Introduction

No one stands to benefit more from targeted therapy strategies than children with cancer. Although conventional chemotherapy induces pancytopenia and mucositis that augment the risk of life-threatening infections in patients of all ages, younger patients are particularly vulnerable to late toxicities due to a lack of chemotherapy specificity for malignant cells. Such effects include, but are not limited to, cardiotoxicity, pulmonary insufficiency, sterility, hormone deficiency, and the development of secondary malignancies. Although the dose intensity of treatment regimens for acute lymphoblastic leukemia (ALL) and Hodgkin disease has declined substantially in recent years, children with acute myeloid leukemia (AML) currently receive the highest dose intensity of chemotherapy that has ever been delivered. While a higher proportion of children with AML treated in this manner experienced prolonged disease-free survival, compared with those who received a less aggressive induction regimen, their overall survival was somewhat reduced by a higher induction death rate in this randomized arm. Strategies that target therapies directly to malignant cells could conceivably spare normal tissues from injury, resulting in a substantial improvement in the long-term quality of life of children who achieve remissions. The use of monoclonal antibodies as a means of delivering either chemotherapy or radiation directly to leukemic blast cells or, in the setting of hematopoietic stem cell transplantation (HSCT), as a means of targeting increased doses of radiation to sites of normal and malignant hematopoiesis (Table 25.1) will be reviewed in this chapter.