title: Interleukin-3 plus low-dose cytosine arabinoside for advanced myelodysplasia: a pilot study. EORTC Leukemia Group.
abstract: In an attempt to reestablish normal hematopoiesis in symptomatic myelodysplasia (MDS) and to show the tolerability of a combination treatment of low-dose cytosine arabinoside (LD AraC) and interleukin-3 (IL-3), we treated 31 patients (pts., median age 65 years) who had more than 10% blasts in the bone marrow (BM) and hematopoietic failure with LD AraC (2 x 10 mg/m2 sc, day 1-14) plus IL-3 (once daily sc, day 8-21) at different dose steps (1.0, 2.5, 5.0, and 10.0 micrograms/kilogram body weight). The numbers of each 21-day cycle varied between 1 (3 pts.), 2 (6 pts.), 3 (8 pts.), 4 (1 pt.), 5 (5 pts.), and 6 (8 pts.), in total 116 cycles on an outpatient basis. Subjective tolerability was good in 20 cases (65%). Toxicities were fever (29 pts.), flu-like symptoms (17 pts.), infections (15 pts.), hepatic toxicity (10 pts.), and skin reactions (8 pts.). Overall response was seen in 13 cases (42%) and 5 complete responses (CR), while 10 pts. had stable disease (SD), 5 progressed (2 to acute leukemia), 2 were considered toxic deaths, and 1 died due to the disease. Median survival is 18 months, progression-free survival is 12.5 months (18.0 months in responding pts.), with an actuarial follow-up of 31 months. The data from this phase I/II study show that a combination of LD-AraC and IL-3 is well tolerated and that stable responses can be achieved in MDS by means of an easy outpatient therapy.
authors.affiliation: Med. Dept. III, Klinikum Grosshadern, Munich, Germany.
authors.forename: H H
authors.initials: HH
authors.lastname: Gerhartz
authors.forename: H H
authors.initials: HH
authors.lastname: Zwierzina
authors.forename: J
authors.initials: J
authors.lastname: Walther
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
authors.forename: M
authors.initials: M
authors.lastname: Hayat
authors.forename: A
authors.initials: A
authors.lastname: Jacobs
authors.forename: A V
authors.initials: AV
authors.lastname: Hoffbrand
authors.forename: M
authors.initials: M
authors.lastname: Dardenne
authors.forename: G
authors.initials: G
authors.lastname: Solbu
authors.forename: S
authors.initials: S
authors.lastname: Suciu
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D006410:Hematopoiesis; D006801:Humans; D007377:Interleukin-3 / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D007377:Interleukin-3; D011994:Recombinant Proteins; D003561:Cytarabine