Tocilizumab, tacrolimus and methotrexate for the prevention of acute graft--host disease: low incidence of lower gastrointestinal tract disease.

Haematologica 2018 04 19;103(4):717-727. Epub 2018 Jan 19.

The Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2017.183434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865423PMC
April 2018
11 Reads

Publication Analysis

Top Keywords

graft--host disease
24
acute graft--host
20
tacrolimus methotrexate
20
gastrointestinal tract
12
tocilizumab tacrolimus
12
lower gastrointestinal
12
grades ii-iv
12
stem cell
8
ii-iv acute
8
disease lower
8
graft--host
7
disease
7
methotrexate
5
tocilizumab
5
acute
5
cases graft--host
4
tract 100
4
95% 1-16
4
7-31 95%
4
1-16 day
4

Altmetric Statistics

Similar Publications