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Background Data on the epidemiology of bacteremias and invasive fungal diseases (IFD) in children with acute myeloid leukemia (AML) are scarce. Design and Methods In a multi-center, retrospective study, we analyzed proportion, rate per 1,000 person-days at risk, and cumulative risk of bacteremias and IFD in children with AML. Results Between January 1998 and December 2005, 240 children were treated for AML at 8 Italian Centers, for a total of 521 treatment courses and 63,232 person-days at risk. Bacteremia was observed in 32% of treatment courses and IFD was seen in 10% (P

Optimizing the therapeutic strategies based on the results of randomized studies comparing different regimens led to a better prognosis of nearly all pediatric malignancies during the past four decades. Fever and neutropenia (FN) is a common complication in patients undergoing chemotherapy to treat cancer. There is no consensus on when standard therapy can be safely reduced; this lack of consensus leads to important variations in management of FN between different institutions, usually conducted according to local attitudes. To address this issue, the Infection working group of the Italian association for pediatric hematology oncology (AIEOP) organized a consensus meeting. This paper reports the agreement derived from this meeting.

The most intensive chemotherapy regimens were used in the past for leukemia patients who were the main focus of trials on infections; today there are increasing numbers of children with solid cancer and considerable risk of infection who do receive intensive stand ard-dose chemotherapy. Despite a continuous will to protect the immune-compromised child from infections, evidence-based indications for intervention by non-pharmacological tools is still lacking in the pediatric hematology-oncology literature. Guidelines on standard precautions as well as precautions to avoid transmission of specific infectious agents are available. As a result of a consensus discussion, the Italian Association for Pediatric Hematology-Oncology (AIEOP) Cooperative Group centers agree that for children treated with chemotherapy both of these approaches should be implemented and vigorously enforced, while additional policies, including strict environmental isolation, should be restricted to patients with selected clinical conditions or complications. We present here a study by the working group on infectious diseases of AIEOP.

Pentraxin-3 (PTX3) is a member of the long pentraxin superfamily and has a nonredundant role in mediating resistance to fungal pathogens. Serial monitoring of PTX3 plasmatic levels was performed in 10 pediatric leukemia patients affected by pulmonary fungal infections. When compared with values of a control pediatric cohort, PTX3 showed significantly higher plasmatic values. Moreover, the response to the antifungal therapy correlated with normalization of PTX3 values. PTX3 may represent a useful tool for the diagnosis and monitoring of fungal infections in immuno-compromised children.

Background Fungal infections are diagnosed increasingly often in patients affected by hematological diseases and their mortality has remained high. The recent development of new antifungal drugs gives the clinician the possibility to assess the combination of antifungal drugs with in-vitro or in animal-model synergistic effect. Methods We analyzed retrospectively the safety and efficacy of caspofungin-based combination therapy in 40 children and adolescents, most of them were being treated for a malignant disease, who developed invasive aspergillosis (IA) between November 2002 and November 2005. Results Thirteen (32.5%) patients developed IA after hematopoietic stem cell transplantation (HSCT), 13 after primary diagnosis, usually during remission-induction chemotherapy, and 14 after relapse of disease. Severe neutropenia was present in 31 (78%) out of the 40 patients. IA was classified as probable in 20 (50%) and documented in 20 (50%) patients, respectively. A favorable response to antifungal therapy was obtained in 21 patients (53%) and the probability of 100-day survival was 70%. Different, though not significant, 100-day survival was observed according to the timing of diagnosis of IA: 51.9% after HSCT; 71.4% after relapse; and 84.6% after diagnosis of underlying disease, p 0.2. After a median follow-up of 0.7 years, 20 patients are alive (50%). Overall, the combination therapy was well tolerated. In multivariate analysis, the factors that were significantly associated to a better overall survival were favorable response to antifungal therapy, p 0.003, and the timing of IA in the patient course of underlying disease, p 0.04. Conclusion This study showed that caspofungin-based combination antifungal therapy is an effective therapeutic option also for pediatric patients with IA. These data need to be confirmed by prospective, controlled studies.

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.

