title: Changes in bone marrow morphology in adults receiving romiplostim for the treatment of thrombocytopenia associated with primary immune thrombocytopenia.
abstract: The effects of romiplostim on bone marrow morphology were evaluated in adults with immune thrombocytopenia (ITP). Patients with platelet counts <50 × 10(9)/L, ≥1 prior ITP therapies, and no collagen at baseline received weekly subcutaneous romiplostim starting at 1 μg/kg, adjusted to maintain platelet counts between 50 and 200 × 10(9)/L. Biopsies were scheduled after 1, 2, or 3 years of romiplostim (cohorts 1, 2, and 3, respectively). Irrespective of scheduled time, biopsies were performed earlier if patients discontinued or failed to achieve/maintain a response to romiplostim. Reticulin (silver stain) and collagen (trichrome stain) were graded by two hematopathologists using the modified Bauermeister scale (0-4). Of 169 patients, 131 had evaluable biopsies; 9/131 (6.9 %) had increases of ≥2 grades on the modified Bauermeister scale (cohort 1: 0/34; cohort 2: 2/39; cohort 3: 7/58), including two with collagen. Three of the nine patients had follow-up biopsies, including one patient with collagen; changes were reversible after romiplostim discontinuation. Of the nine patients, one had neutropenia detected by laboratory test and two had adverse events of anemia, both non-serious and not treatment-related. By actual exposure (as some biopsies did not occur as scheduled), the number of patients with grade increases ≥2 were year 1: 3/41, year 2: 1/38, year 3: 5/52. Twenty-four patients sustained platelet counts ≥50 × 10(9)/L for ≥6 months with no ITP medications after discontinuing romiplostim, i.e., they entered clinical remission of their ITP. In conclusion, in patients with ITP receiving romiplostim, bone marrow changes were observed in a small proportion of patients.ClinicalTrials.gov identifier: NCT#00907478.
authors.affiliation: Department of Hematology, University Hospitals Leuven, Campus Gasthuisberg, Leuven, Belgium. ann.janssens@uzleuven.be.
authors.forename: Ann
authors.initials: A
authors.lastname: Janssens
authors.affiliation: Department of Cell Therapy and Hematology, San Bortolo Hospital, Viale Rodolfi, 37, 36100, Vicenza, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
authors.affiliation: Dalhousie University, QEII-Bethune Building, Suite 442 Bethune Building, 1276 South Park Street, Halifax, NS, B3H 2Y9, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Anderson
authors.affiliation: St. George Hospital, UNSW Medicine, UNSW, Sydney, 2052, Australia.
authors.forename: Beng H
authors.initials: BH
authors.lastname: Chong
authors.affiliation: Clinical Center Department of Medicine, Thrombosis Haemostasis Center, University of Debrecen, H-4012 Debrecen, Nagyerdei krt. 98. POB.: 20, Debrecen, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Boda
authors.affiliation: Medizinische Universitaet Wien, Universitaetsklinik fuer Innere Medizin I Waehringer Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: University Hospital Masaryk University, Jihlavská 340/20, 625 00, Brno, Czech Republic.
authors.forename: Libor
authors.initials: L
authors.lastname: Červinek
authors.affiliation: Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, 801 NE 13th, CHB 333, Oklahoma City, OK, 73104, USA.
authors.forename: Deirdra R
authors.initials: DR
authors.lastname: Terrell
authors.affiliation: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Xuena
authors.initials: X
authors.lastname: Wang
authors.affiliation: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Franklin
mesh_terms: D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D003094:Collagen / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count / Q000379:methods; D011446:Prospective Studies; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D011961:Receptors, Fc / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012155:Reticulin / Q000378:metabolism; D013926:Thrombopoietin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D012155:Reticulin; D003094:Collagen; D013926:Thrombopoietin; C488777:romiplostim
keywords: Bone marrow; Collagen; Immune thrombocytopenia (ITP); Platelet; Reticulin; Thrombopoietin (TPO)