Fatal adenovirus hepatitis during maintenance therapy for childhood acute lymphoblastic leukemia.

Disseminated adenoviral infection with hepatitis is rare in children undergoing standard chemotherapy. We report on a 3(1/2)-year-old male with fatal adenovirus hepatitis receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL). Adenoviral hepatitis was proven by histology, viral culture, and PCR in a liver biopsy. Quantitative real-time PCR in the peripheral blood showed adenoviral DNA copy number >10(9)/ml. Despite aggressive supportive care and antiviral treatment with cidofovir, the patient died rapidly due to fulminant liver failure. Diagnostic and treatment options for adenovirus infection remain unsatisfactory for these patients. We propose suggestions for diagnosis and therapy.

Individual timing of blood counts in G-CSF prophylaxis after myelosuppressive chemotherapy reduces G-CSF injections, blood counts, and costs: a prospective randomized study in children and adolescents.

In children and adolescents, prophylactic application of G-CSF after myelosuppressive chemotherapy reduces the duration of neutropenia, of hospitalization, and of parenteral antibiotic treatment. In acute lymphoblastic leukemia, non-Hodgkin lymphoma, and solid tumors, G-CSF support allows dose intensification of chemotherapy. On the other hand, each G-CSF injection causes pain and costs. We set up the hypothesis that besides strategies as restricted indications, delayed start, lower doses, and stringent rules for discontinuation, individualized timing of blood count might optimize G-CSF prophylaxis. We randomized 64 cycles of G-CSF prophylaxis in eight children and adolescents being treated for acute lymphoblastic leukemia or solid tumors to standard twice a week or to individually timed blood counts. Primary study endpoints were the numbers of G-CSF doses and of blood counts, and the total costs of G-CSF support. Per cycle, individual timing of blood count resulted in a median of one G-CSF injection fewer [estimated population median (EPM) 1.40, 95% confidence interval (CI) 0.57-2.20] and one blood count fewer (EPM 1.00, 95% CI 0.74-1.33). The total costs of G-CSF support and of blood counts were thereby reduced by a median of US $ 152 per cycle (EPM 191, 95% CI 97-318). The results of this study suggest that individual timing of blood counts during prophylactic G-CSF support in children and adolescents undergoing chemotherapy for malignant disease can significantly reduce the number of injections and blood counts performed, thus resulting in less pain and lower costs. These findings need confirmation in a larger randomized trial.

Fever in neutropenia in children and adolescents: evolution over time of main characteristics in a single center, 1993-2001.

GOALS OF WORK: To assess the evolution over time of main characteristics of episodes of fever in severe chemotherapy-induced neutropenia (FN) in children and adolescents with cancer treated for FN following nonmyeloablative chemotherapy, to compare the results with the experiences of other centers, and to assess the impact of the changes found on management of FN and on risk prediction rules. PATIENTS AND METHODS: Retrospective cohort study of all children and adolescents up to 18 years presenting with FN in a single pediatric oncology unit between 1993 and 2001. MAIN RESULTS: In 132 patients, 364 episodes of FN were reported. The relative incidence of FN increased significantly over time in patients with precursor B-cell acute lymphoblastic leukemia (PBC-ALL), reflecting the increased intensity of chemotherapy. At presentation with FN, the proportions of patients (1) with PBC-ALL versus other malignancies, (2) with other malignancies being in complete remission, (3) with a central venous catheter, and (4) with shaking chills all significantly increased over time (overall proportions, 64%, 60%, 50%, and 5%, respectively; p <0.001 for all). In 337 (93%) episodes, ceftriaxone plus amikacin was used as empirical broad spectrum antimicrobial therapy. CONCLUSIONS: This study demonstrates that some characteristics of FN, though not necessarily its management, change over time, implying regular update of risk prediction rules. In contrast to other centers, the first-line antimicrobial therapy did not need modification because of changing resistance patterns.

Neuropsychological long-term sequelae after posterior fossa tumour resection during childhood.

The importance of the cerebellum for non-motor functions is becoming more and more evident. The influence on cognitive functions from acquired cerebellar lesions during childhood, however, is not well known. We present follow-up data from 24 patients, who were operated upon during childhood for benign cerebellar tumours. The benign histology of these tumours required neither radiotherapy nor chemotherapy. Post-operatively, these children were of normal intelligence with a mean IQ of 99.1, performance intelligence quotient (PIQ) of 101.3 and verbal intelligence quotient (VIQ) of 96.8. However, 57% of patients showed abnormalities in subtesting. In addition, more extensive neuropsychological testing revealed significant problems for attention, memory, processing speed and interference. Visuo-constructive problems were marked for copying the Rey figure, but less pronounced for recall of the figure. Verbal fluency was more affected than design fluency. Behavioural deficits could be detected in 33% of patients. Attention deficit problems were marked in 12.5%, whereas others demonstrated psychiatric symptoms such as mutism, addiction problems, anorexia, uncontrolled temper tantrums and phobia. Age at tumour operation and size of tumour had no influence on outcome. Vermis involvement was related to an increase in neuropsychological and psychiatric problems. The observation that patients with left-sided cerebellar tumours were more affected than patients with right-sided tumours is probably also influenced by a more pronounced vermian involvement in the former group. In summary, this study confirms the importance of the cerebellum for cognitive development and points to the necessity of careful follow-up for these children to provide them with the necessary help to achieve full integration into professional life.