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The Use of Myleran in the Treatment of Chronic Myelocytic Leukemia

The Use of Myleran in the Treatment of Chronic Myelocytic Leukemia Abstract A sulfonic acid ester, Myleran (1,4-bis [methylsulfonyloxy] (Fig. 1), synthesized by Timmis,1 was introduced by Galton 2 for the treatment of chronic myelocytic leukemia. This agent appears to be so promising that it seemed worth while to publish a full account of our own experience with it. Preliminary findings in some of our cases have been reported already.3 In addition to the latter and the 19 patients treated by Galton,2 the results of treatment of only 40 other cases have been reported until now.* MATERIAL Since November, 1952. we have used Myleran in the treatment of 16 consecutive cases of chronic myelocytic leukemia (Table 1). Eleven had received no previous therapy; five cases had been treated earlier with x-rays, nitrogen mustard, triethylenemelamine, or radioactive phosphorus. The interval from the apparent onset of leukemia to the start of Myleran therapy ranged from 1 month to 56 months; in seven cases it References 1. References 4-6. 2. W, leucocyte count; t, time; k, the rate constant. 3. Maximum slope was used if the initial segment was convex. 4. Three patients received more than 110γ per kilogram per day (see Table 2). The values of k were 0.091, 0.113, and 0.148 days-1 at doses of 1287, 1907, and 4517 per kilogram per day, respectively. 5. References 2, 6, and 8. 6. References 2 and 6. 7. References 3 and 9. 8. References 3 and 10. 9. References 11-16. 10. References 17-19. 11. References 11-16. 12. References 3, 10, and 20-24. 13. References 1, 2, 4, and 25. 14. References 2, 4, and 6. 15. References 2, 4, and 6. 16. Haddow, A., and Timmis, G. M.: Myleran in Chronic Myeloid Leukemia , Lancet 1:207, 1953.Crossref 17. Galton, D. A. G.: Myleran in Chronic Myeloid Leukemia , Lancet 1:208, 1953.Crossref 18. Wintrobe, M. M.; Cartwright, G. E.; Fessas, P.; Haut, A., and Altman, S. J.: Chemotherapy of Leukemia, Hodgkin's Disease and Related Disorders , Ann. Int. Med. 41:447, 1954.Crossref 19. Wilkinson, J. F.: Discussion on the Chemotherapy of the Reticuloses , Proc. Roy. Soc. Med. 46:685, 1953. 20. Galton, D. A. G.: Myleran in Chronic Myeloid Leukemia , Lancet 1:425, 1955.Crossref 21. Petrakis, N. L.; Bierman, H. R.; Kelly, K. H.; White, L. P., and Shimkin, M. B.: The Effect of 1-4 Dimethanesulfonyloxybutane (GT-41 or Myleran) upon Leukemia , Cancer 7:383, 1954.Crossref 22. Ledlie, E. M.: Chronic Myeloid Leukemia: II. A Comparative Analysis of the Incidence and the Results of Treatment of 56 Cases , Brit. J. Radiol. 26:290, 1953.Crossref 23. Galton, D. A. G.: Chronic Myeloid Leukemia: I. Some Observations on Chronic Myeloid Leukemia , Brit. J. Radiol. 26:285, 1953.Crossref 24. Burchenal, J. H.; Murphy, M. L.; Ellison, R. R.; Sykes, M. P.; Tan, T. C.; Leone, L. A.; Karnofsky, D. A.; Craver, L. F.; Dargeon, H. W., and Rhoads, C. P.: Clinical Evaluation of a New Antimetabolite, 6-Mercaptopurine, in the Treatment of Leukemia and Allied Diseases , Blood 8: 965, 1953. 25. Wintrobe, M. M.: Clinical Hematology , Ed. 3, Philadelphia, Lea & Febiger, 1951, pp. 858-872. 26. Diamond, H. D., and Craver, L. F.: Radioactive Phosphorus: II. In the Treatment of Myeloid Leukemia , Cancer 4:999, 1951.Crossref 27. Friedell, H. L., and Storanski, J. P.: The Therapeutic Application of Radioactive Phosphorus with Special Reference to the Treatment of Primary Polycythemia and Chronic Myeloid Leukemia , J. Clin. Invest. 28:1308, 1949.Crossref 28. Reinhard, E. H.; Moore, C. V.; Bierbaum, O. S., and Moore, S.: Radioactive Phosphorus as a Therapeutic Agent: A Review of the Literature and Analysis of the Results of Treatment of 155 Patients with Various Blood Dyscrasias, Lymphomas and Other Malignant Neoplastic Diseases , J. Lab. & Clin. Med. 31:107, 1946. 29. Lawrence, J. H.; Dobson, R. L.; Low-Beer, B. V. A., and Brown, B.: Chronic Myelogenous Leukemia: A Study of 129 Cases in Which Treatment Was with Radioactive Phosphorus , J. A. M. A. 136:672, 1948. 30. Lawrence, J. H.: The Treatment of Chronic Leukemia , M. Clin. North America 38:525, 1954. 31. Osgood, E. E., and Seaman, A. J.: Treatment of Chronic Leukemia: Results of Therapy by Titrated, Regularly Spaced Total Body Radioactive Phosphorus or Roentgen Irradiation , J. A. M. A. 150:1372, 1952. 32. Minot, G. R.; Buchman, T. E., and Isaacs, R.: Chronic Myelogenous Leukemia: Age Incidence, Duration, and Benefit Derived from Irradiation , J. A. M. A. 82:1489, 1924. 33. Hoffman, W. J., and Craver, L. F.: Chronic Myelogenous Leukemia: Value of Irradiation and Its Effect on the Duration of Life , J. A. M. A. 92:836, 1931. 34. Krebs, C., and Bichel, J.: Results of Roentgen Treatment in Chronic Myelogenous Leukosis , Acta radiol. 28:697, 1947. 35. Forkner, C. E., and Scott, T. F. McN.: Arsenic as a Therapeutic Agent in Chronic Myelogenous Leukemia , J. A. M. A. 92:3, 1931. 36. Axelrod, A. R.; Berman, L., and Murphy, R. V.: Clinical and Hematological Effects of Triethylene Melamine , Am. J. Med. 15:684, 1953. 37. Watkins, C. H.; Cooper, T., and Giffin, H. Z.: The Use of Urethane (Ethyl Carbamate) in Treatment of Leukemia , Blood 8:892, 1948. 38. Rundles, R. W.; Barton, W. B., and Coonrad, E. V.: The Role of Chemotherapy in the Management of Malignant Lymphomas and Leukemia , South. M. J. 46:259, 1953.Crossref 39. Sherwood, F.: The Use of Urethane in Treatment of Leukemia: A Review of the Literature , Acta haemat. 1:253, 1948.Crossref 40. Haddow, A.: Discussion on the Chemotherapy of the Reticuloses , Proc. Roy. Soc. Med. 46:692, 1953. 41. Haut, A.; Altman, S. J.; Cartwright, G. E., and Wintrobe, M. M.: The Influence of Chemotherapy on Survival in Acute Leukemia , Blood , to be published. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png A.M.A. Archives of Internal Medicine American Medical Association

