GRAFT-VERSUS-HOST DISEASE AFTER BONE-MARROW TRANSPLANTATION FOR THALASSEMIA - AN ANALYSIS OF INCIDENCE AND RISK-FACTORS

We analyzed risk factors in 724 patients evaluable for acute graft-ver sus-host disease (GVHD) and in 614 patients evaluable for chronic GVHD who had received bone marrow transplantation (BMT) from HLA-identical siblings and/or parents for thalassemia and/or microdrepanocytosis, i n a single institution. The overall incidence of grade II-IV and III-I V acute GVHD (aGVHD) was 26.9% and 13.5%, respectively, The cumulative incidence of grade II-IV aGVHD in patients treated with cyclosporine (CsA)/methylprednisolone (MP) or CsA/methotrexate (MTX)/MP was 32% and 17%, respectively (P=0.001). In logistic regression analysis, the ris k factors associated with the onset of grade II-IV aGVHD in the entire group of patients were: patient age less than or equal to 4 years (P= 0.009), male patient sex (P=0.023), GVHD prophylaxis with CsA/MP or MT X/MP (P=0.000), more than twofold elevated alanine aminotransferase (P =0.001), and patient seropositivity for two to three herpes viruses (P =0.007). In patients treated with CsA/MP, splenomegaly >2 cm (P=0.042) and donor age greater than or equal to 17 years (P=0.034) predicted a GVHD. Risk factors for grade III-IV aGVHD were similar to the risk fac tors identified for grade II-IV aGVHD. Moreover, moderate and severe l iver fibrosis or cirrhosis predicted grade III-IV aGVHD (P=0.018). The incidence of chronic GVHD (cGVHD) was 27.3%. The probability of cGVHD at 2 years after BMT in patients with grade 0, I, II, and III-IV aGVH D was 15%, 32%, 53%, and 54%, respectively. Among patients with absent or grade I-IV aGVHD, prior aGVHD (P=0.000), female donor sex (P=0.000 ), use of alloimmune female donors for male patients (0.009), and GVHD prophylaxis with CsA/MP or MTX/MP (P=0.003) predicted cGVHD. This dat a should be considered in clinical management and in future investigat ions for improvement of immunosuppressive prophylaxis in BMT patients with thalassemia.