Recombinant interleukin-2 treatment before and after autologous stem cell transplantation in hematologic malignancies: clinical and immunologic effects.
Autologous bone marrow transplantation (ABMT) for hematologic malignancies is associated with a high relapse rate. Interleukin-2 (IL-2) administration is a therapy that may prevent relapse if used when the tumor burden is minimal. In this study we administered recombinant IL-2 (rIL-2) therapy to 12 patients affected by hematologic malignancies either before or after autologous stem cell transplantation (ASCT). rIL-2 was given by a 6 day continuous intravenous infusion with escalating doses, up to 18 x 10(6)/m2/day, depending on patient tolerance. The functional immune responses of the patients were assessed as natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activities and in vitro interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) synthesis. During rIL-2 treatment, the expected side effects occurred; only 3 patients, who showed severe cardiovascular toxicity, required suspension of the treatment. All toxicities reversed after the end of the therapy. Immunologic monitoring was carried out the day before starting rIL-2 infusion and then repeated on days 3, 7, and 14 after rIL-2 was discontinued. Following every rIL-2 course, a pronounced increase in CD3+, CD8+, CD56+ cells was found, with a peak value on day 3. The NK and LAK activities showed a significant increase on day 3 (p < 0.001) over pretherapy values; the increase lasted until day 14, although the difference at later time points was not significant. Before transplant the synthesis of both IFN-gamma and TNF-alpha decreased following rIL-2 therapy, whereas higher levels of these lymphokines were found after posttransplant rIL-2 courses.(ABSTRACT TRUNCATED AT 250 WORDS)
De Laurenzi
A
A
Department of Haematology, S. Camillo Hospital, Rome, Italy.
Iudicone
P
P
Zoli
V
V
De Rosa
L
L
Guglielmetti
M
M
Pescarollo
A
A
Papetti
C
C
Pacilli
L
L
Lapponi
P
P
Petti
N
N
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D003601:Cytotoxicity Tests, Immunologic; D005240:Feasibility Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007938:Leukemia / Q000097:blood / Q000276:immunology / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000276:immunology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000276:immunology / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D007376:Interleukin-2; D011993:Recombinant Fusion Proteins