Management and prognosis of Fanconi anemia
- Timothy S Olson, MD, PhD
Timothy S Olson, MD, PhD
- Assistant Professor of Pediatrics
- Comprehensive Bone Marrow Failure Center and Blood and Marrow Transplant Section
- Divisions of Pediatric Oncology and Hematology
- The Children's Hospital of Philadelphia and University of Pennsylvania
- Section Editors
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by pancytopenia, predisposition to malignancy, and physical abnormalities including short stature, microcephaly, developmental delay, café-au-lait skin lesions, and malformations belonging to the VACTERL-H association. Diagnosis is usually made in childhood, although diagnostic delays and variable disease manifestations are common and some individuals may be diagnosed with FA in adulthood.
Management of patients with FA is challenging because hematopoietic stem cell transplantation (HCT) is curative for bone marrow failure and hematologic malignancies but not for the non-hematologic features. Patients also require increased surveillance for both hematologic and non-hematologic malignancies, and reduced-intensity therapy is typically used for HCT and cancer treatment.
This topic review discusses the management and prognosis of FA. The clinical manifestations and diagnosis of FA is discussed in detail separately. (See "Clinical manifestations and diagnosis of Fanconi anemia".)
Separate topic reviews discuss the diagnosis and management of other inherited bone marrow failure syndromes:
●Dyskeratosis congenita (DC) – (See "Inherited aplastic anemia in children and adolescents", section on 'Dyskeratosis congenita'.)
- Fanconi Anemia: Guidelines for Diagnosis and Management, 4th ed, Frohnmayer D, Frohnmayer L, Guinan E, et al. (Eds), Fanconi Anemia Research Fund, Inc, Eugene, Oregon 2014. http://fanconi.org/index.php/publications/guidelines_for_diagnosis_and_management (Accessed on August 11, 2016).
- Zierhut H, MacMillan ML, Wagner JE, Bartels DM. More than 10 years after the first 'savior siblings': parental experiences surrounding preimplantation genetic diagnosis. J Genet Couns 2013; 22:594.
- Gluckman E, Rocha V, Ionescu I, et al. Results of unrelated cord blood transplant in fanconi anemia patients: risk factor analysis for engraftment and survival. Biol Blood Marrow Transplant 2007; 13:1073.
- Zecca M, Strocchio L, Pagliara D, et al. HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with Fanconi anemia. Biol Blood Marrow Transplant 2014; 20:571.
- Bertaina A, Merli P, Rutella S, et al. HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with nonmalignant disorders. Blood 2014; 124:822.
- MacMillan ML, Wagner JE. Haematopoeitic cell transplantation for Fanconi anaemia - when and how? Br J Haematol 2010; 149:14.
- Barnum JL, Petryk A, Zhang L, et al. Endocrinopathies, Bone Health, and Insulin Resistance in Patients with Fanconi Anemia after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2016; 22:1487.
- Alter BP. Inherited Bone Marrow Failure Syndromes. In: Nathan and Oski's Hematology of Infancy and Childhood, Nathan DG, Orkin SH, Ginsburg D, Look AT (Eds), W.B. Saunders, Philadelphia 2003. p.280.
- Tischkowitz M, Dokal I. Fanconi anaemia and leukaemia - clinical and molecular aspects. Br J Haematol 2004; 126:176.
- Dufour C, Svahn J. Fanconi anaemia: new strategies. Bone Marrow Transplant 2008; 41 Suppl 2:S90.
- SHAHIDI NT, DIAMOND LK. Testosterone-induced remission in aplastic anemia of both acquired and congenital types. Further observations in 24 cases. N Engl J Med 1961; 264:953.
- Diamond LK, Shahidi NT. Treatment of aplastic anemia in children. Semin Hematol 1967; 4:278.
- Scheckenbach K, Morgan M, Filger-Brillinger J, et al. Treatment of the bone marrow failure in Fanconi anemia patients with danazol. Blood Cells Mol Dis 2012; 48:128.
- Velazquez I, Alter BP. Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions. Am J Hematol 2004; 77:257.
- Rose SR, Kim MO, Korbee L, et al. Oxandrolone for the treatment of bone marrow failure in Fanconi anemia. Pediatr Blood Cancer 2014; 61:11.
- Paustian L, Chao MM, Hanenberg H, et al. Androgen therapy in Fanconi anemia: A retrospective analysis of 30 years in Germany. Pediatr Hematol Oncol 2016; 33:5.
- Gillio AP, Gabrilove JL. Cytokine treatment of inherited bone marrow failure syndromes. Blood 1993; 81:1669.
- Guinan EC, Lopez KD, Huhn RD, et al. Evaluation of granulocyte-macrophage colony-stimulating factor for treatment of pancytopenia in children with fanconi anemia. J Pediatr 1994; 124:144.
- Rackoff WR, Orazi A, Robinson CA, et al. Prolonged administration of granulocyte colony-stimulating factor (filgrastim) to patients with Fanconi anemia: a pilot study. Blood 1996; 88:1588.
- Phase I/II Gene Therapy Trial of Fanconi Anemia Patients with a New Orphan Drug Consisting of a Lentiviral Vector Carrying the FANCA Gene: A Coordinated International Action (EuroFancolen). Hum Gene Ther Clin Dev 2015; 26:81.
- Zhang QS, Tang W, Deater M, et al. Metformin improves defective hematopoiesis and delays tumor formation in Fanconi anemia mice. Blood 2016; 128:2774.
- Hasle H, Niemeyer CM. Advances in the prognostication and management of advanced MDS in children. Br J Haematol 2011; 154:185.
- Talbot A, Peffault de Latour R, Raffoux E, et al. Sequential treatment for allogeneic hematopoietic stem cell transplantation in Fanconi anemia with acute myeloid leukemia. Haematologica 2014; 99:e199.
- Peffault de Latour R, Soulier J. How I treat MDS and AML in Fanconi anemia. Blood 2016; 127:2971.
- Khan NE, Rosenberg PS, Lehmann HP, Alter BP. Preemptive Bone Marrow Transplantation for FANCD1/BRCA2. Biol Blood Marrow Transplant 2015; 21:1796.
- Kutler DI, Singh B, Satagopan J, et al. A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood 2003; 101:1249.
- Shimamura A, Alter BP. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev 2010; 24:101.
- Risitano AM, Marotta S, Calzone R, et al. Twenty years of the Italian Fanconi Anemia Registry: where we stand and what remains to be learned. Haematologica 2016; 101:319.
- OVERVIEW OF MAJOR MANAGEMENT ISSUES
- BONE MARROW FAILURE
- Monitoring bone marrow function
- Allogeneic hematopoietic stem cell transplantation (HCT)
- Transfusions and growth factors
- Therapies under development
- HEMATOLOGIC MALIGNANCIES
- SOLID TUMORS
- Screening and prevention
- Management with chemotherapy dose reductions
- IDENTIFICATION AND MANAGEMENT OF ORGAN DYSFUNCTION
- TESTING OF SIBLINGS AND MANAGEMENT OF HETEROZYGOTES
- SUMMARY AND RECOMMENDATIONS