María Luisa Pérez-Saldivar

Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology

BackgroundWorldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City.MethodsIncluded in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level).ResultsAlthough a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high risk. There was a positive correlation between the average number of persons per household and the incidence of the pre-B immunophenotype (Pearsons r, 0.789; P = 0.02).ConclusionsThe frequency of ALL in Mexico City is among the highest in the world, similar to those found for Hispanics in the United States and in Costa Rica.

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 ⩽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 Greavess hypothesis of early infection being protective for developing ALL.

Magnetic fields and acute leukemia in children with Down syndrome.

Background: We analyzed effects of exposure to magnetic fields on the expression of acute leukemia in children with Down syndrome (who have a 20-fold higher risk of leukemia). Methods: We performed a case–control study that included 42 children with both acute leukemia and Down syndrome as cases and 124 healthy children with Down syndrome as controls. We obtained demographic information concerning the children and took spot measurements of magnetic fields at each residence. Results: The odds ratio for direct measurements of magnetic fields ≥6.00 mG was 3.7 (95% confidence interval = 1.05–13.1). Conclusion: The association between magnetic fields and leukemia in children with Down syndrome suggests the possibility of a causal role for magnetic fields in the etiology of leukemia among a genetically susceptible subgroup of children.

Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study)

BackgroundMedical research has not been able to establish whether a fathers occupational exposures are associated with the development of acute leukemia (AL) in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a fathers occupational exposure to carcinogenic agents and the presence of AL in their offspring.MethodsFrom 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR) of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each childs background and the characteristics of the fathers occupation(s). In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI) was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an experts opinion.ResultsThe adjusted ORs and 95% confidence intervals (CI) were 1.69 (0.98, 2.92) during the preconception period; 1.98 (1.13, 3.45) during the index pregnancy; 2.11 (1.17, 3.78) during breastfeeding period; 2.17 (1.28, 3.66) after birth; and 2.06 (1.24, 3.42) for global exposure.ConclusionThis is the first study in which an OEI was used to assess a fathers occupational exposure to carcinogenic agents as a risk factor for the development of childhood AL in his offspring. From our results, we conclude that children whose fathers have been exposed to a high level of carcinogenic agents seem to have a greater risk of developing acute leukemia. However, confounding factors cannot be disregarded due to an incomplete control for confounding.

Genetic rearrangement MLL/AF4 is most frequent in children with acute lymphoblastic leukemias in Mexico City

One of the highest incidences of acute lymphoblastic leukemia (ALL) in the world has been reported in Mexico City. In the current study (26 cases), the frequencies of the most frequent genetic rearrangements TEL-AML1, MLL/AF4, BCR-ABL (major and minor) in ALL in children from Mexico City were determined. For the ALL, the frequency of MLL/AF4 was 65.4%, for TEL-AML1 and that of BCR/ABL was 3.8%. Only 6 of the 17 children with the MLL/AF4 rearrangement were less than 26 months old. The frequency reported for MLL/AF4 in Mexican children with ALL is one of the highest worldwide. These findings could potentially explain the higher frequency of ALL with poor prognosis for children in Mexico City.

The age incidence of childhood B-cell precursor acute lymphoblastic leukemia in Mexico City.

The objective of this population-based survey was to assess the peak age of incidence of B-cell precursor acute lymphoblastic leukemia (ALL) in children in Mexico City (MC). All patients were classified according to their immunophenotype, and only B-cell precursor and T-lineage were analyzed. Rates of incidence were calculated ×106 children. Of the 364 children from MC who were included in this study, immunophenotyping had been performed for 81.6%. The frequency of B-cell precursor ALL was 76.1%, whereas T lineage ALL showed a frequency of 23.6%. Peak age for ALL was 2 to 3 years of age. B-cell precursor ALL was the major contributor to peak age; T lineage ALL showed a peak among 1 and 3 years of age. We conclude that the age peak for children with ALL in MC is within the ranges reported for developed countries and that B-cell precursor ALL is the main contributor to these peak.

