A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma study group

Neuroblastoma, an embryonal cancer of the autonomic nervous system, is the most common cancer diagnosed during the first year of life. Although neuroblastoma accounts for disproportionately high morbidity and mortality among childhood cancers, it has one of the highest rates of spontaneous and complete regression. The author discusses recent advances in our understanding of neuroblastoma.

/pdf/recent-advances-in-neuroblastoma-40yd8bqy2g.pdf

Recent advances in neuroblastoma.

Essential fatty acids in growth and development

Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization

Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group.

This statement proposes recommendations toward increasing the practice of breast feeding. Specific recommendations made for standards of infant formulas as to calorie, protein, fat, vitamin, and mineral levels apply to both milk-based and milk-substitute infant formulas. Such formulas, when used in place of breast-feeding, must supply most or all of the nutrients infants require during the first weeks or months of life. The minimum levels of nutrients per 100 kcal recommended for formulas provide good growth and development in healthy, full-term infants; distinct hazards may be encountered at levels below these. However, no significant advantage is to be gained by providing levels in excess of these minima in normal infants. Recommendations for maximum levels are made only where quantities in excess lead to toxicity; generally, levels near the minima recommended are most desirable because they are the most likely to reflect the composition of human milk, and the least likely to result in any undesirable nutrient to nutrient interaction. The recommendations also can be used as reference standards for formulas for special dietary uses of "medical" formulas. The Committee recommends that "medical" formulas be classified by FDA into a special group under the paragraph dealing with infant formulas.

https://pediatrics.aappublications.org/content/pediatrics/57/2/278.full.pdf

Commentary on Breast-Feeding and Infant Formulas, Including Proposed Standards for Formulas

We prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long-term continuous complete remission (CR) who had received two different regimens of CNS prophylaxis by random assignment. Twenty-three patients were treated with 1,800 cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with parenteral methotrexate only (MTX group). Over half of the RT group had somnolence syndrome, and four developed cerebral calcifications late in their clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients in the MTX group, and six had early, transient white-matter hypodensities apparent on computed tomographic (CT) scans. Mean scores on standard tests of intelligence and academic achievement, administered after remission induction and again at a median of 6 years after treatment cessation, did not differ significantly between the two groups. However, statistically significant decreases in overall and verbal intelligence quotients (IQs) and in arithmetic achievement were found within both treatment groups. Sixteen of 26 in the MTX group and 14 of the 23 in the RT group had clinically important decreases (greater than or equal to 15 points) on one or more neuropsychologic measures. These changes did not correlate with findings on CT scans, EEGs, or other clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and parenteral methotrexate, as used in this study, are associated with comparable decreases in neuropsychologic function.

Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study.

We examined the results of stopping therapy in children with acute lymphocytic leukemia. Of 639 patients in eight consecutive "total therapy" studies, 278 (44 per cent) had all treatment stopped, usually after 2 1/2 years of complete remission. About one fifth (55 of 278) of this group have relapsed, mainly in the bone marrow. The relapse rate for the first year off therapy was higher than that for the next three years (0.16 vs. 0.04, P<0.01). The life-table estimates of the four-year relapse rates were 0.24 for all patients and 0.22 for patients receiving adequate Central-nervous-system prophylaxis. Boys had a higher relapse rate than girls (0.33 vs. 0.15, P<0.01). None of the 79 patients who remained in complete remission for at least four years off therapy have yet relapsed. Acute lymphocytic leukemia appears curable in over one third of all newly diagnosed patients who receive treatment for approximately 2 1/2 years. (N Engl J Med 300:269–273, 1979)

A reappraisal of the results of stopping therapy in childhood leukemia.

The in vivo effects of several chemotherapeutic agents on the mitotic cycle of leukemic blasts in the bone marrow were evaluated by serial measurements of cells in mitosis and in deoxyribonucleic acid (DNA) synthesis as indicated by ability to incorporate tritiated thymidine or tritiated deoxyuridine. 28 studies were done in 23 children and 1 adult. The changes in the marrow after a single injection of L-asparaginase, hydrocortisone, cyclophosphamide, cytosine arabinoside, methotrexate, and an exchange transfusion (62% of the total blood volume) were evaluated. L-asparaginase and hydrocortisone were found to arrest the entry of cells into the S period. Cyclophosphamide appeared to inhibit DNA synthesis, arrest cells in mitosis, and inhibit the entry of cells into the S period. Cytosine arabinoside, and methotrexate inhibited DNA synthesis. During the period of time the cells were inhibited in the S phase by these two drugs, cells continued to enter the S period. Thus partial synchronization was achieved after these two drugs. An exchange transfusion had no consistent effect on the mitotic cycle, but partial synchronization in the S period was seen in one patient. To take advantage of the ability of cystosine arabinoside, to synchronize leukemic cells in the S phase, a second cycle-dependent drug was given at the time the leukemic blasts were synchronized. The second cycle-dependent drugs evaluated were vincristine, methotrexate, and cytosine arabinoside given by intravenous drip over a 12 hr period. Recruitment was found after cytosine arabinoside alone, and after prior synchronization with cytosine arabinoside and then the administration of either of these drugs. The results of these studies indicate that a greater therapeutic advantage can be achieved by a second cycle-dependent drug after synchronization than after the second drug alone.

/pdf/synchronization-and-recruitment-in-acute-leukemia-49388n0lop.pdf

Synchronization and recruitment in acute leukemia

Neutrophils from a boy with recurrent bacterial infections since infancy were found to have unique morphologic abnormalities. The nuclei were bilobed, and the cytoplasm appeared nearly dev...

Alvin M. Mauer

Papers

Commentary on Breast-Feeding and Infant Formulas, Including Proposed Standards for Formulas

Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study.

A reappraisal of the results of stopping therapy in childhood leukemia.

Synchronization and recruitment in acute leukemia

An Anomaly of Neutrophil Morphology with Impaired Function