Low dose interleukin-2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission

Am J Hematol. 2008 Oct;83(10):771-7. doi: 10.1002/ajh.21253.

Abstract

The most important problem in the therapy of patients with acute myeloid leukemia (AML) is relapse after intensive therapy. We sought to determine if interleukin-2 (low-dose with intermittent boluses) administration could be feasibly administered after standard therapy to potentiate anti-tumor immunity in a fashion analogous to the post-allogeneic stem cell transplant "graft-vs-leukemic" effect. Adults with de novo AML received daunorubicin and cytosine arabinoside induction therapy. Patients achieving complete remission received high dose ara-C (HIDAC) for three courses followed by low dose rIL-2 (Amgen), administered by continuous infusion (450,000 U/m(2)/day) for 10 weeks with intermittent boluses (500,000/U/m(2) over 2 hr) given in weekly intervals starting on Week 4. Of the 32 enrolled patients, 27 achieved CR; 8/11 who received rIL-2 completed therapy. 6/11 are long term survivors (median follow-up, 139 months). rIL-2 was well tolerated and associated with a 5-fold increase in circulating NK-lymphocytes and a 3-fold increase in circulating T-cells. Mononuclear cells from patients receiving rIL-2 exhibited enhanced cytolytic activity in vitro against cryopreserved autologous leukemia cells. This study supports further investigation of immunotherapy in the post-intensive chemotherapy setting in the management of patients with AML.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Trials as Topic
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Dose-Response Relationship, Drug
  • Fatigue / chemically induced
  • Feasibility Studies
  • Female
  • Fever / chemically induced
  • Follow-Up Studies
  • Humans
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / genetics
  • Killer Cells, Natural / drug effects
  • Leukemia, Myeloid / classification
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / mortality
  • Male
  • Middle Aged
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Remission Induction
  • Survival Analysis
  • T-Lymphocytes / drug effects
  • Thrombocytopenia / chemically induced
  • Time Factors
  • Treatment Outcome

Substances

  • Interleukin-2
  • Recombinant Proteins
  • Cytarabine