The majority of children and young adults with acute lymphoblastic leukemia (ALL) are cured with contemporary multi-agent chemotherapy regimens. The high rate of survival is largely the result of 70 years of randomized clinical trials performed by international cooperative groups. Contemporary ALL therapy usually consists of cycles of multi-agent chemotherapy given over 2-3 years that includes central nervous system (CNS) prophylaxis, primarily consisting of CNS-penetrating systemic agents and intrathecal therapy. While the treatment backbones vary between cooperative groups, the same agents are used and the outcomes are comparable. ALL therapy typically begins with 5-9 months of more intensive chemotherapy followed by a prolonged low intensity maintenance phase. Historically, a few cooperative groups treated boys with one more year of maintenance therapy than girls; whereas, the majority of groups treated boys and girls with equal therapy lengths. This practice arose because of inferior survival in boys with older less-intensive regimens. The extra year of therapy adds significant burden to patients and families and has short- and long-term risks that can be life-threatening and debilitating. The Children's Oncology Group (COG) recently changed its approach as part of their current generation of trials in B-ALL and is now treating boys and girls with the same duration of therapy. We provide the rationale behind this change, a review of the data and differences in practice across cooperative groups, and our perspective regarding the length of maintenance therapy.

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