Cristina Moroni

A Prospective Study on the Epidemiology of Febrile Episodes during Chemotherapy-Induced Neutropenia in Children with Cancer or after Hemopoietic Stem Cell Transplantation

BACKGROUNDnThe purpose of our study was to evaluate the incidence and clinical characteristics of febrile episodes during neutropenia following chemotherapy in children with cancer.nnnPATIENTS AND METHODSnA prospective, 3-year single-center observational study of periods of neutropenia was performed. Epidemiology and clinical diagnoses of febrile episodes occurring during the neutropenic periods were evaluated, taking into consideration different categories of anticancer treatment based on the type of tumor and phase of therapy.nnnRESULTSnA total of 703 febrile episodes were observed during 614 (34%) of 1792 neutropenic periods (34%), for a total of 28,001 days at risk, accounting for a rate of 0.76 episodes per 30 days at risk. The highest proportions of neutropenic periods with primary febrile episodes were observed after autologous hemopoietic stem cell transplantation (58%), aggressive treatment for acute leukemia or non-Hodgkin lymphoma (48%), and allogeneic hemopoietic stem cell transplantation (44%); the lowest proportion (9%) was observed during maintenance chemotherapy for acute leukemia (P<.001). The most frequent clinical diagnosis was fever of unknown origin (in 79% of cases), followed by bacteremia (10%); invasive mycosis was diagnosed in only 2% of cases.nnnCONCLUSIONSnThe overall incidence of febrile neutropenia and severe infectious complications in children with cancer is low, with differences according to the aggressiveness of chemotherapy. This fact must be considered when designing clinical trials on the management of infectious complications in children with cancer.

Changing pattern of pathogens causing broviac catheter-related bacteraemias in children with cancer

The incidence of pathogens causing catheter-related bacteraemias in children undergoing antineoplastic chemotherapy with or without bone marrow transplantation at G. Gaslini Childrens Hospital, Genoa, Italy, was analysed by comparing data from a retrospective study (1985-1988) with that obtained from a prospective one (1989-1992). In both periods catheter-related bacteraemias one (1989-1992). In both periods catheter-related bacteraemias were more frequent in non-neutropenic than in neutropenic patients. Among catheter-unrelated bacteraemias the pattern of infecting pathogens remained unchanged between the study periods, with Gram-positive bacteria remaining the predominant pathogens. Conversely, among catheter-related bacteraemias, the incidence of Gram-negative bacilli increased significantly from 3 to 38%, and that of Gram-positive bacteria fell from 63 to 32% (P = 0.001, chi 2 test for heterogeneity.

Clostridium difficile-associated disease in children with solid tumors

Goals of workThe goal of this study was to describe the incidence of Clostridium difficile-associated disease (CDAD) in children with solid tumours.Patients and methodsAfter documentation of a case of C. difficile-associated pseudomembranous colitis in a patient with neuroblastoma, the presence of C. difficile toxins A and B was prospectively tested in all children undergoing antineoplastic chemotherapy for solid tumours or lymphomas at the “G. Gaslini” Children Hospital in Genoa who presented abdominal pain.Main resultsFrom January 2005 to December 2006, nine (6%) out of 141 patients treated for solid tumours had C. difficile toxin A detected in their stools in the presence of abdominal symptoms including vomit, abdominal pain and diarrhoea. The majority of patients had a normal neutrophil count at onset of gastrointestinal disease No patient developed pseudomembranous colitis, and none died. All patients received antibiotics and/or antineoplastic drugs previously associated with CDAD.ConclusionsCDAD may be a complication of children with solid tumours. Since this disease may be life threatening and cause epidemic clusters, this possibility must be kept in mind for the differential diagnosis of abdominal diseases in children with cancer, especially in absence of neutropenia.

Infection with Fusarium species in two children with neuroblastoma.

