Gilchrist, Gerald S.

Three children with plasma cell granuloma of the lung had a syndrome characterized by digital clubbing, roentgenographic evidence of an intrapulmonary lesion with a diverse configuration, elevated erythrocyte sedimentation rate, elevated serum immunoglobulin levels, and thrombocytosis.

PURPOSE: To determine the toxicity and response rate in children treated with dexamethasone, etoposide, cisplatin, high-dose cytarabine, and l-asparaginase (DECAL) for recurrent non-Hodgkin’s lymphoma (NHL) and Hodgkin’s disease (HD). PATIENTS AND METHODS: Ninety-seven children with recurrent NHL (n = 68) or HD (n = 29) were enrolled. Treatment consisted of two cycles of DECAL, then bone marrow transplantation or up to four cycles of ifosfamide, mesna, and etoposide alternating with DECAL maintenance therapy. RESULTS: After two cycles of DECAL induction therapy, complete response (CR) or partial response (PR) was reported in 19 (65.5%; 10 CRs and nine PRs) of 29 patients with HD and 29 (41.6%; 23 CRs and six PRs) of 68 patients with NHL. When only 24 patients with HD and 58 patients with NHL who were assessable for response were considered, the response rates were 79.2% (19 of 24 patients) and 50.0% (29 of 58 patients), respectively. Five-year event-free survival was 26% ± 9% and 23% ± 5% in patients with HD and NHL, respectively. Five-year survival was 31% ± 14% and 30% ± 6%, respectively. Although median time to treatment failure was significantly longer in patients with HD (EFS, P = .002; survival, P = .011), this difference did not translate into a higher long-term survival. Grade 3 or 4 toxic effects were observed during induction in 70 (72%) of 97 patients and during maintenance in 45 (70%) of 64 courses of DECAL therapy. Pancytopenia and systemic infections in particular were frequently observed. Other toxic effects were uncommon. Although not a formal part of the therapy or the study design, 42 patients who responded to therapy who underwent bone marrow transplant did not show any benefit from this approach. CONCLUSION: DECAL is an effective and tolerable salvage regimen for treating patients with recurrent NHL and HD.

Purpose In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007. Patients and Methods Between January 1995 and December 1998, 826 eligible patients were enrolled onto CCG 5942. Four hundred ninety-eight patients achieving an initial complete response to chemotherapy were randomly assigned to receive IFRT or no further therapy. EFS and overall survival (OS) were assessed from the date of study entry or random assignment, as appropriate. Results Ten-year EFS and OS rates for the entire cohort were 83.5% and 92.5%, respectively. In an as-treated analysis for randomly assigned patients, the 10-year EFS and OS rates were 91.2% and 97.1%, respectively, for IFRT and 82.9% and 95.9%, respectively, for no further therapy. For EFS and OS comparisons, P = .004 and P = .50, respectively. Bulk disease, “B” symptoms, and nodular sclerosis histology were risk factors for inferior EFS. Conclusion With a median follow-up of 7.7 years, IFRT produced a statistically significant improvement in EFS but no improvement in OS. For individual patients, the relative risks of relapse versus late effects of IFRT must be considered. Patient and disease characteristics and early response assessment will aid in deciding which patients are most likely to benefit from IFRT.

Policy has not adequately addressed the unique circumstances of pediatric subspecialties, many of which are facing workforce shortages. Pediatric subspecialties, which we define to include all medical and surgical subspecialties, are discrete disciplines that differ significantly from each other and from adult medicine subspecialties. Concerns about a current shortage of pediatric subspecialists overall are driven by indicators ranging from recruitment difficulties to long wait times for appointments. The future supply of pediatric subspecialists and patient access to pediatric subspecialty care will be affected by a number of key factors or forces for change. We discuss 5 of these factors: changing physician and patient demographics; debt load and lifestyle considerations; competition among providers of subspecialty care; equitable reimbursement for subspecialty services; and policy to regulate physician supply. We also identify issues and strategies that medical and specialty societies, pediatric subspecialists, researchers, child advocates, policy makers, and others should consider in the development of subspecialty-specific workforce-policy agendas.

PURPOSE: Current standard therapy for children and adolescents with Hodgkin’s disease includes combination chemotherapy and low-dose involved-field radiation (LD-IFRT). Because radiation may be associated with adverse late effects, the Children’s Cancer Group (CCG) investigated whether radiation could be omitted in patients achieving a complete response to initial chemotherapy without jeopardizing the excellent outcome obtained with combined-modality therapy. PATIENTS AND METHODS: Between January 1995 and December 1998, 829 eligible patients were enrolled onto CCG 5942. A total of 501 patients who achieved an initial complete response after risk-adapted combination chemotherapy were randomized to receive LD-IFRT or no further treatment. Event-free survival (EFS) and overall survival were assessed from the date of study entry or the date of randomization, as appropriate. RESULTS: The projected 3-year EFS from study entry for the entire cohort was 87% ± 1.2%. Among patients who achieved a complete response to initial chemotherapy, 92% ± 1.9% of those randomized to receive LD-IFRT were alive and disease free 3 years after randomization, versus 87% ± 2.2% for patients randomized to receive no further therapy (stratified log-rank test; P = .057). With an “as-treated” analysis, 3-year EFS after randomization for the radiation cohort was 93% ± 1.7% versus 85% ± 2.3% for patients receiving no further therapy (stratified log-rank test; P = .0024). Three-year survival estimates for patients treated with and without LD-IFRT were 98% ± 1.1% for patients who received radiation and 99% ± 0.5% for patients who did not receive radiation. CONCLUSION: LD-IFRT after an initial complete response to risk-adapted chemotherapy improved EFS. At this time, there is no survival advantage for LD-IFRT, but follow-up remains short.