Summary:
We studied occurrence, risk factors and outcome of patients with transplant-associated microangiopathy (TAM) after allogeneic stem cell transplantation (HSCT). A total of 221 consecutive patients were transplanted between 1995 and 2002. TAM is defined as evidence of hemolysis and schistocytes in the first 100 days. Outcomes analyzed included TAM and overall survival. Of 221 patients, 68 had TAM. The cumulative incidence was 31 (25–38)% at 100 days. Patients with TAM had higher LDH, higher bilirubin, higher creatinine and more often neurologic symptoms. TAM was not associated with stem cell source, cyclosporine levels and was not more frequent in recent years. In multivariate analysis, risk factors for TAM included donor type, age, gender, ABO-incompatibility and acute graft-versus-host disease (aGvHD). In patients with TAM, 1-year survival was lower than in patients without TAM (27±18% for TAM with high schistocyte counts; 53±15% for TAM with low schistocyte counts; vs 78±7% in patients without TAM; P<0.0001). TAM was independently associated with mortality adjusting for donor type, age and aGvHD occurrence and severity. TAM is frequent after HSCT and is associated with mortality even after adjustment for aGvHD grade. Risk factors of TAM are similar to aGvHD. TAM may represent endothelial damage driven by donor–host interactions.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Uderzo C, Fumagalli M, De Lorenzo P et al. Impact of thrombotic thrombocytopenic purpura on leukemic children undergoing bone marrow transplantation. Bone Marrow Transplant 2000; 26: 1005–1009.
Kanamori H, Maruta A, Sasaki S et al. Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy. Bone Marrow Transplant 1998; 21: 705–709.
Natazuka T, Kajimoto K, Ogawa R et al. Coagulation abnormalities and thrombotic microangiopathy following bone marrow transplantation from HLA-matched unrelated donors in patients with hematological malignancies. Bone Marrow Transplant 1998; 21: 815–819.
Paquette RL, Tran L, Landaw EM . Thrombotic microangiopathy following allogeneic bone marrow transplantation is associated with intensive graft-versus-host disease prophylaxis. Bone Marrow Transplant 1998; 22: 351–357.
Takatsuka H, Takemoto Y, Okamoto T et al. Thrombotic microangiopathy following allogeneic bone marrow transplantation. Bone Marrow Transplant 1999; 24: 303–306.
Roy V, Rizvi MA, Vesely SK, George JN . Thrombotic thrombocytopenic purpura-like syndromes following bone marrow transplantation: an analysis of associated conditions and clinical outcomes. Bone Marrow Transplant 2001; 27: 641–646.
Shimoni A, Yeshurun M, Hardan I et al. Thrombotic microangiopathy after allogeneic stem cell transplantation in the era of reduced-intensity conditioning: the incidence is not reduced. Biol Blood Marrow Transplant 2004; 10: 484–493.
Ruutu T, Hermans J, Niederwieser D et al. Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 2002; 118: 1112–1119.
Takatsuka H, Wakae T, Mori A et al. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome following allogeneic bone marrow transplantation. Bone Marrow Transplant 2002; 29: 907–911.
George JN, Selby GB . Thrombotic microangiopathy after allogeneic bone marrow transplantation: a pathologic abnormality associated with diverse clinical syndromes. Bone Marrow Transplant 2004; 33: 1073–1074.
Iacopino P, Pucci G, Arcese W et al. Severe thrombotic microangiopathy: an infrequent complication of bone marrow transplantation. Gruppo Italiano Trapianto Midollo Osseo (GITMO). Bone Marrow Transplant 1999; 24: 47–51.
Zeigler ZR, Shadduck RK, Nemunaitis J et al. Bone marrow transplant-associated thrombotic microangiopathy: a case series. Bone Marrow Transplant 1995; 15: 247–253.
Chemnitz J, Fuchs M, Blau W et al. Fatal thrombotic thrombocytopenic purpura as a rare complication following allogeneic stem cell transplantation. Ann Hematol 2000; 79: 527–529.
George JN, Li X, McMinn JR et al. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic HPC transplantation: a diagnostic dilemma. Transfusion 2004; 44: 294–304.
Daly AS, Xenocostas A, Lipton JH . Transplantation-associated thrombotic microangiopathy: 22 years later. Bone Marrow Transplant 2002; 30: 709–715.
Fuge R, Bird JM, Fraser A et al. The clinical features, risk factors and outcome of thrombotic thrombocytopenic purpura occurring after bone marrow transplantation. Br J Haematol 2001; 113: 58–64.
Pettitt AR, Clark RE . Thrombotic microangiopathy following bone marrow transplantation. Bone Marrow Transplant 1994; 14: 495–504.
Matsumoto T, Wada H, Nishiyama H et al. Hemostatic abnormalities and changes following bone marrow transplantation. Clin Appl Thromb Hemost 2004; 10: 341–350.
Hahn T, Alam AR, Lawrence D et al. Thrombotic microangiopathy after allogeneic blood and marrow transplantation is associated with dose-intensive myeloablative conditioning regimens, unrelated donor, and methylprednisolone T-cell depletion. Transplantation 2004; 78: 1515–1522.
Daly AS, Hasegawa WS, Lipton JH et al. Transplantation-associated thrombotic microangiopathy is associated with transplantation from unrelated donors, acute graft-versus-host disease and venoocclusive disease of the liver. Transfus Apheresis Sci 2002; 27: 3–12.
