Skip to main content
SpringerLink
Log in

Leukodepletion and Alloimmunization

  • Chapter
Clinical Benefits of Leukodepleted Blood Products

Part of the book series: Medical Intelligence Unit ((MIUN))

  • 75 Accesses

Summary

Platelet alloimmunization remains a dilemma in the management 1 of hematology patients since so little can be done to provide the necessary platelet transfusion support. A number of recent studies have provided information about the role of the passenger leukocytes that remain in blood products and how these initiate antibody development by participating in the immunization process. Small numbers of leukocytes, 106–107, may induce antibody development. As leukodepletion methods have developed from buffy coat depletion and platelet centrifugation to the use of third generation filters, it is now possible to routinely supply blood products with less than 1 × 106 residual leukocyte content for a small (5–10%) loss of the component. Most clinical studies have suggested that the relative risk of refractoriness to platelet transfusions is reduced by blood component leukodepletion. Although the relative risk of refractoriness is reduced by 70–90% in some studies, in others the reduction was not significant. Clearly further studies are needed to better define the immunizing dose of leukocytes, the effects of concurrent chemotherapy and to better relate improvements in clinical outcomes, such as bleeding or number of transfusion episodes, to the levels of leukodepletion. Lastly, the use of ultraviolet irradiation remains an intriguing option in that immunization may be avoided by inhibiting the function of the passenger leukocytes. Further trials are clearly necessary to better define the immunizing dose of leukocytes, the place of UVB irradiation and the role of leukocyte fragments or soluble antigens in order to allow the development of logical strategies to prevent immunization.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Dausset J. Leukoagglutinins IV. Leukoagglutinins and blood transfusion. Vox Sang 4: 190, 1954.

    Google Scholar 

  2. Hogge DE, Dutcher JP, Aisner J, Schiffer CA. Lymphocytotoxic antibody is a predictor of response to random donor platelet transfusion. Am J Hematol 14: 363, 1983.

    Article  PubMed  CAS  Google Scholar 

  3. Roitt I. Essential Immunology, ed S. Oxford Blackwell Scientific, 1984.

    Google Scholar 

  4. Mincheff M, Meryman HT. Stimulation by allo-Ia requires a product of lysosomal processing. XII Int Cong Transplantation Soc., Sydney, p. 177, 1988.

    Google Scholar 

  5. Mueller DL, Jenkins MK, Schwartz RH. An accessory cell-derived costimulatory signal acts independently of protein kinase C activation to allow T-cell proliferation and prevent the induction of unresponsiveness. J Immunol 142: 2617, 1989.

    PubMed  CAS  Google Scholar 

  6. Mincheff MS, Meryman HT. Costimulatory signals necessary for induction of T cell proliferation. Transplantation 49: 768, 1990.

    Article  PubMed  CAS  Google Scholar 

  7. Mincheff MS, Meryman HT. Induction of primary mixed leukocyte reactions with ultraviolet B or chemically modified stimu- lator cells. Transplantation 48: 1052, 1989.

    Article  PubMed  CAS  Google Scholar 

  8. Takahashi T, Inada S, O’Shea JJ, Brown EJ. Osmotic stress and the freeze-thaw cycle cause shedding of Fc and C3b receptors by human polymorphonuclear leukocytes. J Immunol 134: 4062, 1985.

    PubMed  CAS  Google Scholar 

  9. Claas FHJ, Smeenk RJT, Schmidt R, van Steenbrugge GH, Eernisse JG. Allo-immunization against the MHC antigens after platelet transfusions is due to contaminating leukocytes in the platelet suspension. Exp Hematol 9: 84, 1981.

    PubMed  CAS  Google Scholar 

  10. Welsh KI, Burgos H, Batchelor JR. The immune response to allogeneic rat platelets: Ag-B antigen in matrix form lacking Ia. Eur J Immunol 7: 267, 1977.

