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
G. Socie et al., 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, British Journal of Haematology, 103(1), 1998, pp. 249-255
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.