Perfil epidemiológico, incidência, mortalidade e sobrevida de crianças e adolescentes com leucemias em Pernambuco / Epidemiological Profile, Incidence, Mortality, and Survival of Children and Adolescents Diagnosed with Leukemia in Pernambuco, Brazil

Introdução: Leucemia é o câncer mais comum em crianças e a principal causa de óbito relacionada ao câncer na infância. A sobrevida das crianças com leucemia tem melhorado de forma significativa, entretanto, ainda permanece abaixo de 50% na maioria dos países com recursos limitados. Objetivo: Descrever o perfil epidemiológico, incidência, mortalidade, sobrevida das leucemias agudas e os fatores de risco para o óbito em crianças e adolescentes com leucemia mieloide aguda (LMA) em Pernambuco. Metodologia: a) coorte retrospectiva com crianças e adolescentes (0-19 anos), a partir das informações do Registro de Câncer de Base populacional (RCBP) do Recife (período de 1998 - 2007). As tendências da incidência e da mortalidade foram avaliadas utilizando-se o método Joinpoint. A sobrevida relativa foi calculada, utilizando-se a tábua completa de mortalidade disponível no Instituto Brasileiro de Geografia Estatística (IBGE) para o Brasil em 2010. b) Foram analisados o risco cumulativo de óbito precoce (até 6 semanas do diagnóstico) e a sobrevida global (SG) e livre de eventos (recidiva, segunda neoplasia ou óbito) pelo método de Kaplan Meier para leucemia promielocítica aguda (LPA), LMA da síndrome de Down (LMA-SD) e outros subtipos (exceto LMASD e LPA) e os fatores preditivos para o óbito, por características do diagnóstico utilizando-se a regressão multivariada de Cox, distintamente para leucemia promielocítica aguda (LPA) e para outros subtipos de LMA a partir de uma coorte de crianças diagnosticadas entre 2000-2014 com LMA e acompanhadas no Instituto de Medicina Integral Prof. Fernando Figueira (IMIP). Resultados: a) o estudo de base populacional envolveu 175 casos. A taxa de incidência para leucemias foi de 41,1/milhão de habitantes menores de 20 anos, com pico de incidência de 78,3/milhão na faixa de 1 a 4 anos....

Introduction Leukemia is the most common cancer in children and the leading cause of cancerrelateddeath in childhood, with a variable incidence worldwide. The survival rates for children with leukemia have significantly improved. However, it remains below 50% in most countries with limited resources. Objective The aim of the study was to describe the epidemiological profile, incidence,mortality, survival, and risk factors for death in children and adolescents with acute myeloid leukemia (AML) in Pernambuco, Brazil. Methodology Two studies were conducted. a) The first study included a retrospective cohort of children and adolescents aged 0–19 years, based on the data obtained fromthe population-based cancer registry in Recife (1998–2007). Joinpoint method was used to evaluate the incidence and mortality trends. The relative survival was calculated using the complete mortality table available at the Instituto Brasileiro de Geografia e Estatística for Brazil in 2010. b) The second study included a cohort of children who were diagnosed with AML between 2000 and 2014 and treated at the Instituto de Medicina Integral Prof. Fernando Figueira - IMIP. The cumulative risk ofearly death (until 6 weeks of diagnosis), overall survival (OS), and event-free survival (EFS) considered as recurrence, second neoplasia, or death for acute promyelocytic leukemia (APL), AML with Down syndrome (AML-DS), and other subtypes (except AML-DS and APL) were analyzed using the Kaplan-Meier method. Cox multivariate regression model was used to identify factors predictive of death, by the characteristics of the diagnosis, distinctly for APL and for the othersubtypes of AML...

