History of acute leukemia

Abstract

The recognition of acute l eukemia as a malignancy of the blood cells is usually credited to Virchow (Milestones in Leukemia Research and Therapy, The John Hopkins University Press, London, 1991) as is the term leukemia (Weisses Blut) (Neue Notizen Gebiete Natur-Heilkunde 36:151-157, 1845). The following century provided extensive details of the pathology and cytology of this disorder. But the first mention of any attempt to alter its natural history was reported in 1948 by Farber. He described temporary remissions of the disease and reported that the disease almost invariably recurred despite continuous administration of aminopterin (N Engl J Med 238:787-793, 1948). In 1949, Pearson reported cortisone-induced regressions of lymphoid tumors (Cancer 2:943-945, 1949), which was confirmed by Farber in 1950 showing remissions in childhood acute leukemia (Proceedings of the First Clinical ACTH Conference, Blakiston, Philadelphia, pp. 328-330, 1950). Following the Nobel Prize-winning research of Hitchings and Elion on the biochemistry of purine analogs (Ann NY Acad Sci 60:195-199, 1954), Burchenal reported remissions in acute leukemia with 6-mercaptopurine in 1953 (Blood 8:965-999, 1953). Despite having three unique molecules effective in inducing temporary remission in patients with acute leukemia, a careful review of the natural history of the disease was published by McMann and Foreman in 1957. They showed that for over 600 patients studied between 1943 and 1952, the median survival was approximately 6 weeks and 95% of the patients were dead by 12 months after diagnosis (Blood 12:683-693, 1957). In 1955, the largest and most authoritative group in hematology, Wintrobe’s group in Utah, reported, “It was not possible to demonstrate that the newer therapies (folic acid antagonists, ACTH, cortisone, and 6-mercaptopurine) significantly increased the total survival in these representative groups” (Blood 10:875-895, 1955). In fact, the authors recommended that these therapies not be administered to patients since they were simply prolonging the horrible clinical manifestations of a uniformly fatal disease. A lot has happened since 1955 to prove them wrong.