Beverly J. Lange

Duration of Hospitalization as a Measure of Cost on Children’s Cancer Group Acute Lymphoblastic Leukemia Studies

PURPOSE We used duration of hospitalization as a surrogate for cost and event-free survival as a measure of effectiveness to estimate the cost-effectiveness ratios of various treatment regimens on Childrens Cancer Group trials for acute lymphoblastic leukemia. PATIENTS AND METHODS The analyses included 4,986 children (2 to 21 years of age) with newly diagnosed acute lymphoblastic leukemia enrolled onto risk-adjusted protocols between 1988 and 1995. Analyses were based on a model of 100 patients. The marginal cost-effectiveness ratio (hospital days per additional patient surviving event-free) was the difference in total duration of hospitalization divided by the difference in number of event-free survivors at 5 years for two regimens. Relapse-adjusted marginal cost of frontline therapy was the difference in total duration of hospitalization for frontline therapy plus relapse therapy divided by the difference in number of event-free survivors at 5 years on the frontline therapy for two regimens. RESULTS One or two delayed intensification (DI) phases, augmented therapy, and dexamethasone all improved outcome. Marginal cost-effectiveness of these regimens compared with the control regimens was 133 days per patient for DI, 117 days per patient for double DI, and 41 days per patient for augmented therapy. Dexamethasone resulted in 17 fewer days per patient. Relapse-adjusted marginal costs were 68 days per patient for DI and 52 days for double DI. Augmented therapy and dexamethasone-based therapy resulted in 16 and 82 fewer hospital days, respectively. The estimated cost-effectiveness for treating any first relapse was 250 days per patient. CONCLUSION DI, double DI, augmented therapy, and dexamethasone-based therapy are cost-effective strategies compared with current treatment of first relapse.

A pharmacoeconomic analysis of pegaspargase versus native Escherichia coli L-asparaginase for the treatment of children with standard-risk, acute lymphoblastic leukemia: the Children's Cancer Group study (CCG-1962).

Purpose The purpose of this pharmacoeconomic analysis was to compare pegaspargase, a newer chemotherapeutic agent used for treating acute lymphoblastic leukemia, with native Escherichia coli l-asparaginase in induction, delayed intensification 1 and delayed intensification 2. Materials and Methods A subset of patients with newly diagnosed, standard-risk, acute lymphoblastic leukemia enrolled in the Childrens Cancer Group (CCG) study CCG-1962 at seven participating institutions gave consent and was enrolled in our pharmacoeconomic analysis study. Societal (transportation, lodging, missed workdays, food, babysitter) and payer (frequency of encounters) cost data were collected from diaries (n = 27). Additional payer costs, such as drug costs, cost per clinic visit, and cost per inpatient day stay were collected from patients in CCG-1962 and participating institutions. We considered costs of therapy, including higher pegaspargase costs when comparing regimens of pegaspargase versus native E. coli l-asparaginase in induction, delayed intensification 1, and delayed intensification 2. Results Our results showed that the costs of the two therapies were similar from the payer perspective, with pegaspargase costing 1.8% more than E. coli l-asparaginase. The difference between groups also was small (<1%) from the societal perspective. Inpatient stay accounted for 88% of pegaspargase payer costs and 91% of the native E. coli l-asparaginase costs. Conclusion We recommend that pegaspargase not be withheld from treatment protocols solely because of its higher pharmacy costs.

Abnormalities of Chromosome Bands 13q12 to 13q14 in Childhood Acute Lymphoblastic Leukemia

PURPOSE Little is known about nonrandom deletions of chromosome bands 13q12 to 13q14 (13q12-14) in acute lymphoblastic leukemia (ALL). We determined the prognostic significance of cytogenetically identified breakpoints in 13q12-14 in children with newly diagnosed ALL treated on Childrens Cancer Group protocols from 1988 to 1995. PATIENTS AND METHODS Breakpoints in 13q12-14 were identified in 36 (2%) of the 1,946 cases with accepted cytogenetic data. Outcome analysis used standard life-table methods. RESULTS Seventeen patients (47%) with an abnormal 13q12-14 were classified, according to the National Cancer Institute (NCI), as poor risk, and 15 patients (42%) were standard risk; four (11%) were infants less than 12 months of age. Eight cases had balanced rearrangements of 13q12-14, 27 patients had a partial loss of 13q, and one had both a partial gain and a partial loss. The most frequent additional abnormalities among these patients were an abnormal 12p, a del(6q), a del(9p), a 14q11 breakpoint, and an 11q23 breakpoint. Nineteen patients were pseudodiploid, 10 were hyperdiploid, and seven were hypodiploid. Patients with an abnormal 13q12-14 had significantly worse event-free survival than patients lacking such an abnormality, with estimates at 6 years of 61% (SD = 14%) and 74% (SD = 1%), respectively (P =.04; relative risk = 1.74). Overall survival, however, was similar for the two groups (P =.25). The prognostic effect of an abnormal 13q was attenuated in a multivariate analysis adjusted for NCI risk status and ploidy (P =.72). CONCLUSION Aberrations of 13q12-14 may contribute to leukemogenesis of childhood ALL and confer increased risk of treatment failure but are associated with other poor-risk features.