Elva Jiménez-Hernández

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.

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.

Survival of Mexican Children with Acute Lymphoblastic Leukaemia under Treatment with the Protocol from the Dana-Farber Cancer Institute 00-01

Our aim in this paper is to describe the results of treatment of acute lymphoblastic leukaemia (ALL) in Mexican children treated from 2006 to 2010 under the protocol from the Dana-Farber Cancer Institute (DFCI) 00-01. The children were younger than 16 years of age and had a diagnosis of ALL de novo. The patients were classified as standard risk if they were 1–9.9 years old and had a leucocyte count <50 × 109/L, precursor B cell immunophenotype, no mediastinal mass, CSF free of blasts, and a good response to prednisone. The rest of the patients were defined as high risk. Of a total of 302 children, 51.7% were at high risk. The global survival rate was 63.9%, and the event-free survival rate was 52.3% after an average follow-up of 3.9 years. The percentages of patients who died were 7% on induction and 14.2% in complete remission; death was associated mainly with infection (21.5%). The relapse rate was 26.2%. The main factor associated with the occurrence of an event was a leucocyte count >100 × 109/L. The poor outcomes were associated with toxic death during induction, complete remission, and relapse. These factors remain the main obstacles to the success of this treatment in our population.

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.

Treatment with Interferon‐α‐2b in Children with Life‐Threatening Hemangiomas

BACKGROUND Childhood hemangiomas are benign tumors of endothelial cells, characterized by a rapidly proliferating initial phase and followed by a slow involution. However, some grow and may reach a massive size, threatening a patients functions or life. These require immediate medical treatment. OBJECTIVE The objective was to determine the therapeutic effectiveness of interferon (IFN)-α-2b in children with hemangiomas threatening the patients functions or life. MATERIALS AND METHODS All patients were treated with IFN-α-2b at a dosage of 3 million U/m2 corporal surface, applied subcutaneously, 5 days a week for the first 6 months and subsequently three times a week for 6 to 24 months. RESULTS The study included 20 patients with hemangiomas localized in different sites and with diverse functional alterations: ages varied between 3 and 48 months (median, 12.8 months), and 8 were male and 12 female. An excellent response was observed in 17 (85%) patients. Side effects were slight and transitory; there was a follow-up from 7 to 10 years, and no late toxicity was observed. CONCLUSIONS We can conclude that IFN-α-2b is an effective option for treating alarming hemangiomas that are resistant to steroids and that endanger proper functioning of the affected organ or the patients life.

Detection of Epstein-Barr Virus and Genotyping Based on EBNA2 Protein in Mexican Patients With Hodgkin Lymphoma: A Comparative Study in Children and Adults

BACKGROUND Epstein-Barr virus (EBV) is a member of the Herpesviridae family and is associated with Hodgkin lymphoma (HL). Isolates of EBV are classified according to sequence variation in the latency genes such as Epstein-Barr virus nuclear antigen (EBNA). EBNA2 contains the most divergent locus and is classified into type 1 and type 2 or EBNA2A and EBNA2B, respectively. We compared the frequency of EBV and the distribution of EBNA genotypes in Mexican children and adults with HL. PATIENTS AND METHODS Lymph node biopsy specimens from children and adults with HL were embedded in paraffin. EBV was identified by LMP1 amplification and Epstein-Barr-encoded RNA EBER by in situ hybridization (ISH) and genotyped as EBNA2A or EBNA2B using nested polymerase chain reaction (PCR) and specific primers for the detection of subtype. RESULTS Sixty-six samples were obtained from 3 hospitals-42 (63%) from children and 24 (37%) from adults with HL. Thirty-two of the 42 samples (76.1%) were positive for EBV in children and 16 of 24 (66.6%) samples were positive in adults (P = .41). In both children and adults, EBV was found more frequently in male patients. Thirty-four of 48 cases could be typed (70.8%). EBNA2A was found in 7/21 (33.3%) children and in 4/13 (30.8%) adults (P = 1.0), and EBNA2B was found in 10/21 (47.6%) children and in 9/13 (69.2%) adults (P = .22). A mix of subtypes was found in 4/21 (19%) children. CONCLUSION EBV was found frequently in both children and adults with HL. EBNA2B was the most frequent subtype, and a high frequency of mixed subtypes was found in children.

Cytomegalovirus gB Genotype Distribution in Mexican Children Undergoing Allogeneic Bone Marrow Transplantation

We used nested multiplex polymerase chain reaction to determine the distribution of cytomegalovirus gB genotype in 30 Mexican children undergoing bone marrow transplantation. The genotypes were: gB1, 9/30 (30%); gB2, 8/30 (27%); gB3, 4/30 (13%), and gB4, 1/30 (3%); mixed genotypes were identified in 8/30 patients (27%). We conclude that the predominant genotypes identified were gB2 and gB1. The gB5 genotype was not detected, and a high proportion of mixed genotype was found.

The role of cytomegalovirus infection and disease in pediatric bone marrow transplant recipients in Mexico City in the context of viral drug resistance

Arellano‐Galindo J, Vázquez‐Meraz E, Jiménez‐Hernández E, Velazquez‐Guadarrama N, Mikeler E, Hamprecht K, Jahn G, Acosta‐Vázquez F, Emma M‐G, Bello‐González A. The role of cytomegalovirus infection and disease in pediatric bone marrow transplant recipients in Mexico City in the context of viral drug resistance.
Pediatr Transplantation 2011: 15:103–111.

Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.