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-versus-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, in a single institution. The overall incidence of grade II-IV and III-IV 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 risk factors associated with the onset of grade II-IV aGVHD in the entire group of patients were: patient age < or = 4 years (P=0.009), male patient sex (P=0.023), GVHD prophylaxis with CsA/MP or MTX/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 > or = 17 years (P=0.034) predicted aGVHD. Risk factors for grade III-IV aGVHD were similar to the risk factors identified for grade II-IV aGVHD. Moreover, moderate and severe liver 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 aGVHD 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 data should be considered in clinical management and in future investigations for improvement of immunosuppressive prophylaxis in BMT patients with thalassemia.
Gaziev
D
D
Divisione Ematologica e Centro Trapianto Midollo Osseo di Muraglia Azienda Opsedaliera di Pesaro, Italia.
Polchi
P
P
Galimberti
M
M
Angelucci
E
E
Giardini
C
C
Baronciani
D
D
Erer
B
B
Lucarelli
G
G
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D016026:Bone Marrow Transplantation / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology*; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007223:Infant; D008297:Male; D009679:Nuclear Family; D016017:Odds Ratio; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D012727:Sex Characteristics; D013163:Splenomegaly; D013997:Time Factors; D014019:Tissue Donors; D017086:beta-Thalassemia / Q000628:therapy*
D000410:Alanine Transaminase