A pilot study of high-dose interleukin-3 treatment of relapsed follicular small cleaved-cell lymphoma: hematologic, immunologic, and clinical results.
The growth stimulatory effects of interleukin-3 (IL-3) on normal hematopoietic progenitor cells are well established, and clinical trials using IL-3 after bone marrow transplantation for various malignancies including lymphomas are frequently conducted. Although the IL-3 receptor is expressed on the surfaces of follicular small cleaved-cell lymphoma (FSCCL) cells, the in vivo effects of IL-3 on FSCCL have not been studied previously. Because our preclinical data suggested that IL-3 may have dose-dependent inhibitory effects on FSCCL cells in vitro, we treated eight FSCCL patients with high-dose IL-3 in an outpatient setting. Each patient received 1 mg/m2 of IL-3 subcutaneously daily for 14 days followed by 7 days without IL-3. After three courses (9 weeks), the patients were evaluated for clinical responses. One patient had a minor response, and four had no responses. Three patients who had progressive disease before IL-3 treatment continued to have progressive disease. In two patients with bone marrow involvement with lymphoma, IL-3 had no effect on FSCCL cells. One patient with peripheral blood involvement with FSCCL cells that expressed IL-3 receptors had temporary growth arrest of the circulating malignant cells. IL-3 significantly increased the absolute neutrophil count in seven patients (87%) but had little effect on the number of normal circulating B cells. There was an increase in the number of circulating natural killer cells and CD8+ cells in four patients. Treatment was very well tolerated; no life-threatening toxicities were observed. The most common toxicities were injected conjunctivae (100%), fever (100%), fatigue (87%), and skin rash (75%). Most of the side effects subsided with the continued use of IL-3. These preliminary results suggest that high-dose IL-3 does not stimulate the growth of FSCCL cells in vivo and, in some instances, may cause growth inhibition.
Younes
A
A
Department of Hematology, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
Sarris
A
A
Consoli
U
U
Rodriguez
A
A
McLaughlin
P
P
Huh
Y
Y
Starry
S
S
Cabanillas
F
F
Andreeff
M
M
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D006131:Growth Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007377:Interleukin-3 / Q000009:adverse effects / Q000627:therapeutic use*; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D017239:Paclitaxel / Q000627:therapeutic use; D010865:Pilot Projects; D016896:Treatment Outcome
D006131:Growth Inhibitors; D007155:Immunologic Factors; D007377:Interleukin-3; D017239:Paclitaxel