Key Points Germ line mutations in MECOM cause a heterogeneous bone marrow failure syndrome with congenital hypomegakaryocytic thrombocytopenia. MECOM-associated syndrome includes various organ malformations with variable penetrance, including radioulnar synostosis.

The incidence of chemotherapy-induced transient hyperglycemia in the present study cohort is comparable to that reported in previous pediatric ALL patients. This finding is interesting in view of the elevated prevalence of obesity and the underlying dietary behaviors in this Hispanic study cohort.

CD95 mutations are associated with loss of regulation of B lymphocytes, which predisposes to systemic autoimmunity including SLE. The P4 family provides a model of the complex genetic and functional interactions that are required for the development of a lupus-like syndrome.

In our cohort of ALL patients, BMI was elevated at diagnosis (mean standardized BMI z-score = 0.22, standard deviation = 1.4) then increased and remained elevated for the entire duration of chemotherapy. Children who were 2-9 years of age at diagnosis began therapy with a substantially lower BMI and remained lower over the course of chemotherapy than patients aged 10-18 years at diagnosis. It will be important for future investigations to explore the biological and behavioral factors that may underlie such differential patterns of BMI change over time.

The most accurate prognostic indicator in patients with musculoskeletal sarcomas is the percentage of tumor necrosis after intraarterial chemotherapy. Magnetic resonance (MR) imaging was evaluated to determine its ability to indicate the percentage of necrosis in musculoskeletal neoplasms after treatment. Fourteen patients with musculoskeletal neoplasms underwent treatment protocols including intraarterial chemotherapy (n = 14), radiation therapy (n = 6), and systemic chemotherapy (n = 14). All patients underwent MR imaging before and after treatment, and all underwent either limb salvage surgery (n = 8) or amputation (n = 6) within 1 week of the last MR examination. Standard unehanced spin-echo T1-, spin-density-, and T2-weighted MR sequences were used. The MR images were compared with the pathologic specimens. On T2-weighted images, the signal intensities of viable tumor, tumor necrosis, edema, hemorrhage, and necrosis overlapped. With the unenhanced spin-echo technique, MR imaging cannot be used to predict the percentage of tumor necrosis in musculoskeletal neoplasms after intraarterial chemotherapy.

Acute lymphoblastic leukemia (ALL), the most common malignancy in children, constitutes 25% of all pediatric cancer. Childhood cancer patients who are obese at diagnosis represent a particular challenge for the oncologist. Obesity may complicate chemotherapy dose determination, and has been associated with decreased overall and event-free survival in a number of adult cancer patients, and more recently in pediatric patients. The purpose of the present study was to examine whether obesity at diagnosis was associated with decreased overall and event-free survival in a cohort of 322 predominantly Hispanic pediatric patients with B-precursor ALL. Obesity was classified as an age-standardized and sex-standardized body mass index z-score at or above the 95th percentile. Hazard ratios (HRs) for overall and event-free survival were assessed using Cox proportional hazards regression modeling. Obesity at diagnosis was not associated with decreased overall survival (HR = 1.40, 95% confidence interval = 0.69-2.87) or event-free survival (HR = 1.08, 95% confidence interval = 0.65-1.82) in the overall cohort or in either of the 2 age-at-diagnosis (2 to 9 y; 10 to 18 y) subgroups. Our finding of no obesity-related prognostic effect in the overall cohort and in the under 2 to 9-year age-at-diagnosis cohort was consistent with the previous large-scale study of ALL patients; the absence of a prognostic effect in the 10 to 18-year age-at-diagnosis cohort, however, conflicted with previous findings.

BACKGROUND The objective of this study was to examine changes over time in body mass index (BMI) from diagnosis through chemotherapy for pediatric patients with B‐precursor acute lymphoblastic leukemia (ALL). METHODS The study cohort consisted of 141 white Hispanic pediatric patients who were diagnosed with ALL and were treated at 2 South Texas pediatric oncology centers between 1993 and 2002. Changes in age‐standardized and gender‐standardized BMI scores were assessed. RESULTS The study cohort exhibited a steady increase in age‐adjusted and gender‐adjusted BMI scores for the first 12 months of therapy, a modest increase in BMI scores during the 18–23 month and 24–29 month periods, followed by a slight decrease in BMI scores at 30 months (end of therapy). A repeated‐measures analysis indicated significant effects for time (P = 0.019) and time by baseline BMI category interaction (P = 0.0001) but no significant interaction effect between time and gender (P = 0.65). CONCLUSIONS Although it is known that leukemia therapy is associated with prevalent obesity in survivorship, its pattern of development during therapy has not been elucidated. In the current cohort of Hispanic children with ALL, BMI scores were elevated at diagnosis (mean ± standard deviation standardized BMI Z score, 0.33 ± 1.4), then increased, and remained elevated for the entire duration of chemotherapy. Patients who were classified as normal weight exhibited an increase in BMI over time; patients who were classified as overweight at diagnosis exhibited BMI patterns that were relatively stable; and patients who were classified as obese exhibited a very slight decline over time. These findings suggest that the risk for chemotherapy‐related weight gain applies predominantly to children who begin ALL therapy within a normal weight range. Cancer 2005. © 2005 American Cancer Society.

The ability of tumor cells to induce platelet aggregation has been correlated with their capacities to colonize the lungs of experimental animals. We tested this hypothesis by studying the ability of cloned, low-passage metastatic tumor cell lines derived from rat 13762NF mammary adenocarcinoma to aggregate rat platelets in vitro and in vivo, and we then compared this activity to metastatic potential by determining the incidence of lung metastasis after subcutaneous or intravenous inoculation of the tumor cell clones into syngeneic rats. Our results failed to show a correlation between in vitro platelet-aggregating activity and metastatic potential. In this system we could not detect platelet-aggregation activity with the most metastatic tumor clone, while least metastatic clone clearly possessed high platelet-aggregating activity. In addition, by measuring changes in blood platelet and fibrinogen concentrations at various intervals following intravenous injection of tumor cell clones, we were able to confirm in vivo the observed in vitro differences in their platelet-aggregating activities. Thus, platelet aggregating activity is heterogeneously expressed among 13762NF cell clones and appears unrelated to spontaneous or experimental metastasis in this tumor system.