Infection and childhood leukemia: review of evidence / Infeccao e leucemia infantil: revisao das evidencias / Infeccion y leucemia infantil: revision de las evidencias

OBJECTIVE : To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS : A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors “childhood leukemia” and “infection” and later searching for the words “childhood leukemia” and “maternal infection or disease” or “breastfeeding” or “daycare attendance” or “vaccination” resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers’ or infants’ to infections (or proxy of infection), and risk of leukemia. RESULTS : Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori . CONCLUSIONS : Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology. .

OBJETIVO : Analisar estudos que avaliaram o papel de infecções e de medidas indiretas de exposição às infecções no risco de leucemia infantil, principalmente da leucemia linfocítica aguda. MÉTODOS : A busca nas bases de dados Medline, Lilacs e SciELO utilizando-se inicialmente os descritores “leucemia infantil” e “infecção” e, posteriormente, pesquisando-se as palavras “leucemia infantil” e “infecção ou doença materna” ou “aleitamento materno” ou “frequência à creche” ou “vacinação” recuperou 62 publicações que atenderam aos seguintes critérios de inclusão: amostra composta por sujeitos com idade inferior ou igual a 15 anos; análise específica de casos diagnosticados com leucemia linfocítica aguda ou todas as leucemias; avaliação de exposição materna ou infantil a infecções (ou medidas indiretas de exposição à infecção) e risco de leucemia. RESULTADOS : Globalmente, os 23 estudos que avaliaram infecções nas crianças suportam a hipótese de que a ocorrência de infecções no início da infância reduz o risco de leucemia, mas existem discordâncias intra e entre estudos. A avaliação por meio das medidas indiretas de exposição à infecção mostrou evidências de redução do risco de leucemia associado principalmente com frequência à creche. Mais de 50,0% dos 16 estudos que avaliaram exposição materna à infecção observaram aumento do risco de leucemia associado com episódios de gripe, pneumonia, varicela, herpes zoster, infecção do trato genital inferior, doença de pele, doenças sexualmente transmissíveis, vírus Epstein-Barr ...

OBJETIVO : Analizar estudios que evaluaron el papel de infecciones y de medidas indirectas de exposición a las infecciones en el riesgo de leucemia infantil, principalmente de la leucemia linfocítica aguda. MÉTODOS : Se realizó búsqueda en las bases de datos Medline, LILACS y SciELO utilizándose inicialmente los descriptores “leucemia infantil” e “infección” y, posteriormente, investigándose las palabras “leucemia infantil” e “infección o enfermedad materna” o “lactancia materna” o “frecuencia en guardería” o “vacunación” recuperó 62 publicaciones que atendieron los siguientes criterios de inclusión: muestra compuesta por individuos con edad inferior o igual a 15 años; análisis específica de casos diagnosticados con leucemia linfocítica aguda o todas las leucemias; evaluación de exposición materna o infantil a infecciones (o medidas indirectas de exposición a la infección) y riesgo de leucemia. RESULTADOS : Globalmente, los 23 estudios que evaluaron infecciones en los niños soportan la hipótesis de que la ocurrencia de infecciones en el inicio de la infancia reduce el riesgo de leucemia, pero existen discordancias intra y entre estudios. La evaluación por medio de las medidas indirectas de exposición a la infección mostró evidencias de reducción de riesgo de leucemia asociado principalmente con frecuencia a la guardería. Más de 50% de los 16 estudios que evaluaron exposición materna a la infección observaron aumento de riesgo de leucemia asociado con episodios de gripe, neumonía, varicela, herpes zoster, infección del tracto genital inferior, enfermedad de la piel, enfermedades sexualmente transmisibles, virus Epstein-Barr (EBV) y Helicobacter pylori. CONCLUSIONES : A pesar ...

Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL). The so-called "adrenal hypothesis" emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

A Case of Therapy-related ALL with MLL Gene Rearrangement Following Treatment of Breast Cancer / 대한진단검사의학회지

ALL with MLL gene rearrangement secondary to chemotherapy has been rarely reported. We report a case of therapy-related ALL (t-ALL) with MLL gene rearrangement in a patient who had undergone treatment for breast cancer. A 60-yr-old woman with breast cancer underwent breast-conserving surgery followed by 6 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, and fluorouracil) and radiation therapy (dose, 5,040 cGy to the left breast and a 1,000 cGy boost to the tumor bed). A follow-up examination performed 14 months after the chemotherapy revealed no evidence of breast malignancy. However, the patient's complete blood cell count indicated acute leukemia: white blood cell count, 174.1x10(9)/L with 88% blasts; Hb level, 12.5 g/dL; and platelet count, 103.0x10(9)/L. Examination of the bone marrow aspirate smear revealed a high percentage of blasts (85.1% of all nucleated cells); the blasts showed a pro-B immunophenotype and were positive for CD19, CD79a, HLA-DR, CD34, and terminal deoxynucleotidyl transferase (TdT). Cytogenetic and FISH analyses revealed t(4;11)(q21;q23) and MLL gene rearrangement, respectively. The patient received induction chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone and achieved complete remission. Following consolidation chemotherapy, she underwent allogenic peripheral blood stem cell transplantation and has been clinically stable. To our knowledge, this is the first reported case of t-ALL with MLL gene rearrangement following treatment of breast cancer in Korea.

Magnetic fields and acute lymphoblastic leukemia in children: a systematic review of case-control studies / Campos magnéticos e leucemia linfocítica aguda em crianças: revisão sistemática de estudos caso-controle

Leukemia incidence in children has increased worldwide in recent decades, particularly due to the rise in acute lymphoblastic leukemia. Studies have associated exposure to non-ionizing radiation generated by low frequency magnetic fields with childhood leukemia. The current article reviews the case-control studies published on this subject. Of 152 articles tracked in different databases, ten studies from North America, Asia, and Europe met the defined selection criteria, with patients diagnosed from 1960 to 2004. Methodological limitations were observed in these articles, including difficulties with the procedures for assessing exposure. An association may exist between exposure to low frequency magnetic fields and acute lymphoblastic leukemia in children, but this association is weak, preventing the observation of consistency in the findings. Future studies from a wider range of geographic regions should focus on the analysis of acute lymphoblastic leukemia, which is the subtype with the greatest impact on the increasing overall incidence of childhood leukemia.

A incidência de leucemias em crianças tem aumentado nas últimas décadas no mundo, com influência predominante da leucemia linfocítica aguda, principal subtipo em crianças. Estudos têm relacionado a exposição às radiações não-ionizantes geradas pelos campos magnéticos de baixa freqüência com leucemia infantil. Neste artigo foram revisados os estudos caso-controle publicados sobre essa questão. Dos 152 artigos localizados em diferentes bases de dados, dez estudos da América do Norte, Ásia e Europa preencheram os critérios de seleção, comportando pacientes diagnosticados entre 1960 e 2004. Algumas limitações metodológicas foram observadas como dificuldades nos procedimentos de avaliação da exposição. É possível a existência de associação entre exposição a campos magnéticos de baixa freqüência e leucemia linfocítica aguda em crianças, porém, a força desta associação é tênue, impedindo observar consistência entre os resultados. Futuros estudos, com maior diversidade de regiões, deveriam concentrar-se na análise da leucemia linfocítica aguda, pois é o subtipo com maior influência na incidência crescente da leucemia infantil.

