We have studied 127 children from 5 participating institutions as to the effect of acute lymphoblastic leukemia (ALL) or the therapy used in the treatment of ALL on growth, growth hormone concentrations, and somatomedin activity. The study (SWOG No. 7581) was initiated in December 1975 and was closed to new entry in September 1979 and to data collection in February 1981. Heights, weights, and blood samples for growth hormone and somatomedin activity were obtained at the time of initial diagnosis and at intervals during the 55 months of observation. The percentage of boys less than 4 years of age below the 50th percentile is significantly greater than the expected 50% for both initial and final height (P less than 0.01). Girls less than 4 years appeared to have significantly different percentile height distribution from the normal for their final height measurement (P less than 0.05) but not for their initial height measurement. No other significant differences in the percentile height distribution were found. When growth rate, since time of diagnosis of ALL, is compared to the expected growth of normal children of the same age by linear regression analysis, there is a difference in the slope of the lines. Children with ALL are significantly shorter. The mean initial growth hormone and somatomedin concentration, 6.2 ng/ml and 1.3 micrograms/ml, respectively, vs mean remission growth hormone and somatomedin of 2.5 ng/ml and 1.1 micrograms/ml, respectively, were different. This was significant at P less than 0.01. The slope of the computed regression lines for multiple analysis of growth hormone and somatomedin were negative for more than 60% of the patients when compared to the initial concentration. These data suggest that a significant number of the children less than 4 years of age are short prior to the onset of therapy, and this persists throughout the course of their disease. Second, there is a reduction in growth rate during intensive therapy or the first year of the disease, with a normal growth rate thereafter. Third, growth hormone and somatomedin concentrations appear to be higher at the time of onset of the disease and decrease while on therapy.

Summary.-Cell mediated immunocompetence was measured serially in 35 patients with malignant melanoma in order to determine the effect of extent of disease and prognosis as well as the influence of BCG immunotherapy on immune reactivity.Compared with normal adult controls, statistically significant lymphopenia occurred only in patients with widespread disease. Seventeen of 21 patients with negative pre-therapy PPD skin test converted to skin test positivity. PHA blastogenesis was depressed only in patients in the pre-terminal stages of their disease using optimal mitogen concentrations for stimulation. Threshold concentrations of this mitogen more clearly demonstrated a depressed responsiveness which correlated in severity with extent of disease. PPD induced blastogenesis was normal or increased in the majority of patients; however, the degree of stimulation by PPD was less in the BCG induced convertors than in those patients who were skin test positive before BCG treatment. Comparison of the pre-and post BCG assessments reveals no significant differences except in relation to PPD conversion. We conclude that using threshold concentrations of PHA, impaired responses are regularly associated with disease beyond the regional lymph nodes. Routine assessment of lymphocyte function by these parameters did not provide information that was not available from clinical evaluation.

Soft agar culture studies of 43 immunologically characterized patients with childhood acute lymphocytic leukemias (ALL) are presented. The immunologic subsets studied include "null"-cell, pre-B-cell, and T-cell leukemias. Abnormal myelopoiesis, including high peripheral blood and low marrow, colony-forming cell numbers, low colony-stimulating activity, and normal maturation of colony-forming cells in vitro was noted in each group as previously described for immunologically uncharacterized ALL. We conclude that immunologic subsets of childhood lymphoblastic leukemia cause similar abnormalities of myelopoiesis. Lack of differences in growth characteristics among immunologic subsets of ALL make it impossible to use this tissue culture technique in subclassification of these leukemic disorders.

A nine-year-old black girl with essential thrombocythemia developed hemoptysis. Only two other cases in the English literature have been described. Ultrastructure and functional characteristics of this patient's platelets were studied. Twenty-six percent of the patient's platelets were very large (megathrombocytes). Spontaneous aggregated from the patient's platelets were not compact, and the pseudopods did not interdigitate. Both qualitative and quantitative defects in platelet organelles were detected. The microtubular system was faulty in organization. Furthermore, the number of granules (especially alpha granules) was reduced. Platelet aggregation studies demonstrated subnormal aggregation in response to ADP, epinephrine, and collagen, but aggregation with ristocetin was normal. It is postulated that a platelet membrane abnormality may be the cause of their defective platelet aggregation.