Congenital rhabdomyosarcoma: A report from the European paediatric Soft tissue sarcoma Study Group.

PROCEDURE: Congenital rhabdomyosarcoma (RMS) represents a challenging disease due to its characteristics and the difficulties in delivering treatment in this immature population. METHODS: We analyzed treatment and outcome of patients with congenital RMS, defined as tumor diagnosed in the first 2 months of life, enrolled in the European paediatric Soft tissue sarcoma Study Group protocols. RESULTS: Twenty-four patients with congenital RMS were registered. All, except one patient (PAX3-FOXO1-positive metastatic RMS), had favorable histology and localized disease. Three patients had VGLL2-CITED2/NCOA2 fusion. Complete tumor resection was achieved in 10 patients. No radiotherapy was given. Chemotherapy doses were adjusted to age and weight. Only two patients required further dose reduction for toxicity. The 5-year event-free survival (EFS) and overall survival (OS) were 75.0% (95% confidence interval [CI] 52.6-87.9) and 87.3% (95% CI 65.6-95.7), respectively. Progressive disease was the main cause of treatment failure. CONCLUSION: Patients with congenital RMS presented with a favorable disease, allowing weight- and age-adjusted doses of chemotherapy and avoidance of irradiation, without compromising the outcome.

The EpSSG NRSTS 2005 treatment protocol for desmoid-type fibromatosis in children: an international prospective case series.

BACKGROUND: In 2005, the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) proposed a conservative treatment algorithm-consisting of an initial wait-and-see strategy, non-mutilating surgery, and minimal-morbidity chemotherapy (in the case of tumour progression)-for paediatric patients with desmoid-type fibromatosis. We aimed to investigate the outcomes of this algorithm. METHODS: In this case series, patients (<25 years) with desmoid-type fibromatosis from 57 centres in eight countries were prospectively registered through a web-based system. Diagnosis was based on histological analysis of the tumour specimen after biopsy or surgery, and we classified patients by tumour site, clinical stage (TNM system), and post-surgical stage (Intergroup Rhabdomyosarcoma Study system). Progression-free survival was defined as the time from diagnosis until disease progression (clinical or radiological progressive disease, relapse, or death from any cause). FINDINGS: From Oct 1, 2005, to July 31, 2016, 173 patients (median age 11·4 years [IQR 4·0-14·1], 88 [51%] male patients) were registered. After excluding patients with missing data, 54 (35%) patients had no immediate therapy (wait-and-see strategy), 47 (31%) had immediate surgery, and 53 (34%) had immediate chemotherapy after diagnosis. 5-year progression-free survival was 36·5% (95% CI 27·8-45·2) overall, 26·7% (14·2-41·0) in the wait-and-see group, 41·2% (25·8-55·9) in the surgery group, and 42·8% (27·2-57·6) in the chemotherapy group (overall log-rank p=0·17; wait-and-see vs surgery p=0·12; wait-and-see vs chemotherapy p=0·13). In multivariable analysis, large tumour size (>5 cm) was associated with worse progression-free survival (hazard ratio 2·25, 95% CI 1·34-3·76; p=0·0021). Apart from one patient in the chemotherapy group who died from a secondary tumour (head and neck anaplastic embryonal rhabdomyosarcoma), all patients were alive at the time of analysis. 13 (8%) patients had biopsy only (no further treatment), 65 (42%) had chemotherapy only, 31 (20%) had surgery only, 36 (23%) had both chemotherapy and surgery, and nine (6%) had radiotherapy in addition to other therapies. INTERPRETATION: In paediatric patients with desmoid-type fibromatosis, the EpSSG conservative strategy did not compromise outcomes and could be adopted to reduce treatment burden. FUNDING: S Wisnia and la Città della Speranza Foundation.

Burkitt lymphoma in children: the Israeli experience.

