Purpose: Pediatric oncology patients undergoing active chemotherapy are suspected to be at a high risk for severe disease secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection; however, data to support this are lacking. We aim to describe the characteristics of coronavirus disease 2019 (COVID-19) in this population and also its impact on pediatric cancer care in the New York region during the peak of the pandemic.
Treatment with dose-adjusted EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone) chemotherapy and rituximab (DA-EPOCH-R) has become the standard of care for primary mediastinal B-cell lymphoma (PMBCL) at many institutions despite limited data in the multi-centre setting. We report a large, multi-centre retrospective analysis of children and adults with PMBCL treated with DA-EPOCH-R to characterize outcomes and evaluate prognostic factors. We assessed 156 patients with PMBCL treated with DA-EPOCH-R across 24 academic centres, including 38 children and 118 adults. All patients received at least one cycle of DA-EPOCH-R. Radiation therapy was administered in 14·9% of patients. With median follow-up of 22·6 months, the estimated 3-year event-free survival (EFS) was 85·9% [95% confidence interval (CI) 80·3-91·5] and overall survival was 95·4% (95% CI 91·8-99·0). Outcomes were not statistically different between paediatric and adult patients. Thrombotic complications were reported in 28·2% of patients and were more common in paediatric patients (45·9% vs. 22·9%, P = 0·011). Seventy-five per cent of patients had a negative fluorodeoxyglucose positron emission tomography (FDG-PET) scan at the completion of DA-EPOCH-R, defined as Deauville score 1-3. Negative FDG-PET at end-of-therapy was associated with improved EFS (95·4% vs. 54·9%, P < 0·001). Our data support the use of DA-EPOCH-R for the treatment of PMBCL in children and adults. Patients with a positive end-of-therapy FDG-PET scan have an inferior outcome.
Some 75% of highly selected pediatric patients with LPHL may be spared chemotherapy after surgical resection alone. Pediatric LPHL has excellent EFS with chemotherapy that is less intensive than standard regimens; > 90% of patients can avoid radiation therapy. The salvage rate for the few relapses is high, with 100% survival overall.
In childhood Hodgkin lymphoma, estimated 5 years survival rates exceed 90%. Long-term survival continues to decline from delayed toxicities. Key findings from recent Children's Oncology Group trials include: (1) Radiotherapy selection may be based on early chemotherapy response assessed by both FDG-PET and CT imaging, (2) A new prognostic factor score stratifies patients into risk categories; and (3) novel retrieval regimens were identified. A phase I/II trial is investigating Brentuximab vedotin (Bv) with gemcitabine in relapsed patients. A phase 3 trial will modify conventional chemotherapy and radiotherapy approaches through the addition of Bv, while incorporating translational biology to identify molecular targets.
The mechanisms by which insulin and glucocorticoids modulate lipoprotein lipase (LPL) synthesis and degradation were examined in human adipose tissue fragments maintained in organ culture. Tissue fragments were cultured for 7 days in serum-free medium supplemented with or without insulin (7 nM) and with or without dexamethasone (30 nM), a synthetic glucocorticoid. Responses of LPL activity to both insulin and dexamethasone were obtained at doses within the physiological range. At a maximal dose, insulin increased heparin-releasable and total LPL activity (approximately 7-fold) by specifically increasing the rate of LPL synthesis (approximately 5-fold) determined by pulse labeling with [35S]methionine and [35S]cysteine and immunoprecipitation. Dexamethasone added in the presence of insulin increased heparin-releasable and total LPL activity approximately 8-fold but did not alter rates of LPL synthesis compared with insulin alone. Pulse-chase studies showed that the rate of LPL degradation was markedly slowed in the presence of dexamethasone plus insulin compared with insulin alone. These data suggest that, in human adipose tissue, insulin is essential for maintaining rates of LPL synthesis and that cortisol may play a key role in regulating human adipose tissue LPL at the posttranslational level by inhibiting the degradation of newly synthesized LPL.
Background
Histologic prognostic factors have been described for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). This study examines histologic and immunophenotypic variants in a clinical trial for pediatric NLPHL.
Procedure
One hundred sixty-eight cases of localized NLPHL were examined for histologic variants, CD30 and immunoglobulin D (IgD) expression, and outcome. Histologic types were scored categorically as 0 = 0, 1 ≤ 25%, and 2 > 25% of the sample.
Results
Fifty-eight (35.1%) cases showed only typical nodular with or without serpiginous histology (types A and B). The remainder showed mixtures of histologies. The numbers of patients with score 2 are 85 (50.6%) type A, 21 (12.5%) type B, 46 (27.4%) with extranodular large B cells (type C), 3 with T-cell-rich nodular pattern (type D), 55 (32.7%) with diffuse T-cell-rich (type E) pattern, and 2 (1.2%) with diffuse B-cell pattern (type F). Higher level of types C (P = 0.048) and D (P = 0.033) resulted in lower event-free survival (EFS). Cytoplasmic IgD was found in 65 of 130 tested (50%), did not significantly associate with EFS but positively correlated with types C and E histology (P < 0.0001) and negatively correlated with types A (P = 0.0003) and B (P = 0.006). Seventeen (10%) expressed CD30, with no adverse effect.
Conclusions
Variant histology is common in pediatric NLPHL, especially types C and E, which are associated with IgD expression. Type C variant histology and possibly type D are associated with decreased EFS, but neither IgD nor CD30 are adverse features. Variant histology may warrant increased surveillance, but did not affect overall survival.
Background
Treatment of pediatric lymphocyte-predominant Hodgkin lymphoma (LPHL) is controversial but has typically consisted of both chemotherapy and radiation. Radiation therapy is associated with potential late effects in children and adolescents. We examined the impact of radiation therapy on long-term outcome of patients with LPHL treated on CCG-5942, a large pediatric cooperative group study of Hodgkin lymphoma.
Procedure
Eighty-two patients with LPHL were registered on CCG-5942. Fifty-two patients (63%) received chemotherapy alone; 29 patients (35%) received chemotherapy followed by involved-field radiation therapy (IFRT).
Results
The median follow-up of the LPHL patients is 7.7 years; 63 patients (77%) have > 5 years of follow-up. The 5-year event-free survival (EFS) and overall survival (OS) were 97% and 100%. Two relapses occurred, both in patients who did not receive IFRT. There were no significant differences in EFS or OS between patients who received or did not receive IFRT.
Conclusions
This subset analysis demonstrates the chemosensitivity of pediatric LPHL. Patients who had a complete response to chemotherapy had an excellent EFS and OS without the addition of radiotherapy.
Diets rich in fat may promote obesity by leading to a greater deposition of adipose-tissue triglycerides than do isoenergetic diets with less fat. This possibility was examined by a retrospective analysis of the energy needs of 16 human subjects (13 adults, 3 children) fed liquid diets of precisely known composition with widely varied fat content, for 15-56 d (33 +/- 2 d, mean +/- SE). Subjects lived in a metabolic ward and received fluid formulas with different fat and carbohydrate content, physical activity was kept constant, and precise data were available on energy intake and daily body weight. Isoenergetic formulas contained various percentages of carbohydrate as cerelose (low, 15%; intermediate, 40% or 45%; high, 75%, 80%, or 85%), a constant 15% of energy as protein (as milk protein), and the balance of energy as fat (as corn oil). Even with extreme changes in the fat-carbohydrate ratio (fat energy varied from 0% to 70% of total intake), there was no detectable evidence of significant variation in energy need as a function of percentage fat intake.
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