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.

A closer look at specific therapeutic strategies in leukemia.

Leukemia-associated fusion genes are detected in a significant proportion of newly diagnosed cases, where genes encoding transcription factors are usually found at one of the breakpoints. Activated fusion proteins, such as PML-RARalpha and AML1-ETO, have been shown to inhibit cellular differentiation by recruitment of nuclear corepressor complexes, which maintain local histone deacetylase (HDAC) in a variety of hematologic lineage-specific gene promoters. This HDAC-dependent transcriptional repression appears as a common pathway in the development of leukemia and could represent an important target for new therapeutic agents. On the other hand, the Bcr-Abl oncoprotein shows high tyrosine kinase activity and deregulates signal transduction pathways involved normally in both apoptosis and proliferation. This aberrant activity is affected by signal transduction inhibitors (STIs), which block or prevent the oncogenic pathway. In this review, we present a closer look at our understanding of both the reversible transcriptional repression controlled by HDAC and the deregulated Bcr-Abl signal transduction. In addition, the application of low molecular weight drugs for human leukemia treatment based in this knowledge results in durable clinical remission and acceptable risk of toxic effects that should increase the cure rate. We hope that this review will provide timely information to the readers.

Pediatric oncology at Hospital Infantil de Mexico: fifty-five years of accomplishment.

The Department of Oncology at Hospital Infantil de México Federico Gómez (HIMFG) was the first unit in our country, and one of the first in Latin America, to specialize in the management of children with cancer. The HIMFG is part of the National Institutes of Health of Mexico, and is a reference hospital with research, educative, and tertiary care medical function. To date, the HIMFG and the Instituto Nacional de Pediatria are the principal medical centers in which children with cancer receive comprehensive care.

Diagnosis of bone marrow metastases in children with solid tumors and lymphomas. Aspiration, or unilateral or bilateral biopsy?

BACKGROUND: Malignancies are among the most common causes of death in children. The present study was undertaken to evaluate and compare bone marrow aspiration and unilateral biopsy to detect bone marrow metastases in pediatric patients, using bilateral biopsy as the gold standard. METHODS: During a 6-month period, 63 consecutive newly diagnosed children with confirmed malignant diseases other than leukemia were evaluated for bone marrow metastases or infiltration. Biopsies were obtained from both right and left posterior iliac crests whereas aspiration was performed only at the right crest. Interpretation to the right-side biopsy was considered as the unilateral biopsy result, whereas the bilateral biopsy result was as follows: positively was accepted if one or both of the two-side samples were qualified as positive, while a negative result was considered only if both sides were negative. The bilateral biopsy was considered the gold standard, and sensitivity, specificity, positive and negative predictive value, and false positive and negative rates were computed for the unilateral biopsy and aspiration procedure. RESULTS: We identified bone marrow metastases in 11 (17.5%) patients. The sensitivity was the only significant difference (p <0.05) observed between unilateral biopsy and aspiration. Finally, of the 63 patients, unilateral biopsy was reported as inadequate in one patient (1.6%), while aspiration was inadequate in two (3.2%). CONCLUSION: Unilateral biopsy was better than bone marrow aspiration. However, because bilateral biopsy is the gold standard, we recommend using this and bone marrow aspiration simultaneously to evaluate a pediatric patient with any malignancy potentially infiltrating bone marrow.

[Lymphoblastic lymphoma in children. Poor response in advanced disease with chemotherapy for non-Hodgkin's lymphoma]. / Linfoma linfoblástico en niños. Respuesta pobre en enfermedad avanzada con quimioterapia de linfoma no Hodgkin.

Fifty three pediatric patients with the histopathological diagnosis of lymphoblastic lymphoma (LL) were studied in a retrospective analysis during a 14 year period. Their age ranged from 1 to 16 years with a median of 7 years. Clinical staging was performed according to Murphy's system. There was one child in stage I (2%), 11 in stage II (21%), 14 stage III (26%) and 27 stage IV (51%). Patients in stage IV, 21 (78%) had initial bone marrow involvement, 4 (15%) central nervous system (CNS) infiltration and 2 (7%) simultaneous infiltration to the bone marrow and the CNS. The chemotherapy program consisted of induction, consolidation and maintenance with CNS prophylaxis. The whole program lasted 36 months. Out of 53 patients there were only 45 evaluable for treatment analysis response. A total of 14 (31%) are alive and in a continuous complete remission, with a median duration of remission of 66 months, 8 (18%) children abandoned treatment with a median duration of remission of 10 months. Twenty three patients (51%) are dead. The actuarial survival at 11 year is of 39% +/- 11% with a median remission rate for the whole group of 11.8 months. No patient in complete remission for more than 24 months has relapsed. We conclude that our chemotherapy program is more than adequate for early stages, but for advanced disease it has been a failure. There is a need to modify the chemotherapy program using a very similar protocol as the one used in high risk childhood acute lymphoblastic leukemia.

