About 75% of children with acute lymphoblastic leukemia (ALL) can be cured by using current therapies. Despite increasing dose intensity, cure rates have reached a plateau, and late sequelae of treatment exist for many children. Improved outcome must originate from laboratory investigations of the biology of ALL and decreasing the harmful effects of treatment. Over the past fifteen years the investigators in this Program Project have collaborated on studies to maximize therapeutic intensity in children with newly diagnosed ALL. These efforts resulted in significant improvements in event-free survival. We have also developed autologous bone marrow transplantation for relapsed ALL. We now propose to continue collaboration between laboratory and clinical scientists to develop the most effective, least toxic therapies, balancing the quality of life against the rate of cure to maximize the therapeutic ratio in newly diagnosed patients. In both newly diagnosed patients and in relapsed patients undergoing autologous transplantation, we will determine the clinical significance of minimal residual leukemia. We will explore apoptosis, a critical mechanism of tumor cell killing, and its relationship to the p53 gene metabolic pathway. These investigations may provide a scientific basis for optimizing clinical treatments, both to decrease toxicity and improve efficacy in refractory patients. We will continue ongoing studies of the cardiotoxicity of doxorubicin, including the cardioprotective effect of ADR 529, and the value of serial cardiac measurements in predicting the late toxicity of bolus versus continuous infusion of doxorubicin. We also will determine the most efficacious and least toxic combination of radiotherapy and intrathecal drug for prevention of central nervous system leukemia in ongoing studies of neuropsychological and growth toxicities of central nervous system therapy. Because recurrent leukemia is a major cause of relapse and subsequent death, we will develop laboratory-based, novel, non-overlapping treatment strategies which can be added to current treatment approaches to eradicate residual leukemia. By translating basic laboratory observations to clinical trials, we desire to improve outcome and decrease toxicity for children with ALL.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Cancer Centers and Research Programs Review Committee (CCRP)
Program Officer
Wu, Roy S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Dana-Farber Cancer Institute
United States
Zip Code
Bansal, Neha; Barach, Paul; Amdani, Shahnawaz M et al. (2018) When is early septal myectomy in children with hypertrophic cardiomyopathy justified? Transl Pediatr 7:362-366
Mansour, Marc R; He, Shuning; Li, Zhaodong et al. (2018) JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia. J Exp Med 215:1929-1945
Lipshultz, Steven E (2018) Letter by Lipshultz Regarding Article, ""Anthracycline Cardiotoxicity: Worrisome Enough to Have You Quaking?"" Circ Res 122:e62-e63
Temple, Jennifer L; Bernard, Christophe; Lipshultz, Steven E et al. (2017) The Safety of Ingested Caffeine: A Comprehensive Review. Front Psychiatry 8:80
Rahman, Sunniyat; Magnussen, Michael; León, Theresa E et al. (2017) Activation of the LMO2 oncogene through a somatically acquired neomorphic promoter in T-cell acute lymphoblastic leukemia. Blood 129:3221-3226
Hutchins, Kelley K; Siddeek, Hani; Franco, Vivian I et al. (2017) Prevention of cardiotoxicity among survivors of childhood cancer. Br J Clin Pharmacol 83:455-465
Bona, Kira; Blonquist, Traci M; Neuberg, Donna S et al. (2016) Impact of Socioeconomic Status on Timing of Relapse and Overall Survival for Children Treated on Dana-Farber Cancer Institute ALL Consortium Protocols (2000-2010). Pediatr Blood Cancer 63:1012-8
Seftel, Matthew D; Neuberg, Donna; Zhang, Mei-Jie et al. (2016) Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission. Am J Hematol 91:322-9
Fraser, Raphael André; Lipsitz, Stuart R; Sinha, Debajyoti et al. (2016) Approximate median regression for complex survey data with skewed response. Biometrics 72:1336-1347
Lipshultz, Steven E; Anderson, Lynn M; Miller, Tracie L et al. (2016) Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors. Cancer 122:946-53

Showing the most recent 10 out of 214 publications