Hematopoietic stem cell transplantation in patients with Fanconi anemia: the experience of the Russian Children's Clinical Hospital and the Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology

Background. Fanconi anemia (FA) – rare syndrome characterized by congenital malformations, high risk of bone marrow failure and
oncological diseases. Hematopoietic stem cell transplantation (HSCT) – is the only way of correction of hematopoietic insufficiency, but standard very intensive regimens of conditioning are highly toxic for patients with FA.

Patients and methods. During the period from November 1994 to April 2014 transplantations were performed for 29 patients with FA (18 females/11 males, age median – 9.5 years, variation – 3.7–15.4). Indication for HSCT was the transfusion-dependent aplastic anemia at 27 patients and transformation to myelodysplastic syndrome/acute myeloid leukemia at 2 patients. At 17 (58.6 %) patients HLA-matched family donor were used, 12 (41.4 %) patients received unrelated graft. Source: bone marrow (BM) – 18 patients, peripheral blood stem cells – 7 patients, BM + umbilical cord blood (UCB) – 3 patients, UCB – 1 patient. One of the related HSCT was performed from 9/10 donor and 2 unrelated HSCT were from 9/10 donor too. Conditioning regimens: busulphan 4–8 mg/kg, cyclophosphamide – 20–40 mg/kg, fludarabine 150 mg/sq.m., anti-thymocyte globulin. “Graft versus host” disease (GvHD) prophylaxis: cyclosporine A/tacrolimus, methotrexate 5 mg/sq.m. (days +1, +3, +6, +11) /+/– mycophenolate mofetil. Three recipients of unrelated HSCT received TCRα/β grafts.

Results. All patients engrafted. Secondary graft failure diagnosed at 4 (13.8 %) patients – after 1, 2, 6 and 12 months from HSCT. All these patients received second HSCT with conditioning with alemtuzumab, thoracoabdominal irradiation and fludarabine. Two patients died after the second HSCT, causes: GvHD and adenovirus pneumonia. Eighteen patients were free from GvHD, acute GvHD I–II gr. was revealed at 7 (24.1 %) patients, III–IV gr. – at 4 (13,7 %) patients. Limited chronic GvHD was observed at 4 patients, extensive – at 2 patients. Followup median is 31.9 (3.8–246) months. Overall 5 years survival was 67.4 %. Two patients suffered from oropharyngeal squamous cell cancer. Ten patients died in total – 10 from GvHD and one from the cancer.

Conclusion. HSCT with attenuated high immunosuppressive regimens of conditioning can obtain transplant engraftment with minimal visceral toxicity at patients with FA. Frequency of GvHD and infection complications remains high. Non-hematopoietic cancers are the cause of late mortality.

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