title: Posttransplantation thrombotic thrombocytopenic purpura: a single-center experience and a contemporary review.
abstract: 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).
  
  
  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.
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA. elliott.michelle@mayo.edu
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Elliott
authors.forename: William L
authors.initials: WL
authors.lastname: Nichols
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Plumhoff
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Gastineau
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: David J
authors.initials: DJ
authors.lastname: Inwards
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: Ivana N M
authors.initials: IN
authors.lastname: Micallef
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
authors.forename: Mark
authors.initials: M
authors.lastname: Litzow
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000379:methods; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000201:enzymology / Q000453:epidemiology / Q000209:etiology*; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D014841:von Willebrand Factor; D016572:Cyclosporine; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human; D008775:Methylprednisolone