chiniofon and Leukemia--Myeloid

It is now known that syngeneic transplantation, T lymphocyte depletion and absence of graft-versus-host disease all increase the risk of relapse following allogeneic transplantation for the myeloid leukemias, both acute and chronic. Leukemia-specific immune responses appear to play a major role in the therapy of the myeloid leukemias. In recent years attempts have been made to better characterize and effectively utilize these antileukemic immune responses, concentrating on clinical states of minimal residual disease. This review will discuss the role of such immunotherapy following autologous bone marrow transplantation for myeloid leukemias, and will focus on recent experience and ongoing clinical trials using the novel immunomodulator Linomide.

Topics: Adjuvants, Immunologic; Humans; Hydroxyquinolines; Immunotherapy; Interferons; Interleukin-2; Killer Cells, Natural; Leukemia, Myeloid; T-Lymphocytes

Roquinimex, Linomide, is a quinoline derivative with pleiotropic immunomodulatory activities which has been shown to enhance NK function. As part of a phase III placebo-controlled multicenter study patients were randomized to receive Roquinimex, 0.2 mg/kg body weight, or a placebo twice weekly for a duration of 2 yr following autologous bone marrow transplantation for acute myeloid leukemia in remission. At Arhus University Hospital 7 patients were randomized to receive the active drug and 6 to receive the placebo. Surviving patients were followed for 2 yr with immunological monitoring of their natural immune effector cells (NK- and LAK cell activity). Peripheral heparinized blood samples were obtained twice before the onset of conditioning therapy and at several time points after ABMT, and whole blood samples were analyzed by flow cytometry for the detection of leukocyte differentiation antigens as well as by 4 h 51Cr release assays for cytotoxicity. In contrast to previous experience with Linomide, in the present study we found that at 36 wk or later time points Linomide patients exhibited a significant suppression of circulating natural effector cell number and activity when compared with the control group. These observations underline the need for further exploration into novel and manageable immunostimulators.

Topics: Acute Disease; Adjuvants, Immunologic; Adult; Bone Marrow Transplantation; Cytotoxicity, Immunologic; Female; Humans; Hydroxyquinolines; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Leukemia, Myeloid; Leukocytes; Male; Middle Aged; Transplantation, Autologous; Treatment Outcome

Inhibitors of complex III increased the DNA strand scission induced by t-butylhydroperoxide (tB-OOH) and cumene hydroperoxide but did not affect DNA damage induced by H2O2. The hypothesis that these effects are selectively linked to inhibition of the electron transport from cytochrome b to cytochrome c1 is validated by the following observations: (1) two complex III inhibitors, antimycin A and 2-heptyl-4-hydroxyquinoline N-oxide, enhanced the tB-OOH-induced DNA cleavage over the same concentration range as that in which inhibition of oxygen consumption was observed; (2) the complex III inhibitor-mediated enhancement of tB-OOH-induced DNA damage was abolished by the complex I inhibitor rotenone or by glucose omission, and (3) the enhancing effects of antimycin A were not observed in respiration-deficient cells. The mechanism whereby the complex III inhibitors potentiate DNA cleavage promoted by tB-OOH was subsequently investigated with intact as well as permeabilized cells. H2O2, produced at the level of mitochondria via a Ca2+-dependent process, was found to account for the enhancing effects of antimycin A.

Topics: Antimycin A; Benzene Derivatives; Calcium; Cell Respiration; DNA Damage; DNA, Single-Stranded; Electron Transport; Electron Transport Complex III; Enzyme Inhibitors; Glucose; Humans; Hydrogen Peroxide; Hydroxyquinolines; Leukemia, Myeloid; Mitochondria; Peroxides; Rotenone; tert-Butylhydroperoxide; Tumor Cells, Cultured

Roquinimex is being used for posttransplantation immunotherapy of autologous bone marrow transplantation for acute and chronic myelogenous leukemia. This immunotherapeutic agent is a cytokine inducer and may induce an autologous graft-versus-host (GVH) and graft-versus-tumor reactions.. Our purpose was to examine patients undergoing this immunotherapy for clinical signs and symptoms of acute GVH reactions and to correlate these symptoms with their clinical outcome.. We studied eight patients receiving requinimex therapy.. We found autologous GVH reactions in three of eight patients (38%) treated with this immunotherapy. Their disease was manifested by localized or widespread violaceous papules that on histologic evaluation were compatible with a grade II GVH reaction. The acute cutaneous GVH reaction was associated with eccrine sweat gland necrosis, a dermatologic toxicity usually associated with chemotherapy.. Long-term studies of larger numbers of patients treated with this immunotherapy will determine whether these GVH reactions confer significant, sustained, antitumor effects.

Topics: Acute Disease; Adjuvants, Immunologic; Bone Marrow Transplantation; Female; Graft vs Host Reaction; Humans; Hydroxyquinolines; Leukemia, Myeloid; Male; Middle Aged; Necrosis; Skin; Skin Diseases; Sweat Glands; Transplantation, Autologous

The use of 111Indium oxine as a platelet label for the performance of platelet life-span studies has been examined. Platelet life-span in normal subjects varied between 8 X 10 and 10 X 36 d. Patients with primary thrombocythaemia had clearly reduced platelet life-span whether or not they presented with vascular occlusion and this abnormality persisted after reduction of the platelet count to normal by busulphan therapy. Patients with similarly elevate platelet counts due to chronic granulocytic leukaemia or after splenectomy had platelet life-span values in the normal range. Plasma beta-TG levels could not be used to predict platelet life-span in these groups of patients. Measurement of platelet life-span using 111Indium labelled platelets is a useful technique in the examination of platelet function in occlusive vascular disease.

Topics: Adult; Aged; beta-Thromboglobulin; Blood Platelets; Cell Survival; Humans; Hydroxyquinolines; Indium; Leukemia, Myeloid; Lymphoma; Male; Middle Aged; Myeloproliferative Disorders; Organometallic Compounds; Oxyquinoline; Platelet Count; Polycythemia Vera; Radioisotopes; Splenectomy; Thrombocytosis; Time Factors