Validation of the Composite End Point of Graft-Versus-Host Disease-Free, Relapse-Free Survival

Graft-versus-host disease-free, relapse-free survival (GRFS) is a novel composite end point, which includes events such as grade 3-4 acute graft-versus-host disease (GVHD), systemic therapy-requiring chronic GVHD, relapse, or death occurring in the first post-hematopoietic stem cell transplant (HSCT) year. We aimed to investigate GRFS in Japanese patients. We retrospectively investigated the clinical outcome of 734 adult patients who underwent allogeneic hematopoietic stem cell transplantation for hematological malignant disease for the first time between 2000 and 2014 at the institutes of the Yokohama City University Hematological Group in Japan. A total of 734 patients were included in this study and comprised 438 males and 296 females with a median age at SCT of 46 years (range, 16–68 years). Here, 410 patients had acute myeloid leukemia, 154 had acute lymphoid leukemia, 67 had myelodysplastic syndrome, 57 had lymphoid malignancy, 46 had chronic myeloid leukemia, and 404 were considered to be at high risk. As for the stem cell source, 167 received related bone marrow (RBM), 103 received related peripheral blood (RPB), 313 received unrelated bone marrow (UBM), 3 received unrelated peripheral blood (UPB), and 146 received cord blood (CB). A myeloablative conditioning regimen was used in 526 patients and a reduced conditioning regimen was used in 200 patients. Cyclosporine-based GVHD prophylaxis was used in 261 patients and tacrolimus-based prophylaxis was used in 463 patients. There was gender mismatching, female donor to male recipient in 147 patients. For the entire cohort, 1-year GRFS was 34% (95% CI, 31–38), overall survival was 62% (95% CI, 58–65), and disease free survival was 54% (95% CI, 50–57). GRFS in patients at high risk was significantly lower than that in the patients at standard risk (23% vs. 47%, P < 0.01). According to the stem cell source, GRFS after RBM, RPB, UBM, and CB was 43%, 22%, 31%, and 38%, respectively (P < 0.01). On multivariate analysis, disease risk [Hazard ratio (HR), 1.8; 95% CI, 1.4–2.2; P < 0.01], RPB (HR, 1.4; 95% CI, 1.0–2.0; P = 0.04), and cytomegalovirus antibody positivity (HR, 1.4; 95% CI, 1.1–1.9; P = 0.02) were significantly associated with increased risk in GRFS. GRFS was a novel composite end point. Disease risk, RPB, and cytomegalovirus antibody positivity may be adverse factors for GRFS in Japanese patients.