A phase II study of interleukin-2 in 49 patients with relapsed or refractory acute leukemia.
In this report we present the results of a multicenter phase II study of high-dose recombinant Interleukin-2 (rIL-2) in patients with refractory or relapsed acute leukemia. Forty-nine patients with acute myeloid leukemia (AML: 30 patients) or acute lymphoblastic leukemia (ALL: 19 patients) were included. Median age was 30 years (range: 4-71). Four patients were treated for primary refractory disease and 45 for relapsed disease (16 patients > 2nd relapse). Twenty-four patients (49%) had previously received bone marrow transplantation (allogeneic: 5, autologous: 19). Patients were scheduled to receive three 5-day cycles of rIL-2 given every other week. rIL-2 was administered as bolus I.V. infusion of 8 x 10(6) UI/m2 every 8 hours during cycle I and every 12 hours during cycles 2 and 3. Patients received a mean of 76% of rIL-2 planned dose. Main toxicity was hematologic (grade IV thrombopenia: 84%). Hemodynamic and metabolic toxicities lead to treatment discontinuation in 10 patients (20%). Strong immune activation was achieved including a significant increase in activated T-cells and Lymphokine-Activating-Killer cell (LAK) activity. Twenty-seven out of 30 AML patients could be evaluated for response: 2(7%) achieved complete remission (CR) which lasted 3 and 4 months. No response was observed in the 18 assessable ALL patients, most of whom (77 %) presented absolute drug resistance. These results show that this high dose rIL-2 regimen induces significant biological effects and provides some anti-leukemic activity in patients with advanced leukemia. Considering the severe toxicity observed and the limited remission rate achieved here, rIL-2 does not appear to be a valuable therapeutic option for such patients. However, the undoubted anti-leukemic activity of this cytokine invites further investigation especially in the minimal residual disease situation.
Maraninchi
D
D
Institut Paoli-Calmettes and INSERM Unit 119, Marseille, France.
Vey
N
N
Viens
P
P
Stoppa
A M
AM
Archimbaud
E
E
Attal
M
M
Baume
D
D
Bouabdallah
R
R
Demeoq
F
F
Fleury
J
J
Michallet
M
M
Olive
D
D
Reiffers
J
J
Sainty
D
D
Tabilio
A
A
Tiberghien
P
P
Brandely
M
M
Hercend
T
T
Blaise
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology
D007376:Interleukin-2; D011994:Recombinant Proteins