Chemotherapy for myeloid malignancy in children with Fanconi anemia.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Mehta
Parinda A
PA
Fanconi Anemia Comprehensive Care Center, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio 45229, USA. Parinda.Mehta@cchmc.org
Ileri
Talia
T
Harris
Richard E
RE
Williams
David A
DA
Mo
Jun
J
Smolarek
Teresa
T
Auerbach
Arleen D
AD
Kelly
Patrick
P
Davies
Stella M
SM
D000208:Acute Disease; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000150:complications*; D005260:Female; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000150:complications* / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000175:diagnosis / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D015996:Survival Rate; D016896:Treatment Outcome