Therapy reduction in patients with Down syndrome and myeloid leukemia: the international ML-DS 2006 trial

Abstract

Key Points• Reducing therapy intensity in the ML-DS 2006 trial did not impair the excellent prognosis in ML-DS compared with the historical control.• Early treatment response and gain of chromosome 8 are independent prognostic factors.Children with myeloid leukemia associated with Down syndrome (ML-DS) have superior outcome compared with non-DS patients, but suffer from higher constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170 pediatric patients with ) and intrathecal central nervous system prophylaxis while omitting maintenance therapy. Still, 5-year overall survival (89% 6 3% vs 90% 6 4%; P log-rank 5 .64), event-free survival (EFS; 87% 6 3% vs 89% 6 4%; P log-rank 5 .71), and cumulative incidence of relapse/ nonresponse (CIR/NR; 6% 6 3% vs 6% 6 2%; P Gray 5 .03) did not significantly differ between the ML-DS 2006 trial and the historical control arm. Poor early treatment response (5-year EFS, 58% 6 16% vs 88% 6 3%; P log rank 5 .0008) and gain of chromosome 8 (CIR/NR, 16% 6 7% vs 3% 6 2%, P Gray 5 .02; 5-year EFS, 73% 6 8% vs 91% 6 4%, P log rank 5 .018) were identified as independent prognostic factors predicting a worse EFS. Five of 7 relapsed patients (71%) with cytogenetic data had trisomy 8. Our study reveals prognostic markers for children with ML-DS and illustrates that reducing therapy did not impair excellent outcome. The trial was registered at EudraCT as #2007-006219-2. (Blood. 2017;129(25):3314-3321)

Low-dose cytarabine to prevent myeloid leukemia in children with Down syndrome: TMD Prevention 2007 study

“…Immunophenotyping was performed by flow cytometry as described previously. 14 In the follow-up analysis, the specific immunophenotype of the respective patient was monitored. Data for the immunophenotype were available for 85 patients (83%).…”

“…If patients developed ML-DS, they were treated according to the protocol of the ML-DS 2006 trial. 14 In the historical control, treatment and treatment criteria were not applied systematically. 5 A treatment (0.5-1.5 mg/kg cytarabine for 3-12 days) was considered for patients with clinical impairment (WBC .50 3 10 9 /L, platelets ,100 3 10 9 /L, cholestasis, liver dysfunction).…”

Late mortality and morbidity among long‐term leukemia survivors with Down syndrome: A nationwide population‐based cohort study

“…The difference in prognosis is mainly caused by acute toxicities, death in complete remission, less intensive maintenance therapy, and increased relapse rate . In contrast to ALL in DS, individuals with DS and AML (myeloid leukemia of Down syndrome [ML‐DS]) have a superior prognosis than for individuals without DS . The most important factor for survival of ML‐DS is age; the prognosis is excellent if diagnosed before the age of 2 years …”

Development of acute lymphoblastic leukemia following treatment for acute myeloid leukemia in children with Down syndrome: A case report and retrospective review of Children's Oncology Group acute myeloid leukemia trials

“…When we reviewed the literature for cases of ALL following AML in patients with Down syndrome, eight cases were reported, published in three manuscripts . A case report by Hellebostad et al from Norway and a case series of four patients by Tomizawa et al in Japan were published with detailed patient demographics and clinical findings (Table ) .…”

“…Although the risk of developing AML and ALL is significantly increased in children with Down syndrome, the development of both malignancies in the same patient is very rare. To date, there have been only eight published cases describing ALL developing in survivors of AML with Down syndrome …”