Myeloid leukaemia in children with down syndrome: Report of the registry‐based French experience between 1990 and 2003

Abstract

Children with DS can adequately tolerate SD chemotherapy with a significant superiority of EFS relative to LDC. We suggest that higher levels of cure can be obtained in DS-ML with SD chemotherapy including cytarabine and anthracyclines.

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

“…Whereas in most European and North American trials for ML-DS courses with highdose cytarabine (3 g/m 2 per day) are applied, [9][10][11][12] Japanese studies (Japan Pediatric Leukemia/Lymphoma Study Group [JPLSG] AML D05) obtained excellent results (3-year OS: 88% 6 4% 3-year EFS: 83% 6 4%) and low TRM (1.4%) using standard-dose cytarabine (100 mg/m 2 per day) only. 15 Together with the results of the Toronto group that used a low-dose cytarabine-based regimen, 13,32 which contained no anthracyclines and no etoposide, these data indicate that subgroups of patients with ML-DS can be cured even with much lower doses than in the current ML-DS 2006 trial. But the identification of clear prognostic factors that would predict which patients are at risk of relapse and need intense therapy remained elusive.…”

“…[9][10][11][12][13][14][15] The role of high-dose cytarabine and the dosing of anthracyclines especially have yet to be defined. Whereas in most European and North American trials for ML-DS courses with highdose cytarabine (3 g/m 2 per day) are applied, [9][10][11][12] Japanese studies (Japan Pediatric Leukemia/Lymphoma Study Group [JPLSG] AML D05) obtained excellent results (3-year OS: 88% 6 4% 3-year EFS: 83% 6 4%) and low TRM (1.4%) using standard-dose cytarabine (100 mg/m 2 per day) only.…”

“…[9][10][11][12][13][14][15] Different international study protocols for ML-DS vary in their treatment intensity and drug scheduling. [9][10][11][12][13][14][15] Whereas recent North American and European studies use high doses of anthracyclines and cytarabine, [9][10][11][12][13] Japanese studies achieved comparable survival rates using less intense treatment regimens. 14,15 In contrast, the prognosis of relapsed ML-DS patients is extremely poor.…”

“…8 To date, excellent cure rates have been achieved for ML-DS using dose-reduced treatment protocols without hematopoietic stem cell transplantation. [9][10][11][12][13][14][15] The reduced-intensity arm for ML-DS of the Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) 98 trial consisted of 4 courses of chemotherapy, containing cytarabine, idarubicin, etoposide, or mitoxantrone, and resulted in event-free survival (EFS) after 5 years of 89%. 9 This is in contrast to a 5-year EFS of 54% in non-DS children with AML FAB M7 (non-DS-AMKL).…”

What's up with down syndrome and leukemia‐A lot!

“…In 1992, the Pediatric Oncology Group (POG) reported an unexpected and remarkable finding that 12 children with DS and AML had event‐free survival (EFS) rates of 100% compared to 28% for a group of children without DS treated in a similar fashion on the POG 8498 clinical trial 12. Since this initial report, multiple clinical trials reported by POG, the Children's Cancer Group (CCG), Children's Oncology Group (COG), Berlin‐Frankfort‐Münster (BFM)‐AML, Nordic Society of Pediatric Hematology/Oncology (NOPHO), Medical Research Council (MRC), Hospital for Sick Children (Toronto), France, and Japanese Childhood AML cooperative groups have confirmed that children with DS and myeloid leukemias typically have EFS rates of approximately 80% associated with low relapse/induction failure rates 3, 13–20.…”