Topics in Pediatric Leukemia -- Fanconi's Anemia: New Insights

Noah Federman, MD; Kathleen M. Sakamoto, MD, PhD

In This Article


The initial management of FA consists in confirming the diagnosis with a clastogenic assay. Patients should then be examined for clinical signs of disease, as previously described. Renal ultrasound, hearing tests, complete blood counts, and a bone marrow examination should be performed. Furthermore, histocompatibility antigen (HLA) typing should be done in preparation for stem cell transplantation.

Other family members should be offered testing to determine their risk of disease, especially if an allogeneic SCT is being considered. Growth failure has been managed with growth hormone therapy, and an endocrinologist should evaluate these patients. Orthopaedic and plastic surgery evaluations are also important for possible correction of radial ray anomalies.[4]

Further management of FA patients then depends on the presence of hematologic abnormalities. If hematologic abnormalities are absent at the time of diagnosis, serial hematologic measurements should be performed once to several times per year.[4] As patients get older, the treatment is directed at the development of complications and progressive bone marrow failure.

Approximately 50% to 70% of patients with FA and progressive pancytopenia initially respond to androgen therapy with oral oxymetholone.[17] Androgen therapy, however, has many unwanted side effects, including acne, hirsutism, behavioral disturbances, premature closure of the epiphyses, and liver abnormalities (elevated transaminases, hepatic adenomas, and risk of hepatocellular carcinoma). This necessitates a careful surveillance of liver function tests and an annual ultrasonography of the liver. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have also been used alone and with androgen therapy to support pancytopenia, with variable response.[18] However, eventually, almost all FA patients become refractory to androgen and cytokine therapy.

Once the pancytopenia of FA patients becomes refractory to supportive therapy, SCT is the treatment of choice. The general consensus is that in an otherwise healthy FA patient with an HLA-matched sibling and a pancytopenia consisting in an absolute neutrophil count < 1000/mm3, hemoglobin < 8g/dL, and a platelet count < 50,000 mm3, SCT should be strongly considered.[19] In patients with a matched sibling donor, survival with SCT is greater than 70%. In contrast, the survival of patients receiving an alternative-donor SCT is less than 40%.[20] The conditioning regimens in these groups use reduced doses of cyclophosphamide and irradiation, owing to the intrinsic hypersensitivity of FA patients to genotoxic agents. Cyclophosphamide- and irradiation-free conditioning regimens with primarily fludarabine have also given good results.[21,22]

Preimplantation genetic diagnosis has been used to select unaffected embryos of parents with a child affected by FA. The embryos were also selected so that they could be HLA-matched with the affected sibling, in the hope to recover umbilical cord blood cells for an SCT of the affected child. This procedure has been successful in one instance following transplantation of the proband, although controversial from an ethical point of view because there was wastage of multiple healthy embryos that were HLA-mismatched.[23]


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