Medical Hypotheses Medical Hypolkses (1991) 35. 182-183 Q L.nqnmn Group UK Lid 1991
Intractable Chronic Lymphocytic Interferon
Leukemia and
R. SCHREK Research Service, VA Hospital, Hines, IL, USA (Correspondence
to: 2 Atrium Way, Elmhurst, IL 60126, USA)
Abstract - The hypothesis that interferon may be useful for intractable chronic lymphocytic leukemia (CLL) is based on two incidental findings: first, the similarity in the in vitro radioresistance of the blood lymphocytes of intractable CLL and of hairy cells; secondly, the similarity of the incidence of intractable CLL patients and the incidence of CLL patients who respond to interferon treatment.
Introduction Chronic Lymphocytic Leukemia (CLL) was considered a homogeneous disease with low malignancy and was treated with chemotherapy, usually with partial or complete remission. In a study of CLL cells, phase contrast microscopy found a few peculiar cells which were called ‘hairy cells’ (1). Further work demonstrated that some patients had a specific disease, Hairy Cell Leukemia (HCL) which was different from classic CLL (2). These findings led to studies of the treatment of HCL with interferon-a (3). A review of the treatment of HCL with interferon showed that 96% of 158 patients responded to the treatment with complete or partial remission or minor responses (4). Classic CLL is apparently a homogeneous disease according to microscopy, but in vitro radiosensitivity tests showed that some of the CLL patients had radioresistant blood lymphocytes (5). These patients were clinically resistant both to radiotherapy and chemotherapy and were therefore called intractable CLL which is a distinct disease from responsive CLL Date received 6 September 1990 Date accepted 20 November 1990
(6). Lymphocytes of intractable CLL were similar to hairy cells with respect to radioresistance (1). The similarity suggests the hypothesis that the two types of cells may have similar pharmacologic reactions to interferon. The usefulness of interferon for HCL led to studies on the effect of this reagent on CLL patients. A review of these studies on 67 CLL patients showed that 18% underwent partial remission (4). The question arises whether interferon acted on intractable CLL, responsive CLL or both. The incidence of intractable CLL in unselected CLL patients was found in three studies to be 19,24 and 264, with an average of 23% (7). There seems to be a coincidence between the 23% incidence for intractable CLL and 18% response of CLL patients to interferon. The similarity in the two figures may be only a coincidence or may be circumstantial evidence that interferon is a useful agent in intractable CLL. Recently, other agents have been found to be useful for HCL (8,9). Research studies on the treatment of intractable CLL encounter the problems of the low
182
INTRACI’ABLE CHRONIC LYMPHOCPI-IC LEUKEMIA AND INTERFERON
incidence of this disease and the difficulties of the in vitro test for radiosensitivity of cells (10). References 1.
Schrek R, Donnelly WJ. ‘Hairy’ cells in lymphoreticular neoplastic disease and ‘Flagellated’ cells of normal lymph nodes. Blood 27: 199, 1966. 2. Golomb HM, Braylan R, Polliack A. ‘Hairy’ cell leukaemia (Leukaemic reticuloendotheliosis): a scanning electron microscopic study of eight cases. Br J Haematol 29: 455, 1975. 3. Golomb HM, Ratain M, Vardiman JW. Sequential treatment of hairy cell leukemia: A new role for interferon. p 311 in Important Advances in Oncology. J.B. Lippincott Company, Philadelphia, 1986. 4. Roth MS, Bunn PA, Foon KA. Interferon therapy for lymphoproliferative disorders. p 231 in Cancer Treatment and Research. (Bennett JM, Focn KA eds) Kluwer Academic Pub-
183
lishers, 1988. 5. Schrek R, Leithold SL, Friedman IA, Best WR. Clinical evaluation of an in vitro test for radiosensitivity of leukemic lymphocytes. Blood 20: 432, 1962. 6. Schrek R. Diifetmces between responsive and intractable chronic lympbocytic leukemia. Med Hypotheses 31: 81.1990. 7. Schrek R. Intractable chronic lymphocytic leukemia. J Natl Cancer Inst. 80: 604, 1988. 8. Pin, LD, Varrera CT, Carson DA, Buetler E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-Chorodeoxyadenosine. New Engl J Med 322: 1117, 1990. 9. Black M, Lepa-Ziniga JL, Doig R, Quesada JR. Durable complete remission after Z’deoxycorformycin treatment in patients with hairy celJ leukemia resistant to interferon alpha. Am J Hemato133: 205,199O. 10. Schrek R. Essential in vitro tests before treatment of patients with intractable chronic lymphocytic leukemia. Acta Haematol. In Press.
