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Fortunately, pediatric cancers are rare, with only 1 in 300 children being diagnosed before 18 years of age. And, with overall survival (OS) approaching 80%, there is hope for most of these children and for their families. However, just as in adults, if their cancer is metastatic at diagnosis, if the cancer does not respond to standard therapies, or if they suffer a relapse, the prognosis is universally grim. Despite intensified therapies, the survival for most children with relapsed cancer has not improved in decades. In large part, this is due to the toxicities of such regimens as we have likely reached the tolerable limit with most chemotherapeutic agents. Thus, as is the case for adults with cancer, there has been a focus on understanding the underlying biology of the disease to find targetable lesions and to develop novel agents and treatment regimens to improve survival in children with relapse. However, there are multiple challenges we face. First, the spectrum of pediatric cancers is distinctly different from adults (Fig. 46-1), with acute lymphoblastic leukemia (ALL), medulloblastoma and gliomas, neuroblastoma, Hodgkin and non-Hodgkin lymphomas, and sarcomas the most common cancers in children as opposed to the most common carcinomas of the prostate, breast, lung, colon, and so on in adults. Second, the relative rarity of these cancers results in less preclinical research to find and develop potential therapeutic targets and limited patient numbers to enroll and test novel therapeutic strategies.

Figure 46-1

Spectrum of Pediatric and Adult Cancers.

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One of our approaches has been to study the pediatric cancers in parallel with similar adult tumors and to enroll patients on early adult trials to give children access to promising agents and to provide some data on safety and efficacy to support the development of pediatric-specific trials. In this chapter, we present a few examples of tumor types seen commonly in children and describe some of the therapeutic advances and promising strategies for treating children with relapsed cancers.




Acute Lymphoblastic Leukemia


Acute lymphoblastic leukemia is the most common cancer diagnosis in children, accounting for 25% of cancer diagnoses in children 15 years old or less. An estimated 3,000 new cases of childhood ALL are diagnosed yearly in the United States. After a peak incidence of 90 cases per million per year at age 2 to 3 years, ALL incidence rates decrease steadily into adolescence. Initial complete remission (CR) rates are 95%, and survival in childhood ALL is approaching 90% through the application of reliable prognostic factors that permit use of risk-oriented treatment protocols. However, relapse occurs in approximately 20%, with higher rates of relapse in adolescents and young adults as well as children less than 1 year of age (ie, “infants”). Despite excellent outcomes overall, relapsed patients with ALL outnumber ...

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