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Post-Transplant Events

Autoimmune hemolytic anemia following allogeneic hematopoietic stem cell transplantation in adult patients

Abstract

Autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplantation (HSCT) is still not well characterized. The aim of this study was to analyze the incidence and risk factors for the development of AIHA, as well as its prognosis and response to treatment in a series of patients undergoing allogeneic HSCT at a single institution. Between 1996 and 2004, 272 adult patients with a variety of malignant hematopoietic disorders underwent allogeneic HSCT. Direct antiglobulin testing was performed in routine pretransfusion compatibility testing or after clinical suspicion of AIHA. Twelve patients developed AIHA after HSCT at a median time of 147 days (range, 41–170). The 3-year cumulative incidence of AIHA was 4.44%. Eight cold antibodies and four warm antibodies were detected. Multivariate analysis shows that HSCT from unrelated donors (P=0.02) and the development of chronic extensive graft-versus-host disease (GVHD) (P=0.0004) were the only independent factors associated with AIHA. Two patients are still alive. AIHA was never the primary cause of death but added morbidity in patients with other concomitant complications. Patients undergoing HSCT from unrelated donors and those who develop chronic extensive GVHD are especially predisposed for this complication.

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References

  1. Petz LD . Hemolysis associated with transplantation (editorial). Transfusion 1998; 38: 224–228.

    Article  CAS  Google Scholar 

  2. Rowley SD . Hematopoietic stem cell transplantation between red cell incompatible donor-recipient pairs. Bone Marrow Transplant 2001; 28: 315–321.

    Article  CAS  Google Scholar 

  3. Graze PR, Gale RP . Chronic graft versus host disease: a syndrome of disordered immunity. Am J Med 1979; 66: 611–620.

    Article  CAS  Google Scholar 

  4. Drobyski WR, Potluri J, Sauer D, Gottschall JL . Autoimmune hemolytic anemia following T cell-depleted allogeneic bone marrow transplantation. Bone Marrow Transplant 1996; 17: 1093–1099.

    CAS  PubMed  Google Scholar 

  5. O'Brien TA, Eastlund T, Peters Ch, Neglia JP, Defor T, Ramsay NKC et al. Autoimmune haemolytic anaemia complicating haematopoietic cell transplantation in paediatric patients: high incidente and significant mortality in unrelated donor transplants for non-malignant diseases. Br J Haematol 2004; 127: 67–75.

    Article  Google Scholar 

  6. Dovat S, Roberts RL, Wakim M, Stiehm ER, Feig SA . Immune thrombocytopenia after umbilical cord progenitor cell transplant: response to vincristine. Bone Marrow Transplant 1999; 24: 321–323.

    Article  CAS  Google Scholar 

  7. Mullen CA, Thompson JN, Richard LA, Chan KW . Unrelated umbilical cord blood transplantation in infancy for mucopolysaccharidosis type IIB (Hunter syndrome) complicated by autoimmune hemolytic anemia. Bone Marrow Transplant 2000; 25: 1093–1097.

    Article  CAS  Google Scholar 

  8. Sevilla J, González-Vicent M, Madero L, Díaz MA . Acute autoimmune hemolytic anemia following unrelated cord blood transplantation as an early manifestation of chronic graft-versus-host disease. Bone Marrow Transplant 2001; 28: 89–92.

    Article  CAS  Google Scholar 

  9. Hongeng S, Tardtong P, Worapongpaiboon S, Urgkanount A, Jootar S . Succesful treatment of refractory autoimmune haemolytic anaemia in post-unrelated bone marrow transplant paediatric patient with rituximab. Bone Marrow Transplant 2002; 29: 871–872.

    Article  CAS  Google Scholar 

  10. Chen FE, Owen I, Savage D, Roberts I, Apperley J, Goldman JM et al. Late onset haemolysis and red cell autoimmunisation after allogeneic bone marrow transplant. Bone Marrow Transplant 1997; 19: 491–495.

    Article  CAS  Google Scholar 

  11. Sanz GF, Saavedra S, Planelles D, Senent L, Cervera J, Barragán E et al. Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies. Blood 2001; 98: 2332–2338.

    Article  CAS  Google Scholar 

  12. De la Rubia J, Sempere A, Arriaga F, Lopez S, Marty ML . Safety of the antibody screening test as the sole method of pretransfusion testing (letter). Vox Sang 1992; 63: 141.

    Article  CAS  Google Scholar 

  13. López A, de la Rubia J, Arriaga F, Jimenez C, Sanz GF, Carpio N et al. Severe haemolytic anemia due to multiple red cell alloantibodies after an ABO-incompatible allogeneic bone marrow transplant. Transfusion 1998; 38: 247–251.

