Maria Debora De Pasquale

Salivary gland carcinomas in children and adolescents: The Italian TREP project experience

Salivary gland carcinomas are extremely rare in pediatric age. We report the clinical features of a series of children/adolescents with salivary gland carcinomas prospectively registered in the Italian TREP (Rare Tumors in Pediatric Age) project.

Gefitinib in combination with oral topotecan and cyclophosphamide in relapsed neuroblastoma: Pharmacological rationale and clinical response†

Activity and toxiciy of gefitinib in combination with topotecan and cyclophosphamide (CPA) were evaluated in a case‐series of relapsed neuroblastoma (NB) patients. The in vitro activity of the combination was also assessed.

Mature and immature teratoma: A report from the second Italian pediatric study.

Teratomas demonstrate a benign clinical behavior, however they may recur with malignant components or as teratoma, and in a small group of patients prognosis could be fatal. After the first Italian study, we collected cases of teratoma, alongside the protocol for malignant germ cell tumors.

Unmanipulated Donor Lymphocytes for EBV-Related PTLD After T-Cell Depleted HLA-Haploidentical Transplantation

Epstein-Barr virus (EBV)–related post-transplantation lymphoproliferative disorder (PTLD) is a life-threatening complication in patients given T-cell-depleted hematopoietic stem cell transplantation from an HLA-haploidentical relative (haplo-HSCT). We report the case of a child who developed severe EBV-related PTLD after haplo-HSCT from his mother. Despite receiving the anti-CD20 monoclonal antibody, the patient presented with intestinal obstruction due to huge abdominal lymphadenopathy, hematemesis, and nodulary pulmonary lesions. Histology showed that the lesions were due to CD20−/CD19+ large neoplastic B cells. The patient underwent double intestinal resection with partial abdominal lymphadenectomy and then received 3 monthly doses of donor-derived unmanipulated mononuclear cells. The initial dose of CD3+ cells was 3 × 105/kg recipient body weight. The 2 additional doses consisted of 5 × 105 CD3+ cells/kg. No sign or symptom attributable to graft-versus-host disease was observed, and the patient completely cleared EBV-related lesions. The child was disease-free for 13 months after the first lymphocyte infusion. This case demonstrates that repeated infusions of controlled numbers of donor CD3+ cells cure EBV-related PTLD in haplo-HSCT without inducing graft-versus-host disease.

Short topotecan-based induction regimen in newly diagnosed high-risk neuroblastoma

PURPOSE Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma. METHODS Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6mg/m(2) and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria. RESULTS Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55% after two HD-TPT/HD-CPM courses and 80% after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85%) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41%) and bone marrow was in complete remission in 16/24 patients (67%). Grade 4 neutropenia and/or thrombocytopenia occurred in 100% of HD-TPT/HD-CPM and in 95% of ICE courses, while non-haematological toxicities were manageable. CONCLUSIONS These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85% with 41% complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma.

Mediastinal Germ Cell Tumors in Pediatric Patients: A Report From the Italian Association of Pediatric Hematology and Oncology.

Primary mediastinal germ cell tumors (GCTs) are rare in children and still represent a challenge for both adult and pediatric oncologists because of their worse outcome compared to their gonadal counterpart.

Metastatic renal cell carcinoma in children and adolescents: a 30-year unsuccessful story.

Background: Because of the rare occurrence of renal cell carcinoma (RCC) among children very little is known about this malignancy in pediatric age. We aimed adding knowledge on the clinical characteristics and outcome of metastatic (m) RCC in children and adolescents. Patients and Methods: The series included 14 stage 4 RCC patients with a median age at diagnosis of 155.5 months, observed at the Italian Pediatric Hematology and Oncology Association (AIEOP) centers from January 1973 to November 2010. We were able to reevaluate histopatology of 11 out of the 14 patients and perform immunostaining for TFE3 in 9 out of the 11 patients. Results: Of the 14 patients under study, 5 (3 girls) had a translocation morphology TFE+ RCC, 2 were reassigned as papillary type 1 or 2, respectively, 2 tumor specimens with primary clear cell histology had confirmed the initial histologic diagnosis, and 2—whose biopsy specimen was insufficient—had the diagnosis of RCC not further specified with subtyping. In the remaining 3 cases, the initial diagnosis of clear cell carcinoma was left. Overall, 6 patients received chemotherapy, 9 immunotherapy, and 2 adjuvant antiangiogenic therapy. Overall, 11 patients (78.5%) never achieved complete remission and died from progressive disease 1 to 16 months after diagnosis (median overall survival 5.5 mo). Three patients, 2 of whom received adjuvant antiangiogenic therapy, relapsed to lung at 3, 6, and 8 months after diagnosis, and died 18, 32, and 33 months after diagnosis, respectively. Conclusions: Despite their possibly different biology, childhood and adult mRCC seems to be sharing comparable outcomes. Because of the very low incidence of mRCC (about 20%) in children and adolescents, an international pediatric cooperation to address biological studies and assess the novel targeted approaches is needed.

Recurrent metanephric stromal tumor in an infant.

A 9-month-old boy underwent nephrectomy for a renal mass. Congenital mesoblastic nephroma was diagnosed, and the patient received postoperative chemotherapy. Tumor recurred 6 months later as a scrotal mass. After orchiectomy, diagnosis of metanephric stromal tumor (MST) was made; review of the nephrectomy specimens confirmed this diagnosis. No additional treatment was given, and the child is alive and well 31 months later. Taking into account the histopathological entity of MST in the differential diagnosis of stromal renal tumors in childhood can spare the patient further, potentially toxic, treatment even in the case of relapse, as reported here for the first time.

A survey on hematology-oncology pediatric AIEOP centres: The challenge of posterior reversible encephalopathy syndrome

Posterior reversible encephalopathy syndrome (PRES) is one of the most common neurological complications in hematology‐oncology pediatric patients. Despite an increasingly recognized occurrence, no clear consensus exists regarding how best to manage the syndrome, because most cases of PRES have reported in single‐case reports or small series. Aim of this paper is to identify incidence, clinical features, management, and outcome of PRES in a large series of hematology‐oncology pediatric patients.

Outcome after surgery for solid pseudopapillary pancreatic tumors in children: Report from the TREP project-Italian Rare Tumors Study Group

Solid pseudopapillary pancreatic tumors (SPPT) are an extremely rare entity in pediatric patients. Even if the role of radical surgical resection as primary treatment is well established, data about follow‐up after pancreatic resection in children are scant.