Pediatric Acute Lymphoblastic Leukemia: Challenges and Controversies in 2000
Authors: Felix Carolyn A. , Lange Beverly J. , Chessells Judith M. 
Published: October 2019

This article discusses ways in which pediatric patients with acute lymphoblastic leukemia (ALL) can be stratified to receive intensive and less intensive therapies in order to decrease morbidity and mortality. Specifically, the focus may shift away from current intensive therapies for ultra low-risk patients and away from transplantation for certain patients at relapse. In contrast, infants with ALL comprise an ultra high-risk population in need of specialized approaches.

In Section I Dr. Lange describes the need to identify ultra low-risk children. Groups around the world have improved the outcome of children with ALL by identifying the basic “total therapy” model of the 1970s and stratifying treatment according to risk of relapse. Current first-line treatment cures about 85% of children with standard-risk ALL and 70% of children with high-risk disease. However, all children receive anthracyclines, alkylating agents, or moderate- to high-dose antimetabolite infusions. While randomized clinical trials prove that these intensifications reduce relapses, they also show that half of all children with ALL can be cured with the modest therapy of the 1970s and early 1980s. The patients curable with lesser therapy may be considered an ultra low-risk group. Attempts to use age, gender, white count, morphology, and karyotype to identify the ultra low-risk group of patients with a 90-95% cure rate with minimal therapy have failed. An expanded repertoire of tools such as pharmacogenetic profiling, PCR measurement of minimal residual disease and microarray technology may make this goal achievable in this decade.

In section II Dr. Chessells addresses the management of children with relapsed ALL. The chance of successful re-treatment with conventional chemotherapy for relapse depends on the duration of first remission and the site of relapse. Bone marrow transplantation from a histocompatible sibling or other suitable donor, which is widely accepted as the treatment of choice for children with a first remission of < 24 months, is associated with a high risk of relapse. Bone marrow transplantation for later bone marrow relapse improves leukemia-free survival but has significant short-term and long-term toxicities. The challenges are to develop more effective treatment for early relapse and to identify those children with relapsed ALL who are curable with chemotherapy or, failing this, those children who would be candidates for bone marrow transplantation in third remission.

In Section III Dr. Felix addresses the problem of infant ALL. ALL of infancy is clinically aggressive, and infants continue to have the worst prognosis of all pediatric patients with ALL. High white blood cell count, younger age, bulky extramedullary disease, and CNS disease at diagnosis are unfavorable characteristics. These features occur with MLL gene translocations. The probability of an MLL gene translocation and the probability of poor outcome both are greatest in younger infants. Specialized intensive chemotherapy approaches and bone marrow transplantation in first remission for this disease may lead to improved survival.

Refined recognition of pediatric patients with ALL who need more and less intensive therapies is necessary to increase survival and decrease toxicities.