1.
Posttransplant Cyclophosphamide for Prevention of Graft-versus-Host Disease: The Prospective Randomized HOVON-96 Trial
Broers, A. E. C., de Jong, C. N., Bakunina, K., Hazenberg, M. D., van Marwijk Kooy, M., de Groot, M., van Gelder, M., Kuball, J., van der Holt, B., Meijer, E., et al
Blood advances. 2022
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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).
PICO Summary
Population
Patients with haematological malignancy due to undergo non-myeloablative allogeneic stem cell transplant with a matched related or at least 8/8 HLA matched unrelated donor, in six centres in the Netherlands (n=151)
Intervention
Posttransplant cyclophosphamide combined with a short course of cyclosporine A (PT-Cy/CsA, n=99)
Comparison
Cyclosporine A and mycophenolic acid (CsA/MPA, n=52)
Outcome
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). The two-year cumulative incidence of chronic extensive GVHD was 48% versus 16% (HR: 0.36, 95%CI: 0.21-0.64). 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.
2.
Chronic graft-versus-host disease features in double unit cord blood transplantation according to National Institutes of Health 2005 cGVHD Consensus criteria
Hayashi, H., Ruggeri, A., Volt, F., Cornelissen, J. J., SociƩ, G., Sengeloev, H., Michallet, M., Karakasis, D., Petersen, E., Cahn, J. Y., et al
Bone marrow transplantation. 2018;53(4):417-421