Galbusera M, Noris M, Rossi C et al. Increased fragmentation of von Willebrand factor, due to abnormal cleavage of the subunit, parallels disease activity in recurrent hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and discloses predisposition in families. The Italian Registry of Familial and Recurrent HUS/TTP. Blood 1999; 94: 610–620.
Knovich MA, Craver K, Matulis MD et al. Simplified assay for VWF cleaving protease (ADAMTS13) activity and inhibitor in plasma. Am J Hematol 2004; 76: 286–290.
Moake JL . Thrombotic microangiopathies. N Engl J Med 2002; 347: 589–600.
Remuzzi G, Galbusera M, Noris M et al. von Willebrand factor cleaving protease (ADAMTS13) is deficient in recurrent and familial thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Blood 2002; 100: 778–785.
van der Plas RM, Schiphorst ME, Huizinga EG et al. von Willebrand factor proteolysis is deficient in classic, but not in bone marrow transplantation-associated thrombotic thrombocytopenic purpura. Blood 1999; 93: 3798–3802.
Furlan M, Robles R, Galbusera M et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 1998; 339: 1578–1584.
Veyradier A, Obert B, Houllier A et al. Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases. Blood 2001; 98: 1765–1772.
Vesely SK, George JN, Lammle B et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood 2003; 102: 60–68.
Llamas P, Romero R, Cabrera R et al. Management of thrombotic microangiopathy following allogeneic transplantation: what is the role of plasma exchange? Bone Marrow Transplant 1997; 20: 305–306.
Biedermann BC, Sahner S, Gregor M et al. Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft-versus-host disease. Lancet 2002; 359: 2078–2083.
Holler E, Kolb HJ, Hiller E et al. Microangiopathy in patients on cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation. Blood 1989; 73: 2018–2024.
Chappell ME, Keeling DM, Prentice HG, Sweny P . Haemolytic uraemic syndrome after bone marrow transplantation: an adverse effect of total body irradiation? Bone Marrow Transplant 1988; 3: 339–347.
Champlin RE, Schmitz N, Horowitz MM et al. Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT). Blood 2000; 95: 3702–3709.
Kondo M, Kojima S, Horibe K et al. Hemolytic uremic syndrome after allogeneic or autologous hematopoietic stem cell transplantation for childhood malignancies. Bone Marrow Transplant 1998; 21: 281–286.
Carlson K, Smedmyr B, Hagberg H et al. Haemolytic uraemic syndrome and renal dysfunction following BEAC (BCNU, etoposide, ara-C, cyclophosphamide) ±TBI and autologous BMT for malignant lymphomas. Bone Marrow Transplant 1993; 11: 205–208.
van der Lelie H, Baars JW, Rodenhuis S et al. Hemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support. Cancer 1995; 76: 2338–2342.
Sarkodee-Adoo C, Sotirescu D, Sensenbrenner L et al. Thrombotic microangiopathy in blood and marrow transplant patients receiving tacrolimus or cyclosporine A. Transfusion 2003; 43: 78–84.
Cutler C, Kim HT, Hochberg E et al. Sirolimus and tacrolimus without methotrexate as graft-versus-host disease prophylaxis after matched related donor peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2004; 10: 328–336.
Nash RA, Pineiro LA, Storb R et al. FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors. Blood 1996; 88: 3634–3641.
Mbonu CC, Davison DL, El-Jazzar KM, Simon GL . Clostridium difficile colitis associated with hemolytic-uremic syndrome. Am J Kidney Dis 2003; 41: E14.
Matsuda Y, Hara J, Osugi Y et al. Serum levels of soluble adhesion molecules in stem cell transplantation-related complications. Bone Marrow Transplant 2001; 27: 977–982.
Dignat-George F, Sampol J, Lip G, Blann AD . Circulating endothelial cells: realities and promises in vascular disorders. Pathophysiol Haemost Thromb 2003; 33: 495–499.
Pihusch R, Salat C, Schmidt E et al. Hemostatic complications in bone marrow transplantation: a retrospective analysis of 447 patients. Transplantation 2002; 74: 1303–1309.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Martinez, M., Bucher, C., Stussi, G. et al. Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants. Bone Marrow Transplant 36, 993–1000 (2005). https://doi.org/10.1038/sj.bmt.1705160
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1705160
Keywords
This article is cited by
-
Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment
Nature Communications (2024)
-
Treatment outcome and efficacy of therapeutic plasma exchange for transplant-associated thrombotic microangiopathy in a large real-world cohort study
Bone Marrow Transplantation (2022)
-
Acute graft-versus-host disease increase risk and accuracy in prediction model of transplantation-associated thrombotic microangiopathy in patients with myelodysplastic syndrome
Annals of Hematology (2022)
-
Histologic features of hematopoietic stem cell transplant-associated thrombotic microangiopathy are best percepted in deep skin biopsies and renal biopsies, while showing a significant overlap with changes related to severe acute graft-versus-host disease in gastrointestinal biopsies
Bone Marrow Transplantation (2020)
-
High mortality in hematopoietic stem cell transplant-associated thrombotic microangiopathy with and without concomitant acute graft-versus-host disease
Bone Marrow Transplantation (2019)