Rituximab May Allow To Improve Multi-Organ Involvement in Patients with cGVHD.

Background

Chronic graft versus host disease (cGVHD) resembles some clinical and biological features of autoimmune diseases. Only limited data are available concerning the use of rituximab in cGVHD. The preliminary reports in some autoantibodies-related immune disorders encouraged, recently, further application of this agent in the subset of cGVHD with interesting results, particularly in cases with skin involvement.

Objectives

The GITMO (Italian Group Bone Marrow Transplant) performed a retrospective multi-centre study on the use of rituximab in advanced and refractory cGHVD.

Methods

Twenty-eight patients, transplanted with a HLA-matched donor (sibling in 24 and unrelated in 4), 20 with a conventional and 8 with a reduced intensity conditioning, entered this study. The median age was 43 years (range 23–62) and the median interval elapsed from diagnosis of cGVHD to treatment with rituximab was 24 months. All patients had been treated with at least two lines of therapy including cyclosporine or tacrolimus and steroids. Rituximab was given at the conventional dose of 375 mg/m² every week for a median of 4 administrations (range 1–9). Patients were continued on baseline immunosuppressive therapy. The evaluation of response was distinguished analyzing separately the specific organ site of involvement. Response criteria were the following: complete response (CR); partial response (PR); no response (NR).

Results

A better response rate (p=0.02) was evident for patients treated with rituximab earlier in the course of disease (< vs > 6 months). At a median follow up of 6 months from rituximab administration (range 1–72 months) 14 patients maintain a significant clinical response. During the period of rituximab administration 1 patient died after the third dose because of acute respiratory failure, 1 patient had renal failure and 1 patient developed Gram + septicaemia.

Conclusions

Rituximab can induce significant disease control in patients with cGVHD refractory to standard treatment. Its activity in patients with skin involvement, the subgroup higher represented in this survey, appears, at present, the better defined one. The probability to achieve a response seems related with an earlier timing of administration. Prospective studies in larger number of patients and with more homogeneous organ involvement are warranted