Leiomiosarcoma hepático como segunda neoplasia: informe sobre un niño con leucemia aguda linfoblástica y tumor hepático / Hepatic leiomyosarcoma as a second malignancy: report in a child with acute lymphoblastic leukemia and hepatic mass

Los pacientes pediátricos con leucemia aguda linfoblástica (LAL) presentan alto índice de curación, pero con mayor incidencia de segundas neoplasias condicionadas por la radioterapia, por la quimioterapia con agentes alquilantes o las epipodofilotoxinas. Se presenta un paciente con LAL en el Instituto Nacional de Pediatría, quien durante el tratamiento de LAL sin presentar alteración citogénica demostrable, desarrolla un leiomiosarcoma hepático de focos primarios múltiples, no existieron antecedentes de uso de manera importante de agentes alquilantes, epipodofilotoxinas ni radiaciones ionizantes. Consideramos la posibilidad de una susceptibilidad genética, que no podemos demostrar actualmente, como condicionante para el desarrollo de esta segunda neoplasia con patrón de presentación clínica poco usual

[Meningeal sarcoma in childhood. Experiences with 17 cases]. / Sarcoma meníngeo en la infancia. Experiencia con 17 casos.

A total of 17 patients with meningeal sarcoma were diagnosed and treated at the National Institute of Pediatrics in Mexico City in a period of 15 years. Among the diagnostic methodology used in this group we found that angiography is still the best to be used so far. On the other hand, the chemotherapy protocol employed did not improve the survival obtained with surgery and radiotherapy. Therefore we suggest that a new chemotherapy protocol has to be designed in order to obtain better results. Of particular interest, we found in this group of patients that the time elapsed between the first sign of disease to the moment of diagnosis varied from 2 months to 10 years without any prognostic significance.

Langerhans cell histiocytosis: clinical experience with 124 patients.

We cared for 124 pediatric patients with a histologic diagnosis of Langerhans' cell histiocytosis (histiocytosis X) over a period of 14 years. Clinical, laboratory, and radiographic findings were analyzed. The most frequent manifestations were bone lesions, lymph node involvement, and skin infiltration. Liver disease was noted in 50% of patients and lung disease in 23%; hematologic changes were also frequent. Dysfunction and involvement of these three organ systems, plus age of onset, distinguished the group of patients with the highest mortality. All patients with generalized disease or organ dysfunction were treated with systemic chemotherapy. The actuarial survival curve at 10 years was 63%.

Treatment of non-Hodgkin's lymphoma in Mexican children. The effectiveness of chemotherapy during malnutrition.

The histological diagnosis of non-Hodgkin's lymphoma (Burkitt's lymphoma excluded) in 147 children was reviewed. The most common site of presentation was in the abdomen (32.6%). The most frequent site of metastatic disease at diagnosis was the bone marrow (27.2%). The most common histology was diffuse undifferentiated non-Burkitt type (37.4%). According to the Murphy staging system, 40.1% were stage III and 27.2% were stage IV. In a nonrandomized prospective study, 121 patients were submitted to a treatment regimen (protocol 8001) and compared with 26 historical controls treated with the COP regimen, consisting of cyclophosphamide, vincristine, and prednisone. Of those patients treated with protocol 8001, nine had intestinal perforation at the site of primary disease. All patients in this group were malnourished at the time of perforation. The overall rate of initial complete remission in those patients treated with protocol 8001 was 90.7%. The duration of remission was from 16 to 108 months, with a median of 39 months. The actuarial rate of disease-free survival was 69% at 2 years and 63% at 6 years, compared with 36% at 6 years of the control group (COP) (p less than 0.01). None of the patients have relapsed after 4 years.