-year cumulative incidence of extensive chronic GVHD was 48% vs 16% (HR, 0.36; 95% CI, 0.21-0.64; P, .001). The 1-year estimate of GRFS was 21% (11% to 32%) vs 45% (35% to 55%), P, .001. With a median follow-up of 56.4 months, relapse incidence, progression-free survival, and overall survival were not significantly different between the 2 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.
KW - Cyclophosphamide/therapeutic use
KW - Cyclosporine/therapeutic use
KW - Graft vs Host Disease/etiology
KW - Hematopoietic Stem Cell Transplantation/methods
KW - Humans
KW - Mycophenolic Acid/therapeutic use
KW - Neoplasm Recurrence, Local
KW - Prospective Studies
UR - https://www.scopus.com/pages/publications/85131834193
U2 - 10.1182/bloodadvances.2021005847
DO - 10.1182/bloodadvances.2021005847
M3 - Article
C2 - 35143644
SN - 2473-9529
VL - 6
SP - 3378
EP - 3385
JO - Blood Advances
JF - Blood Advances
IS - 11
ER -