Effects of escalating doses of recombinant human interleukin-2 in correcting functional T-cell defects following autologous bone marrow transplantation for lymphomas and solid tumors.
High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in the treatment of malignancies is often associated with immune deficiency following transplantation, possibly contributing to tumor relapse or fatal infection. Interleukin 2 (IL-2), which enhances major histocompatibility complex (MHC)-unrestricted cytotoxicity in vitro, can be applied in vivo as immunotherapy to reduce these potential complications. Recombinant human IL-2 (rIL-2) was administered by continuous i.v. infusion for four courses in 19 patients following ABMT for lymphomas and solid tumors. The patients were assigned to five groups of escalating doses of rIL-2 ranging from 3 to 30 x 10(6) IU/m2/day. The immunological effects and toxicity were monitored. After a transient reduction of lymphocytes in the peripheral blood, a significant lymphocytosis was observed during the rIL-2 infusion with an augmentation of CD2+, CD25+, and CD8(+)-Ia+ T cells and a dose-related increase of CD56+ lymphocytes. Natural killer (NK) activity appeared enhanced in patients treated with as little as 6 x 10(6) IU/m2/day. No statistically significant increase in lymphokine-activated killer (LAK) activity was seen after rIL-2, when compared to LAK activity following ABMT prior to rIL-2 administration. Administration of exogenous rIL-2 to patients who have undergone ablative chemotherapy and ABMT has a role in restoring defective T-cell function. Further trials defining those patients most likely to benefit from rIL-2 integrated with ablative chemotherapy and ABMT are now warranted.
Experimental Oncology and Hematology Laboratory, Catholic University of Louvain, Brussels, Belgium.
A
A
Bosly
T
T
Guillaume
P
P
Brice
Y
Y
Humblet
P
P
Staquet
C
C
Doyen
B
B
Chatelain
C R
CR
Franks
C
C
Gisselbrecht
M
M
Symann
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001772:Blood Cell Count / Q000187:drug effects; D016026:Bone Marrow Transplantation / Q000473:pathology*; D018801:CD2 Antigens; D016827:CD8 Antigens / Q000032:analysis; D018288:Carcinoma, Small Cell / Q000601:surgery*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002822:Choriocarcinoma / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology; D008175:Lung Neoplasms / Q000601:surgery*; D008223:Lymphoma / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000601:surgery*; D010641:Phenotype; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D014182:Transplantation, Autologous
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins