Giampaolo Arcamone

Improved Survival of Children With Neuroblastoma Between 1979 and 2005: A Report of the Italian Neuroblastoma Registry

PURPOSE To describe treatment, clinical course, and survival of a cohort of Italian patients with neuroblastoma. PATIENTS AND METHODS The study includes data from 2,216 children (age 0 to 14 years) diagnosed between 1979 and 2005. Overall survival (OS) was analyzed by clinical and biologic features at presentation and periods of diagnosis: 1979 to 1984, 1985 to 1991, 1992 to 1998, and 1999 to 2005. The relative risk of second malignant neoplasm (SMN) was assessed by the standardized incidence ratio (SIR), with the Italian population selected as referent. RESULTS Yearly patient accrual increased over time from 58 to 102. Patients age 0 to 17 months represented 45.6% of the total population, and their incidence increased over time from 36.5% to 48.5%. The incidence of stage 1 patients increased over time from 5.8% to 23.2%. A total of 898 patients (40.5%) developed disease progression or relapse, 19 patients developed SMN, and two patients developed myelodysplasia. The cumulative risk of SMN at 20 years was 7.1%, for an SIR of 8.4 (95% CI, 5.1 to 13.2). A total of 858 patients (39%) died (779 of disease, 71 of toxicity, six of SMN, and two of tumor-unrelated surgical complications). Ten-year OS was 55.3% (95% CI, 53.0% to 57.6%) and increased over time from 34.9% to 65.0%; it was significantly better for females and patients age 0 to 17 months at diagnosis, with extra-abdominal primary, and stage 1 and 2 disease. OS improved significantly over time in stage 1 and 3 patients. In patients with stage 4 disease, the improvement occurred between the first and second time cohorts (6.7% v 23.5%), but not afterward. CONCLUSION The outcome of children with neuroblastoma has progressively improved. Long-term survivors bear a significant risk of SMN.

Long-term results of AIEOP LNH-92 protocol for the treatment of pediatric lymphoblastic lymphoma: A report of the Italian association of pediatric hematology and oncology

Lymphoblastic lymphoma (LBL) is the second most frequent lymphoma subtype in childhood. It is commonly treated according to therapy strategies for lymphoblastic leukemia.

THROMBIN GENERATION IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA: Effect of Leukemia Immunophenotypic Subgroups

Elevated plasma concentrations of endogenous thrombin generation markers and thrombotic events have been reported in children with leukemia. The aim of this study was to evaluate the effects of cancer and its treatment on thrombin generation (TAT levels) in children with acute lymphoblastic leukemia (ALL). The authors evaluated 32 children (23 M, 9 F) aged between 1 and 15 years (mean 6) affected by ALL (immunophenotypic subgroups: 16 common, 7 T, and 9 pre-B type). In all patients TAT levels at onset and after 5-6 doses of L-asparaginase were evaluated. TAT levels were higher in patients both at onset (13.04 +/- 10.90 ng/L) and after the 5-6 doses of L-asp (19.41 +/- 11.05 ng/L) with respect to controls (4 +/- 1 ng/L) (p < .001 and p < .001). TAT levels after 5-6 doses of L-asp were higher than those at onset (p < .001). Factorial ANOVA showed that at onset there was a significant effect of leukemia immunophenotypic subgroups upon TAT levels (p < .05) and no effect of inherited thrombotic risk factors. These results indicate that in children with ALL an important role is played by acquired thrombotic risk factors, among which the indirect cancer procoagulant activity has its importance.

Hepatic non-Hodgkin lymphoma and hepatoblastoma complicating ataxia-telangiectasia.

Patients with ataxia-telangiectasia (A-T) have an increased risk of developing malignancies and are prone to severe early or late toxicity owing to chemotherapy. Leukemia and lymphoma account for about 85% of malignancies, but solid tumors have also been reported. We describe an unusual case of an 8-year-old child affected by A-T, who presented a primary hepatic B-cell non-Hodgkin lymphoma, treated with reduced doses of R-CHOP cycles plus rituximab. Three years later, the patient developed hepatoblastoma as a second malignancy. This case clearly emphasizes the need for intensive monitoring of A-T patients for early signs of malignancy and the opportunity to consider specific and modified regimens of chemotherapy.

