Interleukin 2 immediately after autologous bone marrow transplantation for acute lymphoblastic leukemia--a phase I study.
Despite intensive conditioning and marrow purging, leukemia relapse frequently follows autologous BMT for acute lymphoblastic leukemia. To generate antileukemic immunologic activity, we performed a phase I study using recombinant human interleukin 2 given immediately posttransplantation. This early period was chosen because of low disease burden; therefore induced in vivo effector:target cell ratios might be most favorable. IL-2 was given by continuous infusion (96 hr/week x 3 weeks) beginning day +1. Fourteen patients with high-risk ALL were treated at 0.5, 1.0, and 2.0 x 10(6) U/m2/day IL-2. The clinical toxicity, hemopoietic recovery, and immune activation in the IL-2-treated patients was compared with that in a group of autologous BMT patients receiving no IL-2. The patients receiving IL-2 had a trend toward earlier neutrophil, platelet, and RBC recovery plus earlier hospital discharge versus non-IL-2 controls. However, IL-2 plus the inherent toxicity of transplantation often produced hepatic, pulmonary, and renal toxicity. Assessment of immune activation induced by in vivo IL-2 (following 3 weeks of IL-2) showed proliferation of CD8+ T cells having in vitro cytotoxicity against the Nalm-6 ALL cell line in most patients. Little enhancement of natural killer activity by immunophenotype or cytotoxicity against K562 cells was observed. IL-2 given immediately post-BMT induces infrequent but significant toxicity at lower doses than in the non-BMT setting. This toxicity may result from pre-BMT conditioning in conjunction with T cell activation. The immunotherapeutic potential, dose, and schedule of IL-2 following BMT require further study along with measures to reduce its toxicity.
Weisdorf
D J
DJ
Department of Medicine, University of Minnesota, Minneapolis 55455.
Anderson
P M
PM
Blazar
B R
BR
Uckun
F M
FM
Kersey
J H
JH
Ramsay
N K
NK
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000401:mortality; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000097:blood; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000601:surgery; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology; D014182:Transplantation, Autologous
D007376:Interleukin-2; D011994:Recombinant Proteins