Limiting Toxicities During Intensified Remission Induction Chemotherapy for Childhood Acute Lymphocytic Leukemia

Abstract

The leukemias of childhood have provided an excellent model with which to test novel therapeutic strategies for human neoplasias [1]. In 1984, we devised an intensive multi-drug regimen for treatment of newly diagnosed patients with acute lymphocytic leukemia (ALL). This therapy is being evaluated in Study XI of the Total Therapy series at St. Jude Children’s Research Hospital, and features drug combinations and scheduling that differ radically from those tested in previous studies. Our rationale follows predictions of the somatic mutation theory of Goldie and Coldman [2] that early and repeated use of nonspecific but intensive combination chemotherapy should decrease the likelihood of drug resistance and, therefore, improve the end results of treatment. However, we encountered unexpectedly severe toxicity from early intensification of therapy that led to amendment of the protocol [3]. In this article, we review the toxic effects of the original treatment regimen and its subsequent modifications, emphasizing the potential hazards of intensive combination chemotherapy for ALL.

Supported by Leukemia Program Project Grant No. CA20180 and by the American Lebanese Syrian Associated Charities (ALSAC).