Human parvoviruses B19, PARV4 and bocavirus in pediatric patients with allogeneic hematopoietic SCT.

Among the immunocompetent, infections with parvovirus B19 (B19V) and human bocavirus (HBoV) 1 range clinically from asymptomatic to severe, while following allogeneic hematopoietic SCT (HSCT) B19V can cause a persistent severe illness. The epidemiology and clinical impact of HBoV1 and the other emerging parvovirus 4 (PARV4) among immunocompromised patients have not been established. To determine the occurrence and clinical spectrum of B19V, PARV4 and HBoV1 infections, we performed a longitudinal molecular surveillance among 53 allogeneic HSCT recipients for pre- and post-HSCT DNAemias of these parvoviruses. Quantitative real-time PCR showed B19V DNA in sera of 16 (30%) patients, at mean levels of 4.6 × 10(3), 9.9 × 10(7), 1.1 × 10(10) and 1.6 × 10(2) B19V DNA copies/mL pre-HSCT (9/53), and at 1 (6/53), 2 (4/53) and 3 months (1/25) post HSCT, respectively. However, no clinical manifestation correlated with the presence of B19V viremia. All B19V sequences were of genotype 1. None of the sera investigated contained PARV4 or HBoV1 DNAs. Our data demonstrate B19V viremia to be frequent among pediatric allogeneic HSCT recipients, yet without apparent clinical correlates. PARV4 or HBoV1 viremias were not seen in these immunocompromised patients.

Cost analysis of the treatment of acute childhood lymphocytic leukaemia according to Nordic protocols.

Some attempts have been made to reduce the costs incurred in the therapy of leukaemia, but no studies are available regarding costs of the entire treatment in children with acute lymphocytic leukaemia (ALL). We analysed all the direct costs of treatment of 11 children with ALL diagnosed and treated in Kuopio University Hospital. The follow-up continued from diagnosis until the end of treatment for each patient. Patient treatment on the ward lasted for 84-210 d and in the outpatient clinic for 24-66 d, depending on the risk group. From 11-54 of the inpatient days were required for the treatment of infections. Total mean cost of the entire treatment was US $103250 (US $55196-166039) per patient, 53% of which were basic hospital costs and 47% patient-specific costs. Laboratory tests and radiology accounted for 18% of all direct costs and cytostatic drugs for 13%, but blood products accounted for only 4% of the total. Infections were the most important extra cause of costs, accounting for 18% of the mean total costs per patient. The complete treatment of a child with ALL came to a total of US $103250. However, since 80% of children with ALL are long-term survivors, the cost must be regarded as a good investment.

Prospective and randomized comparison of early versus delayed prophylactic administration of granulocyte colony-stimulating factor (filgrastim) in children with cancer.

BACKGROUND: The prophylactic use of hematopoietic growth factors has been shown to reduce the duration of neutropenia and related complications encountered after anticancer chemotherapy. However, the optimal timing for initiation of granulocyte colony-stimulating factor (G-CSF) has not been established. PROCEDURE: We evaluated the clinical parameters of the early versus delayed start (+1 day vs. +5 days postchemotherapy) of filgrastim (G-CSF; 5 micrograms/kg) after 36 courses of anticancer chemotherapy in 18 children with cancer in randomized fashion. Each child received two identical anticancer chemotherapeutic courses followed by one early (group 1) and one delayed (group 2) administration of G-CSF. Filgrastim was administered until absolute neutrophil count (ANC) exceeded 1.0 x 10(9)/l. RESULTS: The mean duration of G-CSF therapy was 8.6 (range, 5-14) days in group 1 and 5.4 (range, 3-10) days in group 2 (P = 0.001). The mean duration of neutropenia (ANC < 1.0 x 10(9)/l) did not differ between the study groups (7.8 vs. 8.2 days). Seven infection episodes occurred in group 1 and eight in group 2, respectively. The mean number of hospital days on broad-spectrum antibiotics was 2.3 (range, 0-8) in group 1 and 3.3 (range, 0-11) in group 2 (ns). CONCLUSIONS: We conclude that the delayed start of filgrastim reduced the costs of this treatment, but was not followed by more prolonged neutropenia or febrile neutropenias.

