Induction Therapy Failures in Down Syndrome Patients with Acute Myelogenous Leukemia.

Down Syndrome (DS) is known to increase the risk of acute myelogenous leukemia. Recent cooperative group clinical trials, POG 9421 and CCG 2891, using standard timing and cytarabine/daunomycin based chemotherapy achieved induction rates of 95% and 91%, respectively. In 218 total patients (57 on 9421, 161 on standard timing arm of 2891), 17 induction failures occurred (3/57 on 9421, 14/161 on 2891). Analysis of the 17 induction failures demonstrated 6 died of toxicity/other causes (2 on 9421, 4 on 2891) and 11 failed to achieve complete remission (CR) with initial induction therapy (1 on 9421, 10 on 2891). Overall survival (OS) for patients not achieving CR with induction therapy was 9% (1 of 11). For the 10 who failed to achieve CR and subsequently died, median time to death was 10 months (range 3–59). Available data for these 11 patients indicate 10 underwent at least one attempt to induce a remission using other therapies with cytarabine in combination with asparaginase, anthracycline or etoposide being the most common regimen. The longest survivor was still alive 96 months post on-study after reinduction with mitoxantrone/cytarabine therapy. Three patients received bone marrow transplants (all allogeneic, 1 known matched sibling). One patient was transplanted still in relapse and died of progressive disease 10 months post on-study. One patient died of GvHD 59 months post on-study. While overall induction rates for patients with DS and AML are high (92% versus 78% for non-DS patients), survival rates for induction failures are dismal. Reevaluation of therapeutic approaches to DS patients failing induction chemotherapy is indicated.