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The aims of the present study were to optimize the detection of common fusion gene transcripts associated with childhood B-ALL prognosis through the development and validation of a one-step RT-qPCR assay and to identify the prevalence of these genes in a cohort of pediatric patients attended in public hospitals in Mexico City. The one-step RT-qPCR assay was sensitive, specific, easy to use, fast and cost efficient. The standard curves were linear, with amplification efficiencies between 97-107%; coefficients of variation were 2.1-3.0% in reproducibility and 2.6-3.8% in repeatability, with agreement between two different laboratories. The prevalence of fusion gene transcripts was ETV6-RUNX1, 10.3%; TCF3-PBX1, 7.5%; BCR-ABL1p190, 3.6%; and KMT2A-AFF1, 2.8%. The prevalence of the ETV6-RUNX1 fusion was low, consistent with the findings in Hispanics. The KMT2A-AFF1 fusion was not exclusively present in infants, as we also found it in patients 4-16 years of age, in whom it was related to a poor prognosis. TCF3-PBX1 patients were associated with an intermediate outcome. The present study highlights the importance of the detection of common genetic fusions in Mexican children with ALL, taking into account that some have molecular subtypes associated with a poor prognosis.

Background Refining risk stratification to avoid very early relapses (VER) in Mexican patients with B-lineage acute lymphoblastic leukemia (B-ALL) could lead to better survival rates in our population. Aim of the study The purpose of this study was to investigate the association between the United Kingdom ALL (UKALL)-CNA classifier and VER risk in Mexican patients with childhood B-ALL. Methods A nested case-control study of 25 cases with VER and 38 frequency-matched controls without relapse was conducted within the MIGICCL study cohort. They were grouped into the categories of the UKALL-CNA risk classifier (good [reference], intermediate and poor), according to the results obtained by multiplex ligation dependent probe amplification. Overall and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards analyses were conducted. Results The CDKN2A/B genes were most frequently deleted in the group with relapse. According to UKALL-CNA classifier, 33 (52.4%) patients were classified as good, 21 (33.3%) intermediate and 9 (14.3%) poor-risk B-ALL. The intermediate and poor risk groups were associated with an increased risk of VER (HR = 4.94, 95% CI = 1.87–13.07 and HR = 7.42, 95% CI = 2.37–23.26, respectively) in comparison to the good-risk patients. After adjusting by NCI risk classification and chemotherapy scheme in a multivariate model, the risks remained significant. Conclusions Our data support the clinical utility of profiling CNAs to potentially refine current risk stratification strategies of patients with B-ALL.

Purpose Limited data describe the delivery of pediatric cancer care in Mexico. We report a nationwide survey of pediatric cancer units. Methods An electronic survey was distributed to 74 pediatric cancer units in Mexico to describe case volumes; organization of care; and availability of medical/surgical specialists, supportive care, complex therapies, and diagnostic services. Centers were classified as low (< 30 new patients/year), medium (30 to 59/year) and high (≥ 60/year). Results Sixty-two centers completed the survey (response rate, 84%). The median annual new case volume per center was 50 (interquartile range [IQR], 23 to 81). Thirty-four percent (n = 21), 26% (n = 16), and 40% (n = 25) of units were low-, medium-, and high-volume centers, respectively. Treatment units reported a median of two pediatric oncologists (IQR, 2) and one pediatric hematologist (IQR, 1 to 2). Availability of medical and surgical subspecialists varied by center size, with substantially more specialist support at higher-volume centers ( P < .01). Multidisciplinary tumor boards are available at 29% (six of 21), 56% (nine of 16), and 76% (19 of 25) of low- to high-volume centers, respectively ( P = .005). Radiation and palliative care services are available at 42% (n = 26) and 63% (n = 36) of all centers, which did not vary by center volume. Educational support for hospitalized children and school reintegration programs are available at 56% (n = 36) and 58% (n = 36) of centers, respectively. One third (38% [n = 23]) of centers reported that at least one half of patients were lost to follow-up during the transition from pediatric to adult programs. Conclusion A large variation exists in annual case volumes across Mexican pediatric cancer centers. Additional efforts to increase access to multidisciplinary, supportive, and palliative care across all pediatric cancer units in Mexico are required.

