Special article: 50 years of seminars in hematologyA 50-Year Journey to Cure Childhood Acute Lymphoblastic Leukemia
Section snippets
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).