Advertisement

Chimerism pp 119-134 | Cite as

Passenger Lymphocyte Syndrome

  • Nicole L. Draper
  • Jamie E. Kallan
Chapter

Abstract

Passenger lymphocyte syndrome (PLS) is a well-described but infrequent complication of hematopoietic progenitor cell and solid organ transplantation that occurs when viable donor B lymphocytes present within an allograft are passively transferred to a recipient during transplantation. These donor lymphocytes produce antibodies, which mount an immune response directed primarily against recipient red blood cell (RBC) antigens, resulting in antibody-mediated RBC destruction. Donor-derived antiplatelet antibodies can also result in transient thrombocytopenia. Factors affecting the degree of hemolysis or thrombocytopenia are the quantity of transplanted lymphoid tissue present within the transplanted organ, the antibody titer in the donor before transplantation, and the rate of increasing antibody titer in the recipient following transplantation. Hemolysis due to PLS following transplantation can be severe but is generally self-limited.

Keywords

Passenger lymphocyte syndrome Transplantation-mediated alloimmune thrombocytopenia Hemolysis Solid organ transplant 

Notes

Acknowledgment

Mark R. Hopkins, MD, created Fig. 8.1.

References

  1. 1.
    Peces R, Diaz Corte C, Navascues RA. Hemolytic anemia caused by graft-versus-host reaction in ABO-nonidentical renal transplants from blood O donors. Nefrologia. 2001;21(4):332–5.Google Scholar
  2. 2.
    Rowley S, Brain H. Probably hemolysis following minor ABO-incompatible marrow transplantation. Blood. 1982;60(suppl 1):11.Google Scholar
  3. 3.
    Hows J, Beddow K, Gordon-Smith E, et al. Donor-derived red blood cell antibodies and immune hemolysis after allogenic bone marrow transplantation. Blood. 1986;67:177–81.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Sindhi R, Landmark J, Stratta RJ, Cushing K, Taylor RJ. Humoral graft-versus-host disease after pancreas transplantation with an ABO-compatible and Rh-non-identical donor. Case report and a rationale for preoperative screening. Transplantation. 1996;61:1414–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Yazer MH, Triulzi DJ. Immune hemolysis following ABO-mismatched stem cell or solid organ transplantation. Curr Opin Hematol. 2007;14:664–70.CrossRefPubMedGoogle Scholar
  6. 6.
    Audet M, Panaro F, Piardi T, et al. Passenger lymphocyte syndrome and liver transplantation. Clin Dev Immunol. 2008;2008:1–4.CrossRefGoogle Scholar
  7. 7.
    Squires JE. Passenger lymphocyte syndrome: a case report involving non-ABO antibodies. Transfus Med Hemother. 2014;41:153–5.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Fung MK, Sheikh H, Eghtesad B, et al. Severe hemolysis resulting from D incompatibility in a case of ABO-identical liver transplant. Transfusion. 2004;44:1635–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Ramsey G. Red cell antibodies arising from solid organ transplants. Transfusion. 1991;31:76–86.CrossRefPubMedGoogle Scholar
  10. 10.
    Nadarajah L, Ashman N, Thuraisingham R, et al. Literature review of passenger lymphocyte syndrome following renal transplantation and two case reports. Am J Transplant. 2013;13:1594–600.CrossRefPubMedGoogle Scholar
  11. 11.
    Gordon RD, Iwatsuki S, Esquivel CO, et al. Experience with primary liver transplantation across ABO blood groups. Transplant Proc. 1987;19:4575–9.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Shanwell A, Eloborg L, Blomquist BI, Wiechel B, Ericzon BG. Hemolysis in ABO-compatible liver transplantation – only after O grafts? Transplant Proc. 1989;21:3532.PubMedGoogle Scholar
