Treatment of Pediatric Acute Lymphoblastic Leukemia: A Historical Perspective.

Acute lymphoblastic leukemia (ALL) is the most common disease in pediatric oncology. The history of developmental therapeutics for ALL began in the 1960s with the repetition of "unreliable" medical interventions against this lethal disease. By the 1990s, the development of multi-agent chemotherapy and various types of supportive care rendered ALL treatable. Highly sophisticated, molecular, diagnostic techniques have enabled highly accurate prediction of the relapse risk, and the application of risk-adapted treatments has increased the survival rate in the standard-risk group to nearly 100% in most European nations and North America. Incorporation of state-of-the-art, molecularly targeted agents and novel treatments, including cell and immunotherapy, is further improving outcomes even in the high-risk group. On the other hand, the financial burden of treating children with ALL has increased, imperiling the availability of these diagnostic and treatment strategies to patients in low- and middle-income countries (LMICs). The fundamental treatment strategy, consisting of corticosteroid and classical cytotoxic therapy, has achieved fairly good outcomes and should be feasible in LMICs as well. The present review will discuss the history of developmental therapeutics for childhood ALL in various countries through an extensive literature review with the aim of proposing a model for a treatment backbone for pediatric ALL. The discussion will hopefully benefit LMICs and be useful as a base for future clinical trials of novel treatments.