O papel das infecções virais na etiologia da leucemia linfoblástica aguda comum analisado através de uma abordagem epigenômica

A leucemia linfoblástica aguda (LLA) e o principal subtipo de câncer pediátrico e, apesar do sucesso no tratamento, a sua causa continua enigmática. Acredita-se que o processo que da origem a LLA envolve dois eventos: o primeiro seria responsável por criar o clone pre-leucêmico a partir de mutações ou alterações epigenéticas e o segundo evento iria disparar a proliferação deste clone. Existem evidencias de que as infecções desempenham função importante na leucemogênese. Com o objetivo de investigar se as infecções tem um papel na etiologia das LLAs infantis foram usadas três abordagens: 1) analise do perfil de expressão, por PCR em tempo real, de genes relacionados a via do interferon a fim de avaliar a resposta imune aberrante como fator desencadeador de LLA-c; 2) analise do perfil de mitigação das LLAs, pela técnica de microarranjos, a fim de identificar possíveis alterações causadas por infecções virais e, 3) rastreamento de DNA de adenovírus em cartões do teste do pezinho, a fim de verificar se este vírus poderia ser responsável pela leucemogênese diretamente. Para os estudos de perfil de expressão gênica e mitigação foram utilizadas amostras de 121 casos de LLA infantil e para o estudo de rastreamento de AdV foram utilizadas 202 amostras de cartões Guthrie, entre casos de LLA e controles. Dentre os doze genes estudados, dois (LY6E e MX1) apresentaram expressão 4 e 2,5 vezes mais alta nos casos de LLA-c quando comparados aos outros subtipos de LLA (pré-B e pro-B), respectivamente. Existe uma associação entre os níveis de IgM anti-PVB19 e superexpressão dos genes estudados. Através da analise pelo beadarray, observou-se que os subtipos de leucemia podem ser discriminados de acordo com o perfil de mitigação de alguns genes tais como, BMP3, DAB2,NQO1, DAPK, WNT1 e IFNG. Alem disso, também foi vista uma associação entre infecção pelo PVB19 e mitilação em alguns genes, DAPK, PTGS2, MPO and NRAS. Os AdV humanos A, C e F não foram detectados por PCR no sangue de cartões do teste do pezinho em crianças que desenvolveram LLA, nem em controles saudáveis. A ausência de DNA viral nestes cartões não constitui uma evidencia negativa do papel das infecções na etiologia das leucemias. O AdV ou outro vírus, p.ex, PVB19, poderia estar influenciando o processo leucemogênico através de um mecanismo de “hit and run”, que alteraria o perfil epigenético da célula, causando hipoexpressão de genes que controlam a proliferação e diferenciação celular. Embora o mecanismo ainda não seja claro, nossos dados, corroboram a idéia de que as infecções desempenham um papel na etiologia das LLA-c e que esse efeito, muito provavelmente, e pós-natal

Acute lymphoblastic leukemia (ALL) is the main pediatric cancer subtype and, despite the success in treatment, its cause remains enigmatic. It is believed that the onset of ALL is based in a two hit model: the first hit would promote mutations or epigenetic alterations that create a preleukemic clone and the second one would precipitate ALL through a proliferative expansion of this clone. There are evidences that infections influence the leukemogenesis process. We sought to investigate whether infections have a role in the childhood ALL etiology. We used three approaches to analyze this hypothesis: 1) expression profiling of IFN related genes, by real time PCR, to evaluate the role of aberrant immune response as a trigger of c-ALL; analysis of ALL methylation profile using microarrays to identify possible alterations caused by viral infections and, 3) adenovirus (AdV) DNA screening in Guthrie cards(GC). Samples of 121 childhood ALL cases were used for expression and methylation profiling studies and 202 GC samples from children who later developed leukemia and controls were used for Adv screening. Inside a group of 12 analyzed genes, LY6E and MX1 presented higher expression levels in c-ALL when compared to the other subtypes (pro B and pre B ALL). These results suggest that somehow immune response is related to c-ALL. There is an association between anti-PVB19 IgM levels and higher expression of studied genes. Using the beadarray analysis we observed that leukemia subtypes could be distinguished based on methylation profiling of some genes such as BMP3, DAB2, NQO1, DAPK, WNT1 and IFNG. Moreover, it was observed an association between PVB19 infection and methylation of some genes for instance, DAPK, PTGS2, MPO and NRAS. AdV subtypes A, C, F were not detected by PCR in GC from ALL cases nor in controls. The absence of viral DNA in these cards does not constitute a negative evidence for the role of infections in the etiology of ALL. Adv or other viruses could influence in leukemogenesis through a hit and run mechanism which could alter cell epigenetic profile. These alterations would lead to low expression of some genes that control cell differentiation and proliferation. Although the mechanisms are not clear yet, our results sustain the idea that infections have a role in c-ALL development and this effect is probably post-natal

