Phase I-II study of continuous-infusion high-dose human lymphoblastoid interferon and the in vitro sensitivity of leukemic progenitors in nonlymphocytic leukemia.
Twelve pediatric patients with nonlymphocytic leukemia were treated for 10 days with high-dose (15, 20, or 30 million U/m2/day) human lymphoblastoid interferon (Wellferon) administered by continuous iv infusion. Nine children had acute nonlymphocytic leukemia (ANLL) in relapse, two had Philadelphia chromosome-positive chronic myelocytic leukemia in myeloblastic crisis, and one had juvenile chronic myelocytic leukemia. Blast cell counts in the peripheral blood decreased in five patients with ANLL treated with the higher interferon doses; however, there was no evidence of an antileukemic effect in the marrow. Dose-limiting toxicity, which included malaise, hepatotoxicity, and coagulation abnormalities, was observed in patients given 20 or 30 million U/m2/day. Studies of the growth of leukemic progenitor cells in vitro in the presence of interferon disclosed a concentration-related inhibition of colony formation. Patients who had a decrease in peripheral blast cell counts demonstrated greater in vitro inhibition of clonogenic leukemic progenitors than patients whose blast cell counts did not decrease. However, the serum interferon concentrations in patients given clinically tolerable doses were lower than those concentrations which inhibited leukemic cell growth in vitro by a median of 42% (1000 U/ml). This study failed to demonstrate clinically significant antileukemic activity against nonlymphocytic leukemia in patients given high-dose constant-infusion interferon, and the toxicity of this approach was prohibitive.
Mirro
J
J
Dow
L W
LW
Kalwinsky
D K
DK
Dahl
G V
GV
Weck
P
P
Whisnant
J
J
Murphy
S B
SB
D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007370:Interferon Type I / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000628:therapy*; D008099:Liver / Q000187:drug effects; D008297:Male; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D014410:Tumor Stem Cell Assay
D007370:Interferon Type I; D011994:Recombinant Proteins