Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia.

BACKGROUND: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). METHODS: A case-control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. Odds ratios (OR) were calculated. RESULTS: Asthma was positively associated with AL development (OR=4.18; 95% confidence interval (CI): 1.47-11.87), whereas skin allergies were negatively associated (OR=0.42; 95% CI: 0.20-0.91). CONCLUSION: Our findings suggest that allergies and AL in children with DS share biological and immune mechanisms. To our knowledge, this is the first study reporting associations between allergies and AL in children with DS.

Breastfeeding and early infection in the aetiology of childhood leukaemia in Down syndrome.

BACKGROUND: For a child to develop acute leukaemia (AL), environmental exposure may not be sufficient: interaction with a susceptibility factor to the disease, such as Down syndrome (DS), may also be necessary. We assessed whether breastfeeding and early infection were associated with the risk of developing AL in children with DS. METHODS: Children with DS in Mexico City, and either with or without AL, were the cases (N=57) and controls (N=218), respectively. Population was divided in children with AL and with acute lymphoblastic leukaemia (ALL) and also in children < or = 6 and >6 years old. RESULTS: Breastfeeding and early infections showed moderate (but not significant) association for AL, whereas hospitalisation by infection during the first year of life increased the risk: odds ratios (confidence interval 95%) were 0.84 (0.43-1.61), 1.70 (0.82-3.52); and 3.57 (1.59-8.05), respectively. A similar result was obtained when only ALL was analysed. CONCLUSION: We found that breastfeeding was a protective factor for developing AL and ALL, and during the first year of life, infections requiring hospitalisation were related to a risk for developing the disease in those children with DS >6 years of age. These data do not support the Greaves's hypothesis of early infection being protective for developing ALL.

BCR-ABL, ETV6-RUNX1 and E2A-PBX1: prevalence of the most common acute lymphoblastic leukemia fusion genes in Mexican patients.

This study was conducted to determine the frequency of the most common fusion genes in Mexican pediatric patients with acute lymphoblastic leukemia (ALL). Molecular analysis using RT-PCR was carried out in 53-blood samples: 52 patients with de novo ALL and one with relapsed ALL. The ETV6-RUNX1 fusion was found in 7 cases (13.5%), BCR-ABL fusion was detected in 2 cases (3.8%), and 6 patients (11.5%) expressed the chimeric gene E2A-PBX1. The prevalence of E2A-PBX1 is one of the highest that has been described thus far in childhood ALL. Furthermore, we detected both the BCR-ABL, and E2A-PBX1 fusion in the relapsed patient. With regards to the immunophenotype, ETV6-RUNX1 was expressed in both pre-B and T-cell cases, while the presence of E2A-PBX1 and BCR-ABL was associated with the pre-B ALL phenotype. The prevalence of E2A-PBX1 in Mexican pediatric cases supports the existence of ethnic differences in the frequency of molecular markers of ALL.

Flow cytometric analysis of cell-surface and intracellular antigens in the diagnosis of acute leukemia.

To evaluate the usefulness of flow cytometric detection of intracellular antigens (Ags) in establishing proper lineage affiliation and its contribution to the diagnosis of acute leukemia, we studied 100 consecutive patients in whom acute leukemia was diagnosed between January 1997 and July 1998. Immunological classification was assessed using a three-line panel of monoclonal antibodies for phenotypic characterization of leukemic blast cells as proposed at the First Latin American Consensus Conference for Flow Cytometric Immunophenotyping of Leukemia. We found 74 cases of B-cell lineage acute lymphoblastic leukemia (ALL), seven cases of T-cell ALL, and 19 cases of acute myeloid leukemia (AML). In this study cytoplasmic (cy) CD79a, cyCD22, cyCD3, and cyMPO were highly sensitive, specific B, T, and myeloid markers that were expressed in virtually all cases of B and T cell ALL and in all subtypes of AML. Applied in combination with immunophenotyping this knowledge led to improvement in diagnostic precision and refinement of immunological classification, ensuring the selection of the most appropriate therapy for the patients studied. In conclusion, intracellular Ags detection was of utmost importance in establishing correct lineage affiliation in cases lacking expression of B, T, or myeloid surface Ags or disclosing equivocal or ambiguous immunophenotypic features and in identifying biphenotypic acute leukemia. In combination with FAB morphology and immunophenotyping, we were able to reliably classify all patients with acute leukemia in this study.

