Late Mortality and Relapse Following HLA-Identical Sibling Donor Marrow Transplantation for Chronic Myeloid Leukemia.

Abstract

We studied the incidence and reasons for late failure following allogeneic transplantation for chronic myeloid leukemia (CML). Three-hundred thirty-five adult patients (median age 37, 229 chronic, 62 accelerated, 44 blastic phase) who underwent allogeneic marrow transplantation from HLA identical siblings at 7 institutions from 1984 – 1995 following preparation with busulfan and cyclophosphamide (BuCy2), the most commonly used regimen in this circumstance. Cyclosporine or tacrolimus-based regimens were used to prevent graft-versus-host-disease (GVHD). Median follow-up of surviving patients exceeded 14 years. Of 182 patients alive and free of leukemia at 3 years, 77.0% (95% CI: 65 to 83.6%) survive at 18 years and 61.9% (95% CI: 52.1 – 70.3%) survive without relapse. Twenty-seven (42.2%) of the 64 total relapses occurred beyond 3 years. Death occurred less frequently (P<.001) and the interval from relapse to death was longer (P=.01) in patients who relapsed late compared to those who relapsed early. The hazard rate for relapse fell rapidly from year 1 through 5, then remained low but constant through year 15. The cumulative incidence of late (beyond 3 years) relapse for patients alive and free of disease at 3 years was 22.8%.. The cumulative incidence of non-relapse mortality was 18.1% for those alive and leukemia-free at 3 years and in the 36 patients who died beyond 3 years, the primary cause of death was chronic GVHD in 11, relapse in 7, new malignancy in 6, organ failure in 6 (pulmonary in 4) and infection in 2. Multivariate analysis demonstrated that advanced disease stage (HR 2.75, P=.001) and older age (HR 1.39, P = .032) were associated with diminished LFS of patients alive and free of disease at 3 years. Overall survival was also adversely influenced by older age (HR 3.86, P < .001) and advanced stage (HR 1.54, P=.024). Advanced disease phase was associated with a higher incidence of late relapse (HR ≥ 2.50, P=.039) and late NRM (HR 3.18, P=.008). Acute GVHD and short interval from diagnosis to transplant influenced early, but not late failure. Chronic GVHD was associated with lower incidence of late relapse (HR=.30, P=.002) but did not significantly influence survival or LFS. Overall, nearly 2 of every 5 patients alive and free of leukemia at 3 years died or relapsed over the subsequent 15 years. No plateau in LFS was seen. [Display omitted]