Abstract

Acute GVHD is one of the most serious complications and the main cause of morbidity and mortality for patients undergoing allogeneic bone marrow transplantation (BMT). So choice of GVHD prophylaxis has great impact on transplant outcome. We performed large-scale retrospective study for acute GVHD by using the data on patients who underwent BMT from unrelated donors (UR-BMT) facilitated by Japan Marrow Donor Program (JMDP). From January 1993 to September 2004, 4,999 patients were registered in the JMDP. The study population consisted of 3,410 out of 4,999 patients who received UR-BMT from HLA A,B,DR genotyping matched or HLA DR DNA allele mismatched donors(2,626 and 784, respectively). We evaluated the effect of age, HLA compatibility, disease status, GVHD prophylaxis (Cyclosporine:CsA+Methotrexate:MTX or Tacrolimus:FK+MTX), severity of acute GVHD and other factors. The Kaplan-Meier estimates of over all survival(OS) were higher for the FK group than for the CsA group in the case of HLA A,B,DR genotyping matched BMT with 5-year survival rates of 54 and 51.4% (P<0.05) and also in the case of HLA DR DNA allele mismatched BMT, 53.2 and 43.4% (P<0.05), respectively. Those of OS were higher for the FK group than for the CsA group in HLA A,B,DR genotyping matched patients with standard-risk leukemia with 5-year survival rates of 65.9 and 60.8% (P<0.05) but in those patients with high-risk leukemia were not different significantly between FK and CsA group (27.4 and 31%: p=0.61). Those of OS in HLA DR DNA allele mismatched patients with standard-risk leukemia were higher for the FK group than for the CsA group with 5-year survival rates of 64.1 and 52.2%(P<0.05) and also in those patients with high-risk leukemia were higher for the FK group than for the CsA group with 5-year survival rates of 42.4 and 27%(P<0.05). Those of OS in patients under 16 years were higher for the FK group than for the CsA group with 5-year survival rates of 78% and 62.2%(P<0.005) and in patients of 16 and over were comparable for the FK and CsA groups with 5-year survival rates of 48.3% and 45.2%(p=0.179). During the first 100 days post-transplant the incidence of grade I- IV acute GVHD was lower in the FK group compared with CsA group (65.8% and 72.7%, respectively: P<0.005), but the incidence of grade II- IV acute GVHD was similar between FK and CsA groups (40.3% and 41.5%, respectively). The incidence of grade I- IV acute GVHD was lower in the HLA A,B,DR genotyping matched group than in the HLA DR DNA allele mismatched group (68.5% and 74.7%, respectively: P<0.001). Multivariate analysis demonstrated that OS was higher for the younger age group (<16 y/o) than for the older age group (≥16 y/o)(HR:1.86, 95%CI:1.58–2.18) and for the standard-risk leukemia group than for the high-risk leukemia group(HR:2.27, 95%CI:1.58–2.59). These findings indicate that the use of FK for acute GVHD prophylaxis is beneficial for patients undergoing UR-BMT, especially for patients under 16 years and with standard-risk leukemia.

Author notes

Disclosure: No relevant conflicts of interest to declare.