A Case of Relapsed Down Syndrome–Associated Acute Megakaryoblastic Leukemia Cured with Non-Myeloablative Chemotherapy

Despite the excellent prognosis for patients with newly diagnosed Down syndrome–associated acute megakaryoblastic leukemia (DS-AMKL), patients with relapsed DS-AMKL have very poor prognosis, and there is no standard treatment for such patients. We report a case of a child with relapsed DS-AMKL who was cured with non-myeloablative chemotherapy. A 19-month-old boy with Down syndrome, who had transient leukemia as a newborn, developed DS-AMKL (positive for GATA1 mutation), after a brief phase of myelodysplastic syndrome. He was treated with cytarabine, daunorubicin, oral thioguanine, and intrathecal cytarabine for induction; and high-dose cytarabine plus L-asparaginase and intrathecal cytarabine for intensification and consolidation. He exhibited remission but relapsed within 6 weeks after the completion of therapy. A second remission was achieved with high-dose cytarabine plus mitoxantrone (HAM), after which he received 4 more cycles of chemotherapy: 1 course of HAM; 1 course of high-dose cytarabine; and 2 courses of cytarabine, fludarabine, and granulocyte colony-stimulating factor. He has been disease-free for 65 months after the completion of chemotherapy. His bone marrow aspirate became negative for GATA1 mutation after the fourth cycle of chemotherapy, and he has remained negative at 5, 7, and 8 months after completion of therapy. A non-myeloablative chemotherapy regimen with high-dose cytarabine, mitoxantrone, and fludarabine could be curative for children with DS-AMKL.