Maria Licciardello

Performance of the galactomannan antigen detection test in the diagnosis of invasive aspergillosis in children with cancer or undergoing haemopoietic stem cell transplantation

Serum galactomannan (GM) antigen detection is not recommended for defining invasive aspergillosis (IA) in children undergoing aggressive chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT). The ability of the GM test to identify IA in children was retrospectively evaluated in a cohort of children. Test performance was evaluated on samples that were collected during 195 periods at risk of IA. Proven IA was diagnosed in seven periods, all with positive GM test results (true positives, 4%), and possible IA was diagnosed in 15 periods, all with negative GM test results (false negatives, 8%). The test result was positive with negative microbiological, histological and clinical features in three periods (false positives, 1%), and in 170 periods it was negative with negative microbiological, histological and clinical features (true negatives, 87%). The sensitivity was 0.32 and the specificity was 0.98; the positive predictive value was 0.70 and the negative predictive value was 0.92. The efficiency of the test was 0.91, the positive likelihood ratio was 18.3, and the negative likelihood ratio was 1.4. The probability of missing an IA because of a negative test result was 0.03. Test performance proved to be better during at-risk periods following chemotherapy than in periods following allogeneic HSCT. The GM assay is useful for identifying periods of IA in children undergoing aggressive chemotherapy or allogeneic HSCT.

Incidence of bacteremias and invasive mycoses in children with acute non-lymphoblastic leukemia: results from a multi-center Italian study.

Data on the epidemiology of bacteremias and invasive fungal diseases (IFD) in children with acute myeloid leukemia (AML) are scarce.

Iron Deficiency Anemia as the Only Sign of Infection with Helicobacter pylori : A Report of 9 Pediatric Cases

Recently, an association betweenHelicobacter pylori (HP) and iron deficiency anemia (IDA) was proposed. We describe 9 pediatric patients with a history of long-standing IDA and HP infection. After HP test results were confirmed to be positive, anti-HP therapy consisting of omeprazole, clarithromycin, and amoxicillin was administered for 2 weeks. The hematologic profile and iron status were assessed before and periodically after the end of the eradication regimen. The eradication of HP was associated with stable normalization of iron stores. HP infection may be involved in cases of IDA of unknown origin, and the eradication of HP is associated with the resolution of anemia.

Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory symptomatic immune thrombocytopenic purpura: efficacy and safety of treatment

This retrospective study investigated the effects of rituximab in 19 pediatric patients (15 girls and 4 boys) with chronic refractory symptomatic immune thrombocytopenic purpura (ITP). Patients received from 2 to 5 weekly infusions of rituximab (375 mg/m2); 15 patients were younger than 12 years when treated. The median follow-up time was 30 months (range, 9–43 months). The overall response rate was 68% (13/19 patients). Six responders relapsed at a median of 4.5 months (range, 3–8 months). Seven patients still displayed a platelet count >150,000/μL at a median of 33 months (range, 14-43 months) after rituximab treatment. Six of 15 patients treated with 4 or 5 weekly infusions and 1 of 4 patients treated with 2 or 3 infusions are still in remission. No difference was detected between splenectomized and nonsplenectomized patients. The duration of ITP disease at the time of treatment did not influence the response rate. Patients still in remission showed significantly lower levels of CD19+ cells after 4 and 6 months than nonresponding or relapsed patients (P < .05). No major infections were reported during follow-up. Our data show the efficacy and tolerability of rituximab in young children with refractory symptomatic ITP. Nonrelapsed patients showed a more prolonged B-cell depletion.

A survey on hematology-oncology pediatric AIEOP centers: prophylaxis, empirical therapy and nursing prevention procedures of infectious complications

A nationwide questionnaire-based survey was designed to evaluate the management and prophylaxis of febrile neutropenia in pediatric patients admitted to hematology-oncology and hematopoietic stem cell transplant units. Of the 34 participating centers, 40 and 63%, respectively, continue to prescribe antibacterial and antimycotic prophylaxis in low-risk subjects and 78 and 94% in transplant patients. Approximately half of the centers prescribe a combination antibiotic regimen as first-line therapy in low-risk patients and up to 81% in high-risk patients. When initial empirical therapy fails after seven days, 63% of the centers add empirical antimycotic therapy in low-and 81% in high-risk patients. Overall management varies significantly across centers. Preventive nursing procedures are in accordance with international guidelines. This survey is the first to focus on prescribing practices in children with cancer and could help to implement practice guidelines.

