EBV, HCMV, HHV6, and HHV7 screening in bone marrow samples from children with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis.

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.

In vitro characterization of the hematopoietic system in pediatric patients with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) has been recognized as a hematologic neoplasia that originates at the level of a primitive lymphoid stem/progenitor cell. To date, however, the biology of the hematopoietic system in this disorder is still not fully understood. In the present study, we have determined the progenitor cell content (including myeloid, erythroid and multipotent progenitors) in 14 children with ALL and followed the proliferation kinetics of these cells in Dexter-type long-term marrow cultures. We have also characterized some aspects related to the composition and function of the hematopoietic microenvironment developed in vitro. All patients included in this study showed extremely reduced levels of progenitor cells (median of 6.2% of the levels found in normal marrow). Proliferation of these cells in long-term cultures was markedly deficient, since they showed very low numbers - compared to normal cultures - and reached undetectable levels after only a few weeks. Regarding the microenvironment developed in vitro, whereas normal marrow samples contained a median of 8 fibroblastic progenitors/10(5) marrow cells and the stromal cell layers developed in culture contained a median of 341000 adherent cells per well, ALL marrow samples showed no fibroblastic progenitors and the numbers of adherent cells were 21% of those in normal cultures. Interestingly, the levels of TNFalpha and IL-6 in ALL culture supernatants were significantly increased, compared to normal cultures. Bone marrow samples from all 14 children were also analyzed once they reached a complete clinical and hematological remission. Myeloid, erythroid and multipotent progenitor cell levels were significantly increased, compared to patients at diagnosis, and proliferation of myeloid progenitors in long-term cultures was also improved. In contrast, proliferation of erythroid progenitors showed no difference to that in cultures from patients at diagnosis. The numbers of fibroblastic progenitors and adherent cells were significantly increased, compared to patients at diagnosis, and TNFalpha and IL-6 levels returned to normal. In summary, in the present study, we have demonstrated significant in vitro alterations of the hematopoietic system, both in terms of its composition and function, in pediatric patients with ALL. Importantly, most of these alterations are corrected, at least partially, after chemotherapy.

[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.

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.