Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim.
Romiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia (ITP). Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow. This report describes bone marrow findings from romiplostim-treated rats, a retrospective analysis of reticulin observed in romiplostim ITP clinical trials, and a prospective clinical study of the effects of romiplostim on bone marrow morphology. In rats, romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal. Of 271 ITP patients in romiplostim clinical trials, 10 were reported to have reticulin deposition; reticulin grade was increased in 4 of 5 patients with both pretreatment and on-treatment bone marrow results. Reticulin grade often decreased soon after romiplostim discontinuation. In the prospective study, reticulin grade during romiplostim treatment remained within the normal range for all patients and was increased in only 1 of 6 patients with pretreatment and on-treatment bone marrow results. This report suggests that romiplostim produces reversible, dose-dependent bone marrow changes in rats and produces modest increases in bone marrow reticulin in some ITP patients that decrease when therapy is discontinued. These studies were registered at www.clinicaltrials.gov as #NCT00102323, #NCT00102336, #NCT00861224, and #NCT00116688.
Kuter
David J
DJ
Massachusetts General Hospital, Boston, MA 02114, USA. kuter.david@MGH.harvard.edu
Mufti
Ghulam J
GJ
Bain
Barbara J
BJ
Hasserjian
Robert P
RP
Davis
Wende
W
Rutstein
Mark
M
D000328:Adult; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011961:Receptors, Fc / Q000008:administration & dosage*; D053628:Receptors, Thrombopoietin / Q000819:agonists; D011993:Recombinant Fusion Proteins; D012155:Reticulin / Q000378:metabolism*; D012189:Retrospective Studies; D013926:Thrombopoietin
D002352:Carrier Proteins; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D012155:Reticulin; D013926:Thrombopoietin; C488777:romiplostim