Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia

Abstract

To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA-identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P < .033) and CML in blast crisis (RR = 0.37, P < .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% with GVHD, 45% with acute and chronic GVHD, 35% without only acute GVHD, and 34% with only chronic GVHD (P < .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P < .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.