Roberto Bernáldez-Ríos

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.

Malnutrition in Childhood Lymphoblastic Leukemia

BACKGROUND Previous reports have shown that undernourished children with acute lymphoblastic leukemia (ALL) have a poorer long-term survival as compared with children with normal nourishment status. It has been shown that both the relapse and mortality rates of undernourished children with ALL are higher during the continuation phase of the chemotherapy and are apparently related to a poor tolerance of ablative chemotherapy. No previous articles have analyzed the early mortality rate of these patients. METHODS We carried out a case-control study, and have studied the effect of severe malnutrition on the mortality of 17 children with ALL during the initial induction-to-remission phase of the treatment. These 17 cases were compared with 76 controls who had survived at least the phases of induction and consolidation. RESULTS It was found that the chance of dying during the initial phase of the treatment was 2.6 times higher (confidence interval 95%: 0.55-11.89) in undernourished children with ALL than in those children with normal nourishment status. The risk of death increased with the severity of undernourishment (p = 0.04). CONCLUSIONS These data confirm the prognostic value of malnutrition in children with ALL and suggest that undernourishment may also influence early mortality during the induction-to-remission phase of the treatment.

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.

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.

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.

Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each childs diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.

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.

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. Mejia-Arangure JM, Fajardo-Gutierrez A, Bernaldez-Rios R, Paredes-Aguilera R, Flores-Aguilar H, Martinez-Garcia MC. Incidencia de las leucemias agudas en ninos de la ciudad de Mexico, de 1982 a 1991. Salud Publica Mex 2000;42:431-437.

Guidelines for diagnosing and treating pulmonary infiltrates in children with acute leukaemia: impact of timely decisions

Aim: Children with leukaemia are at increased risk of pulmonary complications, often with unspecific clinical data, delayed diagnosis and a high mortality rate. We evaluated the usefulness of diagnostic–therapeutic guidelines (DTG) in which specific times for decision making were incorporated.

Diagnoses unveiled by early bronchoscopy in children with leukemia and pulmonary infiltrates.

Pulmonary complications in children with leukemia often display nonspecific clinical and radiologic manifestations that lead to a delay in diagnosis. The role of fiberoptic bronchoscopy (FOB) and the proper time for its performance are controversial. The aim of our study was to evaluate the frequency and nature of specific diagnoses revealed by FOB. Children with leukemia submitted to FOB because of suspicion of pulmonary involvement (mainly pneumonia) were retrospectively analyzed. A total of 33 FOB procedures performed in 31 patients (20 males) with an average age of 9.4 years (range, 3.5 to 15 y) were evaluated. Microorganisms isolated from 21 (63.6%) bronchoalveolar lavage samples were mainly fungi including Candida in 13 cases (39.4%) and Aspergillus in 3 cases (9.1%). Isolation rate in 10 procedures performed within the first 3 days was 90%. Tracheobronchitis was present in >50% of patients, pulmonary hemorrhage was seen in 7 (21.0%) patients, and leukemic infiltration was demonstrated in 2 patients (6.1%), among other conditions visualized by FOB. Complications of FOB were minimal and transient. Our study suggests that FOB is a useful and safe procedure in patients with leukemia and pulmonary infiltrates. The earlier the FOB was performed, the higher the isolation rate of causative agents. In addition, this procedure allowed the identification of noninfectious airway comorbidities. Further studies in regard to this issue are warranted.