Summary:
Seven children with Fanconi anaemia (FA) (five female, two male), who had not undergone transformation, received nine haemopoietic stem cell transplantation (HSCT) between 2000 and 2004. Conditioning regimen was: fludarabine 25–30 mg/m2/day for 5 days, antilymphocyte globulin 12.5 mg/kg/day for 3 days and cyclophosphamide 5–7.5 mg/kg/day for 4 days. Radiation was not used. One male patient who had multiple HSCT and one female who was retransplanted, received slightly different conditioning regimens. Four patients received fully matched unrelated umbilical cord blood (UCB), two matched unrelated peripheral blood stem cell (PBSC) grafts, and three haploidentical T-cell-depleted (TCD) PBSC grafts. None of the patients had any significant conditioning-related toxicity or severe infections. All engrafted within 2–3 weeks. One patient rejected her first HSCT after 10 weeks and had a second successful transplant from the same donor. One male patient rejected his TCD haploidentical HSCT from his mother, and subsequently had a successful fully matched unrelated UCB transplant. Rejection rate was 22%. Acute and chronic graft-versus-host disease (GVHD) was seen in 77 and 22% patients. In all, 57% patients developed autoimmune complications, all of which have resolved. All patients are well with stable or full donor chimerism after a median follow-up of 37 months (range 13–54).
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References
Auerbach AD, Buchwald M, Joenje H . Fanconi anemia. In: Vogelstein B, Kinzler KW (eds). The Genetic Basis of Human Cancer. McGraw-Hill: New York, 1997, p 317.
Butturini A, Gale RP, Verlander PC et al. Hematologica abnormalities in Fanconi anaemia: an international Fanconi anemia registry study. Blood 1994; 90: 105–110.
Dufour C, Rondelli R, Locatelli F et al. Stem cell transplantation from HLA-matched related donor for Fanconi's anaemia: a retrospective review of the multicentric Italian experience on behalf of Associazone Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) – Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Br J Haematol 2001; 112: 796–806.
Guardiola P, Pasquini R, Dokal I et al. Outcome of 69 allogenic stem cell transplantations for Fanconi anaemia using HLA-matched unrelated donors. A study on behalf of the European Group for Blood and Marrow Transplantation. Blood 2000; 95: 422–429.
Davies SM, Khan S, Wagner JE et al. Unrelated donor bone marrow transplantation for Fanconi anemia. Bone Marrow Transplant 1996; 17: 43–47.
Hows JM, Chapple M, Marsh JC et al. Bone marrow transplantation for Fanconi's anemia: the Hammersmith experience 1977–89. Bone Marrow Transplant 1989; 4: 629–634.
Gluckman E, Auerbach AD, Horowitz MM et al. Bone marrow transplantation for Fanconi anemia. Blood 1995; 86: 2856–2862.
Berger R, Bemheim A, Gluckman E, Gisselbrecht C . In vitro effect of cyclophosphamide metabolites on chromosomes of Fanconi's anaemia patients. Br J Haematol 1980; 45: 565–568.
Gluckman E, Devergie A, Dutreix J . Bone Marrow transplantation in Fanconi anemia. A modified conditioning regimen. Exp Hematol 1982; 10: 26–27.
Fisher A, Friedrich W, Fasth A et al. Reduction in graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anaemia: a European Group for Immunodeficiency/European Group for Bone Marrow transplantation report. Blood 1991; 77: 249–256.
Elhasid R, Weyl Ben Arush M, Katz T et al. Successful haploidentical bone marrow transplantation in Fanconi anaemia. Bone Marrow Transplant 2000; 26: 1221–1223.
Rossi G, Giorgiani G, Comoli P et al. Successful T-cell- depleted, related haploidentical peripheral blood stem cell transplantation in a patient with Fanconi anaemia using a fludarabine-based preparative regimen without radiation. Bone Marrow Transplant 2003; 31: 437–440.
Boulad F, Gillio A, Small TN et al. Stem cell transplantation for the treatment of Fanconi anaemia using a fludarabine-based cytoreductive regimen and a T-cell-depleted related HLA-mismatched peripheral blood stem cell grafts. Br J Haematol 2000; 111: 1153–1157.
Gluckman E, Rocha V, Boyer-Chammard A et al. Outcome of cord-blood transplantation from related and unrelated donors. N Engl J Med 1998; 337: 373–381.
Rubinstein P, Carrier C, Scaradavou A et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 1998; 339: 1565–1577.
Yoshimasu T, Tanaka R, Suenobu S et al. Prompt and durable haemopoietic reconstitution by unrelated cord blood transplantation in a child with Fanconi anaemia. Bone Marrow Transplant 2001; 27: 767–769.
Medeiros CR, Silva SM, Pasquini R . Unrelated cord blood transplantation in a Fanconi anaemia patient using fludarabine based conditioning. Bone Marrow Transplant 2001; 28: 110–112.
Slavin S, Nagler A, Naparstek E et al. Non-myeloabllative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and non-malignant haematologic disease. Blood 1998; 91: 756–763.
Storb R, Yu C, Wagner JL et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before pharmacological immunosuppression after marrow transplantation. Blood 1997; 89: 3048–3054.
Giralt S, Estey E, Albitar M et al. Engraftment of allogenic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative chemotherapy. Blood 1997; 89: 4531–4536.
Aker M, Varadi G, Slavin S, Nagler A . Fludarabine based protocol for human umbilical cord blood transplantation in children with Fanconi anemia. J Pediatr Hematol Oncol 1999; 21: 237–239.
Giempietro PF, Adler-Brecher B, Verlander PC et al. The need for more accurate and timely diagnosis in Fanconi anaemia: a report from the International Fanconi Anemia Registry. Pediatrics 1993; 91: 1116–1120.
Kohli-Kumar M, Morris C, Delaat C et al. Bone marrow transplantation in Fanconi anaemia using matched sibling donors. Blood 1994; 84: 2050–2054.
McCloy M, Almeida A, Daly P, Dokal I et al. Fludarabine based stem cell transplantation protocol for Fanconi's anaemia in myelodysplastic transformation. Br J Haematol 2001; 112: 427–429.
Deeg HJ, Socie G, Schoch G et al. Malignancies after marrow transplantation for aplastic anaemia and Fanconi anaemia: a joint Seattle and Paris analysis of results in 700 patients. Blood 1996; 87: 386–392.
Zecca M, Prete A, Rondelli R et al. Chronic graft versus host disease in children: incidence, risk factors, and an impact on outcome. Blood 2002; 100: 1192–1200.
Locatelli F, Giorgiani G, Pession A, Bozzola M . Late effects in children after bone marrow transplantation: a review. Haematologica 1993; 78: 319–328.
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Motwani, J., Lawson, S. & Darbyshire, P. Successful HSCT using nonradiotherapy-based conditioning regimens and alternative donors in patients with Fanconi anaemia – experience in a single UK centre. Bone Marrow Transplant 36, 405–410 (2005). https://doi.org/10.1038/sj.bmt.1705071
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DOI: https://doi.org/10.1038/sj.bmt.1705071
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