RESUMO
OBJECTIVE: To assess leukemia risks among children with Down syndrome in a large, contemporary cohort. STUDY DESIGN: Retrospective cohort study including 3 905 399 children born 1996-2016 in 7 US healthcare systems or Ontario, Canada, and followed from birth to cancer diagnosis, death, age 15 years, disenrollment, or December 30, 2016. Down syndrome was identified using International Classification of Diseases, Ninth and Tenth Revisions, diagnosis codes. Cancer diagnoses were identified through linkages to tumor registries. Incidence and hazard ratios (HRs) of leukemia were estimated for children with Down syndrome and other children adjusting for health system, child's age at diagnosis, birth year, and sex. RESULTS: Leukemia was diagnosed in 124 of 4401 children with Down syndrome and 1941 of 3 900 998 other children. In children with Down syndrome, the cumulative incidence of acute myeloid leukemia (AML) was 1405/100 000 (95% CI 1076-1806) at age 4 years and unchanged at age 14 years. The cumulative incidence of acute lymphoid leukemia in children with Down syndrome was 1059/100 000 (95% CI 755-1451) at age 4 and 1714/100 000 (95% CI 1264-2276) at age 14 years. Children with Down syndrome had a greater risk of AML before age 5 years than other children (HR 399, 95% CI 281-566). Largest HRs were for megakaryoblastic leukemia before age 5 years (HR 1500, 95% CI 555-4070). Children with Down syndrome had a greater risk of acute lymphoid leukemia than other children regardless of age (<5 years: HR 28, 95% CI 20-40, ≥5 years HR 21, 95% CI 12-38). CONCLUSIONS: Down syndrome remains a strong risk factor for childhood leukemia, and associations with AML are stronger than previously reported.
Assuntos
Síndrome de Down/epidemiologia , Leucemia Megacarioblástica Aguda/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Ontário/epidemiologia , Sistema de Registros , Medição de Risco , Estados Unidos/epidemiologiaRESUMO
The clinical and molecular findings of 77 cases of neonatal leukemia (NL) and 380 of infant leukemia (IL) were selected to distinguish features between NL and IL. Somatic gene mutations associated with acute leukemia including FLT3, RAS and PTPN11 were revisited. There were 42 cases of congenital leukemia associated with Down syndrome (DS) and 39 of these cases presented features of acute myeloid leukemia (AML)-M7. Twenty-seven of the DS cases underwent spontaneous remission and were reclassified as a transient myeloproliferative disorder. GATA1 mutations were found in 70% of these cases. In non-DS, frequent abnormalities were MLL rearrangements, mainly MLL-AFF1 in acute lymphoblastic leukemia and MLL-MLLT3 in AML. The FLT3 mutation was not found, while RAS (n = 4) and PTPN11 (n = 2) mutations were identified and reported for the first time in NL. There was substantial evidence to support that somatic abnormalities occur in utero. Thus, congenital leukemia is a good model for understanding leukemogenesis.
Assuntos
Leucemia/epidemiologia , Leucemia/genética , Mutação , Brasil/epidemiologia , Análise Citogenética/métodos , Análise Mutacional de DNA , Feminino , Seguimentos , Fator de Transcrição GATA1/genética , Histona-Lisina N-Metiltransferase/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Leucemia/tratamento farmacológico , Leucemia Megacarioblástica Aguda/tratamento farmacológico , Leucemia Megacarioblástica Aguda/epidemiologia , Leucemia Megacarioblástica Aguda/genética , Masculino , Epidemiologia Molecular , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Tirosina Quinase 3 Semelhante a fms/genética , Proteínas ras/genéticaRESUMO
In order to characterize the clinical, cytogenetic, and outcome features of childhood acute megakaryoblastic leukemia (AMKL), we reviewed 24 cases; 14 were identified among 150 consecutive newly diagnosed acute myelogenous leukemia (AML) patients at St. Jude Children's Research Hospital, and 10 were cases referred to the National Institute of Cancer in Rio de Janeiro, Brazil. There were 5 Down syndrome patients and one patient with chronic myeloid leukemia (Ph+) in blastic crisis. Twelve patients had significant hepatosplenomegaly. Leukemic cell morphology and cytochemistry were consistent with the M7 classification in 17 cases, and all cases tested expressed megakaryocytic surface antigens. AMKL patients were significantly younger than other AML patients (P = 0.0001) and had poorer responses to therapy (P = 0.03, univariate analysis only). Ten of 24 failed induction, and only 5 are disease-free at 6 months to 4.5+ years. We conclude that AMKL usually affects young children, frequently producing marked organomegaly. It comprises approximately 10% of pediatric AML cases, and responds poorly to intensive AML therapies.