In recent years there has been great increase in the relationship between the Latin American Societies of Hematology and the American Society of Hematology. This led to the meeting Highlights of the American Society of Hematology (ASH) in Latin America (HOA-LA), first held in Sao Paulo and Rio de Janeiro, Brazil with its third meeting taking place in 2011 in Punta del Este in Uruguay. With this exchange, it soon proved necessary to know the reality of hematology in Latin America and the context of development in different countries, so that the links between the different scientific societies of the area would become stronger. With this in mind, information was collected using a standardized questionnaire provided to the participants of the 2011 HOA-LA accompanied by guidelines on how to complete the questionnaire. The information provided was discussed during a specific section of the 2011 HOA-LA on April 30 coordinated by Drs. Raul Gabus, Carmino Antonio de Souza and Scott Howard. The session was attended by representatives of Argentina, Brazil, Bolivia, Chile, Colombia, Mexico, Paraguay, Peru, Uruguay and Venezuela as well as those from the United States of America, Canada, Spain and Italy. The aim of the meeting was to prepare a document to evaluate the current status of hematology in Latin America in order to improve interactions between Latin American Societies of Hematology. An additional objective was to encourage the organization of cooperative projects on support and training for the diagnosis and treatment of patients with blood diseases in Latin America. Member societies of the OAH-LA were asked to designate a spokesperson for this activity before 15 December 2010. Questionnaires were distributed to these spokespeople to obtain a representative sample of partners and hematology services of each country. The questionnaires were then sent to the coordinators in January 2011. In February 2011, each representative wrote a brief summary of data on the general situation in their country that reflected the opinion of the respective Society of Hematology. Data were collected and analyzed by the coordinators of the LA-HOA in Uruguay in March 2011 with the reports being divulged to the participating scientific societies. In April 2011 the results were presented and the final text of the document was discussed. The estimated population of the countries involved (Argentina, Bolivia, Brazil, Chile, Colombia, Mexico, Paraguay, Peru, Uruguay and Venezuela) is approximately 475 million people in an area of 19,046,336 km2. There are currently 4,306 hematologists for this population which is a rate of 0.9/100,000 hematologists/inhabitants with a heterogeneous distribution between the countries and between regions within each country. A total of 76.7% hematologists are connected to hematology institutions in their countries (range: 45-100%). In the case of Colombia, the Hematology Society is linked to oncology and in five countries (Bolivia, Brazil, Chile, Paraguay and Venezuela) to transfusion medicine. In seven countries (Argentina, Bolivia, Brazil, Colombia, Paraguay, Uruguay and Venezuela), there are formal medical fellowships programs in hematology. Three countries (Brazil, Colombia and Uruguay) reported that it is the National Health System that regulates funds and supportive care. In the other countries the health care system is divided between the public health insurance, prepayments, loans and others. The participation of the public sector in different countries varies between 25 and 73%. Exclusive private healthcare covers 10 and 20% of care. There are few national records and those that exist are limited to specific diseases. The registries are mainly of isolated Hematology Centers with partial data and with little intervention of Hematology Societies (Figure 1). Figure 1 Registry With regards to healthcare in hematology, although most people can easily have access to referral centers, however there are geographic areas far from these centers, such as the Brazilian Amazon and Bolivian Altiplano (Figure 2). Figure 2 Healthcare in hematology accessibility The availability of cytogenetics, flow cytometry, molecular biology, immunohistochemistry, computed tomography, magnetic resonance imaging (MRI) and positron emission tomography (PET-CT) was found to be heterogeneous across countries and even within the same country. Some complex techniques such as computed tomography or immunophenotyping by flow cytometry (IHC) are generally accessible to the public. Some countries do not have cytogenetics, molecular biology, MRI or PET-CT availability. Moreover, even in countries that rely on these resources, access to them is not universal for all inhabitants (Figure 3). The reports also mention a need to develop IHC to assist diagnosis of hematologic diseases. Figure 3 Healthcare in hematology diagnosis About the availability of blood components and other resources in transfusion medicine, packed red blood cell and platelet concentrates are availability to the entire population and usually at no cost to the patient. The availability of platelets by apheresis and irradiated blood products is generally limited; normally they are only available to patients in Hematopoietic Stem Cell Transplantation (HSCT) units (Figure 4). It was found that in most countries, patients have access to basic hematology-oncology treatment, but only a part of the population has access to high-cost treatment. Monoclonal antibodies, new drugs and access to HSCT are considered high-cost (Figure 5). There are countries where HSCT is not performed or the program is poorly developed. Figure 4 Healthcare in hematology support Figure 5 Access to treatment and medications The financing of regular treatment is guaranteed by the state, by health insurance or medical organization to which the patient is affiliated. However, there are situations that hematological patients lack coverage (Figure 5). There is no guarantee of coverage of high-cost treatments and medications to all populations. In some countries it is the responsibility of the state, parastatal organizations, other health insurance institutions or medical organizations to which the patient is affiliated. Occasionally, this coverage is funded by a foundation or through a support program of the pharmaceutical industry (Figure 5). Regarding the study protocol and / or treatment, some hematology centers with guidelines or consensus on certain conditions, however almost none of them are national protocols. Most treatment programs follow international protocols with little or no adaptation to the country or region (Figure 6). Figure 6 Hemato-oncological protocol treatment This survey showed that the number of hematologists is inadequate and they are unevenly distributed (Figure 7). Figure 7 Human resources Most societies stated that the number of doctors who are currently in hematology specialist courses is insufficient to meet the needs of the population (Figure 7).

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 x10 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.

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).: 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.: The odds ratio for direct measurements of magnetic fields/=6.00 mG was 3.7 (95% confidence interval = 1.05-13.1).: 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.

BackgroundMedical research has not been able to establish whether a father's 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 father's 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 child's background and the characteristics of the father's 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 expert's 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 father's 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.

Background Worldwide, 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. Methods Included 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). Results Although 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 (Pearson's r, 0.789; P = 0.02). Conclusions The 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.