Refractory / Relapsed Myeloid Leukemia of Down Syndrome Is Resistant to Second-Line Chemotherapy and Hardly Salvaged by Hematopoietic Stem Cell Transplantation: A Retrospective Study by the Japanese Pediatric Leukemia / Lymphoma Study Group (JPLSG)

Abstract

Abstract 4276 Introduction:Myeloid leukemia in Down syndrome patients (ML-DS) is known to have good sensitivity against cytotoxic agents, especially to cytarabine, and outcomes in recent clinical trials are favorable with more than 80 % probability of long-term event-free survival (EFS). However, little have been focused on refractory / relapsed cases, since most of the treatment failures consist of toxicities rather than resistant or recurrent leukemia. We present here a retrospective analysis of the patients with refractory / relapsed ML-DS. Patients and Method:Among the ML-DS patients diagnosed between 2000 and 2011 at the 120 hospitals in Japan, twenty-nine refractory / relapsed patients were enrolled in this retrospective study. Result:Median follow-up period for all 29 patients was 10.9 months (range, 2.8 –76.7 months). Male/Female ratio was 18/11. The age at initial diagnosis for ML-DS was between 7 months and 16 years old (median, 2 years old). All the patients were initially treated with one of the protocols specifically designed for ML-DS; twenty patients with AML99 Down protocol, eight with JPLSG AML-D05 protocol, and one with JCCLSG AML9805 Down protocol. There were 3 induction failures and 26 relapsed cases. Among the 26 relapsed cases, duration from initial diagnosis to relapse was 2.4 month to 71.8 months (median 8.6 months); Twenty-eight relapsed at bone marrow and one patient relapsed at skin site. Twenty-six out of the 29 patients received various re-induction chemotherapies and 13 of them achieved complete remission (CR). Eight of the 13 patients with CR subsequently received allogeneic stem cell transplantation (SCT) and 4 survived. On the other hand, five of the 13 cases with CR were treated with chemotherapy alone, and 4 were alive with no evidence of leukemia. All the 12 patients who failed to achieve CR and the 2 patients who only received palliative therapy eventually died. The 3-year overall survival rate was 22.6 ± 8.8 %. Achievement of CR with second-line chemotherapy and longer duration from initial diagnosis to relapse were significant favorable prognostic factors. SCT did not influence the prognosis even if performed after achieving further remission. Conclusion:The Japanese strategy treating ML-DS have been successful with very low-intensive chemotherapy regimen, however, rescue of refractory / relapsed patients with ML-DS seems difficult even with SCT.No relevant conflicts of interest to declare. Disclosures:No relevant conflicts of interest to declare.