A unique case of transient spontaneous regression complicated with tumor lysis syndrome of T-cell lymphoblastic lymphoma in HIV-infected patient without antiretroviral therapy.

Spontaneous regression in high-grade non-Hodgkin lymphoma is rare. Herein, the authors report the case of a 26-year-old asymptomatic HIV-infected patient presenting with bleeding per gum after a dental extraction. Initially, a complete blood count showed lymphoblasts and thrombocytopenia. Laboratory investigations were compatible with acute tumor lysis syndrome. Without any steroid or chemotherapy, both clinical and laboratory abnormalities were spontaneously returned to normal limits. However, three weeks later he developed generalized lymphadenopathy. A submandibular gland biopsy revealed to be T-cell lymphoblastic lymphoma. This was followed by the second episode of spontaneous tumor lysis syndrome and spontaneous regression of lymphadenopathy again. At this time, he was treated with cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) with whole brain irradiation. During seven months of chemotherapy, the physical examination and blood chemistry were normal. Unfortunately, after seven courses of CHOP, the disease rapidly progressed and ultimately lead to his death.

Acute leukemia in early childhood

Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months) has detected TEL/AML1+ve (N = 9), E2A/PBX1+ve (N = 4), PML/RARA+ve (N = 4), and AML1/ETO+ve (N = 2) cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95 percentCI = 1.05-2.07), OR = 2.27 (95 percentCI = 1.56-3.31) and OR = 9.08 (95 percentCI = 2.95-27.96)], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

Assistência de enfermagem no pós-transplante de medula óssea na Leucemia Linfócita Aguda na infância / Nursing assistance on post-bone marrow transplantation in Acute Leukemia on childhood

Revisão da literatura científica sobre Transplante de Medula nas Leucemias Agudas na Infância. Descreve as condições de emprego desse tratamento e indica a assistência de enfermagem correspondente...

Normas para el abordaje de las enfermeddes hemato-oncológicas pediátricas / Norms for the boarding of the illnesses hemato-oncológicas pediátrics

Se presenta documento con el objetivo de contribuir a mejorar el conocimiento sobre el cáncer y otras enfermedades hematológicos en el niño, a fin de poder realizar un diagnóstico mas oportuno, asegurar una más rápida referencia, un mejor abordaje terapeútico, así como enfrentar las posibles complicaciones. Existe un registro desde 1990 hasta el año 2000 de 1,2000 casos en el departamento de Hemato-Oncología del Hospital Infantil "La Macota", diagnosticados de diferentes tipos de cáncer, además de un número de enfermedades hematológicas no oncológicas (principalmente Drepanocitosis, PTI y Anemia Aplástica), los cuales son referidos de todo el territorio. Uno de los principales problemas que encuentran en el abordaje de los niños con enfermedades hemoto-oncológicas es el diagnóstico tardío, la referencia no oportuna y por lo tanto los niños presentan enfermedades avanzadas con el consecuente pronóstico desfavorable, así como la falta de un manejo intrahospitalario mas uniforme y adecuado cuando el paciente ingresa a al centro. En nuestro país se estan diagnosticando cerca de 200 casos anuales y que el cáncer ocupa el quinto lugar cmo causa de muerte en los niños mayores de 4 años

Estudios citogenéticos en médula ósea en pacientes pediátricos leucemia linfoblástica en el hospital Dr. Juan Tanca Marengo / Citogenéticos studies in bony marrow in pediátricos patients linfoblástica leukemia in hospital Dr Juan Tanca Marengo