Childhood Acute Leukemias in Hispanic Population: Differences by Age Peak and Immunophenotype

Childhood cancer represents 0.5–5.7% of all cancers (Birch & Blair, 1992; Smith & Gloecker, 2002). The most important kinds of cancer during childhood differ from those most frequently found in adulthood (Schellong, 1985). During infancy, the principal cancers are not epithelial, in contrast to those in the later stages of life (Miller, 1983). Therefore, it is possible that the risk factors for cancer are different during infancy than during adulthood; for children, risk factors may be present in utero or during the firsts months of the life (Draper, 1994). The age peak of cancer during infancy, especially those for leukemias and lymphomas, varies among countries. Although the peak age for leukemias worldwide is principally between 2–5 years of age, a peak as late as 7–13 years of age was reported for Niger (William, 1975). In developed countries such as Germany or the United States of America (USA), the age peak for lymphomas is between 10–14 years of age, whereas in less developed countries, Mexico for example, the age peak is between 5–9 years of age (FajardoGutierrez et al., 1995; Kaatsch et al., 1995; Nully-Brown et al., 1989; Young et al., 1986). Leukemia is the most common cancer in children under 15 years old, representing between 25–35% of all childhood cancers in most populations (Parkin et al., 1988, 1998). Leukemia is a heterogeneous group of hematopoietic malignancies, with several biologically distinct subgroups. The main subtypes of leukemia described by most cancer registries include acute lymphoblastic leukemia (ALL), representing about 80% of all leukemias; AML, with a frequency of 15%; and chronic myeloid leukemia (CML) with a frequency of 3–5% (Bathia, 2003). ALL is the most frequent leukemia in infancy (Mejia Arangure et al., 2005a). The age

Infections and Acute Leukemia in Children with Down Syndrome

Down syndrome (DS), or trisomy 21, is a genetic alteration caused by the presence of an extra chromosome 21. In different parts of the world, the incidence of DS varies from 0.3 to 3.4 per 1000 births, with a ratio of 1:1000 births being reported principally in America and Europe (Canfield et al., 2006; Hassold et al., 1996; Wahab et al., 2006; Webb et al., 2007). DS is associated with cardiovascular diseases; deficiencies of the digestive, immune, and endocrine systems; hematological problems; and also early onset of Alzheimer disease (Freeman et al., 2008; Holland et al., 2000; Linabery et al., 2008; Van Cleeve & Cohen, 2006; Wiseman et al., 2009). Compared to children without this syndrome, children with DS have tento twenty-fold higher risk of developing acute leukemia (AL) (Fong & Brodeur, 1987; Malinge et al., 2009; Ross et al., 2005a; Taub, 2001); it is estimated that approximately 1–2% will develop leukemia (Hasle et al., 2000; Malinge et al., 2009; Taub, 2001). Of those children with DS who develop leukemia, 60% is classified as having acute lymphoblastic leukemia (ALL) and 40%, with acute myeloblastic leukemia (AML). Of those with AML, the most common type is M7, or acute megakaryoblastic leukemia (AMKL), found in 62% of this group of children (Hitzler & Zipursky, 2005). Approximately 10% of children with DS are born with a transitory myeloproliferative syndrome (TMS) that, in some cases, spontaneously disappears during the first few months of life; nevertheless, approximately, 20% of these children irreversibly develop AML. Children with DS have up to 500-fold higher risk of developing AMKL during the first four years (Hasle et al., 2000, 2001; Malinge et al., 2009; Zipursky, 2003). Because the high incidence of AL in children with DS is strong evidence of the participation of chromosome 21 in the development of AL, investigation has been directed toward the

Early mortality in children with acute lymphoblastic leukemia in a developing country: the role of malnutrition at diagnosis. A multicenter cohort MIGICCL study

Abstract The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children through the first population-based study. A total of 794 newly diagnosed ALL pediatric patients from public hospitals of Mexico City were enrolled. A multivariate Cox proportional hazards regression model was constructed and adjusted by patient’s age at diagnosis, gender, hospital of treatment, and socioeconomic status. Early mortality was high (12.1%) and malnutrition by different indicators was not associated with mortality at induction phase and at 6th month; a high risk of dying (RR = 2.08; 95% CI: 1.08–4.01) was observed in the group of malnourished children with a high-risk ALL.

EBV, HCMV, HHV6, and HHV7 screening in bone marrow samples from children with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis.