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Interleukin 4 therapy for patients with chronic lymphocytic leukaemia: a phase I/II study
Author(s) -
Lundin J.,
Kimby E.,
Bergmann L.,
Karakas T.,
Mellstedt H.,
Österborg A.
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02525.x
Subject(s) - medicine , lymphocytosis , gastroenterology , chronic lymphocytic leukemia , chemotherapy , lymphoma , toxicity , b symptoms , immunology , leukemia
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 µg/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 µg/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.