Antecedentes y objetivos: La leucemia linfoblástica aguda (LLA) es el cáncer pediátrico más frecuente, con una incidencia del 25 por ciento al 33 por ciento. El análisis citogenético en LLA es parte del estudio integral de estos pacientes, encontrándose alteraciones a este nivel en un 50-90 por ciento de los casos. Las anomalías cromosómicas numéricas y estructurales tienen relación con la fisiopatología de la enfermedad, con el pronóstico y la respuesta al tratamiento de los pacientes con LLA. El presente trabajo tiene como intención determinar la frecuencia de alteraciones cromosómicas en el grupo de pacientes pediátricos afectos con LLA, realizar una descripción adecuada de las mismas y comparar los datos obtenidos con la literatura...

Translocación t4 11 en médula ósea de infantes con leucemia linfocítica aguda / Translocation t4 11 in bone marrow of infants with acute lymphocyte leukemia

La translocación t(4;11) es el hallazgo cromosómico más común en infantes con LLA, es un indicador de pobre pronóstico y es un factor de riesgo independiente. Estos pacientes requieren de una quimioterapia intensiva. Recientes avances en comprender la alteración en la función de los genes fusionados al compararlos con los genes normales provee conocomiento para nuevas estrategias terapéuticas, que permitirá mejorar la respuesta clínica, con menor toxicidad.

Epidemiologia das leucemias em crianças de um Centro de Referência Estadual / Epidemiologia of the in children of a center of state referencia

A leucemia é o mais comum tipo de câncer que ocorre nas crianças. O presente estudo visa estimar a ocorrência e a mortalidade das crianças com leucemia, assim como estabelecer a correlaçäo destas crianças com algumas variáveis demográficas. Foram analisados cento e quarenta e cinco prontuários de crianças de 0 e 14 anos, procedentes de Santa Catarina e admitidas no Hospital Infantil Joana de Gusmäo (HIJG), com diagnóstico de leucemia, estabelecido entre 01/01/94 e 31/12/98...

La importancia de los factores pronósticos en leucemia aguda linfoblÁstica (LAL) de la población pediátrica en un país en vías de desarrollo / Prognostic factors in Mexican children with acute lymphoblastic leukemia

La sobrevida de los niños con LAL se ha modificado favorablemente en los últimos 25 años. Sin embargo, estos cambios se han debido no nada más a tratamientos más racionales, pero en forma muy importante a la identificación de una serie de factores pronósticos que han contribuido a identificar a una población de niños con pronóstico favorable, otro intermedio y un tercero con pronóstico desfavorable. Los factores identificados inicialmente fueron edad, sexo y aquellos que representan gran carga leucémica como visceromegalia por abajo de la cicatriz umbilical. Otros factores son los de laboratorio incluyendo la hemoglobina, cuenta de leucocitos y cuenta de plaquetas. Otros son la elevación de deshidrogenasa láctica y alteraciones de las inmunoglobulinas. La literatura en los años 70 señaló la citomorfología de los linfoblastos como de importancia pronóstica. La identificación de los marcadores de los linfoblastos a través de epifluorescencia y posteriormente con citometría de flujo ha permitido una precisión aun mayor de la estirpe inmunológica de estas células. La descripción de la ploidía, el índice del ADN, las alteraciones citogenéticas y la presencia de alteraciones moleculares han permitido al clínico ofrecer un pronóstico y por ende un tratamiento más selectivo. Rutinariamente en la República Mexicana es difícil que las instituciones que se dediquen a la atención de estas enfermedades las lleven a cabo. De tal manera que deben existir centros de referencia especializados.

