Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498 [see comments]

Abstract

The treatment of acute myeloid leukemia (AML) in children with Down's syndrome (DS) has engendered considerable controversy. Because of the concerns for toxicity and increased rate of infections, treatment approaches varied considerably in the past with mixed results. However, experience on the recently completed Pediatric Oncology Group (POG) 8498 AML study suggests that DS children with AML constitute a distinct subgroup that responds well to therapy. Twelve of 285 children on POG 8498 (protocol for newly diagnosed AML) had DS. Children with DS and AML were predominantly male (9 of 12) and were quite younger at diagnosis (< 24 months in 10). The white blood cell count was less than 50 x 10(3)/microL in all 12 and French-American-British types M6 and M7 were frequent (5 of 12). An abnormal cytogenetic marker, in addition to constitutional trisomy 21, was present in 9 of 12 and involved chromosome 8 in 4 of 9. All cases studied (n = 5) were positive for myeloid cell surface markers (CD33, CD13, or CD11b) and, interestingly, were also positive for the CD7 antigen. Chemotherapy included daunorubicin, cytarabine (Ara-C), and 6-thioguanine for remission induction and featured high-dose Ara-C (3 g/m2 per dose) with or without L-asparaginase early in remission. Compared with children without DS, children with DS had a superior event-free survival (EFS at 4 years 100% v 28% +/- 6.2%; P = .003). The EFS remained superior even when compared with non-DS children less than 2 years of age with a white blood cell count less than 10 x 100,000/microL (100% v 48% +/- 17.3%; P = .01).

A population‐based study of childhood myelodysplastic syndrome in British Columbia, Canada

“…The present trend of increasing incidence of childhood MDS warrants further studies, but seems in part to be explained by a higher number of patients with Down syndrome in the most recent period. A change in attitude towards the treatment of leukaemia in Down syndrome (Ravindranath et al, 1992) may have resulted in a higher likelihood of diagnosing MDS in Down syndrome in the most recent years. Unexpectedly, we found an over-representation of Down syndrome among MDS patients of Asian origin, it remains to be studied whether this represents a chance association.…”

The Management of Neoplastic Disorders of Haematopoeisis in Children with Down's Syndrome

“…The unique features of AML in DS patients are the young age, an antecedent MDS, FAB M7 or M6/M7 morphology and the response to therapy. Almost all AML in children with DS occurs between the ages of 1 and 5 years, with a median of 2 years (Table III) (Zipursky et al, 1987;Kojima et al, 1990;Levitt et al, 1990;Ravindranath et al, 1992;Creutzig et al, 1996;Lie et al, 1996;Lange et al, 1998). The blasts consistently express the myeloid surface antigens CD33 and/or CD13 or CD11b, but only rarely have the glycophorin A, glycoprotein IIb/IIIa or factor VIII reactivity (Table III) Fisher et al, 1994).…”

“…The profile of cytogenetic abnormalities is different in DS and non-DS patients with AML (Table III) (Kaneko et al, 1981;Hecht et al, 1986;Groupe Francaise de Cytogenetique Haematologique, 1988;Ravindranath et al, 1992;Creutzig et al, 1996;Lange et al, 1998). About 25% of DS patients show only constitutional trisomy 21.…”

“…Table IV compares the remission induction rate and event-free survival (EFS) among those with and without DS in recent series. In general, the DS patients treated according to AML protocols have significantly better outcomes than those who had no treatment or minimal treatment (Levitt et al, 1990;Ravindranath et al, 1992;Creutzig et al, 1996;Lie et al, 1996). There are two exceptions.…”

current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation? – A European view

“…1. is uniform concerning the subtype M3 and children with Down's syndrome who have an excellent prognosis when treated with balanced chemotherapy concerning intensity (Ravindranath et al, 1992;Creutzig et al, 1996;Lie et al, 1996).…”