Objective: To assess the activity of von Willebrand factor-cleaving protease (vWF-CP) in patients with thrombotic thrombocytopenic purpura (TTP) complicating bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT). Patients and Methods: From March 1, 1999, to June 30, 2001, allogeneic and autologous hematopoietic stem cell transplantation was performed in 118 and 400 patients, respectively. We reviewed risk factors for development of posttransplantation TTP and measured vWF-CP activity during active TTP in 10 recipients. Results: The incidence of TTP after allogeneic and autologous transplantation was 6.8% (8/118) and 0.25% (1/400), respectively. Among the allogeneic transplant recipients, the incidence of TTP after nonmyeloablative (NMA) PBSCT, matched unrelated donor BMT, and sibling BMT or PBSCT was 15.4% (2/13), 11.8% (2/17), and 4.5% (4/88), respectively. Of the 10 patients with TTP, 9 (90%) had received extensive prior therapy, including autologous transplantation in both NMA recipients. Acute graft-vs-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in most affected patients. The vWF antigen level was elevated in all patients, and no patients showed evidence of vWF-CP deficiency. During active TTP, 6 patients had grade II-IV acute GVHD, 1 had extensive chronic GVHD, and 4 had cytomegalovirus viremia. Risk factor analysis for development of TTP showed that transplant type (NMA and matched unrelated donor) and source of stem cells (bone marrow vs peripheral blood stem cell) were significant. Conclusions: Posttransplantation TTP was not found to be associated with severe vWF-CP deficiency. The elevated levels of vWF antigen are consistent with diffuse endothelial injury likely because of multiple interacting factors such as extensive prior therapy, GVHD, cyclosporine, and reactivation of cytomegalovirus. The disorder appears to be more frequent among patients with, or at risk for, acute GVHD, suggesting a possible role in the pathogenesis. Nonmyeloablative transplantation does not appear to confer a lesser risk, possibly for these reasons.
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