roquinimex and Leukemia--Myeloid--Acute

Roquinimex, Linomide, a quinoline derivative with pleiotropic immunomodulatory activity, has previously been shown to enhance natural killer (NK) cell number and activity after ABMT in patients with AML. In this study 278 AML patients in remission were randomized to receive Roquinimex 0.2 mg/kg body weight or placebo twice weekly for 2 years following ABMT. Out of 139 patients in each group, 109 Roquinimex patients and 108 placebo patients were in their first CR. Median age at inclusion was 41 years for Roquinimex patients and 39 years for placebo patients. Twelve patients in each group had their marrow purged prior to reinfusion. Relapse and death were study endpoints. Surviving patients were followed for 2.6 to 6. 9 years. The total number of relapses was 60 in the Roquinimex group and 63 in the placebo group (not significant). Leukemia-free and overall survivals were similar in the two groups. Recovery of platelet counts was significantly delayed in the Roquinimex group as compared to placebo. No other significant differences regarding toxicity parameters were recorded. In conclusion, previous findings on NK cells could not be confirmed and the study showed no benefit for Roquinimex over placebo regarding relapse or survival following ABMT for AML in remission.

Topics: Adolescent; Adult; Aged; Angiogenesis Inhibitors; Bone Marrow Purging; Bone Marrow Transplantation; Child; Combined Modality Therapy; Disease-Free Survival; Female; Follow-Up Studies; Humans; Hydroxyquinolines; Killer Cells, Natural; Leukemia, Myeloid, Acute; Male; Middle Aged; Placebos; Recurrence; Survival Rate; Time Factors; Transplantation, Autologous

Immunostimulatory therapy is at present considered after autologous bone marrow transplantation (ABMT) in order to mimic the allogeneic graft-versus-leukemia effect and thereby reduce the relapse rate. In a pilot study, five adults with acute myeloid leukemia were treated with the new immunomodulator Linomide post-ABMT. Linomide (0.3 mg/kg/week orally) was given in cycles of three weeks followed by three weeks of rest for up to six months. During treatment periods cyclic increases of CD56+CD3- and CD16+ NK cells were observed in parallel with enhanced cytotoxic activity of patient cells against both the NK-sensitive K562 and NK-resistant Daudi cell lines. A cyclic increase of CD14+ monocytic cells was also recorded. The proliferative responses of patient cells to PHA and allogeneic cells (MLC) were enhanced during Linomide therapy. The in vitro production of TNF alpha, IFN gamma, and IL-1 followed the same cyclic increase during treatment periods. Side effects were generally mild, and no harmful effects on engraftment were seen. Linomide therapy after ABMT thus induces a broad immunostimulation that offers a potential benefit with regard to leukemia-free survival.

Topics: Adjuvants, Immunologic; Antigens, CD; Bone Marrow Transplantation; Cytokines; Female; Humans; Hydroxyquinolines; Killer Cells, Natural; Leukemia, Myeloid, Acute; Lymphocyte Activation; Male; Middle Aged; Monocytes; Pilot Projects; T-Lymphocytes

Topics: Adjuvants, Immunologic; Antibodies, Monoclonal; Graft vs Host Disease; Humans; Hydroxyquinolines; Immunotherapy; Interleukin-2; Leukemia, Myeloid, Acute; Leukocyte Transfusion; Neoplasm, Residual