Two cases ofFusarium infection in children with neuroblastoma are reported. One of the patients had an overwhelming infection and the diagnosis was based on isolation ofFusarium moniliforme from blood and skin biopsy, and histological findings. The second patient developed chronic polyarthritis andFusarium solani was cultured from synovial fluid samples taken from two different joints four months apart. No histological documentation of infection was obtained. The response to antifungal therapy was unfavourable. Both patients died, but in the second case the relationship between fungal infection and death was not established.

Incidence of catheter-related infections within 30 days from insertion of Hickman-Broviac catheters.

To evaluate the incidence of surgical site infections and bacteremias occurring within 30 days from insertion of partially implanted central venous catheters.

HIGH-DOSE CISPLATIN AND ETOPOSIDE IN ADVANCED MALIGNANCIES OF CHILDHOOD

Thirty-two children with poor-prognosis solid tumors were treated with a combination of high-dose cisplatin (CDDP) (200 mg/m2 over 5 days) and VP16. In the 30 children evaluable for antitumor effect, there were 7 complete, 12 partial, and 3 minor tumor responses. Wilms tumor and rhabdomyosarcoma responded best. There were no therapy-related deaths. Severe neutropenia (PMN less than 500/mmc) developed after 29 out of the 45 evaluable courses and lasted a median of 8 days; during periods of neutropenia 8 episodes of fever occurred, 1 of which was caused by streptococcal sepsis. Platelet levels were depressed to less than 50,000/mmc after 17/45 cycles and this thrombocytopenia lasted a median of 8 days. No neurological toxicity occurred. One case developed acute renal failure. A hearing deficit for high frequencies was documented in 14/22 patients evaluated after the first cycle and in all cases after the subsequent cycles; the deficits correlated with the total dose of CDDP administered. High-dose cisplatin and VP16 is an effective association in children with advanced cancer, but cumulative dosage is limited by ototoxicity.

HHV-8-related visceral Kaposi’s sarcoma following allogeneic HSCT: Report of a pediatric case and literature review

Sala I, Faraci M, Magnano GM, Sementa A, di Marco E, Garaventa A, Micalizzi C, Lanino E, Morreale G, Moroni C, Castagnola E. HHV‐8‐related visceral Kaposi’s sarcoma following allogeneic HSCT: Report of a pediatric case and literature review.u2028Pediatr Transplantation 2011: 15:E8–E11.

Role of management strategies in reducing mortality from invasive fungal disease in children with cancer or receiving hemopoietic stem cell transplant: a single center 30-year experience.

Background: In the last decades, several diagnostic and therapeutic strategies have been implemented for management of invasive fungal diseases (IFD) in patients with cancer or receiving allogeneic hemopoietic stem cell transplant. Few data are available on their impact on mortality in children. Methods: All IFD episodes diagnosed at tertiary care center during a 30-year period between 1983 and 2012 were analyzed for 90-day mortality and risk factors. Diagnoses were coded according to international (European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group) criteria. Four treatment eras (1983–1990, 1991–1999, 2000–2005 and 2006–2012) were defined according to availability of diagnostic technologies, new antifungal drugs and use of a diagnostic-driven approach without empiric antifungal therapy. Results: A total of 198 IFD were diagnosed in 191 patients; 71.2% were proven/probable infections; 39.9% were caused by yeasts and 31.3% by molds. Within 90 days from IFD diagnosis, 58 (30.4%) patients died for a 28.3% cumulative probability of death. A multivariable analysis showed that the highest risk of death was associated with alternative donor-hemopoietic stem cell transplant [hazard ratio (HR): 3.96] and mold etiology (HR: 1.34). The risk of death significantly decreased across the treatment eras, with almost a 3-fold reduced risk for patients diagnosed during the 2006–2012 period (HR: 0.24). Also if the variable year of diagnosis was considered as continuous, the hazard of death significantly decreased by 5% per year (HR: 0.95). Conclusions: New management strategies resulted in a better prognosis of IFD in children with cancer or hemopoietic stem cell transplant. A diagnostic-driven approach was not associated with an increase in mortality.

