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.

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. METHODS: Clinical charts of children with acute leukaemia and suspicion of pulmonary involvement were reviewed. Patients were allocated to group I if their diagnostic and therapeutic decisions were in accordance with the DTG, and to group II if not. RESULTS: Children from group I (n=32) and group II (n=28) did not differ with respect to age (9.3+/-0.5 years old, mean+/-SEM), gender, type, risk and stage of leukaemia, anaemia and neutropenia. Total length of hospital stay and hospitalization due to the pulmonary disease were shorter in group I than in group II (14.8+/-2.1 vs. 28.5+/-3.7 days, p=0.0016; and 10.8+/-1.0 vs. 18.4+/-1.8 days, p=0.0003, respectively). Two patients (6.3%) died due to the pulmonary pathology in group I, and nine (32.1%, p=0.016) in group II. CONCLUSIONS: Diagnostic-therapeutic guidelines that incorporate timely decisions constitute a useful algorithm to reduce the length of hospital stay and mortality in children with acute leukaemia and pulmonary infiltrates. A prospective study is needed to validate these results.

[Incidence of acute leukemia in children in Mexico City, from 1982 to 1991]. / 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.

Malnutrition in childhood lymphoblastic leukemia: a predictor of early mortality during the induction-to-remission phase of the treatment.

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.

[Neurological and psychological sequelae in children with acute lymphoblastic leukemia who had received radiotherapy and intrathecal methotrexate]. / Secuelas neurológicas y psicológicas que deja la radioterapia o el metotrexate intratecal en niños con leucemia linfoblástica aguda.

UNLABELLED: Our objective was to compare the neurologic and psychological sequelae of children with acute lymphoblastic leukemia (ALL) after three or more years without antineoplasic treatment who underwent cranial irradiation plus intrathecal methotrexate (Group 1) or just intrathecal methotrexate (Group 2). In both groups, a neurologic evaluation, electroencephalogram (EEG) and cranial computed tomography (CCT) were performed. Intellectual quotient and the Bender test were done for the psychological evaluation. Investigators did not know the kind of treatment of each patient. STATISTICS: Fisher's exact test and Mann-Whitney U. There were fourteen patients in group 1 and eight patients in group 2. Intellectual quotient was statistically lower in the first group (median 83.5) than in the second (90.5). Neurologic impairments were found in one patient of each group, alterations of the EEG were found in 6 and 4 in group 1 and 2, respectively, and in the CCT of two patients in group 2 without statistical difference. Children with ALL after cranial irradiation have a greater alteration of intellectual performance than children with intrathecal methotrexate. Neurologic alterations were seen in both groups.

Empirical antimicrobial therapy in pediatric patients with neutropenia and fever. Risk factors for treatment failure.

BACKGROUND: The use of combinations of antibiotics has been the cornerstone of therapy for febrile patients with cancer and severe neutropenia. Each empirical regimen should be selected according to the epidemiology and susceptibility patterns in each center. We describe here the experience with empirical antimicrobial treatments in pediatric patients with cancer, fever and severe neutropenia, and identify the risk factors associated with treatment failure. METHODS: This is a prospective study including 145 patients with cancer, and 171 episodes of neutropenia and fever. Blood cultures were taken before initiating empirical treatment: a) carbenicillin (400 mg/kg/day) plus amikacin (21 mg/kg/day) (Cb/ak), and b) ceftazidime (100 mg/kg/day), plus amikacin at the same dosage (Cz/ak). RESULTS: The overall response rate was 54.9% and 56.3% for Cb/ak and Cz/ak, respectively. Fifty-seven episodes (33.3%) were microbiologically documented, gram-positive isolated in 38% and gram-negative in 49%. Risk factors associated significantly with treatment failure were acute myelocytic leukemia (AML) (RR 2.59, CI 95% 1.42-4.7, p = 0.003); bacteriological identification (RR = 4.41, CI 95% 2.21-8.8, p < 0.001), and the presence of two or more sites of infection (RR = 2.89, CI 95% 1.03-8.11, p = 0.03). CONCLUSIONS: The rates of response are similar to the combinations used in the hospital (Cb/ak, Cz/ak). The risk factors associated with treatment failure were AML diagnosis, bacteriological identification, and the presence of two or more sites of infection.

Nutritional state alterations in children with acute lymphoblastic leukemia during induction and consolidation of chemotherapy.

