title: Phase I/II trial of PIXY321 (granulocyte-macrophage colony stimulating factor/interleukin-3 fusion protein) for treatment of inherited and acquired marrow failure syndromes.
abstract: Fourteen paediatric patients with advanced amegakaryocytic thrombocytopenia (AMT) or other bone marrow (BM) failure syndromes were enrolled on one of two phase I/II dose escalation studies of PIXY321. PIXY321 was administered subcutaneously in doses ranging from 250 to 750 mg/m2/d. No dose-limiting toxicity was observed. Peak absolute neutrophil count (ANC) was higher than baseline in all patients. Most transfusion-independent patients demonstrated elevation in haematocrit and/or platelet count. Trilineage haemopoietic responsiveness was evident in the three transfusion-independent patients. In these paediatric populations PIXY321 is well tolerated and merits consideration as a potential therapy.
authors.affiliation: Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Taylor
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.forename: C A
authors.initials: CA
authors.lastname: Sieff
authors.forename: A
authors.initials: A
authors.lastname: Homans
authors.forename: L
authors.initials: L
authors.lastname: Garrison
authors.forename: E C
authors.initials: EC
authors.lastname: Guinan
mesh_terms: D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology; D001855:Bone Marrow Diseases / Q000628:therapy*; D002648:Child; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006400:Hematocrit; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007223:Infant; D007377:Interleukin-3 / Q000627:therapeutic use*; D008297:Male; D010976:Platelet Count; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000628:therapy*
chemical_list: D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor