Inf. J. Radiation Oncology Biol. Pkys.,
0
1976,
Vol. 1. pp. 559-560.
Pergamon Press.
Printed in the U.S.A.
Editorials CHRONIC LYMPHOCYTIC LEUKEMIA: THERAPEUTIC OPTIONS-! JOHN University
M. BENNETT,
of Rochester Cancer Center and Department 601 Elmwood Avenue, Rochester,
Chronic Lymphocytic
Leukemia
M.D. of Medicine, Strong Memorial Hospital, NY 146442,U.S.A.
(CLL), Total body irradiation.
Despite a prevailing attitude that chronic lymphocytic leukemia (CLL) is a relatively benign illness, the overall five year survival is no higher than 55%, comparable to that of in breast cancer.5 The considerable variability
the duration of this disease and its prognosis is, to a considerable extent, based on whether the disease is “indolent” or “active”. The traditional therapy for CLL has been either no treatment for the indolent cases or a single chemotherapeutic alkylating agent such as chlorambucil or cyclophosphamide. Approximately 10% of patients treated with either daily chlorambucil’ or intermittent high dose “pulse” chlorambuciL3 enter complete remission (CR) with remission durations of less than 2 years. The addition of corticosteroids, usually prednisone, may improve the CR rate to approximately 20%. Han et al.’ described three CR’s of 15 patients treated with daily chlorambucil and low dose prednisone. In a more recent study by the Southeastern Cancer Study Group (SEG 355), four complete remissions were noted out of 30 evaluable cases, utilizing the intermittent high dose chlorambucil program combined with five days of prednisone treatment for a response rate of 13% (oral communication, J. W. Keller, W. Knopse, and C. M. Huguley, Jr., SEG Operations Office, 16 January 1976). Finally, the combination of phase-specific agents (such as cytosine arabinoside) with alkylating agents and corticosteroids may
Supported in part by United States Public Health Service grants: CA 11083 and CA 11198
increase the complete remission rate above 30% based on preliminary studies (written communication, Jeane P. Hester, 22 July 1974). In an article in this issue, Johnson and Ruhl* have updated their early report of the effectiveness of total body irradiation (TBI) with a five year follow up of 83% of the population treated. The patients were all in the “active” category; of 42 treated there were 14 complete remissions. Toxicity was modest, although the long term effects of ionizing radiation as a potential inducing agent of second malignancies is discussed. The median survival of the group was 65 months, almost twice that of a much smaller group of patients treated with daily chlorambucil or cyclophosphamide. Of great interest was the restoration of normal immunoglobulins in four of the patients who achieved complete remission, suggesting the re-immergence of a normal immunoblast stem cell line. It is not clear to what extent corticosteroids were employed by the authors in the TBI series; the assignment of treatment modalities surely was not random, and the assessment criteria were modified from those in common use by the cooperative groups. Nevertheless, TBI must be viewed as a significant addition to the therapeutic armamentarium that is available to clinicians who treat CLL. The Eastern Cooperative
(National 559
Institutes
of Health).
560
Chronic lymphocytic leukemia: therapeutic options 0 J. M. BENNETT
Oncology Group currently is proposing a randomized trial of combination chemtherapy against TBI in an attempt to confirm the observations which Johnson and Ruhl present in this issue. Since infectious complications present a major clinical problem in CLL (they occur in over 50% of patients) the potential for
re-establishment of normal host immunity in this disease is very appealing. Hopefully, the future of therapy for CLL will include a combined modality approach, utilizing both TBI and combination chemotherapy, with the ultimate goal, greater than 50% complete remission. Only when this is accomplished will the overall survival curve be improved.
REFERENCES lymphocytic leukemia. Cancer 33: 555462, 1. Han, T., Ezdinli, E.Z., Shimaoka, K., Desai, 1974. D.V.: Chlorambucil versus combined chloram4. Rundles, R. W., Grizzle, J., Bono, V.H., Jonsson, buck corticosteroid therapy in chronic lymU., Huguley, C.M., Jr., Corley, C.C., Jr.: phocytic leukemia. Cancer 32: 502-508, 1973. Comparison of CB 1348 and CB 1364. Cancer 2. Johnson, R.E., Ruhl, U.: Treatment of chronic Ckemotherapy Rpts 16: 223-230, 1962. lymphocytic leukemia with emphasis on total body irradiation. ht. J. Radiat. Oncol. Biol. 5. Zippin, C., Cutler, S.J., Reeves, W.J., Jr., Lum, D.: Survival in chronic lymphocytic leukemia. Phys. 1: 387-397, 1976. Blood 42, 367-376, 1973. 3. Knospe, W.H., Loeb, U., Jr., Huguley, C.M., Jr.: Bi-weekly chlorambaucil treatment of chronic
0
1976,
Vol. 1. pp. 559-560.