The Use of Myleran in the Treatment of Chronic Myelocytic Leukemia

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References (25)

Publisher
American Medical Association
Copyright
Copyright © 1955 American Medical Association. All Rights Reserved.
ISSN
0888-2479
DOI
10.1001/archinte.1955.00250150025002
Publisher site
See Article on Publisher Site

Abstract

Abstract A sulfonic acid ester, Myleran (1,4-bis [methylsulfonyloxy] (Fig. 1), synthesized by Timmis,1 was introduced by Galton 2 for the treatment of chronic myelocytic leukemia. This agent appears to be so promising that it seemed worth while to publish a full account of our own experience with it. Preliminary findings in some of our cases have been reported already.3 In addition to the latter and the 19 patients treated by Galton,2 the results of treatment of only 40 other cases have been reported until now.* MATERIAL Since November, 1952. we have used Myleran in the treatment of 16 consecutive cases of chronic myelocytic leukemia (Table 1). Eleven had received no previous therapy; five cases had been treated earlier with x-rays, nitrogen mustard, triethylenemelamine, or radioactive phosphorus. The interval from the apparent onset of leukemia to the start of Myleran therapy ranged from 1 month to 56 months; in seven cases it References 1. References 4-6. 2. W, leucocyte count; t, time; k, the rate constant. 3. Maximum slope was used if the initial segment was convex. 4. Three patients received more than 110γ per kilogram per day (see Table 2). The values of k were 0.091, 0.113, and 0.148 days-1 at doses of 1287, 1907, and 4517 per kilogram per day, respectively. 5. References 2, 6, and 8. 6. References 2 and 6. 7. References 3 and 9. 8. References 3 and 10. 9. References 11-16. 10. References 17-19. 11. References 11-16. 12. References 3, 10, and 20-24. 13. References 1, 2, 4, and 25. 14. References 2, 4, and 6. 15. References 2, 4, and 6. 16. Haddow, A., and Timmis, G. M.: Myleran in Chronic Myeloid Leukemia , Lancet 1:207, 1953.Crossref 17. Galton, D. A. G.: Myleran in Chronic Myeloid Leukemia , Lancet 1:208, 1953.Crossref 18. Wintrobe, M. M.; Cartwright, G. E.; Fessas, P.; Haut, A., and Altman, S. J.: Chemotherapy of Leukemia, Hodgkin's Disease and Related Disorders , Ann. Int. Med. 41:447, 1954.Crossref 19. Wilkinson, J. F.: Discussion on the Chemotherapy of the Reticuloses , Proc. Roy. Soc. Med. 46:685, 1953. 20. Galton, D. A. G.: Myleran in Chronic Myeloid Leukemia , Lancet 1:425, 1955.Crossref 21. Petrakis, N. L.; Bierman, H. R.; Kelly, K. H.; White, L. P., and Shimkin, M. B.: The Effect of 1-4 Dimethanesulfonyloxybutane (GT-41 or Myleran) upon Leukemia , Cancer 7:383, 1954.Crossref 22. Ledlie, E. M.: Chronic Myeloid Leukemia: II. A Comparative Analysis of the Incidence and the Results of Treatment of 56 Cases , Brit. J. Radiol. 26:290, 1953.Crossref 23. Galton, D. A. G.: Chronic Myeloid Leukemia: I. Some Observations on Chronic Myeloid Leukemia , Brit. J. Radiol. 