  13. 13.
    Sokol RJ, Stamps R, Booker DJ, et al. Posttransplant immune-mediated hemolysis. Transfusion. 2002;42(2):198–204.CrossRefPubMedGoogle Scholar
  14. 14.
    Romero S, Solves P, Lancharro A, et al. Passenger lymphocyte syndrome in liver transplant recipients: a description of 12 cases. Blood Transfus. 2015;28:1–6.Google Scholar
  15. 15.
    Bailen R, Perez-Corral AM, Pascual C, Buno I, et al. Transient hemolysis due to anti-D and anti-A1 produced by engrafted donor’s lymphocytes after allogenic unmanipulated haploidentical hematopoietic stem cell transplantation. Transfusion. 2017;57:2355–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Leo A, Mytilineos J, Voso MT, et al. Passenger lymphocyte syndrome with severe hemolytic anemia due to anti-Jka after allogenic PBPC transplantation. Transfusion. 2000;40:632–6.CrossRefPubMedGoogle Scholar
  17. 17.
    Hareuveni M, Merchav H, Austerlitz N, et al. Donor anti-Jka causing hemolysis in a liver transplant recipient. Transfusion. 2002;42:363–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Young PP, Goodnough LT, Westervelt P, et al. Immune hemolysis involving non-ABO/RhD alloantibodies following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;27:1305–10.CrossRefPubMedGoogle Scholar
  19. 19.
    Yokoi Y, Noorchasm H, Rostami S, Barker C, Naj A. Origin, kinetics, and function of chimeric B lymphocytes in liver allografts. Transplantation. 1999;68(1):118–23.CrossRefPubMedGoogle Scholar
  20. 20.
    Schlitt HJ, Kanehiro H, Raddatz G, Steinhoff G, Richter N, Nashan B, Ringe B, Wonigeit K, Pichlmayr R. Persistence of donor lymphocytes in liver allograft recipients. Transplantation. 1993;56(4):1001–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Ramsey G, Israel L, Lindsay GD, Mayer TK, Nusbacher J. Anti-Rho (D) in two Rh-positive patients receiving kidney grafts from an Rh immunized donor. Transplantation. 1986;41:67–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Hjelle B, Donegan E, Cruz J, et al. Antibody to c antigen consequent to renal transplantation. Transfusion. 1988;28:496–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Larrea L, de la Rubia J, Arriaga F, Sanchez J, Marty ML. Severe hemolytic anemia due to anti-E after renal transplantation. Transplantation. 1997;64(3):550–1.CrossRefPubMedGoogle Scholar
  24. 24.
    Sternberg AJ, Lee G, Croxton T, et al. Severe hemolysis after minor ABO unmatched kidney transplant – a non-secretor transplanted from a donor with high anti-A titre. Transfus Med. 2000;10(1):87–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Schwartz D, Gotzinger P. Immune-haemolytic anaemia (IHA) after solid organ transplantation due to rhesus antibodies of donor origin: report of 5 cases. Beitr Infusionsther. 1992;30:367–9.PubMedGoogle Scholar
  26. 26.
    Brunetta DM, Albuquerue LM, Morais Batista AH, Santos LHO, et al. Passenger lymphocyte syndrome in liver transplantation. Rev Bras Hematol Hemoter. 2017;39(4):364–7.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Triulzi DJ, Shirey RS, Ness PM, et al. Immunohematologic complications of ABO-unmatched liver transplants. Transfusion. 1992;32:829–33.CrossRefPubMedGoogle Scholar
  28. 28.
    Lee JH, Mintz PD. Graft versus host anti-Rho(D) following minor Rh-incompatible orthotopic liver transplantation. Am J Hematol. 1993;44(3):168–71.CrossRefPubMedGoogle Scholar
