Blood Journal
Leading the way in experimental and clinical research in hematology

The Effect of 6-Mercaptopurine on the Duration of Steroid-induced Remissions in Acute Leukemia: A Model for Evaluation of Other Potentially Useful Therapy

  1. ACUTE LEUKEMIA GROUP B,
  2. EMIL J FREIREICH, M.D.,
  3. EDMUND GEHAN, Ph.D.,
  4. EMIL FREI III, M.D.,
  5. LESLIE R. SCHROEDER, M.D.,
  6. IRVING J. WOLMAN, M.D.,
  7. RACHAD ANBARI, M.D.,
  8. E. OMAR BURGERT, M.D.,
  9. STEPHEN D. MILLS, M.D.,
  10. DONALD PINKEL, M.D.,
  11. OLEG S. SELAWRY, M.D.,
  12. JOHN H. MOON, M.D.,
  13. B. R. GENDEL, M.D.,
  14. CHARLES L. SPURR, M.D.,
  15. ROBERT STORRS, M.D.,
  16. FARID HAURANI, M.D.,
  17. BARTH HOOGSTRATEN, M.D., and
  18. STANLEY LEE, M.D.
  1. National Cancer Institute, Bethesda, Md., Children’s Hospital of Philadelphia, Philadelphia, Pa., Mayo Clinic, Rochester, Minn., Roswell Park Memorial Institute, Buffalo, N. Y., Medical College of Virginia, Richmond, Va., Emory University, Department of Medicine, Atlanta, G., Bowman Gray School of Medicine, Winston-Salem, N. C., Hitchcock Hospital, Dartmouth Medical School, Hanover, N. H., Jefferson Medical College Hospital, Philadelphia, Pa., Mount Sinai Hospital, New York, N. Y., and the State University of New York, Maimonides Hospital of Brooklyn, Brooklyn, N. Y.
  2. National Cancer Institute, National Institutes of Health, Bethesda, Md.
  3. National Cancer Institute, National Institutes of Health, Bethesda, Md. Present address: University of London, Birkbeck College, London, England
  4. National Cancer Institute, National Institutes of Health, Bethesda, Md.
  5. National Cancer Institute, National Institutes of Health, Bethesda, Md. Present address: Taunton Hill, Assonet, Mass.
  6. Children's Hospital of Philadelphia, Philadelphia, Pa.
  7. Children's Hospital of Philadelphia, Philadelphia, Pa.
  8. Mayo Clinic, Rochester, Minn.
  9. Mayo Clinic, Rochester, Minn.
  10. Roswell Park Memorial Institute, Buffalo, N. Y. Present address: St. Jude Hospital, Memphis, Tenn.
  11. Roswell Park Memorial Institute, Buffalo, N. Y.
  12. Medical College of Virginia, Richmond, Va.
  13. Emory University, Department of Medicine, Atlanta, Ga.
  14. Bowman Gray School of Medicine, Winston-Salem, N. C.
  15. Hitchcock Hospital, Dartmouth Medical School, Hanover, N. H.
  16. Jefferson Medical College Hospital, Philadelphia, Pa.
  17. Mount Sinai Hospital, New York, N. Y.
  18. State University of New York, Maimonides Hospital of Brooklyn, Brooklyn, N. Y.

Abstract

The effect of 6-MP therapy on the duration of remissions induced by adrenal corticosteroids has been studied as a model for testing of new agents. Ninetytwo patients under age 20 entered the study and were accepted for analysis. Sixty-two (67 per cent) had complete or partial remissions induced by corticosteroids. Patients in remission were randomly assigned to maintenance therapy with either 6-MP or placebo. The median duration of 6-MP-maintained complete remissions was 33 weeks and for placebo, 9 weeks. A sequential experimental design was used to analyze remission times while the study was in progress. This resulted in the study being stopped after analysis of the remission times of 21 pairs of patients (42 patients). Overall survival was not significantly different for the two treatment programs, since patients maintained on placebo were treated with 6-MP when relapse occurred.

The activity of the known active antileukemic compound 6-MP was readily detected by this experimental design without compromise of optimal survival. Such a design should prove useful for the evaluation of new agents and also permit study of the remission maintenance activity of a compound separately from its remission inducing activity.