ALBERT

Description: 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.