  29. 29.
    El Ansary M, Hanna MO, Saadi G, et al. Passenger lymphocyte syndrome in ABO and Rhesus D minor mismatched liver and kidney transplantation: a prospective analysis. Hum Immunol. 2015;76:447–52.CrossRefGoogle Scholar
  30. 30.
    Peck JR, Elkhammas EA, Stanich PP, Latchana N, Black S, Michaels A. Passenger lymphocyte syndrome: a forgotten cause of postliver transplant jaundice and anemia. Exp Clin Transplant. 2014;13(2):200–2.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Solves P, Carpio N, Moscardo F, et al. Transfusion management and immunohematologic complications of liver transplantation: experience of a single institution. Transfus Med Hemother. 2015;42:8–14.CrossRefPubMedGoogle Scholar
  32. 32.
    Bruijn S, Philipse E, Couttenye MM, Bracke B, et al. Passenger lymphocyte syndrome (PLS): a single-center retrospective analysis of minor ABO-incompatible liver transplants. J Clin Transl Hepatol. 2017;5:9–15.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Najfeld V, Bunett W, Vlachos A, et al. Interphase FISH analysis of sex-mismatched BMT utilizing dual color XY probes. Bone Marrow Transplant. 1997;19:829–34.CrossRefPubMedGoogle Scholar
  34. 34.
    Knoop C, Andrien M, Antoine M, et al. Severe hemolysis due to a donor anti-D antibody after heart-lung transplantation: association with lung and blood chimerism. Am Rev Respir Dis. 1993;148(2):504–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Saba NF, Sweeny JD, Penn LC, et al. Anti-D in a D-positive renal transplant patient. Transfusion. 1997;37:321–4.CrossRefPubMedGoogle Scholar
  36. 36.
    Kim BK, Whitsett CF, Hillyer CD. Donor origin Rh antibodies as a cause of significant hemolysis following ABO-identical orthotopic liver transplantation. Immunohematology. 1992;8(4):100–1.PubMedGoogle Scholar
  37. 37.
    Koukoutsis I, Bellagambga R, Tamijmarane A, et al. Outcomes after identical and compatible orthotopic liver transplantation for fulminant hepatic failure: a single center experience in UK. Transpl Int. 2007;20:659–65.CrossRefPubMedGoogle Scholar
  38. 38.
    Shortt J, Westall GP, Roxby D, et al. A ‘dangerous’ group O donor: severe hemolysis in all recipients of organs from a donor with multiple red cell alloantibodies. Am J Transplant. 2008;8:711–4.CrossRefPubMedGoogle Scholar
  39. 39.
    Cserti-Gazdewich CM, Waddell TK, Singer LG, et al. Passenger lymphocyte syndrome with or without immune hemolytic anemia in all Rh-positive recipients of lungs from rhesus alloimmunized donors: three new cases and a review of the literature. Transfus Med Rev. 2009;23:134–45.CrossRefPubMedGoogle Scholar
  40. 40.
    Grosskreutz C, Gudzowaty O, Shi P, et al. Partial HLA matching and Rh incompatibility resulting in graft versus host reaction and Evans syndrome after liver transplantation. Am J Hematol. 2008;83:599–601.CrossRefPubMedGoogle Scholar
  41. 41.
    Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, Dunbar NM, Witt V, Wu Y, Shaz BH. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the writing committee of the American society for apheresis: the seventh special issue. J Clin Apher. 2016;31(3):149–62.PubMedGoogle Scholar
  42. 42.
    Cyclosporine. In: Micromedex Solutions, Truven Health Analytics Inc. Updated 1 Feb 2018, Accessed 2 Feb 2018. http://www.micromedexsolutions.com/micromedex2/librarian/
  43. 43.
    Tacrolimus. In: Micromedex Solutions, Truven Health Analytics Inc. Updated 1 Feb 2018, Accessed 2 Feb 2018. http://www.micromedexsolutions.com/micromedex2/librarian/