BACKGROUND: We analyzed the results of the French-American-British-LMB 96 protocol performed in 9 centers in Israel on 88 patients with B-cell non-Hodgkin lymphoma treated from 2000 to 2005. PROCEDURE: The majority of the patients was male (63/88, 72%), with a median age of 8.9 years (range, 2.5 to 20 y). Ethnic origin was Jewish in 73% (64/88), and Arabic in 27%. Fifty (57%) patients were classified as Burkitt lymphoma, 5 (5.7%) as Burkitt-like lymphoma, 22 (25%) as diffuse large B cell (DLBC), and 9 (10.2%) as Burkitt leukemia with over 25% of their bone marrow (BM) involved. Initial disease sites included the abdomen in 43%, head and neck in 45%, and mediastinum in 7%. Stage I: 9.1%; stage II: 28.4%; stage III: 45.5%, stage IV: 17%. Two patients had BM involvement alone, 5 patients had central nervous system (CNS) involvement alone, and 4 had both CNS and BM. The children were divided into 3 groups according to risk factors, with 5 in group A, 69 in group B, and 14 in group C. RESULTS: With a median follow-up of 3 years (12 mo to 7.6 y), the Kaplan-Meier for event-free survival (EFS) and overall survival (OS) according to whole group treatment was 88.6% and 90.9%, group A was 100% and 100%; group B was 89.9% and 92.8%; and group C was 78.6% and 78.6%. There were no untoward events or deaths in group A, whereas 6 patients relapsed in group B, 4 of whom died (all relapsed during the first year), with tumor lysis syndrome in 3 patients and death of toxicity in 1 patient who had multiorgan failure 2 days after initiation of COP. Three patients in group C relapsed and died (all patients relapsed during the first 6 months), with tumor lysis syndrome in 4 patients but no deaths from toxicity. EFS for LDH less than twice was 96.4%, EFS for LDH more than twice was 73.3% (P=0.002). OS according to primary site: bone and ovary: 100%; head and neck: 95%; abdomen: 92%; mediastinum: 50%. The difference between the mediastinal primary site to all other primary sites was statistically significant with P=0.003. All the mediastinal tumors were of DLBC origin but no significant differences in outcome were found when DLBC was compared with other histologies (DLBC: 81.8%, other B line: 90.9%). OS for patients of Arabic ethnic origin was 79.2%, for Jewish patients was 95.3%, P=0.02. We could not determine any prognostic factors that were different between the groups, which raises the question of a genetic influence. CONCLUSIONS: In nonresected mature B-cell lymphoma of childhood and adolescence with no BM or CNS involvement, a 93% cure rate can be achieved, similar to the French-American-British/LMB 96 trial. Patients with primary DLBC mediastinal mass had a significantly reduced OS, indicating the need for a different therapeutic approach.

Safe and efficacious allogeneic bone marrow transplantation for nonmalignant disorders using partial T cell depletion and no posttransplantation graft-versus-host-disease prophylaxis.

In an attempt to abrogate the deleterious effects of graft-versus-host disease (GVHD), allogeneic transplantation for nonmalignant diseases was performed using high-dose CD34-cell infusion, partial T cell depletion, and no posttransplantation GVHD prophylaxis. Between 1998 and 2004, 16 patients with matched related donors were treated. Median age was 1.5 years (range, 5 months-18 years). The conditioning regimen consisted of busulphan 16 mg/kg, cyclophosphamide 200 mg/kg, antithymocyte globulin (ATG) 25 mg/kg, and fludarabine 200 mg/m(2). No GVHD prophylaxis was given. High doses of CD34 cells, positively selected by immunomagnetic beads, were infused at a median dose of 10.7 x 10(6) CD34/kg (range, 7.4-50 x 10(6)). A total of 1 x 10(5)/kg T cells were given. All patients engrafted, with no graft rejections. All were alive and well at a median of 37 months posttransplantation (range, 18-89 months). Only 1 patient developed chronic GVHD. No episodes of severe infection occurred during or after transplantation. Immunologic reconstitution with CD3/CD4 T cells > 200/microL was observed at a median of 117 days and that with naive T cells (CD4/CD45RA) at a median of 188 days posttransplantation. Our findings suggest that allogeneic transplantation from a matched family donor for nonmalignant disorders can be successfully performed using high doses of CD34 cells, moderate T cell depletion, and no posttransplantation immunosuppression.