Prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group.

CCAAT/enhancer-binding protein alpha (CEBPA) mutations are a favorable prognostic factor in adult acute myeloid leukemia (AML) patients; however, few studies have examined their significance in pediatric AML patients. Here we examined the CEBPA mutation status and clinical outcomes of pediatric AML patients treated in the AML-05 study. We found that 47 (14.9%) of the 315 evaluable patients harbored mutations in CEBPA; 26 cases (8.3%) harbored a single mutation (CEBPA-single) and 21 (6.7%) harbored double or triple mutations (CEBPA-double). After excluding core-binding factor-AML cases, patients harboring CEBPA mutations showed better overall survival (OS; P=0.048), but not event-free survival (EFS; P=0.051), than wild-type patients. Multivariate analysis identified CEBPA-single and CEBPA-double as independent favorable prognostic factors for EFS in the total cohort (hazard ratio (HR): 0.47 and 0.33; P=0.02 and 0.01, respectively). CEBPA-double was also an independent favorable prognostic factor for OS (HR: 0.30; P=0.04). CEBPA-double remained an independent favorable factor for EFS (HR: 0.28; P=0.04) in the normal karyotype cohort. These results suggest that CEBPA mutations, particularly CEBPA-double, are an independent favorable prognostic factor in pediatric AML patients, which will have important implications for risk-stratified therapy.

Extremely low-frequency magnetic fields and survival from childhood acute lymphoblastic leukemia: an international follow-up study.

A previous US study reported poorer survival in children with acute lymphoblastic leukemia (ALL) exposed to extremely low-frequency magnetic fields (ELF-MF) above 0.3 µT, but based on small numbers. Data from 3073 cases of childhood ALL were pooled from prospective studies conducted in Canada, Denmark, Germany, Japan, UK and US to determine death or relapse up to 10 years from diagnosis. Adjusting for known prognostic factors, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival and event-free survival for ELF-MF exposure categories and by 0.1 µT increases. The HRs by 0.1 µT increases were 1.00 (CI, 0.93-1.07) for event-free survival analysis and 1.04 (CI, 0.97-1.11) for overall survival. ALL cases exposed to >0.3 µT did not have a poorer event-free survival (HR=0.76; CI, 0.44-1.33) or overall survival (HR=0.96; CI, 0.49-1.89). HRs varied little by subtype of ALL. In conclusion, ELF-MF exposure has no impact on the survival probability or risk of relapse in children with ALL.

Busulfex (i.v. BU) and CY regimen before SCT: Japanese-targeted phase II pharmacokinetics combined study.

To evaluate the toxicity and efficacy of an i.v. preparation of BU (12.8 mg/kg), combined with CY (120 mg/kg), a prospective study was performed on 30 Japanese patients (median age, 30 years) with hematologic malignancies undergoing hematopoietic SCT (28 allogeneic transplants from an HLA-matched donor and 2 autologous transplants). There were no significant toxicities, and all but one patient showed evidence of granulocyte engraftment at a median of 14 days for allogeneic and 11 days for autologous transplantation. Grades II-IV acute and chronic GVHD occurred in 9 (9/27, 33%) and 16 patients (16/27, 59%), respectively. Non-relapse mortality at days 100 and 365 was 3 and 17%, respectively. The pharmacokinetics of i.v. BU showed close inter- and intrapatient consistency; the area under the plasma concentration-time curve of the first administration remained at less than 1500 micromol min/l in 27 of the 29 patients (93%), and between 900 and 1350 micromol min/l in 22 patients (73%). As all of the profiles overlap with data from non-Japanese patients, we conclude that racial factors may not seriously influence the bioactivity of i.v. BU.

Lower costs associated with hematopoietic cell transplantation using reduced intensity vs high-dose regimens for hematological malignancy.

We compared inpatient and outpatient costs alongside clinical outcomes associated with hematopoietic cell transplantation between 2000 and 2003 with high-dose regimens (HDCT, n=185) and with reduced intensity regimens (RICT, n=90) from human leukocyte antigen (HLA)-matched donors for patients with hematological malignancies. With a comparable median follow-up of 3 years, long-term clinical outcomes, including cumulative incidence of chronic graft-vs-host disease, disease-free survival and overall survival, were similar between the two groups. In the univariate analysis, median costs for the first 100 days ($104,380 vs $42,149) and 1 year ($128,253 vs $80,499) in the HDCT group were higher than those in the RICT group. Median days of hospitalization are also higher for HDCT recipients (39 vs 21), although the number of outpatient clinic visits for HDCT recipients were fewer compared to that for RICT recipients (16 vs 25) during the first year. Adjusting for patient characteristics, RICT recipients had approximately 16 fewer days of hospitalization and cost $53,030 less than HDCT recipients within the first year after transplantation. Our data suggest that substantially lower costs and fewer days of hospitalization within the first year after RICT procedures can be obtained with no compromise of long-term clinical outcomes compared to HDCT procedures.