No effect of irinotecan in patients with resistant desmoplastic small round cell tumor

In 2002 we opened a multicenter phase II trial to test irinotecan (CPT-11) on children with resistant soft tissue sarcoma surgically unresectable and refractory to or relapsing after one or more chemotherapy regimens [3]. We then continued to administer CPT11 for selected histiological subtypes such DSRCT, using a dosage of 20 mg/m/day in a 1-hr infusion for five consecutive days, followed by a 2-day rest then another 5-day treatment; the interval between cycles was 4 weeks. Tumor response was assessed after two courses according to standard response criteria. Eight patients (3.8–17.1 years old, median 10.5) were treated (Table I). At diagnosis, six had intraabdominal/pelvic masses and two had mediastinal lesions. Six had regional spread (lymph node 6, ascites 3, serosal implants 2) and four had distant lesions. At the time

Coagulation Contact Phase Factors and Inhibitors in β-Thalassemia Major Children

Selected hemostatic parameters of 23 children affected by β-thalassemia major were studied and compared to an age- and sex-matched group. Plasma prekallikrein level was reduced in all patients, splenectomized or not. In splenectomized patients, platelet count and in vitro platelet aggregability were significantly increased and Protein C was slightly increased. The activated partial thromboplastin time was prolonged and the normotest reduced. Finally, a reduction in the plasma levels of fibrinogen and of vitamin K-dependent proteins, including the antithrom-botic Protein C, was observed in nonsplenectomized patients. Our data indicate that the hemostatic system in patients with thalassemia major may be altered. The relationship between these laboratory changes and clinical manifestations remains to be established.

Hepatic Veno-Occlusive Disease during chemotherapy for nephroblastoma: successful and safe treatment with defibrotide. Report of a clinical case

Here we report a case of administration of defibrotide in an 11 months old infant with hepatic veno-occlusive disease during chemotherapy for nephroblastoma. He presented with abdominal distension, a weight gain of 15%, ascites, hepatomegaly with right upper quadrant pain, thrombocytopenia and hypertransaminasemia. Despite therapy, his clinical conditions aggravated, and, therefore intravenous administration of defibrotide on a compassionate-use basis was started. The dosage was 15 mg/kg/day in 4 divided doses, which was increased gradually (in 3 days) to 40 mg/kg/day in 4 divided doses. Defibrotide proved safe and effective in resolving clinical symptoms and normalizing serological findings in the syndrome.

Successful treatment with Protein C of febrile neutropenia in pediatric patients during cancer therapy

Febrile Neutropenia (FN) is a complication of chemotherapy in childhood cancer and at the same time secondary deficit of Protein C (PC) is often present during sepsis in children with cancer. In this study we have compared the clinical outcome of two different groups. At the onset of FN during chemotherapy the first group (patients with a secondary deficit of PC) received Protein C Concentrate (PCC) replacement while the other group without PC deficiency received only symptomatic therapies. We report that PC replacement could shorten duration of FN and improve the clinical outcome. The administration of PCC was safe and without any complications.

Non activated protein C supplementation in septic pediatric hematological patients

The purpose of the study was to examine safety and efficacy of non-activated Protein C (PC) supplementation in our cohort of septic pediatric hematological patients. We conducted a retrospective study of 22 septic patients receiving human plasma-derived PC concentrate from 2008 to 2015 at our Pediatric Oncology Center (Bari, Italy). The Surviving sepsis campaign definitions for sepsis, severe sepsis and septic shock were used to define the patients’ septic status. For each patient, we calculated Lansky performance status scale (LPSS) and a risk score defined the Hematologic risk score (HRS) that we created in 2007. Patients were defined as High risk for severe sepsis/septic shock in case of HRS>3. HRS<3 identified low risk patients. Baseline serum PC levels, PC administration dosage and duration and days until a 20% improvement in LPSS. Observed baseline serum PC levels (bPC) blood concentrations ranged from 31 to 80%. Patients received PC supplementation in case of low age-related bPC levels or >10% PC concentration decrease within 12 hours from the first evaluation. All patients received 80 U/kg/day PC, intravenously, every twenty-four hours. No drug-related adverse event was observed. The observed sepsis-related mortality rate in our cohort was 9%. PC supplementation in our cohort appeared to be safe, and, probably due to prompt PC administration, we observed an overall mortality that was much lower than expected mortality in cancer severe septic patients.

Necrotizing fasciitis of the lower limbs.

We report an uncommon severe soft-tissue infection of the thighs in a male child with acute lymphoblastic leukemia. Early and aggressive medical treatment and the conservative surgical approach were successful. Necrotizing fasciitis should be suspected in any soft-tissue infection until it can be definitely ruled out, since prompt deliver of medical and surgical intervention is essential.