Special article: 50 years of seminars in hematology
A 50-Year Journey to Cure Childhood Acute Lymphoblastic Leukemia

https://doi.org/10.1053/j.seminhematol.2013.06.007Get rights and content

The 50th anniversary of Seminars in Hematology coincides with the 50th anniversary of St. Jude Children's Research Hospital, and both milestones are inexorably linked to studies contributing to the cure of childhood acute lymphoblastic leukemia (ALL). We thought it fitting, therefore, to mark these events by traveling back in time to point out some of the achievements, institutions, study groups, and individuals that have made cure of childhood ALL a reality. In many instances, progress was driven by new ideas, while in others it was driven by new experimental tools that allowed more precise assessment of the biology of leukemic blasts and their utility in selecting therapy. We also discuss a number of contemporary advances that point the way to exciting future directions. Whatever pathways are taken, a clear challenge will be to use emerging genome-based or immunologic-based treatment options in ways that will enhance, rather than duplicate or compromise, recent gains in outcome with classic cytotoxic chemotherapy. The theme of this journey serves as a reminder of the chief ingredient of any research directed to a catastrophic disease such as ALL. It is the audacity of a small group of investigators who confronted a childhood cancer with the goal of cure, not palliation, as their mindset.

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EDITOR’S NOTE

This is a “special” article celebrating the 50th anniversary of Seminars in Hematology. Drs Ching-Hon Pui and William E. Evans from St. Jude Children’s Research Hospital and Colleges of Medicine and Pharmacy, University of Tennessee, Memphis TN, offer us a “50-year journey to cure childhood acute lymphoblastic leukemia.” In this paper the reader will find a complete history of therapeutic advances in ALL in childhood, but also recent research developments in biology and treatment. Flow

Therapeutic Advances

In 1948, Farber et al1 described “temporary remissions” induced by aminopterin, a folic acid antagonist, in five children with acute leukemia, opening the era of chemotherapy for this disease. This landmark demonstration was reinforced in 1961, when Frei et al2 achieved a complete remission rate of 59% and a 2-year survival rate of approximately 20% in 39 pediatric patients, using a combination of mercaptopurine and methotrexate. Nonetheless, despite the introduction of several new antileukemic

Recent Research Development in Biology and Treatment

The optimal use of antileukemic agents, improved supportive care, and precise risk assessment have improved 5-year event-free survival rates to more than 85% and 5-year overall survival rates to more than 90% in several contemporary clinical trials (Table 3).10, 28, 29, 30, 31, 32, 33, 34, 35 Paralleling these advances has been the improved understanding of ALL pathobiology, the mechanisms of drug resistance, and the disposition of antileukemic drugs in the host. With the advent of

Future Directions

Although protocol-directed therapy remains the best option for patients with cancer, it was estimated that only 56% of children with ALL were enrolled in COG protocols between 1990 and 2005 in the United States.29 Indeed, the low proportion of patients in the Surveillance, Epidemiology and End Results (SEER) program who had been treated in COG protocols may partly account for their inferior outcome as compared to that in single-institution studies.56 Hence, efforts should be made to improve

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    Conflicts of interest: none.

    Supported in part by National Institutes of Health Grants No. CA21765, CA36401 and GM92666, and by the American Lebanese Syrian Associated Charities (ALSAC).

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