Oral voriconazole versus intravenous low dose amphotericin B for primary antifungal prophylaxis in pediatric acute leukemia induction: a prospective, randomized, clinical study.

PURPOSE: Invasive fungal infections (IFI) are a major cause of infection-related mortality during induction chemotherapy of acute leukemia (AL) patients. Data on antifungal prophylaxis (AFP) in children are limited by retrospective design, small sample size, and variability of chemotherapy phases having different risk of IFI. There are no data comparing voriconazole versus amphotericin B (AmB) as AFP in either adult/pediatric AL. The objectives of this study were to compare efficacy and toxicity of AmB and voriconazole as AFP in pediatric AL patients. PATIENTS AND METHODS: As a pilot study, total 100 children (≤15 y) with denovo acute myeloid leukemia and acute lymphoblastic leukemia were randomized to either oral voriconazole or low dose intravenous AmB as AFP during induction chemotherapy. RESULTS: Failure of prophylaxis occurred in 14/50 patients in voriconazole arm (1 proven mucormycosis, 1 possible IFI, 11 empirical antifungal therapy, and 1 withdrawal owing to hepatotoxicity) and 17/50 patients in AmB arm (3 possible IFI, 13 empirical antifungal therapy, and 1 withdrawal owing to difficult venous access) (P=0.66). Of the 29 patients who had failure of prophylaxis unrelated to drug toxicity, computed tomography of the chest showed infiltrates in 10 patients with 3/12 in voriconazole arm and 7/16 in AmB arm (P=0.43). Drug-related serious adverse events were 6% versus 30% in voriconazole and AmB arms, respectively (P<0.01). Further, total number of toxicities per patient in AmB arm were significantly higher as compared with voriconazole arm (P<0.0001). CONCLUSION: This is the first randomized study comparing voriconazole with AmB in pediatric AL patients as AFP during induction chemotherapy; our results showed that oral voriconazole seems to be comparable with AmB with less toxicity and more convenience. (ClinicalTrials.gov identifier: NCT00624143).

Detection and clinical relevance of BCR-ABL fusion gene in childhood T-lineage acute lymphoblastic leukemia: a report on 4 cases.

The bcr-abl rearrangement has rarely been reported in T-lineage acute lymphoblastic leukemia and the clinical significance of this translocation is currently unknown. We screened 28 children with T-lineage acute lymphoblastic leukemia at diagnosis by reverse transcription polymerase chain reaction for major and minor break point regions of bcr-abl fusion gene. Four out of 28 patients (14.2%) were bcr-abl positive for the minor breakpoint transcript. One of these patients was refractory to therapy, whereas the other 3 relapsed on therapy.

Outpatient consolidation chemotherapy in pediatric acute myeloid leukemia: a retrospective analysis.

BACKGROUND: To assess the outcomes of outpatient high dose cytosine arabinoside consolidation cycles in pediatric acute myeloid leukemia (AML) patients in comparison to inpatient treatment. METHODS: We retrospectively analyzed 90 cycles of AML consolidation given to 30 patients between July 2003 and July 2007. RESULTS: Median age was 8 years (range 1.5-15) and 22/30 (73.3%) were males. Sixty-nine of 90 (76.7%) cycles were given on an ambulatory basis; readmission occurred in 25/69 (36.2%) and there was one death. The outpatient cycles in comparison to the inpatient cycles required significantly fewer invasive blood investigations (p<0.001) but had comparable number of blood products administered as supportive therapy. There was no significant difference in the frequency of granulocyte colony stimulating factor usage and recovery time of absolute neutrophil count and platelet count. The incidence of febrile neutropenia though was comparable in the groups (72.5% outpatient versus 76.2% inpatient), but the duration (p=0.003) and subsequent therapeutic antifungal usage (p=0.001) was significantly more in inpatient administered cycles. Second line antibiotics were needed in 16/50 (32%) outpatient episodes of febrile neutropenia in contrast to 10/16 (72.5%) episodes of febrile neutropenia in inpatient courses (p=0.030). CONCLUSIONS: Outpatient AML consolidation therapy is safe and feasible in children. It appears to result in less frequent invasive blood studies; shorter duration of febrile neutropenia and consequently less antimicrobial and antifungal usage as compared to inpatient consolidation cycles. To our knowledge, this report is the first of its kind looking specifically at outpatient consolidation chemotherapy in AML.

Randomized controlled trial comparing oral amoxicillin-clavulanate and ofloxacin with intravenous ceftriaxone and amikacin as outpatient therapy in pediatric low-risk febrile neutropenia.

BACKGROUND: Outpatient oral therapy is infrequently used in pediatric low-risk febrile neutropenia (LRFN) as there is insufficient data regarding its equivalence as compared with parenteral therapy. METHODS: This is a single institutional, randomized control trial in pediatric LRFN aged 2 to 15 years, in which 123 episodes in 88 patients were randomized to outpatient oral ofloxacin 7.5 mg/kg 12 hourly and amoxycillin-clavulanate 12.5 mg/kg 8 hourly or outpatient intravenous (IV) ceftriaxone 75 mg/kg and amikacin 15 mg/kg once daily after blood cultures. RESULTS: Out of 119 evaluable episodes, one-third were leukemia patients in maintenance and rest were solid tumors. Success was achieved in 55/61 (90.16%) and 54/58 (93.1%) in oral and IV arms, respectively, (P=0.56). There were 3 hospitalizations but no mortality. Median days to resolution of fever, absolute neutrophil count >500/mm(3) and antibiotic use were 3, 5, and 6 days in both arms. There were 5 blood culture isolates (3 gram-positive and 2 gram-negative bacteria). Failure of outpatient therapy was associated with perianal infections, bacteremia, febrile neutropenia onset before day 9 of chemotherapy in solid tumors and Vincristine, actinomycin-D, and cyclophosphamide chemotherapy for rhabdomyosarcoma. All gram-positive isolates were successes, whereas both gram-negative isolates were failures. Diarrhea in IV arm and Vincristine, actinomycin-D, and cyclophosphamide chemotherapy in the oral arm predicted failure in subgroup analysis. CONCLUSIONS: Outpatient therapy is efficacious and safe in pediatric LRFN. There was no difference in outcome in oral versus IV outpatient therapy. Amoxycillin-clavulanate and ofloxacin may be the oral regimen of choice.