Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Tocilizumab, tacrolimus and methotrexate for the prevention of acute graft--host disease: low incidence of lower gastrointestinal tract disease. Haematologica 2018 Apr;103(4):717-727 PMID: 29351985 PMCID: PMC5865423

Pubmed ID

29351985

Abstract

We conducted a phase 2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received tocilizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft--host disease prophylaxis. Thirty-five patients were enrolled between January 2015 and June 2016. The median age of the cohort was 66 (range: 22-76). All patients received busulfan-based conditioning, and were transplanted with human leukocyte antigen-matched related or matched unrelated bone marrow or peripheral stem cell grafts. The cumulative incidences of grades II-IV and III-IV acute graft--host disease were 14% (95% CI 5-30) and 3% (95% CI 0-11) at day 100, and 17% (95% CI 7-31) and 6% (95% CI 1-16) at day 180, respectively. Notably, there were no cases of graft--host disease of the lower gastrointestinal tract within the first 100 days. A comparison to 130 matched controls who only received tacrolimus and methotrexate demonstrated a lower cumulative incidence of grades II-IV acute graft--host disease (17% 45%, =0.003) and a significant increase in grades II-IV acute graft--host disease-free survival at six months (69% 42%, =0.001) with tocilizumab, tacrolimus and methotrexate, which was the primary endpoint of the study. Immune reconstitution was preserved in patients treated with tocilizumab, tacrolimus and methotrexate, as T-cell and B-cell subsets recovered to near normal levels by 6-12 months post-transplantation. We conclude that tocilizumab has promising activity in preventing acute graft--host disease, particularly in the lower gastrointestinal tract, and warrants examination in a randomized setting.

Author List

Drobyski WR, Szabo A, Zhu F, Keever-Taylor C, Hebert KM, Dunn R, Yim S, Johnson B, D'Souza A, Eapen M, Fenske TS, Hari P, Hamadani M, Horowitz MM, Rizzo JD, Saber W, Shah N, Shaw B, Pasquini M

Authors

Anita D'Souza MD Assistant Professor in the Medicine department at Medical College of Wisconsin
William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Mary Eapen MBBS, DCh, MRCPI, MS Professor in the Medicine department at Medical College of Wisconsin
Timothy Fenske MD Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Associate Professor in the Medicine department at Medical College of Wisconsin
J. Douglas D. Rizzo MD, MS Director, Ctr Associate Director, Professor in the Medicine department at Medical College of Wisconsin
Wael Saber MD, MS Associate Professor in the Medicine department at Medical College of Wisconsin
Nirav N. Shah MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Bronwen E. Shaw MBChB, PhD Professor in the Medicine department at Medical College of Wisconsin
Aniko Szabo PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Fenlu Zhu PhD Assistant Professor in the Medicine department at Medical College of Wisconsin




jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6