TRANSPLANTATION FOR FANCONI ANEMIA - LONG-TERM FOLLOW-UP OF 50 PATIENTS TRANSPLANTED FROM A SIBLING DONOR AFTER LOW-DOSE CYCLOPHOSPHAMIDE AND THORACOABDOMINAL IRRADIATION FOR CONDITIONING

We describe the long-term follow-up of 50 Fanconi's anaemia patients w ho were transplanted from a related donor with a median follow-up of > 6 years. The survival estimate was 74.4% at 54 months and 58.5% at 100 months, All patients were conditioned with low-dose cyclophosphamide and thoraco-abdominal irradiation. Acute graft-versus-host disease (GV HD) of grade II or more developed in 26 patients and chronic GvHD deve loped in 30/43 (69.9%) patients, The survival of patients without chro nic GVHD (n = 13) was 100%. In addition to chronic GVHD, 20 pre-transp lant transfusions was shown to have an adverse impact on survival by m ultivariate analysis (relative risk = 7.08, P=0.0003). Prospective fol low-up of growth and endocrine function could be performed in 31 patie nts. Of 20 boys, six have already reached normal puberty within the ex pected time. Among the 11 girls, three were at the pubertal age at the time of analysis. Growth retardation was common, whereas late complic ations (e.g. peripheral hypothyroidism, cataract) were rare. However, the most important long-term complication was the occurrence of cancer in seven patients (8-year projected incidence 24%), Among the 32 surv ivors, 27 (84.5%) had a normal and four a moderately reduced performan ce status, and all achieved complete engraftment with donor cells. The refore transplantation was able to cure these patients who remain at h igh risk for developing late complications. Clearly, a genetic predisp osition and chronic GvHD could have led to the development of these ca ncers, However, we cannot completely rule out irradiation as a cofacto r in the genesis of these cancers, and therefore no longer use irradia tion for the conditioning of Fanconi's anaemia patients.