Intensive therapy has cured 70-75% of children diagnosed with acute lymphoblastic leukemia (ALL); most have sequelae of treatment. In this Project, we will assess the long-term outcome of antileukemia therapy and augment the usual event-free survival comparisons of treatment programs by use of methods to adjust survival for its quality. The focus will be on those aspects of our treatment program that have contributed to increased prevention of leukemia relapse, but have been associated with late sequelae. Specifically, we will concentrate on evaluating doxorubicin- induced cardiotoxicity, central nervous system (CNS) treatment-induced neuropsychological toxicity, and overall health-related quality of life. In the context of a prospective randomized clinical trial, we will determine whether the cardioprotectant drug ADR-529 (ICRF-187) diminishes late doxorubicin-induced cardiotoxicity. We will also assess the value of serial cardiac monitoring during doxorubicin therapy. We will determine the relative efficacy of intensive intrathecal therapy compared to hyperfractionated cranial radiation, an innovative CNS treatment which we began to study in 1987 in order to decrease CNS toxicity in high risk patients. No child randomized to this radiation schedule between 1987- 1991 has had a CNS relapse (N=84), compared with one CNS relapse among children randomized to receive conventional radiation (N=97). Hyperfractionated cranial radiation will be evaluated for its long-term toxicity compared to conventional cranial radiation. Quality-adjusted survival analysis using Q-TWiST and QALY methods will characterize 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 childhood ALL, balancing the health-related quality of life against the rate of cure to maximize the therapeutic ratio.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA068484-04
Application #
6269730
Study Section
Project Start
1998-08-01
Project End
1999-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
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