One hundred fifty-six episodes of fever occurred in 102 children during the first 100 days after bone marrow transplantation (BMT) performed at a single institution: fever of undetermined origin (FUO), 40.3%; septicemia, 7.1%; pneumonia, 19.2%; other infections, 33.4% of cases. The overall incidence of mortality was 22.6% and of mortality due to infections 17.4%. All FUO episodes resolved. Pneumonia was the major cause of death; 60% of recipients who developed pneumonia died, accounting for 90% of deaths attributable to febrile complications. Interstitial pneumonia occurred rarely, in 3.9% of all febrile episodes. The Cox model showed that the presence of graft-versus-host disease (GVHD) was related to an approximately ninefold increase in the risk of a first episode of FUO (P value .03). The risk of developing pneumonia was fourfold greater in children who received a transplant from a matched unrelated donor or a mismatched family donor (P value .01). Developments in diagnostic tools are needed to diagnose febrile episodes earlier and more precisely with the aim of reducing early mortality after BMT. One hundred fifty-six episodes of fever occurred in 102 children during the first 100 days after bone marrow transplantation (BMT) performed at a single institution: fever of undetermined origin (FUO), 40.3%; septicemia, 7.1%; pneumonia, 19.2%; other infections, 33.4% of cases. The overall incidence of mortality was 22.6% and of mortality due to infections 17.4%. All FUO episodes resolved. Pneumonia was the major cause of death; 60% of recipients who developed pneumonia died, accounting for 90% of deaths attributable to febrile complications. Interstitial pneumonia, occurred rarely, in 3.9% of all febrile episodes. The Cox model showed that the presence of graft-versus-host disease (GVHD) was related to an approximately ninefold increase in the risk of a first episode of FUO (P value .03). The risk of developing pneumonia was fourfold greater in children who received a transplant from a matched unrelated donor or a mismatched family donor (P value .01). Developments in diagnostic tools are needed to diagnose febrile episodes earlier and more precisely with the aim of reducing early mortality after BMT

Introduction Autoimmune hemolytic anemia in children younger than 2 years of age is usually characterized by a severe course, with a mortality rate of approximately 10%. The prolonged immunosuppression following specific treatment may be associated with a high risk of developing severe infections. Recently, the use of monoclonal antibodies (rituximab) has allowed sustained remissions to be obtained in the majority of pediatric patients with refractory autoimmune hemolytic anemia. Case presentation We describe the case of an 8-month-old Caucasian girl affected by a severe form of autoimmune hemolytic anemia, which required continuous steroid treatment for 16 months. Thereafter, she received 4 weekly doses of rituximab (375 mg/m2/dose) associated with steroid therapy, which was then tapered over the subsequent 2 weeks. One month after the last dose of rrituximab, she presented with recurrence of severe hemolysis and received two more doses of rrituximab. The patient remained in clinical remission for 7 months, before presenting with a further relapse. An alternative heavy immunosuppressive therapy was administered combining cyclophosphamide 10 mg/kg/day for 10 days with methylprednisolone 40 mg/kg/day for 5 days, which was then tapered down over 3 weeks. While still on steroid therapy, the patient developed an interstitial pneumonia with Acute Respiratory Distress Syndrome, which required immediate admission to the intensive care unit where extracorporeal membrane oxygenation therapy was administered continuously for 37 days. At 16-month follow-up, the patient is alive and in good clinical condition, with no organ dysfunction, free from any immunosuppressive treatment and with a normal Hb level. Conclusions This case shows that aggressive combined immunosuppressive therapy may lead to a sustained complete remission in children with refractory autoimmune hemolytic anemia. However, the severe life-threatening complication presented by our patient indicates that strict clinical monitoring must be vigilantly performed, that antimicrobial prophylaxis should always be considered and that experienced medical and nursing staff must be available, to deliver highly specialized supportive salvage therapies, if necessary, during intensive care monitoring.

Between 1 July 1984 and 30 June 1986 all children treated for acute hematologic malignancy at our center were randomized to receive continuous (group A) or intermittent (3 days/week, group B) prophylaxis with trimethoprim-sulfamethoxazole (5–25 mg/kg /day/p.o.) against interstitial pneumonia with the aim of investigating if an intermittent regimen is as effective as and less toxic than a continuous regimen. The number of severe infections (group A, 17; group B, 21) and side-effects (group A, 30; group B, 34) was similar in the two groups, and compliance was also similar. We conclude therefore that neither regimen offers advantages over the other and the decision which to use should be based on cost (where regimen B has the advantage) and the children's and parents' preferences and compliance.

This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluable patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.