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Next Article 
Blood, 1953, Vol. 8, No. 11, pp. 965-999.
© 1953 American Society of Hematology, Inc.
Clinical Evaluation of a New Antimetabolite, 6-Mercaptopurine, in the Treatment of Leukemia
and Allied Diseases
J. H. BURCHENAL M.D.1,
M. L. MURPHY M.D.1,
R. R. ELLISON M.D.1,
M. P. SYKES M.D.1,
T. C. TAN M.D.1,
L. A. LEONE M.D.1,
D. A. KARNOF-SKY M.D.1,
L. F. CRAVER M.D.1,
H. W. DARGEON M.D.1, and
C. P. RHOADS M.D.1
1 Chemotherapy, Pediatric, and Medical Neoplasia Services, Memorial Center,
the Division of Experimental Chemotherapy, Sloan-Kettering Institute, and the Sloan-Kettering Division of Cornell University Medical College, New York, N. Y.
1. A new antimetabolite, 6-mercaptopurine, has been shown to produce good
clinical and hematologic remissions in fifteen out of forty-five children with
acute leukemia. Another ten showed partial remissions and clinical improvement.
2. Remissions in adults with acute leukemia have occasionally been brought
about by 6-mercaptopurine, and in a few cases it has produced temporary remissions in both the early and the late stages of chronic myelocytic leukemia.
3. The compound has been effective in some children whose disease was resistant to the folic acid antagonists, as shown by the fact that out of twenty-four
children with acute leukemia whose disease had been proved to be resistant to
amethopterin, five had good clinical and hematologic remissions and five had
partial remissions with some marrow and clinical improvement. Some benefit
was seen in eight out of eighteen patients whose disease was resistant to ACTH
and cortisone.
4. In children the daily oral administration of 2.5 mg./Kg. rarely caused toxic
manifestations, but continued therapy at this dose in adults or at higher levels
in children occasionally produced bone marrow depression or gastrointestinal
symptoms.
5. There is evidence that the therapeutic resistance of the acute leukemias to
6MP develops somewhat more rapidly than it does to the folic acid antagonists
but there is, as yet, no laboratory or clinical evidence of cross resistance between
these two types of antimetabolites.
6. In a total of thirty-five patients with lymphomas and miscellaneous carcinomas and sarcomas, 6MP did not produce any definite clinical improvement at
doses which produced hematologic toxicity.
7. Although 6-mercaptopurine acts as a purine antagonist in certain forms of
bacteria, the exact mechanism of its action in leukemia is at present unknown.
Since its mode of action appears to differ from that of other agents previously
employed clinically in the treatment of leukemia, this compound would appear to
be of fundamental as well as practical interest.
Submitted on May 19, 1953
Accepted on June 19, 1953
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