title: Interleukin 4 therapy for patients with chronic lymphocytic leukaemia: a phase I/II study.
abstract: Interleukin 4 (IL-4) is a pleiotropic type II cytokine which has been shown to have a direct killing effect on lymphoma and B-cell chronic lymphocytic leukaemia (B-CLL) cells in vitro. The clinical effects and toxicity of IL-4 treatment in patients with B-CLL were evaluated. Fourteen patients with B-CLL who were in partial remission after chemotherapy received one, two or three 8-week cycles of escalating doses (2, 4 or 6 microg/kg/d s.c.) of IL-4 for 3 d/week. Clinical response was analysed after each treatment cycle and toxicity was monitored continuously. Ten patients (71%) had progressive disease (PD) during IL-4 treatment. This was mainly attributable to an increase (two- to fourfold) of the blood lymphocyte count during IL-4 therapy. After cessation of IL-4 treatment, the lymphocytosis decreased spontaneously in 8 out of 12 evaluable patients. Splenomegaly remained unchanged in 7/7 patients, whereas enlarged lymph nodes were reduced by > 50% in 1/13 patients and by 25-50% in 4/13 patients. None of the patients achieved an objective tumour regression (complete or partial remission). A temporary increase (16-60%) of the platelet count was observed during IL-4 treatment. The platelet count decreased in 8/11 patients after the end of IL-4 therapy. World Health Organization (WHO) grade I/II fever, arthralgia and fatigue was observed in one-third of the patients and was more commonly seen with the highest dose (6 microg/kg/d). One patient developed pulmonary oedema and WHO grade III neutropenia was recorded in three patients. IL-4 was well tolerated by most patients in an outpatient setting. The anti-tumour activity observed in previous in vitro studies was not verified by the present in vivo trial which showed that IL-4 may instead increase the number of CLL cells in blood, indicating that IL-4 may have induced a stimulatory or antiapoptotic effect on the CLL cells in blood. These results may have important implications for the development of immunotherapy of CLL. In addition, the potential platelet-stimulatory effect of IL-4 warrants further studies.
authors.affiliation: Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Lundin
authors.forename: E
authors.initials: E
authors.lastname: Kimby
authors.forename: L
authors.initials: L
authors.lastname: Bergmann
authors.forename: T
authors.initials: T
authors.lastname: Karakas
authors.forename: H
authors.initials: H
authors.lastname: Mellstedt
authors.forename: A
authors.initials: A
authors.lastname: Osterborg
mesh_terms: D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D018655:Lymphocyte Count; D008218:Lymphocytosis; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D011654:Pulmonary Edema / Q000209:etiology; D017211:Treatment Failure
chemical_list: D015847:Interleukin-4