Rossella Mura

Fungal Infections in Children With Cancer A Prospective, Multicenter Surveillance Study

Background: Data on epidemiology and survival after fungal infections in patients with cancer are primarily based on studies in adults, whereas few data are available on children. Methods: A prospective, multicenter, 2-year surveillance of fungal infections in children receiving antineoplastic treatment was performed in 15 Italian centers. For each case, defined by means of EORTC-IFIG/NIAID-MSG, information was collected on age, phase of treatment, presence of neutropenia or lymphocytopenia, administration of antifungal drugs and survival. Results: Ninety-six episodes (42 proven [19 fungemias, 23 deep tissue infections], 17 probable and 37 possible invasive mycoses) were reported. Most of them (73%) followed aggressive chemotherapy, 21% allogeneic hematopoietic stem cell transplantation and only 6% moderately aggressive treatment. Neutropenia was present in 77% of the episodes, and it had a longer duration before deep tissue mycosis as compared with fungemia (P = 0.020). Lymphocytopenia was present in 75% of the episodes observed in nonneutropenic patients. As compared with children with fungemia, patients with probable invasive mycoses had a 25.7-fold increased risk of death, whereas it was 7.7-fold greater in children with possible invasive mycoses and 5-fold higher in those with proven deep tissue infection (P = 0.004). The risk of death was also 3.8-fold higher in patients already receiving antifungals at the time of diagnosis of infection as compared with those not receiving antimycotic drugs. Conclusions: In children with cancer, aggressive antineoplastic treatment, severe and longlasting neutropenia and lymphocytopenia are associated with fungal infections. These features as the clinical pictures are similar to those reported in adults, but in children, the overall and the infection-specific (fungemia or mycosis with deep tissue infection) mortalities are lower.

Bloodstream infections in children with cancer: a multicentre surveillance study of the Italian Association of Paediatric Haematology and Oncology

A one-year prospective, multicentre surveillance study on aetiology, main clinical features and outcome of bloodstream infections in children with cancer was conducted in 18 paediatric haematology centres belonging to the Italian Association for Paediatric Haematology and Oncology. A total of 191 bloodstream infections were reported during the study period. Of them, 123 (64%) occurred in neutropenic and 68 (36%) in non-neutropenic patients. Gram-positive cocci caused 45% (85/191) of the episodes, gram-negative rods 41% (78/191), and fungi 9% (18/191). The remaining 5% (10/191) of the episodes were poly-microbial infections. A total of 204 pathogens were isolated (46% gram-positive cocci; 44% gram-negative rods; and 10% fungi). The aetiologic distribution was similar among neutropenic and non-neutropenic patients. A correlation between the infection and the presence of an indwelling central venous catheter was found in 20% (23/114) of the episodes among neutropenic patients and in 55% (23/62) among non-neutropenic patients. Gram-negative micro-organisms were isolated in an unusually high proportion of catheter-related infections (48%). The overall mortality rate from any cause within 30 days from the first positive blood culture was 11%, and was higher among patients who were neutropenic at the onset of the infection than among those who were not neutropenic (15 versus 4%, P = 0.03). In addition, the mortality was significantly higher in recipients of bone marrow transplantation than in patients with acute leukaemia or solid tumour (21, 11 and 6%, respectively) and was also higher in fungaemias and poly-microbial infections (22 and 30%) than in single gram-positive and gram-negative bacteraemias (11 and 6%).

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.

Single-day trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis pneumonia in children with cancer.

OBJECTIVE To determine whether a simplified, 1-day/week regimen of trimethoprim/sulfamethoxazole is sufficient to prevent Pneumocystis (jirovecii [carinii]) pneumonia (PCP). Current recommended regimens for prophylaxis against PCP range from daily administration to 3 consecutive days per week dosing. STUDY DESIGN A prospective survey of the regimens adopted for the PCP prophylaxis in all patients treated for childhood cancer at pediatric hematology-oncology centers of the Associazione Italiana Ematologia Oncologia Pediatrica. RESULTS The 20 centers participating in the study reported a total of 2466 patients, including 1093 with solid tumor and 1373 with leukemia/lymphoma (or primary immunodeficiency; n = 2). Of these patients, 1371 (55.6%) received the 3-day/week prophylaxis regimen, 406 (16.5%) received the 2-day/week regimen, and 689 (27.9%), including 439 with leukemia/lymphoma, received the 1-day/week regimen. Overall, only 2 cases of PCP (0.08%) were reported, both in the 2-day/week group. By intention to treat, the cumulative incidence of PCP at 3 years was 0.09% overall (95% CI, 0.00-0.40%) and 0.51% for the 2-day/week group (95% CI, 0.10%-2.00%). Remarkably, both patients who failed had withdrawn from prophylaxis. CONCLUSION A single-day course of prophylaxis with trimethoprim/sulfamethoxazole may be sufficient to prevent PCP in children with cancer undergoing intensive chemotherapy regimens. This simplified strategy might have implications for the emerging need for PCP prophylaxis in other patients subjected to the increased use of biological and nonbiological agents that induce higher levels of immune suppression, such as those with rheumatic diseases.

A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood ‘high-risk’ acute lymphoblastic leukaemia: a study of the AIEOP group

Summary. The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high‐dose idarubicin and high‐dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete remission; eight (8%) died during induction and 11 (11%) failed to respond. A total of 42 out of the 80 responders (52·5%) received a SCT: 19 from an identical sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood cells. The estimated 4‐year overall survival and event‐free survival were 25% and 21% respectively. Disease‐free survival at 4 years was 25·8% for the 80 responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free of leukaemia. This induction therapy has shown antileukaemic efficacy with acceptable toxicity; moreover, all responders proved eligible for intensive consolidation.

Breast metastases in children and adolescents with rhabdomyosarcoma: Experience of the Italian soft tissue sarcoma committee†

Breast metastasis from rhabdomyosarcoma (RMS) is an uncommon event but may be problematic in treatment decision‐making. Aim of the study was to evaluate clinical characteristics, treatment, and subsequent outcome, of patients with RMS metastasis in the breast, enrolled in four consecutive Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) Soft Tissue Sarcoma Committee protocols during the last 20 years, in order to obtain information to establish a more adequate diagnostic and therapeutic approach.

Long-term results of the AIEOP LNH-97 protocol for childhood lymphoblastic lymphoma.

Treatment intensification was considered a suitable strategy to increase the cure rate of lymphoblastic lymphoma (LBL) in children.

Non‐Hodgkin lymphoma in children with an associated inherited condition: A retrospective analysis of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)

Inherited conditions affecting genetic aberration, viral oncogenesis, reduced immune surveillance, and long‐lasting antigen stimulation may build the way to lymphomagenesis in humans.

Primary mediastinal large B-cell lymphoma: Outcome of a series of pediatric patients treated with high-dose methotrexate and cytarabine plus anti-CD20

Between 2007 and 2013, 13 children diagnosed with primary mediastinal large B‐cell lymphoma (PMLBL) were treated according to a modified version of AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) LNH‐97 protocol based on high‐dose methotrexate, anthracyclines, and addition of anti‐CD20. Ten patients achieved a continuous complete remission with front‐line therapy. The overall 5‐year survival was 91.7%, and event‐free survival was 83.9%, with only one patient dying of progressive disease. Despite the few cases, these results demonstrate that this therapy, which includes anti‐CD20, given in a multicenter setting, is feasible with acceptable toxicity in children with PMLBL.