Leucemia linfoblástica aguda: características al diagnóstico en 100 niños / Acute lymphoblastic leukaemia: characteristics at diagnosis in 100 patients

Objetivo: El objetivo es comunicar los hallazgos al diagnóstico en niños con LLA, describiendo las formas de presentación que permiten sospechar esta entidad. Pacientes y método: revisión retrospectiva de las fichas clínicas de 100 niños tratados en el Hospital Roberto del Río entre enero 1992 y junio 1998. Resultados: 62 por ciento varones, incidencia peak entre 1-6 años (60 por ciento). El tiempo medio antes del diagnostico fue 2,5 semanas. Los sintomas más frecuentes son compromiso del estado general (81 por ciento), palidez (66 por ciento), dolor óseo (30 por ciento) y púrpura (24 por ciento). Los hallazgos más comunes en el examen físico: hepatomegalia (71 por ciento), adenomegalia (71 por ciento), esplenomegalia (24 por ciento). El hemograma es siempre anormal con anemia (90 por ciento), trombocitopenia (72 por ciento), neutropenia (62 por ciento) y/o linfoblastos (67 por ciento). Muchos pacientes debutan con una mezcla de síndromes (anémico, febril, tumoral, dolor óseo) y sólo 23 fueron monosintomaticos ( todos con neutropenia). Conclusión : Una anamnesis y examen físico detallados, junto a una adecuada interpretación del hemograma, permiten al pediatra sospechar esta enfermedad, la que actualmente tiene alta probabilidad de curación

Childhood cancer: improved prospects for survival but is prevention possible?

With optimum treatment 65-70% of children diagnosed with cancer should be long term survivors and probably cured. Prevention is better than cure. Recent studies into the causes of childhood malignancy are reviewed. The incidence of childhood acute lymphoblastic leukaemia (ALL) is steadily increasing. The cause for this may be increasing social and economic development. Exposure to electromagnetic fields has been a cause of concern for almost 20 years. A recent large case control study has shown no increased risk of cancer or leukaemia in those who have measurably increased exposure to electromagnetic fields. Leukaemia which has the cytogenetic abnormality 11q23 or MLL gene rearrangement characteristically occurs as a second malignancy after exposure to epipodophyllotoxins which act by inhibiting topoisomerase. Infant leukaemia has the same cytogenetic profile. Mothers of babies who develop infant leukaemia have high exposure to potential dietary inhibitors of topoisomerase during pregnancy. Clusters of leukaemia can probably best be accounted for by population mixing. There may be an increased risk of ALL following vitamin K given to newborns.

Pancytopenic prodrome (pre-ALL) of acute lymphoblastic leukemia in adults: possible pathogenesis

We report two cases of adult acute lymphoblastic leukemia presenting with preleukemic phase of pancytopenia with a few abnormal lymphoid cells in bone marrow aspirates. The initial diagnosis of each case was suspicious aplastic anemia and hypoplastic anemia. Both cases progressed to overt acute lymphoblastic leukemia within 1 year. We suggest that initial pancytopenic phase (pre-ALL) may precede the diagnosis of acute lymphoblastic leukemia in adults and differential diagnosis from myelodysplastic syndrome and primary aplastic anemia will be needed. We also suggest that primary bone marrow lymphoma and "primary unknown metastatic lymphoma of bone marrow" may be possible as the pathogenesis in a case like ours.

Lymphoblastic transformation of myelodysplastic syndrome

Mielodysplastic syndromes (MDS) are clonal disorders of the hemopoietic stem cell. About one third of the cases terminate in an acute leukemia, usually acute myeloblastic leukemia. However, few cases of transformation into acute lymphoblastic leukemia (ALL) have been described. We present a case of refractory anemia that transformed into ALL two months after diagnosis and was successfully treated with conventional chemotherapy. Two years later a hyperfibrotic form of MDS was detected in the patient, that soon after terminated in acute megakaryoblastic leukemia. The course of MDS in the present case provides evidence that MDS can involve a pluripotent stem cell, presenting clonal evolution, documented by successive changes in its clinical and hematological features.