  44. 44.
    Azathioprine. In: Micromedex Solutions, Truven Health Analytics Inc. Updated 1 Feb 2018, Accessed 2 Feb 2018. http://www.micromedexsolutions.com/micromedex2/librarian/
  45. 45.
    Mycophenolate. In: Micromedex Solutions, Truven Health Analytics Inc. Updated 25 Apr 2017, Accessed 2 Feb 2018. http://www.micromedexsolutions.com/micromedex2/librarian/
  46. 46.
    De Vecchi A, Zanella A, Egidi F, Ponticelli C. Autoimmune hemolytic anemia in a cadaveric renal transplant recipient treated with cyclosporine. Acta Haematol. 1985;73:216–8.CrossRefPubMedGoogle Scholar
  47. 47.
    Chatzipetrou MA, Tsaroucha AK, Weppler D, et al. Thrombocytopenia after liver transplantation. Transplantation. 1999;67:702–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Reindl-Schwaighofer R, Oberbauer R. Blood disorders after kidney transplantation. Transplant Rev (Orlando). 2014;28:63–75.CrossRefGoogle Scholar
  49. 49.
    Sonnerborg IV, Hoglund P, Nordstrom J, Wikman A, et al. Severe transplantation-mediated alloimmune thrombocytopenia in 2 recipients of organs from the same donor. Transplantation. 2017;101(5):e190–2.CrossRefPubMedGoogle Scholar
  50. 50.
    Friend PJ, McCarthy LJ, Filo RS. Transmission of idiopathic (autoimmune) thrombocytopenic purpura by liver transplantation. N Engl J Med. 1990;323(12):807–11.CrossRefPubMedGoogle Scholar
  51. 51.
    Kaestner F, Kutsogiannis DJ. Successful kidney and liver transplantation from a donor with immune thrombocytopenia. Transplant Proc. 2013;45(7):2838–40.CrossRefPubMedGoogle Scholar
  52. 52.
    Bellamy MC, Galley HF, Webster NR. Changes in inflammatory mediators during orthotopic liver transplantation. Br J Anaesth. 1997;79(3):338–41.CrossRefPubMedGoogle Scholar
  53. 53.
    Trotter PB, Robb M, Summers D, Watson CJE, et al. Donors with immune thrombocytopenia: do they pose a risk to transplant recipients? Am J Transplant. 2017;17:796–802.CrossRefPubMedGoogle Scholar
  54. 54.
    Hill QA, Harrison LC, Padmakumar AD, Owen RG, et al. A fatal case of transplantation-mediated alloimmune thrombocytopenia following liver transplantation. Hematology. 2017;22(3):162–7.CrossRefPubMedGoogle Scholar
  55. 55.
    Herron R, Clark M, Tate D, Kruger A, Smith DS. Immune haemolysis in a renal transplant recipient due to antibodies with anti-c specificity. Vox Sang. 1986;51(3):226–7.CrossRefPubMedGoogle Scholar
  56. 56.
    Swanson J, Sebring E, Sastamoinen R, Chopek M. Gm allotyping to determine the origin of the anti-D causing hemolytic anemia in a kidney transplant recipient. Vox Sang. 1987;52:228–30.CrossRefPubMedGoogle Scholar
  57. 57.
    Gonzalez-Molina M, Cabello M, Uyonarte S, Frutos MA, Martin Reyes G, Lopez de Novales E. Haemolytic anemia in renal transplant patients treated with cyclosporin A. Nefrologia. 1988;8:380–3.Google Scholar
  58. 58.
    Rougier JP, Viron B, Ronco P, Khayat R, Michel C, Mignon F. Autoimmune haemolytic anaemia after ABO-match, ABDR full match kidney transplantation. Nephrol Dial Transplant. 1994;9:693–7.CrossRefPubMedGoogle Scholar
  59. 59.
    Frohn C, Jabs WJ, Fricke L, Goerg S. Hemolytic anemia after kidney transplantation: case report and differential diagnosis. Ann Hematol. 2002;81:158–60.CrossRefPubMedGoogle Scholar
  60. 60.
    Pomper GJ, Joseph RA, Hartmann EL, et al. Massive immune hemolysis caused by anti-D after dual kidney transplantation. Am J Transplant. 2005;5:2586–9.CrossRefPubMedGoogle Scholar
  61. 61.