Pergamon Press.
Printed in the U.S.A.
Editorials CHRONIC LYMPHOCYTIC LEUKEMIA: THERAPEUTIC OPTIONS-! JOHN University
M. BENNETT,
of Rochester Cancer Center and Department 601 Elmwood Avenue, Rochester,
Chronic Lymphocytic
Leukemia
M.D. of Medicine, Strong Memorial Hospital, NY 146442,U.S.A.
(CLL), Total body irradiation.
Despite a prevailing attitude that chronic lymphocytic leukemia (CLL) is a relatively benign illness, the overall five year survival is no higher than 55%, comparable to that of in breast cancer.5 The considerable variability
the duration of this disease and its prognosis is, to a considerable extent, based on whether the disease is “indolent” or “active”. The traditional therapy for CLL has been either no treatment for the indolent cases or a single chemotherapeutic alkylating agent such as chlorambucil or cyclophosphamide. Approximately 10% of patients treated with either daily chlorambucil’ or intermittent high dose “pulse” chlorambuciL3 enter complete remission (CR) with remission durations of less than 2 years. The addition of corticosteroids, usually prednisone, may improve the CR rate to approximately 20%. Han et al.’ described three CR’s of 15 patients treated with daily chlorambucil and low dose prednisone. In a more recent study by the Southeastern Cancer Study Group (SEG 355), four complete remissions were noted out of 30 evaluable cases, utilizing the intermittent high dose chlorambucil program combined with five days of prednisone treatment for a response rate of 13% (oral communication, J. W. Keller, W. Knopse, and C. M. Huguley, Jr., SEG Operations Office, 16 January 1976). Finally, the combination of phase-specific agents (such as cytosine arabinoside) with alkylating agents and corticosteroids may
Supported in part by United States Public Health Service grants: CA 11083 and CA 11198
increase the complete remission rate above 30% based on preliminary studies (written communication, Jeane P. Hester, 22 July 1974). In an article in this issue, Johnson and Ruhl* have updated their early report of the effectiveness of total body irradiation (TBI) with a five year follow up of 83% of the population treated. The patients were all in the “active” category; of 42 treated there were 14 complete remissions. Toxicity was modest, although the long term effects of ionizing radiation as a potential inducing agent of second malignancies is discussed. The median survival of the group was 65 months, almost twice that of a much smaller group of patients treated with daily chlorambucil or cyclophosphamide. Of great interest was the restoration of normal immunoglobulins in four of the patients who achieved complete remission, suggesting the re-immergence of a normal immunoblast stem cell line. It is not clear to what extent corticosteroids were employed by the authors in the TBI series; the assignment of treatment modalities surely was not random, and the assessment criteria were modified from those in common use by the cooperative groups. Nevertheless, TBI must be viewed as a significant addition to the therapeutic armamentarium that is available to clinicians who treat CLL. The Eastern Cooperative
(National 559
Institutes
of Health).
560
Chronic lymphocytic leukemia: therapeutic options 0 J. M. BENNETT
Oncology Group currently is proposing a randomized trial of combination chemtherapy against TBI in an attempt to confirm the observations which Johnson and Ruhl present in this issue. Since infectious complications present a major clinical problem in CLL (they occur in over 50% of patients) the potential for
re-establishment of normal host immunity in this disease is very appealing. Hopefully, the future of therapy for CLL will include a combined modality approach, utilizing both TBI and combination chemotherapy, with the ultimate goal, greater than 50% complete remission. Only when this is accomplished will the overall survival curve be improved.
REFERENCES lymphocytic leukemia. Cancer 33: 555462, 1. Han, T., Ezdinli, E.Z., Shimaoka, K., Desai, 1974. D.V.: Chlorambucil versus combined chloram4. Rundles, R. W., Grizzle, J., Bono, V.H., Jonsson, buck corticosteroid therapy in chronic lymU., Huguley, C.M., Jr., Corley, C.C., Jr.: phocytic leukemia. Cancer 32: 502-508, 1973. Comparison of CB 1348 and CB 1364. Cancer 2. Johnson, R.E., Ruhl, U.: Treatment of chronic Ckemotherapy Rpts 16: 223-230, 1962. lymphocytic leukemia with emphasis on total body irradiation. ht. J. Radiat. Oncol. Biol. 5. Zippin, C., Cutler, S.J., Reeves, W.J., Jr., Lum, D.: Survival in chronic lymphocytic leukemia. Phys. 1: 387-397, 1976. Blood 42, 367-376, 1973. 3. Knospe, W.H., Loeb, U., Jr., Huguley, C.M., Jr.: Bi-weekly chlorambaucil treatment of chronic
