Impact of Reduction in Gvhd-Related Mortality for Recent Improvement of Non-Relapse Mortality after Allogeneic Hematopoietic Cell Transplantation

We retrospectively assessed changes in the incidence and causes of non-relapse mortality (NRM) over the last 12 years in allo-HCT patients. We analyzed a nationwide registry database that includes patients aged 16 years or older with AML or ALL in remission, or low-risk MDS who received allo-HCT from 1997 to 2008. We compared the incidence of NRM and overall survival (OS) after allo-HCT in three consecutive four-year periods (1997-2000, 2001-2004, and 2005-2008) for younger patients (16-49 years), and in the later two periods for older patients (≥ 50 years). Subgroup analyses were performed based on patient age and donor source: HLA-matched/1-Ag mismatched related donor (related donor) versus unrelated BM or CB donor (alternative donor). A total of 6517 patients with a median age of 40 years were analyzed and the median follow-up was 39 months. A total of 1354, 2298, and 2865 allo-HCT were performed in 1997-2000, 2001-2004, and 2005-2008, respectively. The incidence of NRM was 23% at 3 years after allo-HCT. A subgroup analysis of younger patients who received allo-HCT from a related donor showed that there was no significant change in NRM (12-15%). In younger patients who received allo-HCT from an alternative donor, the NRM incidence significantly decreased over the three periods (30%, 24%, and 22%, p < 0.001) mainly due to a reduced risk of death associated with organ failure (14%, 9%, and 7%, p = 0.005) and GVHD (7%, 3%, and 3%, p < 0.001), which led to a significantly improved OS (58%, 59%, and 64%, p = 0.008). In older patients who received allo-HCT from a related donor, NRM significantly improved in 2005-2008 compared to 2001-2004 (29% vs 18%, p < 0.001) due to a reduced risk of death associated with organ failure (11% vs 6%, p = 0.007) and GVHD (6% vs 3%, p = 0.11). However, due to the increase in the incidence of relapse in 2005-2008, this decreased NRM did not lead to an improvement of OS (51% vs 55%, p = 0.21). In older patients who received allo-HCT from an alternative donor, NRM and OS significantly improved in 2005-2008 compared to 2001-2004 (NRM, 43% vs 31%; OS, 40% vs 51%, p < 0.001). The reduction in NRM was mainly due to a decrease in death associated with infection (17% vs 11%, p = 0.007) and GVHD (7% vs 4%, p = 0.152). NRM and OS have recently improved, especially for allo-HCT from unrelated BM or CB donors. These advances seemed to be due to a reduced risk of death associated with GVHD in both younger and older patients.