[Incidence of acute leukemia in children in Mexico City, from 1982 to 1991]. / Incidencia de las leucemias agudas en niños de la ciudad de México, de 1982 a 1991.

OBJECTIVE: To measure the incidence rate and trend of acute leukemia (AL) in political districts of Mexico City. MATERIAL AND METHODS: Descriptive longitudinal study conducted at six hospitals that care for nearly 97.5% of all cancer cases among children in Mexico City. Study data were collected in 1995 and 1996, and were analyzed in 1999, at the National Medical Center "Siglo XXI" Children's Hospital, of the Mexican Institute for Social Security. Calculations of acute leukemia annual incidence rates, standardized rates, and standardized morbidity rates (SMR) with 95% confidence intervals, were obtained for each district. Morbidity trends were assessed through average change rates. RESULTS: In this study we observed an increasing trend of acute lymphoblastic leukemia (ALL) incidence in five districts: Alvaro Obregon, Cuauhtemoc, Gustavo A. Madero, Iztacalco, and Venustiano Carranza. Acute myeloblastic leukemia (AML) showed no significantly statistic increase of incidence in any district. AML did show a significant SMR in Alvaro Obregon district (SMR = 2.91, 95% CI 1.63-4.80). Higher SMRs were found in the south and southwest areas of the city. CONCLUSIONS: Increasing incidence of ALL was observed in five districts of Mexico City. AML incidence was the highest in Alvaro Obregon district.

[Immunophenotyping of acute lymphoblastic leukemia in Mexican children]. / Inmunofenotipo de la leucemia aguda linfoblástica en niños mexicanos.

PURPOSE: To analyse the immunophenotype of leukaemic cells in a group of children diagnosed of lymphoblastic leukaemia in order to assess the frequency of the different immunologic subtypes. PATIENTS AND METHODS: In the period comprised between APR 1987 and MAR 1995, 402 Mexican children were studied in a prospective way. Conventional immunological markers were used, either associated to or specific for B, T, myelo-monocytic or megakaryocytic-platelet cell populations. RESULTS: Five major immunologic subtypes were disclosed, showing a series of specific surface markers: null-ALL, 5%; early pre-B, 7.5%; common, 74.6%; B-cell, 3.5%, and T-cell, 9.4%. A net predominance of B-cell precursor CD10- ALL was found in children under one year of age, and of CD10+ B-cells beyond that age. Although there was only slight predominance of male sex, the prevalence of B and TALL in males was not confirmed. CONCLUSIONS: These results show that the incidence of the different immunologic subtypes of lymphoblastic leukaemias and their distribution according to age and sex are closely similar to those reported among Caucasians in other parts of the world.

[Antiphospholipid syndrome: a new diagnostic option in rheumatology in children. Analysis of 3 clinical cases]. / Síndrome antifosfolípido: nueva opción diagnóstica en la reumatología pediátrica. Análisis de tres casos clínicos.

There are some patients with a clinical picture that suggests to be a rheumatological problem. However, it does not have all the criteria to be accepted such as specific problems like systemic lupus erythematosus, juvenile rheumatoid arthritis, etc. Now we know that a relation between high levels of antiphospholipid antibodies exist in these special patients and the name of the disease is antiphospholipid syndrome. This problem can be primary or secondary. This disease has been studied mainly in adults with SLE an there is not a description of this syndrome in national pediatric literature. For this reason we present three clinical cases that permit us to review both forms of the syndrome. In this way we alert want to the pediatric community about this topic, and if the number of cases increases, it will improve the knowledge and prognosis of the patients at this age.