Intractable Chronic Lymphocytic Interferon
Leukemia and
R. SCHREK Research Service, VA Hospital, Hines, IL, USA (Correspondence
to: 2 Atrium Way, Elmhurst, IL 60126, USA)
Abstract - The hypothesis that interferon may be useful for intractable chronic lymphocytic leukemia (CLL) is based on two incidental findings: first, the similarity in the in vitro radioresistance of the blood lymphocytes of intractable CLL and of hairy cells; secondly, the similarity of the incidence of intractable CLL patients and the incidence of CLL patients who respond to interferon treatment.
Introduction Chronic Lymphocytic Leukemia (CLL) was considered a homogeneous disease with low malignancy and was treated with chemotherapy, usually with partial or complete remission. In a study of CLL cells, phase contrast microscopy found a few peculiar cells which were called ‘hairy cells’ (1). Further work demonstrated that some patients had a specific disease, Hairy Cell Leukemia (HCL) which was different from classic CLL (2). These findings led to studies of the treatment of HCL with interferon-a (3). A review of the treatment of HCL with interferon showed that 96% of 158 patients responded to the treatment with complete or partial remission or minor responses (4). Classic CLL is apparently a homogeneous disease according to microscopy, but in vitro radiosensitivity tests showed that some of the CLL patients had radioresistant blood lymphocytes (5). These patients were clinically resistant both to radiotherapy and chemotherapy and were therefore called intractable CLL which is a distinct disease from responsive CLL Date received 6 September 1990 Date accepted 20 November 1990
(6). Lymphocytes of intractable CLL were similar to hairy cells with respect to radioresistance (1). The similarity suggests the hypothesis that the two types of cells may have similar pharmacologic reactions to interferon. The usefulness of interferon for HCL led to studies on the effect of this reagent on CLL patients. A review of these studies on 67 CLL patients showed that 18% underwent partial remission (4). The question arises whether interferon acted on intractable CLL, responsive CLL or both. The incidence of intractable CLL in unselected CLL patients was found in three studies to be 19,24 and 264, with an average of 23% (7). There seems to be a coincidence between the 23% incidence for intractable CLL and 18% response of CLL patients to interferon. The similarity in the two figures may be only a coincidence or may be circumstantial evidence that interferon is a useful agent in intractable CLL. Recently, other agents have been found to be useful for HCL (8,9). Research studies on the treatment of intractable CLL encounter the problems of the low
182
INTRACI’ABLE CHRONIC LYMPHOCPI-IC LEUKEMIA AND INTERFERON
incidence of this disease and the difficulties of the in vitro test for radiosensitivity of cells (10). References 1.
Schrek R, Donnelly WJ. ‘Hairy’ cells in lymphoreticular neoplastic disease and ‘Flagellated’ cells of normal lymph nodes. Blood 27: 199, 1966. 2. Golomb HM, Braylan R, Polliack A. ‘Hairy’ cell leukaemia (Leukaemic reticuloendotheliosis): a scanning electron microscopic study of eight cases. Br J Haematol 29: 455, 1975. 3. Golomb HM, Ratain M, Vardiman JW. Sequential treatment of hairy cell leukemia: A new role for interferon. p 311 in Important Advances in Oncology. J.B. Lippincott Company, Philadelphia, 1986. 4. Roth MS, Bunn PA, Foon KA. Interferon therapy for lymphoproliferative disorders. p 231 in Cancer Treatment and Research. (Bennett JM, Focn KA eds) Kluwer Academic Pub-
183
lishers, 1988. 5. Schrek R, Leithold SL, Friedman IA, Best WR. Clinical evaluation of an in vitro test for radiosensitivity of leukemic lymphocytes. Blood 20: 432, 1962. 6. Schrek R. Diifetmces between responsive and intractable chronic lympbocytic leukemia. Med Hypotheses 31: 81.1990. 7. Schrek R. Intractable chronic lymphocytic leukemia. J Natl Cancer Inst. 80: 604, 1988. 8. Pin, LD, Varrera CT, Carson DA, Buetler E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-Chorodeoxyadenosine. New Engl J Med 322: 1117, 1990. 9. Black M, Lepa-Ziniga JL, Doig R, Quesada JR. Durable complete remission after Z’deoxycorformycin treatment in patients with hairy celJ leukemia resistant to interferon alpha. Am J Hemato133: 205,199O. 10. Schrek R. Essential in vitro tests before treatment of patients with intractable chronic lymphocytic leukemia. Acta Haematol. In Press.
