The outcome of children with Fanconi anemia given hematopoietic stem cell transplantation and the influence of fludarabine in the conditioning regimen: a report from the Italian pediatric group.
OBJECTIVE
Hematopoietic stem cell transplantation (HSCT) still represents the only treatment potentially able to prevent/rescue the development of marrow failure and myeloid malignancies in patients with Fanconi anemia (FA). While in the past HSCT from an HLA-identical sibling was proven to cure many patients, a higher incidence of treatment failure has been reported in recipients of an unrelated donor (UD) or HLA-partially matched related allograft.


METHODS
We analyzed the outcome of 64 FA patients (age range, 2-20 years) who underwent HSCT between January 1989 and December 2005. Patients were transplanted from either an HLA-identical sibling (n=31), an UD (n=26), or an HLA-partially matched relative (n=7). T-cell depletion of the graft was performed in patients transplanted from an HLA-disparate relative.


RESULTS
The 8-year estimate of overall survival (OS) for the whole cohort was 67%; it was 87%, 40% and 69% when the donor was an HLA-identical sibling, an UD and a mismatched relative, respectively (p<0.01). The outcome of recipients of grafts from an UD improved over time, the probability of survival being 10% and 72% for patients transplanted before and after 1998, respectively (p<0.05). The OS probability of children who did or did not receive fludarabine in preparation for the allograft was 86% and 59%, respectively (p<0.05).


CONCLUSIONS
These data, useful for counselling, provide support to the concept that a relevant proportion of FA patients undergoing HSCT can now be successfully cured, even in the absence of an HLA-identical sibling, especially if the conditioning regimen includes fludarabine.
Locatelli
Franco
F
Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo e Università di Pavia, Pavia, Italy. f.locatelli@smatteo.pv.it
Zecca
Marco
M
Pession
Andrea
A
Morreale
Giuseppe
G
Longoni
Daniela
D
Di Bartolomeo
Paolo
P
Porta
Fulvio
F
Fagioli
Franca
F
Nobili
Bruno
B
Bernardo
Maria Ester
ME
Messina
Chiara
C
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000473:pathology* / Q000601:surgery*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007558:Italy; D008297:Male; D011336:Probability; D015996:Survival Rate; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
D014740:Vidarabine; C024352:fludarabine