title: Recombinant human interleukin-3 (rH IL-3) in combination with remission induction chemotherapy in patients with relapsed acute myelogenous leukemia (AML): a phase I/II study.
abstract: Patients with AML who relapse after an initial remission, have a poor prognosis. Administration of hemopoietic growth factors (HGFs) such as interleukin-3 (IL-3) during chemotherapy may result in an increased cell kill by cytotoxic agents. In addition, administration of IL-3 following chemotherapy may potentially accelerate hemopoietic recovery from chemotherapy-induced bone marrow hypoplasia. We performed an open labelled, phase I/II study in which patients received IL-3 by continuous infusion from 24 h before the beginning of chemotherapy until day 28. Chemotherapy included daunorubicin or mitoxantrone days 1-3 and cytarabine 200 mg/m2 days 1-7. IL-3 was given at a dose of 5 microgram(s)/kg/day in 10 patients, 7.5 microgram(s)/kg /day in six patients and 10 microgram(s)/kg/day in four patients. Complete remissions (CR) after one cycle of this treatment were obtained in 5/10 patients and 5 microgram(s)/ kg group, 2/6 in the 7.5 microgram(s)/kg group and 3/4 in the 10 microgram(s)/kg group). Thus, 50% (10/20) of all individuals and 45% (5/11) of the elderly patients attained CR. Eight of 20 patients entered PR, and 2/20 patients died during the hypoplastic phase from infectious complications. Neutrophils and platelets recovered to 0.5 x 10(9)/l at day 25 (median) and to 50 x 10(9)/l at day 32, respectively. Adverse events during IL-3 and concomitant chemotherapy were fluid retention (4/20), rash (14/20), bone pain (2/20), headache (10/20), chest pain (1/20), arthritis (1/20), fever and nausea. IL-3 (at the dose of 10 microgram(s)/kg) was discontinued in two patients because of side-effects (fluid retention, fever, rash and chest pain), and in two other patients the high IL-3 dose was tolerated with no problems for 29 days. Thus, IL-3 applied to patients with high-risk AML at dosages of 5-10 microgram(s)/kg is tolerated with acceptable toxicity and results in a satisfactory frequency of complete responses following a single treatment cycle.
authors.affiliation: Department of Hematology, University Hospital, Rotterdam, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Wielenga
authors.forename: E
authors.initials: E
authors.lastname: Vellenga
authors.forename: A
authors.initials: A
authors.lastname: Groenewegen
authors.forename: P
authors.initials: P
authors.lastname: Sonneveld
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D010976:Platelet Count; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D007377:Interleukin-3; D011994:Recombinant Proteins; D003561:Cytarabine; D008942:Mitoxantrone; D003630:Daunorubicin