Continuous antibiotic infusion for salvage therapy of partially implanted central venous catheter tunnel infections due to staphylococci

Tunnel infection is an uncommon but serious complication observed in patients with partially implanted central venous catheters. International guidelines suggest that should include antibiotics and catheter removal. A success rate of only 5–20% was reported without catheter removal. We treated 13 episodes of tunnel Gram‐positive bacterial infection occurring in pediatric patients with cancer or serious blood disorders with 24‐hr intra‐catheter antibiotic continuous infusion. This approach led to a 69% success rate. Continuous infusion might be an attractive option to treat tunnel Gram‐positive bacterial infections when catheter removal might not be feasible or advisable. Pediatr Blood Cancer 2007;49:1010–1012.

Pneumonia due to Mycoplasma pneumoniae in granulocytopenic children with cancer.

To the Editor: Mycoplasma pneumoniae causes communityacquired pneumonias in children and adults [1]. Diagnosis is based on clinical symptoms, radiological signs, and detection of IgM and IgG by enzyme-linked immunosorbent assay, but polymerase chain reaction (PCR) on a throat swab specimen represents a specific and rapid diagnostic method [1]. Oddly, M. pneumoniae is not included among the possible causes of pneumonia in immunocompromised hosts [2] and a comprehensive MEDLINE search yielded only a total of 11 cases [3–5]. After the observation of a severe pneumonia with diffuse bilateral lung infiltrates and hemolytic anemia due to M. pneumoniae in a splenectomized patient previously treated for Hodgkin disease, we checked for M. pneumoniae infection in pneumonias observed in children with cancer or receiving hemopoietic stem cell transplant (HSCT) at G.Gaslini Children Hospital, Genoa, Italy. From 2006 to 2008, 463 children were treated for a malignancy or received a HSCT for a non-neoplastic disease. The Table reports on the 30 cases of pneumonia observed. In the 3 (10%) cases due to M. pneumoniae, two in patients with non-Hodgkin lymphoma and one with acute myelogenous leukemia, the pathogen was detected by PCR on throat swabs. In all cases the onset of the disease was represented by febrile granulocytopenia with symptoms of pneumonia (14% of pneumonias in granulocytopenic patients), with lung infiltrates (Fig. 1), in two cases bilateral (Fig. 1, panels B,C) at CT scan. All patients were receiving co-trimoxazole for P. jiroveci prophylaxis. Empirical antibacterial (piperacillin-tazobactam) and antifungal (liposomal amphotericin B) therapy were administered, associated with clarithromycin, according to our protocol for patients with severe pneumonia, until the availability of specific diagnosis [6]. In all cases galactomannan antigen resulted negative and antifungals were discontinued at documentation of M. pneumoniae infection. Antimycoplasma therapy was administered for 21 days and all patients survived without sequelae. In granulocytopenic cancer patients, fungal pneumonia represents a serious complication because of its high mortality. CT imaging may be not specific, since a halo sign is present very early and for a short period of time and in the subsequent days radiological features of IFD may be aspecific [7]. According to the most recent classification [8], a possible pulmonary IFD is defined by the presence of appropriate host factors in a patient with fever, respiratory symptoms, chest CT scan with dense, well-circumscribed lesions with or without a halo sign, in absence of mycological support. Even if the definitions of IFD should be used for research purposes only [8], actually they are adopted in the everyday clinical practice. The three cases we described would have fulfilled the criteria for a possible IFD, if we had not checked for M. pneumoniae infection, and it must be stressed that they represented 1/3 of cases of pneumonias that we could have classified as possible IFD. In these cases also the possibility of a polymicrobial infection, including Aspergillus, should be considered [9,10]. Our report indicates that M. pneumoniae should be included in the differential diagnosis of pneumonia in granulocytopenic children since it requires specific therapy.