Recombinant interleukin-2 (rIL-2) after autologous bone marrow transplantation (BMT): a pilot study in 19 patients.
In vivo use of rIL-2 autologous BMT may be the means of reproducing a kind of "adoptive immunotherapy" from grafted cells after allogeneic BMT. This approach may enhance the spontaneous generation of cytotoxic T-cells and NK cells which are presumably involved in this immunotherapy. Potential risks of such an approach would be to increase the usual toxicity of rIL-2 and to jeopardize the hemopoietic reconstitution. To determine the feasibility of this approach we have treated 19 poor prognosis patients with a succession of autologous BMT followed 78 +/- 12 days later by a continuous infusion of rIL-2. Eighteen million international units (IU) per m2 per day of Proleukine (CETUS, Amsterdam, The Netherlands) were administrated over 6 or 12 days. No patient died of the procedure. Clinical toxicity related to rIL-2 was not increased. Hemopoietic toxicity, significant both for platelets and granulocytes, was transient. Immune stimulation was dramatic for lymphocytes and subpopulations (CD3+ and NK cells) and for cytolytic functions (NK and LAK activity). This trial establishes the feasibility of administration of high doses of rIL-2, 2 months after autologous BMT. In this setting a 6 day period of continuous infusion of 18 million per m2 per day of Proleukine appears to be a regularly tolerable dosage conducting to a major immune activation and invites further studies to determine the clinical impact of such an approach.
Blaise
D
D
BMT Unit, Institut Paoli Calmettes, Marseille, France.
Viens
P
P
Olive
D
D
Stoppa
A M
AM
Gabert
J
J
Pourreau
C N
CN
Attal
M
M
Gaspard
M H
MH
Mannoni
P
P
Jasmin
C
C
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000380:Agranulocytosis / Q000139:chemically induced; D001002:Anuria / Q000139:chemically induced; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004066:Digestive System Diseases / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006087:Graft vs Host Reaction / Q000187:drug effects; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007376:Interleukin-2 / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000601:surgery*; D010865:Pilot Projects; D011379:Prognosis; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced; D014182:Transplantation, Autologous
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D011994:Recombinant Proteins