Hematologic and immunologic effects of the systemic administration of recombinant interleukin-2 after autologous bone marrow transplantation.
T cells from allogeneic bone marrow grafts are responsible for a graft versus leukemia effect. Use of recombinant Interleukin-2 (rIL-2) after autologous bone marrow transplantation (BMT) may enhance immune function and hopefully reproduce the allogeneic reaction. We report here the hematologic and immunologic changes observed in the first 10 patients of a phase 1 trial studying the infusion of IL-2 after autologous BMT. All patients had high-risk malignancies and received 6 days of a constant infusion of IL-2 (Eurocetus, Amsterdam, The Netherlands) at dose of 3 x 10(6) Cetus Units/m2/d, 79 +/- 12 days after autologous BMT. Clinical toxicities involving cutaneous, cholestatic, gastrointestinal, and hemodynamic effects occurred during IL-2 treatment but reversed in all cases. Completion of treatment was 91% of the scheduled dose of IL-2. Hematologic toxicity was moderate and transient with no graft failure. Increases in eosinophil and lymphocyte counts were significant (P less than .05). Stimulation of the immune system was intense and prolonged, manifested by increase numbers of CD3+, CD3+DR+, CD3+ CD25+ lymphocytes, and natural killer (NK) cells (all P less than .01), and increase of Lymphokine-activated killers (LAK) and NK activities (P less than .01 and P less than .05). This study establishes the feasibility of a 6-day administration of rIL-2 after autologous BMT leading to a major immune activation 2.5 months after BMT.
Marrow Transplant Unit, Institut Paoli Calmettes, Marseille, France.
D
D
Blaise
D
D
Olive
A M
AM
Stoppa
P
P
Viens
C
C
Pourreau
M
M
Lopez
M
M
Attal
C
C
Jasmin
G
G
Monges
C
C
Mawas
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D001772:Blood Cell Count / Q000187:drug effects; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology*; D002648:Child; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014182:Transplantation, Autologous / Q000276:immunology / Q000473:pathology*
D015703:Antigens, CD; D007376:Interleukin-2; D011994:Recombinant Proteins