    Ainsworth CD, Crowther MA, Treleaven D, et al. Severe hemolytic anemia post-renal transplantation produced by donor anti-D passenger lymphocytes: case report and literature review. Transfus Med Rev. 2009;23:155–9.CrossRefPubMedGoogle Scholar
  62. 62.
    Karanth P, Birchall J, Day S, Unsworth DJ, Ravanan R. Immune hemolysis resulting from passenger lymphocyte syndrome derived anti-Rh(D) reactivity after kidney transplantation: a case report and literature review. Transplantation. 2014;97(9):e54–5.CrossRefPubMedGoogle Scholar
  63. 63.
    Seltsam A, Hell A, Heymann G, et al. Donor-derived alloantibodies and passenger lymphocyte syndrome in tow of four patients who received different organs from the same donor. Transfusion. 2001;41:365–70.CrossRefPubMedGoogle Scholar
  64. 64.
    Aguilera V, Arriaga F, de la Rubia J, Prieto M, Sanchez J. Hemolytic anemia due to ABO or Rh antibodies in recipients of solid organ transplants. Med Clin (Barc). 2003;120(5):177–9.CrossRefGoogle Scholar
  65. 65.
    De Luna MMI, Behan K. ABO discrepancy and hemolytic anemia post liver transplant due to passenger lymphocyte syndrome. Lab Med. 2011;42(3):137–9.CrossRefGoogle Scholar
  66. 66.
    Turino-Luque J, Zambudio-Carroll N, Muffak-Granero K, Villegas-Herrera T, Garrote-Lara D, Ferron-Orihuela JA. Early detection of biliary complications and graft rejection in a non-Rh identical liver transplant recipient from a non-heart beating donor: a case report. Transplant Proc. 2012;44:2124–5.CrossRefPubMedGoogle Scholar
  67. 67.
    Gniadek TJ, McGonigle AM, Shirey RS, Brunker PA, et al. A rare, potentially life-threatening presentation of passenger lymphocyte syndrome. Transfusion. 2017;57(5):1262–6.CrossRefPubMedGoogle Scholar
  68. 68.
    Solheim BG, Albrechtsen D, Egeland T, et al. Auto-antibodies against erythrocytes in transplant patients produced by donor lymphocytes. Transplant Proc. 1987;19:4520–1.PubMedGoogle Scholar
  69. 69.
    Makuria AT, Langeberg A, Fishbein TM, et al. Nonhemolytic passenger lymphocyte syndrome: donor-derived anti-M in an M+ recipient of a multiorgan transplant. Immunohematology. 2009;25:20–5.PubMedGoogle Scholar
  70. 70.
    Hurtarte-Sandoval AR, Navarro-Cabello MD, Alvarez-Rivas MA, Robles-Lopez AI, et al. Passenger lymphocyte syndrome after simultaneous pancreas-kidney transplantation: a case report of an unusual cause of alloimmune hemolytic anemia. Transplant Proc. 2015;47:2667–8.CrossRefPubMedGoogle Scholar
  71. 71.
    de la Torre AN, Fisher A, Wilson DJ, et al. A case report of donor to recipient transmission of severe thrombocytopenia purpura. Transplantation. 2004;77(9):1473–4.CrossRefPubMedGoogle Scholar
  72. 72.
    Diaz GC, Prowda J, Lo IJ, Arepally GM, Evans N, et al. Transplantation-mediated alloimmune thrombocytopenia: guidelines for utilization of thrombocytopenia donors. Liver Transpl. 2008;14:1803–9.CrossRefPubMedGoogle Scholar
  73. 73.
    Pereboom IT, de Boer MT, Haagsma EB, et al. Transmission of idiopathic thrombocytopenic purpura during orthotopic liver transplantation. Transpl Int. 2010;23(2):236–8.CrossRefPubMedGoogle Scholar
  74. 74.
    West KA, Anderson DR, McAlister VC, Hewlett TJC, Belitsky P, Smith JW, KElton JG. Alloimmune thrombocytopenia after organ transplantation. N Engl J Med. 1999;341(20):1504–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyUniversity of Colorado School of MedicineAuroraUSA
  2. 2.Transfusion ServicesUniversity of Colorado HospitalAuroraUSA

Personalised recommendations