The objective of the study was to determine if children with high risk acute lymphoblastic leukemia (ALL) exhibit higher frequency of alterations in nutritional state during the phases of induction and consolidation of chemotherapy than children with low risk ALL, based on the arm muscle area. The design was concurrent comparative cohorts. It was performed at pediatric hematology service of the Hospital General del Centro Médico Nacional "La Raza" and hematology service of the Hospital de Pediatría del Centro Médico Nacional "Siglo XXI". One hundred-five patients were incorporated into the study: 53 with high risk (HR) ALL and 52 with low risk (LR) ALL. Basal measurements of arm circumference and tricipital skinfold were surveyed monthly (for 3 months) by standardized personnel. Altered nutritional state during follow-up was defined as the loss of 10% or more of the arm muscular area (AMA) measured at diagnosis. Statistics of proportion analysis with a significance level of 0.05 and relative risk (RR) with confidence intervals (CI) were calculated. In the first month the RR was 0.77 (CI 0.31-1.87); the LR group was the most affected. In the second month the RR was 7.31 (CI 1.41-38.03); the most affected group was the HR. In the third month the RR was 1.77 (CI 0.60-4.92); the HR group was the most affected. High-risk patients show a higher frequency of nutritional state alterations reflected in AMA during the second month after diagnosis. This may be caused by the more aggressive chemotherapy received by these patients.

[Amikacin in single daily doses in children with fever]. / Amikacina en dosis única diaria en ninõs con fiebre.

A randomized clinical trial was performed in children with cancer, fever and neutropenia, to evaluate the efficacy of amikacin once daily versus thrice daily dosing plus carbenicillin in both groups. Fifty patients were included, 25 patients in group A who received amikacin once daily and 25 in group B who received amikacin thrice daily. No intergroup differences were observed, i.e., fever diminished in a median of 6 days (2-8 days) vs. 7 days (3-12 days) in groups A and B respectively (p = 0.37);clinical improvement was observed in a median of 6 days (3-10 days) vs 7 days (2-14 days) (p = 0.68). One patient in group A and two in B died. The peak levels of amikacin on the 7th day of treatment were 10-60 and 7-25 micrograms/mL in groups A and B respectively, and the serum creatinine levels were 0.3 - 0.7 for group A and 0.2 - 0.8 mg/dL for group B; none of the patients presented a creatinine above 40% of the basal value. Three patients of group A had amikacin levels higher than 40 micrograms/mL without increasing the creatinine levels; our observations do not suggest that toxicity is higher. We conclude that the administration of aminoglycoside once daily seems to be as effective as the traditional dosing.

[Instrument to measure quality of life based on daily performance in pediatric patients with leukemia]. / Un instrumento para medir la calidad de vida por medio del desempeño diario en pacientes pediátricos con leucemia.

The objective of this study was to determine the validity of a questionnaire to measure daily performance as an evaluation of quality of life in pediatric leukemia patients. A questionnaire of the daily activities of a child according to Lickert's criteria was done. A pilot survey was performed in patients without a chronic or disabling disease in order to assess its validity. The impression of the medical attendance of each pediatric patient with leukemia, of their daily performance, was compared with the results of the instrument. A trained nurse applied the questionnaire to 60 mothers of patients (29 female/31 male) as outpatients during the clinical review. Fifteen questionnaires were applied twice to evaluate its consistency. According to the results, 77% of the patients were in remission. 15% in relapse, and 8% during induction to remission. The mean age of the patients was 9 = 3.6 years, ranging from 2-16 years. One hundred percent of the patients obtained a satisfactory grade greater than 35 points. In conclusion, the questionnaire identified adequately the level of the daily performance in addition to the specific affected areas of the patients with leukemia. Our findings are that their level of performance is satisfactory and is not affected because of the disease or the phase of the treatment.

Incidence trends of acute leukemia among the children of Mexico City: 1982-1991.

The objective of this study was to identify the tendency of acute leukemia among children in Mexico City from 1982 to 1991. A hospital survey was performed. Medical records of children under 15 years of age with a diagnosis of acute leukemia were reviewed. The cases were chosen from hospitals which provide medical attention to children with cancer in Mexico City. The annual incidence rate (AIR) was calculated in general, by sex, age groups (under 1 year of age, from 1 to 4 years, 5 to 9 years and 10 to 14 years) and standardized with the world population. The trend was evaluated with Spearman's correlation method. Acute lymphoblastic leukemia showed a significantly increasing trend during the study period. The AIR was 7.75 (per million) in 1982 and 22.19 (per million) in 1991. For age groups a tendency to increase was observed in females of age group 1 to 4 years and in males of age group 10 to 14 years. Acute non-lymphoblastic leukemia did not display a specific trend. In conclusion, acute lymphoblastic leukemia shows a tendency to increase in the children of Mexico City.