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)

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.

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.

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.

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.

No relevant conflicts of interest to declare.