26:285, 1953.Crossref 24. Burchenal, J. H.; Murphy, M. L.; Ellison, R. R.; Sykes, M. P.; Tan, T. C.; Leone, L. A.; Karnofsky, D. A.; Craver, L. F.; Dargeon, H. W., and Rhoads, C. P.: Clinical Evaluation of a New Antimetabolite, 6-Mercaptopurine, in the Treatment of Leukemia and Allied Diseases , Blood 8: 965, 1953. 25. Wintrobe, M. M.: Clinical Hematology , Ed. 3, Philadelphia, Lea & Febiger, 1951, pp. 858-872. 26. Diamond, H. D., and Craver, L. F.: Radioactive Phosphorus: II. In the Treatment of Myeloid Leukemia , Cancer 4:999, 1951.Crossref 27. Friedell, H. L., and Storanski, J. P.: The Therapeutic Application of Radioactive Phosphorus with Special Reference to the Treatment of Primary Polycythemia and Chronic Myeloid Leukemia , J. Clin. Invest. 28:1308, 1949.Crossref 28. Reinhard, E. H.; Moore, C. V.; Bierbaum, O. S., and Moore, S.: Radioactive Phosphorus as a Therapeutic Agent: A Review of the Literature and Analysis of the Results of Treatment of 155 Patients with Various Blood Dyscrasias, Lymphomas and Other Malignant Neoplastic Diseases , J. Lab. & Clin. Med. 31:107, 1946. 29. Lawrence, J. H.; Dobson, R. L.; Low-Beer, B. V. A., and Brown, B.: Chronic Myelogenous Leukemia: A Study of 129 Cases in Which Treatment Was with Radioactive Phosphorus , J. A. M. A. 136:672, 1948. 30. Lawrence, J. H.: The Treatment of Chronic Leukemia , M. Clin. North America 38:525, 1954. 31. Osgood, E. E., and Seaman, A. J.: Treatment of Chronic Leukemia: Results of Therapy by Titrated, Regularly Spaced Total Body Radioactive Phosphorus or Roentgen Irradiation , J. A. M. A. 150:1372, 1952. 32. Minot, G. R.; Buchman, T. E., and Isaacs, R.: Chronic Myelogenous Leukemia: Age Incidence, Duration, and Benefit Derived from Irradiation , J. A. M. A. 82:1489, 1924. 33. Hoffman, W. J., and Craver, L. F.: Chronic Myelogenous Leukemia: Value of Irradiation and Its Effect on the Duration of Life , J. A. M. A. 92:836, 1931. 34. Krebs, C., and Bichel, J.: Results of Roentgen Treatment in Chronic Myelogenous Leukosis , Acta radiol. 28:697, 1947. 35. Forkner, C. E., and Scott, T. F. McN.: Arsenic as a Therapeutic Agent in Chronic Myelogenous Leukemia , J. A. M. A. 92:3, 1931. 36. Axelrod, A. R.; Berman, L., and Murphy, R. V.: Clinical and Hematological Effects of Triethylene Melamine , Am. J. Med. 15:684, 1953. 37. Watkins, C. H.; Cooper, T., and Giffin, H. Z.: The Use of Urethane (Ethyl Carbamate) in Treatment of Leukemia , Blood 8:892, 1948. 38. Rundles, R. W.; Barton, W. B., and Coonrad, E. V.: The Role of Chemotherapy in the Management of Malignant Lymphomas and Leukemia , South. M. J. 46:259, 1953.Crossref 39. Sherwood, F.: The Use of Urethane in Treatment of Leukemia: A Review of the Literature , Acta haemat. 1:253, 1948.Crossref 40. Haddow, A.: Discussion on the Chemotherapy of the Reticuloses , Proc. Roy. Soc. Med. 46:692, 1953. 41. Haut, A.; Altman, S. J.; Cartwright, G. E., and Wintrobe, M. M.: The Influence of Chemotherapy on Survival in Acute Leukemia , Blood , to be published.

Journal

A.M.A. Archives of Internal MedicineAmerican Medical Association

Published: Oct 1, 1955

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