[Indwelling central venous catheters after discontinuation of therapy and risk of infection in children with cancer]. / Permanenza del catetere venoso centrale dopo la sospensione della terapia e rischio infettivo in bambini affetti da neoplasia.

In this retrospective study we report the incidence of CVC-related infections in a pediatric oncology population during the off therapy period. We analysed 128 children with oncologic diseases (solid tumors and leukemia), 78 boys and 50 girls, aged 1 to 21 years, who maintained the CVC in situ at least 6 months after the cessation of chemotherapeutic protocols. Seventy-eight patients had a single lumen Broviac-Hickman CVC, 8 patients had a double lumen Broviac-Hickman and 42 a implantable port device. The permanence of CVC in situ after discontinuation of treatment varied between 6 and 24 months. CVC was removed in 5 patients that presented a CVC-related infection, respectively 6, 6, 6, 7 and 10 months from discontinuation of therapy, in 85 patients because was considered no more necessary. 38 patients are still with CVC in situ; in this group 11 patients relapsed more than 6 months after discontinuation of the therapy and were analysed until the time of relapsed. The result of our study show that the incidence of CVC related infections in patients off therapy is very low. Considering the discomfort that frequent blood withdrawals cause to children and the relapse risk, we think that CVC may be maintained in situ more than 6 months after discontinuation of the therapy without risks for the patients.

[Prognostic factors in neuroblastoma. Usefulness of DNA analysis using flow cytometry on paraffin-embedded material]. / Fattori prognostici nel neuroblastoma. Utilità dell'analisi del DNA mediante citometria a flusso su materiale incluso in paraffina.

Nuclear DNA content was determined on paraffin blocks of 28 neuroblastic tumors retrieved from Surgical Pathology files. In 26 cases cytofluorimetric analysis for DNA content was satisfactory. 8 tumor were diploid, 12 were aneuploid and 6 tetraploid. All but one of the children with diploid neuroblastoma (NB) died after a survival ranging from 14 to 32 months. The only surviving child had a Stage I thoracic ganglioneuroblastoma (GNB) and was alive after 27 months. Conversely 11 of 12 patients with aneuploid tumors were alive with prolonged follow-up. Two children are alive after a period exceeding 146 months. The only exception in this group of aneuploid tumors was a child with Stage IV neuroblastoma of the adrenal gland with pleuro pulmonary metastasis who died after 6 months. In the group with tetraploid tumors 3 patients died (2 children with Stage III and IV died early while the third, with thoracic Stage II GNB, survived for 72 months). Two patients with tetraploid GNB Stage II and III are alive 65 and 72 months after diagnosis respectively. Another child with Stage IV adrenal NB is alive after 14 months but with metastatic spread to bones, bone marrow and lymph nodes. Cox analysis of the cases demonstrated ploidy as an independent prognostic factor. These results are in agreement with other molecular analysis linking near-ploidy of Neuroblastic tumors to poor prognosis. Ploidy, as detected by flow cytometry for nuclear DNA content, may represent an important prognostic factor in Neuroblastic tumors. The advantage of flow cytometry over other techniques of molecular analysis is represented by the simple methodology suitable for fixed and paraffin embedded tissue, even on retrieval material.

[Treatment of metastatic osteosarcoma with verapamil, cyclosporine and chemotherapy. A case report]. / Trattamento dell'osteosarcoma metastatico con verapamile, ciclosporina e chemioterapia. Descrizione di un caso clinico.

Studies on the use of revertants to overcome MDR have aroused a great interest even if they failed to prove their actual usefulness. A case of 10 years and 6 months old boy is described. He suffered from osteoblastic osteosarcoma and underwent chemotherapy following CNR-NEO3 protocol, wide surgical resection and postoperative chemotherapy. Nineteen months after diagnosis he underwent the removal of a little subpleural nodule in the right lung. Forty-five days later, in the same site, a large local metastasis was observed together with many others secondaries localizations spred in both lungs. Because of the rapid evolution they were considered not suitable for surgical treatment. A cyclosporine and verapamil treatment in association with adryamicin and etoposide was begun with the aim overcoming multidrug resistance. Five treatments were provided. ECG monitoring during verapamil infusion did not show any trouble; mielotoxicity was mild, with no need of transfusions. A lung CT scan at the end of the therapy demonstrated an important decrease of the subpleural metastasis and the vanishing of lung nodules. Another surgical intervention was provided together with 2 postoperative chemotherapy treatments. Twenty-six months later no sign of the disease was observed. Association of verapamil and cyclosporine with chemotherapy allowed to get a good clinical response with a very low toxicity, in a critical situation in which chemotherapy alone did not seem to offer any real possibility.

[Use of cyclosporin and verapamil in association with chemotherapy in the treatment of pediatric patients with advanced-stage neoplasms. A pilot study]. / Impiego della ciclosporina e del verapamile in associazione a chemioterapici nel trattamento di pazienti pediatrici con neoplasia in fase avanzata. Studio pilota.

Multidrug resistance represents one of the most important factors that may lead to a therapeutic failure in some patients affected by malignancies. One of the best known mechanisms is linked to the genic amplification or the overproduction of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine, quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro is well known. We studied 20 pediatric patients (median age 9 years) affected by acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and medulloblastoma, in advanced stage of disease. We employed in all cases the association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5-8 mg/kg i.v.) with different infusion schedules. In leukemias we administered vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150 mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed: 39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On the whole 5 complete remissions were achieved in ALL patients and 1 in an osteosarcoma patient. We did not observe a significant myelosuppression during treatment, therefore few infectious complications occurred; furthermore electrocardiographic changes have been mild and promptly resolved after temporary discontinuation of verapamil infusion. Our data suggest a synergy of verapamil and cyclosporine in the inhibition of multidrug resistance induced by gp170, without the occurrence of heavy toxicity. The results obtained in ALL patients are encouraging., especially in view of a possible subsequent bone marrow transplantation, while in solid tumors they are not as satisfying.

[Pulmonary complications after bone marrow transplantation]. / Complicanze polmonari dopo trapianto di midollo osseo.

Pulmonary toxicity occurs in approximately 10 to 50% of patients undergoing bone marrow transplantation (BMT). Bacterial pneumonia very commonly affects patients within the first 6 months post-BMT. Etiologic factors include neutropenia and the presence of graft-versus-host disease (GVHD). Pulmonary fungal infections, due to candida and aspergillus, may develop in 16% of patients receiving BMT, with a high mortality rate, being about 80%. A prolonged neutropenia as well as GVHD and associated immunosuppressive treatments are important factors in predisposing a patient to develop fungal pneumonitis. Interstitial pneumonitis occurs in 10-40% of patients; herpes viruses are the most commonly documented cause, with cytomegalovirus (CMV) being the most common pathogen. No causative organism is identified in up to 60% of the cases. It is likely that some of these cases may result from drug or radiation toxicity. Lung shielding and fractionation of the dose have decreased the incidence of interstitial pneumonitis to less than 5%. Patients with GVHD are predisposed to lung infections because of the immunosuppression that accompanies GVHD and its treatment. In addition, GVHD itself appears to have a direct effect on pulmonary epithelium. Cultural and serologic studies as well as radiographic investigations and other diagnostic procedures (ie bronchoalveolar lavage) are needed for appropriate management of pulmonary complications.