Stem cell transplantation from HLA‐matched related donor for Fanconi's anaemia: a retrospective review of the multicentric Italian experience on behalf of Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)–Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

Abstract

Twenty‐seven consecutive Italian patients with Fanconi's anaemia (FA) underwent stem cell transplantation (SCT) from an HLA‐matched related donor in 10 Italian centres of the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP), Gruppo Italiano di Trapianto di Midollo Osseo (GITMO). Twenty‐two patients (81·5%) were conditioned with low‐dose (median 20 mg/kg) cyclophosphamide (Cy) and thoraco‐abdominal or total body irradiation (median dose 500 cGy), five patients (18·5%) with high‐dose Cy (median 120 mg/kg). Graft‐vs.‐host disease (GVHD) prophylaxis was carried out with cyclosporin A in 26 cases; methotrexate (MTX) was added in eight cases. One patient received MTX alone. The median follow‐up was 36 months. Ninety‐two percent of patients (25 out of 27) engrafted, grade II and III acute GVHD occurred in 28% and 8% of patients, respectively, with chronic GVHD in 12·5%. Conditioning‐related toxicity was mild: 4% of patients had grade III mucositis, 7·4% had grade II haemorrhagic cystitis, 14·8% had grade III liver toxicity and 11·1% had grade III renal toxicity. Transplant‐related mortality at 12 months was 19·2%, survival at 36 months was 81·5%, with a median Karnofsky score of 100%. No late tumours occurred after a mean follow‐up of the survivors of 5 years. None of the studied variables significantly affected the survival, including conditioning regimen, acute GVHD and clinical non‐haematological phenotype. Among the studied variables, only conditioning regimens containing high‐dose Cy and the presence of genital abnormalities were significantly (P < 0·05) associated with an increased rate of acute GVHD. Our study demonstrates that the Italian FA patients undergoing SCT from an HLA‐matched related donor have a very good outcome. These patients, when compared with others of different ethnic origin who underwent allogeneic bone marrow transplantation, showed a less severe non‐haematological phenotype, raising the possibility that this milder phenotype may have, at least in part, contributed to the outcome. Our data may provide a useful tool for further studies aiming to correlate genotype with phenotype.