Multicenter phase ii study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group CBMTCGReport as inadecuate




Multicenter phase ii study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group CBMTCG - Download this document for free, or read online. Document in PDF available to download.

Journal of Hematology and Oncology

, 7:59

First Online: 21 August 2014Received: 21 January 2014Accepted: 31 July 2014DOI: 10.1186-s13045-014-0059-3

Cite this article as: Lai, Y., Chen, Y., Hu, D. et al. J Hematol Oncol 2014 7: 59. doi:10.1186-s13045-014-0059-3

Abstract

BackgroundImprovement of current GVHD prophylactic therapies remains an important goal in the allo-HSCT. We have described a novel prophylaxis regimen in a single institution trial. The Chinese Bone Marrow Transplant Cooperative Group CBMTCG initiated a phase II multicenter study.

MethodsThe study was designed as a prospective, single arm phase II open-label, multicenter clinical trial. The primary endpoint was improvement of aGVHD by 25% over historical control 40% in Chinese patients. 508 patients were enrolled. All of the patients received cyclosporine A CsA, methotrexate MTX and mycophenolate mofetil MMF 0.5-1.0 g daily for 30 days as GVHD prophylaxis regimen.

ResultsThe primary endpoint was met with cumulative incidences of grades 2 to 4 and grades 3 to 4 aGVHD of 23.2% and 10.3%, respectively. Incidence for cGVHD was 67.4%. The non-relapse mortality NRM rate was 18.4% at 2 years. The probabilities of leukemia free survival LFS for non-advanced stage and advanced stage patients at 2 years were 69.7% and 44.8% respectively p = 0.000. Recipient age ≥ 40 years, advanced stage and Busulfan-FludarabineBuFlu conditioning regimen were identified as major risk factors for aGVHD. Recipient age ≥ 40 years, BuFlu conditioning regimens, female donor-male recipient and prior aGVHD were associated with cGVHD. Despite lower RM relapse mortality, patients with grade 2–4 aGVHD had higher NRM and worse OS and LFS compared to patients with grade 0–1 aGVHD. In contrast, patients with cGVHD had better OS and LFS and lower RM compared to patients without cGVHD.

ConclusionThe novel GVHD regimen decreased the risk for aGVHD by 42% without improving the risk for cGVHD compared to historical controls. Development of aGVHD was associated with worse OS and LFS as well as higher NRM. In contrast, cGVHD was associated with improved OS and LFS likely attributed to a GVL effect.

KeywordsAllogeneic hematopoietic stem cell transplantation allo-HSCT Graft-versus-host disease GVHD prophylaxis Mycophenolate mofetil MMF Abbreviationsallo-HCSTAllogeneic hematopoietic cell transplantation

GVHDGraft-versus-host disease

aGVHDAcute GVHD

cGVHDChronic GVHD

CsACyclosporine

MTXMethotrexate

MMFMycophenolate mofetil

HLAHuman leukocyte antigen

LFSLeukemia free survival

OSOverall survival

CRComplete remission

TBITotal body irradiation

G-CSFGranulocyte colony-stimulating factor

MNCMononuclear cells

NRMNon-relapse mortality

RMRelapse mortality

Electronic supplementary materialThe online version of this article doi:10.1186-s13045-014-0059-3 contains supplementary material, which is available to authorized users.

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Author: Yong-rong Lai - Yu-hong Chen - Deng-ming Hu - Ming Jiang - Qi-fa Liu - Lin Liu - Jian Hou - Paul Schwarzenberger - Qiao-ch

Source: https://link.springer.com/







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