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.

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.

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.

Genotype and immunophenotype can be used to define biological species of acute lymphoblastic leukemia (ALL). The purpose of these two pilot studies, conducted between 1986 and 1994, was to explore the feasibility and acceptability of classifying ALL in this manner for selection of treatment rather than using conventional risk for failure factors such as age and initial white blood cell count. The possibility that conventional risk factors would be overcome and survival improved by this approach was also considered. Flow cytometry and chromosome analysis were used to classify the ALL of 150 children into one of five biologic categories as defined by cell surface antigens, DNA index and chromosome number and arrangement. Chemotherapy regimens depended on the assigned category. There was no provision for cranial irradiation and use of alkylating agents, anthracyclines and epipodophyllotoxins was restricted in order to reduce risk of late adverse sequelae. All patients are included in the analysis regardless of presenting condition or adherence to protocol. The majority of patients were Mexican-American or African-American. Eight-year event-free survival (EFS) is 60.7% (±4%) and 8-year overall survival (OAS) 72.6% (±3.7%). EFS and OAS varied significantly among the biologic categories despite differences in chemotherapy regimens. When the patients with B-precursor ALL were retrospectively classified by current Pediatric Oncology Group (POG) criteria, 8-year EFS was 82% (±7.3%) for the good risk group, 68.9% (±5.9%) for the standard risk and 48.8% (±7.6%) for the poor risk, all significant differences. However, when retrospectively classified according to the Rome/NCI prognostic criteria the 8-year EFS for standard risk patients was 69.1% (±5.1%) and for high risk 58.8% (±6.9%), not a statistically significant difference. Numbers of T cell and B cell patients are too few for comparison. Gender and ethnicity influenced survival as in treatment based on prognostic factors. Initial central nervous system (CNS) relapse occurred in five patients (3%) and combined CNS and hematological relapse in six (3%). Factors significantly associated with CNS and combined relapse were leukemic pleocytosis in the initial CSF sample, pro-B immunophenotype and DNA index Ͻ1.16, but not initial white blood cell count. Only three survivors appear to have serious late adverse sequelae, the only neurologic the result of asparaginase-induced cortical vein thrombosis. The results suggest that use of biologic species as defined by immunophenotype and genotype to select therapy of ALL is feasible and acceptable but under the conditions of these studies offered no apparent therapeutic advantage over conventional risk grouping. However, the introduction of molecular genotyping and novel gene targeted therapeutic agents justify further exploration of this approach. Leukemia (2000) 14, 1354-1361.

Satellite association (SA) in lymphocytes obtained from women was found in 89.9% of cells after 48 h in culture and in 66.1% of cells after 96 h. After 48 h, 33.7% of acrocentrics participate in SA, whereas 30.7%, and 17.7% participate after 72 and 96 h. Prophase through prometaphase nucleoli were found in 26.8% of cells after 48 h and in 13.1% of cells after 96 h. SA and mitotic nucleoli are most common in 48 h cultures, and both decrease with increasing in vitro duration. These findings suggest a relationship between nucleolar persistence and SA.

Two children with primary intracranial mixed germ cell tumors are described who were successfully treated by partial resection of the tumor followed by sequential combination chemotherapy without radiation therapy. The chemotherapy consisting of VP-16 and cisplatin alternating with vincristine, methotrexate, and bleomycin resulted in apparent complete response after 6 to 7 months of treatment. Disease-free remission has continued 30-34 months off therapy. A small residual mass in one patient continues to decrease in size on magnetic resonance imaging and is presumed to represent postsurgical change rather than malignant tumor. This report demonstrates that chemotherapy may be effective in primary germ cell tumors of the suprasellar and pineal regions and could be considered for primary treatment instead of radiotherapy.

BACKGROUND The objective of the current study was to compare chemotherapy dose modifications in obese (a body mass index [BMI] > 95%) and nonobese (a BMI ≤ 95%) pediatric patients with acute lymphoblastic leukemia (ALL). METHODS The study cohort was comprised of 199 pediatric patients diagnosed with ALL who were treated at 1 of 2 South Texas pediatric oncology centers between 1990–2000. The relative chemotherapy dose modification during the induction phase of chemotherapy was calculated as the ratio of 1) the actual administered dose of L‐asparaginase and 2) the protocol‐calculated dose of L‐asparaginase. The extent to which the chemotherapy dose modification varied according to obesity status was assessed using stratified Student t tests and an ordinary least‐squares regression analysis. RESULTS Obese ALL patients were found to exhibit a 7% decrease in the mean relative modification of L‐asparaginase during induction chemotherapy compared with their nonobese counterparts. This finding was statistically significant (P = 0.009), even after adjustment for gender, age, ethnicity, and clinical institution. CONCLUSIONS To the authors' knowledge, the current study is the first published report of an obesity‐associated chemotherapy dose modification in pediatric patients with ALL, the most common childhood malignancy. It will be important to examine whether these findings are consistent with those observed in future studies, and ultimately to assess the association between obesity‐related dose modifications and long‐term cancer outcomes. Cancer 2005. © 2005 American Cancer Society.