Acquired X-chromosome aneuploidy in children with acute lymphoblastic leukemia.

BACKGROUND: A cytogenetic study of 75 consecutive children with ALL revealed a normal karyotype, a low hyperdiploid karyotype (including 47-50 chromosomes), and a high hyperdiploid karyotype (including > 50 chromosomes) in 10, 12, and 33 patients, respectively. An acquired extra X-chromosome was detected at diagnosis by conventional cytogenetics in 29 (88%) of 33 children with a high hyperdiploid karyotype and in 4 (33%) of 12 children with a low hyperdiploid karyotype. X-chromosome aneuploidy was retrospectively studied by fluorescence in situ hybridization (FISH) in eight and 20 patients with a normal and a hyperdiploid karyotype, respectively. PROCEDURE: A classical cytogenetic study was performed according to standard methods. FISH with the centromeric probe specific to X-chromosome was used to study interphase cells of bone marrow or blood samples. RESULTS: An extra X-chromosome was found by FISH in all 13 patients with a high hyperdiploid or tetraploid, in 6 of 7 patients with a low hyperdiploid, and in none with a normal karyotype. Two children with a normal karyotype displayed monosomy X. Altogether, 57.3% of newly diagnosed children displayed X-chromosome aneuploidy. CONCLUSIONS: Out study indicates that X-chromosome aneuploidy may be the most common chromosome abnormality in childhood ALL. It can be detected in nearly all children with a high hyperdiploid karyotype and up to one-half of the patients with a low hyperdiploid karyotype. FISH with an X-chromosome centromeric probe is a rapid and simple tool to detect an abnormal clone at diagnosis in the majority of children with ALL and is useful in confirming remission in these patients.

Infections occurring during the courses of anticancer chemotherapy in children with ALL: a retrospective analysis of 59 patients.

In a retrospective analysis we evaluated the occurrence of infections in 59 children with acute lymphoblastic leukemia (ALL) during the entire duration of their anticancer chemotherapy. We recorded a total of 245 infection episodes, 118 (50%) being during neutropenia and 119 (50%) during nonneutropenia. The infections most commonly detected during neutropenia were fevers of undetermined origin (36%), clinically or microbiologically defined focal infections (33%), and bacteremias (28%). During nonneutropenia, upper respiratory tract infections (55%) were the most common. Patients needed hospitalization for infections for a total of 1951 days (i.e., a mean of 33 days per patient) and the mean number of infection episodes was 4.2 per patient. Recurrent fever developed in 21% of the children with bacteremia. Mortality caused by bacteremias was 10%. Infections during the chemotherapy of ALL were a significant cause of morbidity in children, but mortality was low.

Prophylactic administration of granulocyte colony-stimulating factor (filgrastim) after conventional chemotherapy in children with cancer.

We evaluated granulocyte colony-stimulating factor (G-CSF) as an adjunct to courses of conventional chemotherapy in 16 children with cancer. One course followed by G-CSF (20 episodes) was compared to identical courses without G-CSF (20 episodes) in the same patients. The mean duration of G-CSF therapy was 8.8 (5-13) days. The periods of neutropenia (4.8 days versus 16.5 days; p < 0.0001), days of hospitalization for febrile neutropenia (13 days versus 65 days; p = 0.02) and days on broad-spectrum antibiotics (13 days versus 95 days; p = 0.003) were significantly reduced. With the use of G-CSF the profound neutropenia could be prevented in 11 (55%) episodes. There were two episodes of fever and neutropenia in the G-CSF group as compared to 10 febrile neutropenias in the control group (p = 0.04). G-CSF was well tolerated and did not cause additional expenses when compared to the expenses needed for the treatment of febrile neutropenias. The cost benefit analyses showed that through using G-CSF a savings was realized in the amount of U.S. $20,650 for 20 cycles of chemotherapy, i.e., U.S. $1,033/chemotherapy cycle. We conclude that the use of G-CSF was efficacious and did not increase the total costs of therapy.