Clofarabine/Cyclophosphamide/Etoposide Combination Chemotherapy Well Tolerated in An Infant with Refractory AML

Refractory AML in children under one year of age is rare. Generally the high induction remission rate is offset by higher treatment-related mortality. We report a male infant who presented with generalised lymphadenopathy and hepatosplenomegaly aged 3 months. Morphology was consistent with M5 AML and cytogenetics showed a t(9;11)(p22;q23) MLL rearrangement. He was started on standard AML induction treatment for children under 1 year of age according to the AML15 protocol (daunorubicin 37.5mg/m2 days 1, 3, 5 with etoposide 75mg/m2 days 1 through 5 and cytarabine 75mg/m2 twice daily for 10 days). He never demonstrated count recovery and by day 25 post treatment, lymphadenopathy had returned. A bone marrow aspirate showed M5 morphology with 80% of cells showing MLL rearrangement by FISH. He was therefore taken off protocol and administered fludarabine 30mg/m2 and cytosine 2g/m2 once daily for 5 days and gemtuzamab ozogamicin 3g/m2 on day 1 (FLA-GO). At day 21 post chemo, his platelet count rose into the normal range but he remained neutropenic. A bone marrow showed some normal haematopoiesis but 33% of cells were blasts with MLL rearrangement by FISH. It was decided to repeat the FLA-GO but by day 25 post chemotherapy lymphadenopathy and organomegaly had returned and marrow examination showed 50% blasts with MLL rearrangement. At this point it was decided to administer clofarabine 25mg/m2 on days 1 to 4 with etoposide 75mg/m2 and cyclophosphamide 340mg/m2 on days 1 to 5. He tolerated the regimen well, the only side effect being myelosupression. By day 24 he had recovered peripheral counts, had no lymphadenopathy or organomegaly and a marrow showing 9% blasts with MLL rearrangement. He was able to proceed with allogeneic stem cell transplantation. This shows that clofarabine-containing combination regimens can be well tolerated in the very young.