Chemotherapy for myeloid malignancy in children with Fanconi anemia

Children with Fanconi anemia (FA) have a markedly increased risk of developing myeloid malignancies. Historically, patients with FA and myeloid malignancy have extremely poor outcomes. There are currently no clinical trials or case series addressing the use of chemotherapy for children with FA, except in the context of preparative regimens for stem cell transplantation (SCT). In this report we describe the toxicity of a chemotherapy approach for patients with FA and myeloid malignancy to achieve cytoreduction prior to SCT.

Four patients with FA and myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) were treated with chemotherapy (fludarabine 30 mg/m(2) and cytosine arabinoside 300 mg/m(2) each on days 2-4 and granulocyte-colony stimulating factor (G-CSF) 5 microg/kg on days 1-5), termed reduced intensity FLAG prior to SCT.

The chemotherapy was well tolerated with expected hematologic toxicity and no measurable toxicity in other organs. Two of the three patients with AML cleared blasts from their bone marrow. Reduction in marrow cellularity was also achieved in one patient with hypercellular MDS.

These data indicate that children with FA and myeloid malignancy can tolerate chemotherapy and achieve clearance of disease. It remains unclear whether pre-SCT chemotherapy improves currently poor survival rates for SCT in FA patients with myeloid malignancies and further studies are needed to determine if there is a clinical role for this strategy.