Down Syndrome Patients with Relapsed Acute Myelogenous Leukemia.

Down Syndrome (DS) is known to increase the risk of acute myelogenous leukemia (AML). 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. 218 patients (57 on 9421, 161 on standard timing arm of 2891) were treated. Induction failures occurred in 17/218 (3/57 on 9421, 14/161 on 2891). Relapses occurred in 11% (24/218) [4/57 on 9421, 20/161 on 2891]. Analysis of these 24 patients demonstrate overall survival (OS) of 12% (3/24). One patient on 9421 relapsed with ALL and successfully underwent ALL chemotherapy. The remaining 23 patients had relapsed AML with OS of 8% (2/23), while 13 died of progressive disease, five of infection, two of toxicity and one of graft-versus-host disease. Median time to relapse from on-study was nine months (range 5-17). Median time to death from relapse was five months (range 1–18). Reinduction attempts were known to occur in 16 patients. Combination chemotherapy with cytarabine was the most common regimen. Seven patients achieved M1 marrows, one M2 and eight nonresponders. Mitoxantrone/cytarabine was used in 5/16 reinduction attempts with three M1 marrows, one M2 and one nonresponder. Of nine patients who underwent BMT (eight known allogeneic), two are long-term survivors (OS 22%). These patients relapsed 12 and 22 months post on-study. Both achieved second remission with induction therapy consisting of mitoxantrone/cytarabine and were consolidated with an allogeneic, related, haploidentical BMT using a busulfan/cyclophosphamide preparative regimen. Outcome for DS patients with relapsed AML is dismal. Mitoxantrone/cytarabine chemotherapy followed by allogeneic BMT may improve survival. Further evaluation of therapies is needed for this group of patients.