Epidemiology of infections in children with acquired aplastic anaemia: A retrospective multicenter study in Italy

Infection is a significant cause of death in patients with aplastic anaemia (AA). However, few studies have examined the characteristics of infections in patients with AA, especially in children. The aim of this retrospective study was to evaluate the incidence and types of infections in a large cohort of paediatric patients with AA referred to eight AIEOP (Italian Association of Paediatric Oncology and Haematology) centres in Italy. The study included 78 patients, 45 boys and 33 girls, median age 9.29 yrs (1st–3rd quartile 3.59–13.09) diagnosed with AA. During the study period, 111 infectious episodes were observed in 42 (54%) patients. Fifty‐one (46%) episodes were fever of unknown origin and 60 (54%) were documented infections (DI). In this group, microbiologically documented infection (MDI) with bacteremia accounted for 23 (38%) episodes, MDI without bacteremia for 7 (12%), clinically documented infection for 25 (42%) and invasive fungal diseases for 5 (8%). The rate (episodes/1000 d at risk) was similar in severe aplastic anemia and very severe aplastic anemia both before and after day 120. During the first 120 d from diagnosis, the cumulative risk of a DI was 21% (95% CI 12–29) with the last episode at day 117, but the 50% of episodes were observed in the first 24 d. After day 120, the cumulative risk of DI was again 21% (95% CI 12–29), with the last episode at day 445 of follow‐up, with 50% of episodes observed in the first 120 d of observation (240 d from the diagnosis of AA). We found a statistically significant association between the grade of aplasia at diagnosis and the incidence of IEs (P = 0.0002). No association was found between gender, age at diagnosis, response at day +120 and at day +180, use of G‐CSF and occurrence of IEs. The actuarial overall survival at 5 yrs was 90% ± 3.6. The mortality rate attributable to infection complication was 9%. This is a large paediatric cohort study reporting the epidemiology of infectious complications in children with AA and that allow us to compare the epidemiological data in this diseases with that of the most recent studies in neutropenic children with cancer. Our findings confirm that infections represent the main cause of death in patients with AA and they are important for the design of management strategies of febrile neutropenia in these patients.

Kabuki syndrome and cancer in two patients

Both hepatoblastoma and neuroblastoma are occasionally associated with congenital syndromes such as Beckwith–Wiedemann syndrome and trisomy 18. There have been no reports of hepatoblastoma in patients with Kabuki syndrome, whereas one patient with neuroblastoma and this syndrome has been reported. In this paper we present two patients with Kabuki syndrome and a neoplasm: a child of 6 years with hepatoblastoma and an infant, of 6 months affected by neuroblastoma.

Isolated congenital amastia: a subclavian artery supply disruption sequence?

Isolated Congenital Amastia: A Subclavian Artery Supply Disruption Sequence? Sebastiano Bianca,* Maria Licciardello, Barbara Barrano, and Giuseppe Ettore Centro di Consulenza Genetica e di Teratologia della Riproduzione, Dipartimento Materno Infantile, ARNAS Garibaldi Nesima, Catania, Italy Dipartimento di Pediatria, Universit a di Catania, Italy U.O.C. Ginecologia e Ostetricia, Dipartimento Materno Infantile, ARNAS Garibaldi Nesima, Catania, Italy

Rituximab in children with idiopathic thrombocytopenic purpura: does it really work?

Sir: Pusiol et al. [1] describe two paediatric cases of successful use of rituximab in idiopathic thrombocytopenic purpura (ITP). They conclude that controlled clinical trials are needed to evaluate both the efficacy and long-term side-effects of the drug. We strongly agree, since case reports are often anecdotal and describe mainly successful outcomes, whereas negative results are neglected. As a matter of fact, our experience with the use of Rituximab in children with chronic ITP is somewhat disappointing, having had only a transient response in one out of three children (Table 1). None experienced immediate side-effects. All of them showed a transient dramatic decrease of CD20+ cells, while serum Ig levels decreased by 20% at most. As paediatric haematologists we constantly experience the frustration of curing chronic cases of ITP whose condition is poorly controlled by conventional therapy, due to either refractoriness or dependence on high dosages or unacceptable side-effects of the various medicaments. We share with other physicians the need for new effective therapies for such cases. Therefore, we feel that an optimistic attitude is a frequent pitfall in such clinical settings and that only rigorously conducted trials can minimise, to an acceptable level, the inevitable bias due to the interpretation of biological phenomena. Furthermore, clinical trials are mandatory in the paediatric population because the experience obtained with adult patients cannot be transferred ‘‘tout court’’ to children. ITP itself may be a different disease in children and adults and the whole pharmacological behaviour may differ greatly in various age groups.

Prophylaxis and therapy of viral infections in pediatric patients treated for malignancy

Infections are still an important cause of mortality and morbidity in pediatric cancer patients. Most of the febrile episodes in immunocompromised patients are classified as a fever of unknown origin (FUO) while bacteria are the more frequent causes of documented infections. Viral infections are also feared during chemotherapy but less data are available on their incidence and morbidity. We reviewed the literature on incidence, morbidity, and mortality of viral infections in children undergoing chemotherapy and discussed the evidence concerning the prophylaxis and the therapy.