Correction of a large animal model of type I Glanzmann's thrombasthenia by nonmyeloablative bone marrow transplantation. Exp Hematol 2003 Dec;31(12):1357-62
Date
12/10/2003Pubmed ID
14662345DOI
10.1016/j.exphem.2003.09.005Scopus ID
2-s2.0-0345097306 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
OBJECTIVE: The purpose of this study was to determine if nonmyeloablative bone marrow transplantation would induce stable hematopoietic chimerism that would correct the bleeding diathesis associated with type I Glanzmann's thrombasthenia (GT).
METHODS: Three young dogs (less than 12 weeks of age) with GT were transplanted with DLA-matched bone marrow from littermates. Recipients received a sublethal dose (200 cGy) of total-body irradiation (TBI) prior to infusion with bone marrow (1-4 x 10(8) cells/kg). Recipient dogs were immunosuppressed with cyclosporine (15 mg/kg) and mycophenolate mofetil (10 mg/kg). Chimerism was determined by quantitation of donor microsatellite repeat polymorphisms in peripheral blood DNA and by flow cytometry to detect the presence of glycoproteins IIb and IIIa on platelets. Platelet function was assessed by a clot retraction test.
RESULTS: One dog died one week posttransplant due to hemorrhage. Another dog died four weeks posttransplant from an unrecognized congenital heart defect and complications due to canine distemper virus infection. At the time of death, microsatellite analysis indicated 35 to 50% chimerism. Flow cytometry showed 20% of circulating platelets positive for glycoproteins IIb and IIIa. The third dog is alive and doing well approximately two years posttransplant. Hematopoietic chimerism has been sustained at 35 to 60% with approximately 30% of the platelets positive for glycoproteins IIb and IIIa. Platelet function is normal based on clot retraction. The animal does not have clinical signs of bleeding.
CONCLUSIONS: These observations suggest that GT and perhaps other severe inherited platelet disorders can be corrected using nonmyeloablative bone marrow transplantation to establish partial chimerism with normal platelets in the platelet compartment.
Author List
Niemeyer GP, Boudreaux MK, Goodman-Martin SA, Monroe CM, Wilcox DA, Lothrop CD JrAuthor
David A. Wilcox PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBone Marrow Transplantation
Cyclosporine
Dogs
Microsatellite Repeats
Models, Animal
Mycophenolic Acid
Platelet Function Tests
Platelet Glycoprotein GPIIb-IIIa Complex
Thrombasthenia
Transplantation Chimera
Transplantation Conditioning
Treatment Outcome
Whole-Body Irradiation
