Correction of a large animal model of type I Glanzmann's thrombasthenia by nonmyeloablative bone marrow transplantation.
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.
Niemeyer
Glenn P
GP
The Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
Boudreaux
Mary K
MK
Goodman-Martin
Susan A
SA
Monroe
Christine M
CM
Wilcox
David A
DA
Lothrop
Clinton D
CD
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D016572:Cyclosporine / Q000008:administration & dosage; D004285:Dogs; D007165:Immunosuppression Therapy / Q000379:methods; D018895:Microsatellite Repeats; D023421:Models, Animal; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis; D013915:Thrombasthenia / Q000628:therapy*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D016572:Cyclosporine; D009173:Mycophenolic Acid