Durable discontinuation of systemic therapy in patients affected by chronic graft versus host disease.

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Abstract

Successful treatment of chronic graft-versus-host disease (GVHD) often requires long term systemic therapy (ST). Durable discontinuation of ST reflects the resolution of active chronic GVHD. We evaluated the factors associated with durable ST discontinuation, defined as cessation of all ST for =12 months, using data from 2 prospectively followed cohorts from the chronic GVHD Consortium (N=684). Transplant sources were peripheral blood (89%), bone marrow (6.6%), and cord blood (4.4%) from HLA matched related (37.6%), HLA matched unrelated (45%), and other donor types (18%). Half received non-myeloablative conditioning. The median time from HCT to chronic GVHD diagnosis was 7.7 (range 1.0 - 141.3) months, and the median time from chronic GVHD onset to enrollment into the cohorts was 0.9 (range 0.0-12.0) months. The cumulative incidence estimate of durable ST discontinuation was 32% (95% CI: 28%-37%) at 10 years after cohort enrollment. Among patients who discontinued ST, the median time from chronic GVHD diagnosis to durable ST discontinuation was 3.6 (range 1.2-10.5) years. In multivariate analysis, patients who received myeloablative conditioning, had chronic GVHD manifested as moderate / severe lower gastrointestinal (GI) involvement, and had a higher (worse) Lee symptom overall score were less likely to attain durable ST discontinuation. In contrast, mild lower GI involvement and cord blood (vs. peripheral blood) as a graft source were associated with a greater likelihood of ST discontinuation. Although a minority of patients can discontinue systemic treatment permanently, most patients require prolonged systemic treatment. Viewing chronic GVHD in this way has implications for management approaches.

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