RESUMO
The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Technology Associates (FTA) filter paper cards were used to transfer dried blood samples from five Iraqi hospitals to Japan. DNA sequencing was performed to identify class I mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations were analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples, the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD, and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %), and 9 (6.7 %) children had PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 transcripts, respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1 mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of AML children were proved to carry favorable prognostic genetic abnormalities, whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special treatment plan including allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is likely that molecular diagnosis using FTA cards in underdeveloped countries could guide doctors towards an appropriate treatment strategy.
Assuntos
Aberrações Cromossômicas , Leucemia Mieloide Aguda/genética , Mutação , Análise de Sequência de DNA , Manejo de Espécimes/métodos , Adolescente , Alelos , Coleta de Amostras Sanguíneas/instrumentação , Coleta de Amostras Sanguíneas/métodos , Medula Óssea/patologia , Criança , Pré-Escolar , DNA de Neoplasias/genética , Feminino , Humanos , Lactente , Iraque , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Leucemia Mielomonocítica Aguda/sangue , Leucemia Mielomonocítica Aguda/genética , Leucemia Mielomonocítica Aguda/patologia , Leucemia Mielomonocítica Aguda/terapia , Masculino , Nucleofosmina , Proteínas de Fusão Oncogênica/genética , Oncogenes , Papel , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Manejo de Espécimes/instrumentação , Translocação Genética , Resultado do TratamentoRESUMO
Modern treatments have dramatically improved the prognosis of childhood acute promyelocytic leukemia (APL). This progress has not yielded equivalent benefit in developing countries, where biological studies and supportive cares are insufficient and often unavailable. Since 2003, an all-trans retinoic (ATRA)-based, risk-adapted protocol was initiated in Baghdad. Patients were defined: high-risk with WBC ≥10 × 109/L and standard-risk with WBC <10 × 109/L. ATRA was included in induction and maintenance and, from 2010, in consolidation. Of 429 pediatric acute myeloid leukemia (September 2003-August 2019), 118 (27.5%) were APL. Six children died before therapy, 4 refused; 94/108 (87%) achieved a remission; 12 (11%) died early and 2 abandoned. The 5-year overall survival and event-free survival are 61.8% and 55.5% for all patients, 51.7% and 43.6% for first protocol, 68.4% and 63.9% for second one. Baseline WBC count was a risk factor for induction mortality; early hemorrhagic death remains a major cause of failure. ATRA extended consolidation improved results.
Assuntos
Leucemia Promielocítica Aguda , Criança , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/efeitos adversos , Iraque/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encaminhamento e ConsultaRESUMO
We performed a retrospective analysis of 1415 acute lymphoblastic leukemia children diagnosed between January 2000 and December 2016 at Children Welfare Teaching Hospital, Baghdad, Iraq. Patients were divided into three cohorts according to treatment period (2000-2005; 2006-2011; 2012-2016). Treatments were based on modified-UKALL protocols; a steroid-pre-phase was introduced from September 2008. The overall complete remission was 86%, increased from 80% to 91% in the last period. Early deaths occurred in 10%, decreasing to 6%, overtime. Relapses were 23%; toxic deaths and abandonment 8% and 13%, respectively. At a median follow-up of 65.3 months, with abandonment considered as an event, the 5-year overall survival (OS) and event-free survival were 62.2% and 46.3%, statistically influenced by treatment period (5-year OS 62.6%, 59.1%, 66.3%; p=.057, respectively). Though pediatric ALL survival in Iraq is still below that observed in high income countries, survival rates progressively improved. Toxic deaths remain an important cause of failure.