Porcine hematopoietic cell xenotransplantation in nonhuman primates is complicated by thrombotic microangiopathy
| Autor: | David H. Sachs, Q. Chang, Robert Sackstein, R. Wise, Satoshi Gojo, Julian D. Down, Christian Goepfert, Simon C. Robson, David K. C. Cooper, L. Bühler, M. Basker, H. Tsai, Hiroshi Kitamura, Ian P. J. Alwayn |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Thrombotic microangiopathy Transplantation Conditioning Swine medicine.medical_treatment Transplantation Heterologous Anti-Inflammatory Agents Thrombotic thrombocytopenic purpura Anti-Inflammatory Agents/administration & dosage/pharmacology Hematopoietic stem cell transplantation Gastroenterology Fibrinolytic Agents Internal medicine hemic and lymphatic diseases medicine Transplantation Heterologous/adverse effects Animals Platelet Hematopoietic Stem Cell Transplantation/adverse effects Thrombosis/blood/drug therapy/etiology Purpura Thrombotic Thrombocytopenic/etiology Transplantation Microcirculation/pathology Purpura Thrombotic Thrombocytopenic ddc:617 business.industry Microcirculation Hematopoietic Stem Cell Transplantation Thrombosis Hematology Leukapheresis Fibrinolytic Agents/administration & dosage/pharmacology medicine.disease Thrombocytopenia Blood Coagulation Factors Platelet transfusion Thrombocytopenia/blood/drug therapy/etiology Immunology Models Animal Drug Therapy Combination business Blood Coagulation Factors/drug effects/metabolism Fibrinolytic agent Papio |
| Zdroj: | Bone Marrow Transplantation, Vol. 27, No 12 (2001) pp. 1227-36 |
| ISSN: | 0268-3369 |
| Popis: | Thrombotic microangiopathy (TM) is a serious complication of bone marrow transplantation (BMT) that resembles thrombotic thrombocytopenic purpura (TTP). In attempting to achieve hematopoietic cell chimerism in the pig-to-baboon model, we have observed TM following infusion of high doses (>10(10) cells/kg) of porcine peripheral blood mobilized progenitor cells (PBPC) into baboons. We performed investigations to analyze the pathobiology of this TM and to test therapeutic interventions to ameliorate it. PBPC were obtained by leukapheresis of cytokine-stimulated swine. The initial observations were made in two baboons that underwent a non-myeloablative regimen (NMR) prior to PBPC transplantation (TX) (group 1). We then studied three experimental groups. Group 2 (n = 2) received NMR without PBPC TX. Group 3 (n = 2) received PBPC TX alone. Group 4 (n = 6) received NMR + PBPC TX combined with prostacyclin, low-dose heparin, methylprednisolone, and cyclosporine was replaced by anti-CD40L mAb in five cases. Baboons in groups 1 and 3 developed severe thrombocytopenia (10/high powered field (hpf)), increase in plasma lactate dehydrogenase (LDH) (2500-9000 U/l), transient neurologic changes, renal insufficiency, and purpura. Autopsy on two baboons confirmed extensive platelet thrombi in the microcirculation, and, similar to clinical BMT-associated TM/TTP, no unusually large vWF multimers or changes in vWF protease activity were observed in the plasma of baboons with TM. In group 2, self-limited thrombocytopenia occurred for 10-15 days following NMR. Group 4 baboons developed thrombocytopenia ( |
| Databáze: | OpenAIRE |
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