) Childhood acute lymphoblastic leukemia (ALL) is a model of a curable malignancy. The best therapies to date have resulted in cure for 75-80 percent of childhood ALL, although only 35 percent for adult ALL. Most survivors of childhood ALL have sequelae of treatment. The goal of Project 4 is to maximize the therapeutic index (the efficacy:toxicity balance) in the treatment of ALL. We seek to increase the proportion of patients cured, assess the long-term outcome of anti-leukemia therapy, and augment the usual event-free survival comparisons of treatment programs by use of methods to adjust survival for its quality. In a randomized clinical trial, we will determine the relative efficacy of an augmented intensification regimen and a conventional intensification regimen (Core 9001). We will also extend our program to adult patients (ages 18-40 years) and assess biological (Projects 4, 7, 8, 9) and outcome differences of adults compared to children with ALL.
Specific Aim 1 will determine the efficacy and toxicity of pharmacokinetically-based, individualized dosing of E.coli asparaginase - a pillar of our successful program.
Specific Aim 2 will test the hypothesis that L-carnitine can decrease late doxorubicin-induced cardiomyopathy. (We will continue our long-term assessment of the value of serial cardiac monitoring during doxorubicin therapy, as well as the long-term natural history of doxorubicin-induced cardiomyopathy, continuous infusions of doxorubicin, and cardioprotection with dexrazoxane).
Specific Aim 3 will define the efficacy and neuropsychologic morbidity of either intensive intrathecal therapy or radiation therapy.
In Specific Aim 4 quality-adjusted analyses using Q-TWiST and QALY methods will evaluate the trade-off between the benefit of improved cure rates and the cost in terms of treatment-related toxicity. We seek to determine the most effective, least toxic therapies for ALL, balancing health-related quality of life against the proportion of patients cured, thus maximizing the therapeutic index.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA068484-06
Application #
6352772
Study Section
Project Start
2000-09-15
Project End
2001-04-30
Budget Start
Budget End
Support Year
6
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
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