    Article  Google Scholar 

  14. Walker RH (ed). Technical Manual, 10th edn. American Association of Blood Banks: Arlington, 1990.

    Google Scholar 

  15. Branch DR, SySiok Hian AL, Petz LD . A new elution procedure using a nonflammable organic solvent (abstract). Transfusion 1980; 20: 635.

    Google Scholar 

  16. Freedman J, Masters CA, Newlands M, Mollison PL . Optimal conditions for the use of sulphydryl compounds in dissociating red cell antibodies. Vox Sang 1976; 30: 231–239.

    Article  CAS  Google Scholar 

  17. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman P, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of HLA-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  Google Scholar 

  18. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  Google Scholar 

  19. Shulman HM, Sullivan KM, Weiden PI, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man: a long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  Google Scholar 

  20. Kaplan EL, Meier P . Nonparametric estimations from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  21. Gray RJ . A class of K-sample test for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141–1154.

    Article  Google Scholar 

  22. Pepe MS, Mori M . Kaplan–Meier, marginal or conditional probability curves in summarizing competing risk failure time data? Stat Med 1993; 12: 737–751.

    Article  CAS  Google Scholar 

  23. Cox DR . Regression models and life tables (with discussion). J R Stat Soc B 1972; 34: 187–220.

    Google Scholar 

  24. Horn B, Viele M, Mogck N, DeSantes K, Cowan M . Autoimmune hemolytic anemia in patients with SCID after T cell-depleted BM and PBSC transplantation. Bone Marrow Transplant 1999; 24: 1009–1013.

    Article  CAS  Google Scholar 

  25. Rouquette-Gally AM, Boyeldieu D, Prost AC, Gluckman E . Autoimmunity after allogeneic bone marrow transplantation: a study of 53 long-term surviving patients. Transplantation 1988; 46: 238–240.

    Article  CAS  Google Scholar 

  26. Rouquette-Gally AM, Boyeldieu D, Gluckman E, Abuaf N, Combrisson A . Comparison of autoimmunity in 28 patients after allogeneic bone marrow transplantation: comparison with Sjogren syndrome and scleroderma. Br J Haematol 1987; 66: 45–47.

    Article  CAS  Google Scholar 

  27. Lister J, Messner H, Keystone E, Miller R, Fritzler MJ . Autoantibody analysis of patients with graft-versus-host disease. J Clin Lab Immunol 1987; 24: 19–30.

    CAS  PubMed  Google Scholar 

  28. Tivol E, Komorowski R, Drobyski WR . Emergent autoimmunity in graft-versus-host disease. Blood 2005; 105: 4885–4891.

    Article  CAS  Google Scholar 

  29. Godder K, Pati AR, Abhyankar SH, Lamb LS, Armstrong W, Henslee-Downey PJ . De novo chronic graft-versus-host disease presenting as hemolytic anemia following partially mismatched related donor bone marrow transplant. Bone Marrow Transplant 1997; 19: 813–817.

    Article  CAS  Google Scholar 

  30. Kamezaki K, Fukuda T, Makino S, Harada M . Evans' syndrome following autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. Clin Lab Haematol 2004; 26: 291–293.

    Article  CAS  Google Scholar 

  31. Richard S, Fruchtman S, Scigliano E, Skerret D, Najfeld V, Isola L . An immunological syndrome featuring transverse myelitis, Evans syndrome and pulmonary infiltrates after unrelated bone marrow transplant in a patient with severe aplastic anemia. Bone Marrow Transplant 2000; 26: 1225–1228.

    Article  CAS  Google Scholar 

  32. Jacobsen N, Andersen HK, Skinhoj P, Ryder LP, Platz P, Jerne D et al. Correlation between donor cytomegalovirus immunity and chronic graft-versus-host disease after allogeneic bone marrow transplantation. Scand J Haematol 1986; 36: 499–506.

    Article  CAS  Google Scholar 

  33. Varani S, Muratori L, De Ruvo, Vivarelli M, Lazzarotto T, Gabrielli L et al. Autoantibody appearance in cytomegalovirus-infected liver transplant recipients: correlation with antigenemia. J Med Virol 2002; 66: 56–62.

    Article  CAS  Google Scholar 

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Correspondence to M A Sanz.

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Sanz, J., Arriaga, F., Montesinos, P. et al. Autoimmune hemolytic anemia following allogeneic hematopoietic stem cell transplantation in adult patients. Bone Marrow Transplant 39, 555–561 (2007). https://doi.org/10.1038/sj.bmt.1705641

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