Chronic myelocytic leukemia as a second neoplasia in the course of chronic lymphocytic leukemia. Case report and review of the literature.

A patient with chronic lymphocytic leukemia developed Ph1-positive chronic myelocytic leukemia after a 6-yr course of CLL. Chemotherapy for CLL consisted of chlorambucil and steroids, later vincristine and bleomycin; after resistance to these agents, cyclophosphamide, vincristine and prednisolone were applied. When CML was diagnosed, we found two morphologically distinct populations of malignant cells in the bone marrow; the Ph1-chromosome was identified, and immunological surface marker studies also demonstrated two distinct malignant cell populations. Up to now, only five cases of CML have been reported following CLL and one case accompanying it. Three patients were treated with cytostatic drugs, one patient by total body irradiation and two patients received no therapy. At present, it is not clear whether the development of CML during CLL represents a therapy-induced complication or an increased susceptibility to second malignancies due to the leukemic process itself or possibly to immunological deficiencies in CLL. Since two patients received no treatment for CLL, previous therapy does not seem to be a prerequisite for the development of CML.

Modulation of immune functions by long-term treatment with recombinant interferon-alpha 2 in a patient with hairy-cell leukemia.

Serial in vitro immune function studies of peripheral blood mononuclear cells (PBMC) were carried out during the long-term treatment with recombinant interferon-alpha 2 (IFN-alpha 2) in a patient with hairy-cell leukemia (HCL). Parameters of B- and T-cell functions as well as NK-cell activity were determined. Treatment with IFN-alpha 2 is associated with temporary and long-term depression of some immune functions, but can also normalize immune responses: in vitro-induced immunoglobulin synthesis, which was normal at diagnosis, was inhibited during the first weeks of IFN therapy but subsequently rose to normal levels. Lymphocyte proliferative responses to mitogens and antigens that were markedly reduced pretherapeutically were further depressed by IFN treatment but, with the exception of pokeweed mitogen (PWM)-induced responses, normalized completely by the 15th to 17th week of treatment. Cocultivation of PBMC with monocytes from normal individuals enhanced depressed lymphocyte proliferative responses. NK-cell activity, which was low at diagnosis, did not rise to the normal range during IFN treatment, but rapidly normalized when IFN therapy was stopped. A discussion is presented on the implications of the alteration of immune functions by treatment with IFN.

Immunosuppressive effects of recombinant interferon-alpha during long-term treatment of cancer patients.

Interferons (IFN) are known to modulate immune responses in an either stimulatory or inhibitory manner. Most of the knowledge about immunomodulatory activities of IFN comes from investigations of IFN effects on cells in vitro. This study examines the influence which long-term treatment with recombinant interferon-alpha 2 exerts on immune functions in cancer patients. Serial in vitro immune function studies of peripheral blood mononuclear cells were done to determine parameters of B-cell and T-cell functions as well as natural killer (NK)-cell activity. The authors detected profound suppression of in vitro immunoglobulin synthesis and lymphocyte proliferation as well as depression of NK-cell activity during IFN treatment. All suppressed immune functions normalized on discontinuation of IFN therapy. The authors conclude from these observations that, apart from their beneficial effects, IFN produce substantial immunosuppression.