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L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS-directed anti-leukaemia therapy. The objective of this study was to describe CSF asparagine depletion during 30 weeks of pegylated asparaginase therapy, 1000 iu/m(2) i.m. every second week, and to correlate CSF asparagine concentration with serum L-asparaginase enzyme activity. Danish children (1-17 years) with ALL, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, standard and intermediate risk, were included. CSF samples were obtained throughout L-asparaginase treatment at every scheduled lumbar puncture. A total of 128 samples from 31 patients were available for analysis. Median CSF asparagine concentration decreased from a pre-treatment level of 5·3 μmol/l to median levels ≤1·5 μmol/l. However, only 4/31 patients (five samples) had CSF asparagine concentrations below the limit of detection (0·1 μmol/l). In 11 patients, 24 paired same day serum and CSF samples were obtained. A decrease in CSF asparagine corresponded to serum enzyme activities above 50 iu/l. Higher serum enzyme activities were not followed by more extensive depletion. In conclusion, pegylated asparaginase 1000 iu/m(2) i.m. every second week effectively reduced CSF asparagine levels., (© 2014 John Wiley & Sons Ltd.)

Introduction: Herpes zoster rarely occurs in healthy children, but may occur frequently and may take a complicated course in children receiving chemotherapy. We aimed to assess morbidity from herpes zoster in children with acute lymphoblastic leukemia (ALL)., Material and Methods: Reviewing records, treatment and course of zoster eruptions were registered in a cohort of 67 children with newly diagnosed ALL. Of these, 45 had had varicella at the time of diagnosis and 15 contracted varicella or were vaccinated during the course of therapy., Results: Eleven children had a total of 17 eruptions while receiving chemotherapy. All eruptions were treated with acyclovir, in eight cases intravenously, and in six cases chemotherapy was interrupted. Cutaneous dissemination occurred in two cases, visceral dissemination in none. One child had postherpetic trigeminal neuralgia for two months. The eruption rate was higher among small children than among school-aged children (0.22 vs. 0.13 per year of chemotherapy) and was related to the intensity of chemotherapy (0.30 per year of consolidation treatment vs. 0.13 for maintenance therapy). Three children on prolonged intensive chemotherapy had recurrent zoster episodes., Conclusion: Chemotherapy causes zoster eruptions in approximately one quarter of children with ALL, and with intensive protocols recurrent zoster can cause significant morbidity. Attempts to improve immunity by vaccine boosting after attaining remission seems warranted.

Introduction: In children with cancer, varicella can be complicated by visceral dissemination with a risk of fatal outcome, especially in children with acute lymphoblastic leukaemia (ALL). Immunoprophylaxis and antiviral therapy have reduced the mortality, but the morbidity remains significant and is explored here in a cohort of children with ALL., Material and Methods: Among 67 children diagnosed with ALL during 1992-2007, 22 were seronegative for varicella-zoster virus (VZV) at the time of diagnosis. Patient records were reviewed to describe varicella exposures, eruptions and vaccinations during chemotherapy (24-30 months) and the following six months of immune recovery., Results: Fifteen exposures were recognised in eight children and were managed with oral acyclovir prophylaxis; three resulted in clinical infection. Adoption of brief prophylaxis in the second week of incubation has not - so far - increased the infection rate (one in six versus two in nine). A further six varicella cases occurred without recognised exposure. All nine eruptions (in eight children) were uncomplicated but entailed hospitalisation days for intravenous therapy with acyclovir and loss of chemotherapy days. Seven children were VZV-vaccinated during maintenance chemotherapy; none developed varicella or zoster later in the course., Conclusion: Despite protective isolation and prophylactic treatment, seronegative children with ALL have a high risk of varicella during or shortly after chemotherapy. We recommend that susceptible siblings should be vaccinated at the time of diagnosis and the child should receive vaccination once oral maintenance chemotherapy has been initiated.

Introduction: Children with acute lymphoblastic leukaemia (ALL) are treated with intensive chemotherapy, which results in profound immunosuppression. Treatment with trimethoprim/sulphamethoxazole (TMP-SMX) is therefore used in some departments as prophylaxis against infections with both bacteria and Pneumocystis carinii. The use of TMP/SMX for prophylaxis during the induction therapy is not uniform in the four departments of paediatric oncology in Denmark. This gave us the opportunity to describe the effect of TMP/SMX on bacterial infections in children with ALL during the induction therapy., Material and Methods: Between 1 January 1992 and 31 December 1997, 210 children were diagnosed with ALL in Denmark. From a retrospective review of the medical charts, the number of children with fever (> 38 degrees C), the number of febrile days, days of antibiotic treatment, and the number of positive blood cultures were registered for each febrile episode., Results: One hundred and fourteen children received TMP/SMX prophylaxis (10-30 mg/SMX/kg/day) and 76 did not. Children who received TMP/SMX prophylaxis had significantly fewer episodes of fever (66/114 (58%) vs. 60/76 (79%), p < 0.01) and significantly fewer children who received the prophylaxis had positive blood cultures before the start of antibiotic treatment compared with children who did not receive prophylaxis (23/114 (20%) vs 37/76 (49%), p < 0.001)). Nineteen different species were isolated from the blood stream before the start of antibiotic treatment. In the non-prophylaxis group there were a preponderance of isolates with Staph. aureus, Str. pneumoniae, E. coli, and P. aeruginosa. There was no difference in the mortality between the two groups (p = 0.44). There were no cases of P. carinii pneumonia in the period of induction therapy., Discussion: TMP/SMX prophylaxis during induction therapy for childhood ALL seems to reduce the risk of bacteraemias and febrile illness.