    Article  PubMed  CAS  Google Scholar 

  11. Dausset J, Rapaport FT. Transplantation antigen activity of human blood platelets. Transplantation 4: 182, 1966.

    Article  PubMed  CAS  Google Scholar 

  12. Rapaport FT, Dausset J, Converse JM, Lawrence HS. Biological and ultrastructural studies of leukocyte fractions as transplantation antigens in man. Transplantation 4: 490, 1965.

    Article  Google Scholar 

  13. Walker RH. Special report: Transfusion risks. Am J Clin Pathol 88: 374, 1987.

    PubMed  CAS  Google Scholar 

  14. Menitove JE, McElligott MC, Aster RH. Febrile transfusion reaction: What component should be given next? Vox Sang 42: 318, 1982.

    Article  PubMed  CAS  Google Scholar 

  15. Slichter SJ. Platelet transfusion therapy. Hematol Oncol Clin North Am 4: 291, 1990.

    PubMed  CAS  Google Scholar 

  16. Howard JE, Perkins HA. The natural history of alloimmunization to platelets. Transfusion 18: 496, 1978.

    Article  PubMed  CAS  Google Scholar 

  17. Klingemann FIG, Self S, Banaji, et al. Refractoriness to random donor platelet transfusions in patients with aplastic anemia: A multvariate analysis of data from 264 cases. Br J Haematol 66: 115, 1987.

    PubMed  CAS  Google Scholar 

  18. Schiffer CA, Lichtenfield JL, Wiernik PH, Mardiney MR, Joseph JM. Antibody response in patients with acute non-lymphocytic leukemia. Cancer 37: 2177, 1976.

    Article  PubMed  CAS  Google Scholar 

  19. Klein CA, Blajchman MA. Alloantibodies and platelet destruction. Sem Thromb Hemostas 8: 105, 1982.

    Article  CAS  Google Scholar 

  20. Murphy MF, Metcalfe P, Thomas H, Eve J, Ord J, Lister TA, Waters AH. Use of leu-kocyte-poor blood components and HLA matched platelet donors to prevent HLA alloimmunization. Br J Haematol 62: 529, 1986.

    Article  PubMed  CAS  Google Scholar 

  21. Duquesnoy RJ. Donor selection in platelet transfusion therapy of alloimmunized thrombocytopenic patients. In: The Blood Platelet in Transfusion Therapy. Alan R. Liss, New York p. 229, 1978.

    Google Scholar 

  22. Menitove JE, Aster RH. Transfusion of platelets and plasma products. Clin Haematol 12: 239, 1983.

    PubMed  CAS  Google Scholar 

  23. Duquesnoy RJ, Filip DJ, Rodey GE, Rimm AA, Aster RH. Successful transfusion of platelets “mismatched” for FILA antigens to alloimmunized thrombocytopenic patients. Am J Hematol 2: 219, 1977.

    Article  PubMed  CAS  Google Scholar 

  24. Freedman J, Hooi C, Garvey MB. Prospective platelet crossmatching for selection of compatible random donors. Br J Haematol 56: 9, 1984.

    Article  PubMed  CAS  Google Scholar 

  25. Freedman J, Garvey MB, Salomon de Friedberg Z, et al. Random donor platelet crossmatching: Comparison of four platelet antibody detection methods. Am J Hematol 28: 1, 1988.

    Article  PubMed  CAS  Google Scholar 

  26. O’Connell BA, Schiffer CA. Donor selection for alloimmunized patients by platelet crossmatching of random-donor platelet concentrates. Transfusion 30: 314, 1990.

    Article  PubMed  Google Scholar 

  27. Kekomaki R, Elfenbein G, Gardner R, Graham-Pole J, Mehta P, Gross S. Improved response of patients refractory to random-donor platelet transfusions by intravenous gamma globulin. Am J Med 76: 199, 1984.

    Article  PubMed  CAS  Google Scholar 

  28. Kickler T, Braine HG, Piantadosi S, et al. A randomized, placebo-controlled trial of intravenous gammaglobulin in alloimmunized thrombocytopenic patients. Blood 75: 313, 1990.

    PubMed  CAS  Google Scholar 

  29. Zeigler ZR, Shadduck RK, Rosenfeld CS, et al. High-dose intravenous gamma globulin improves responses to single-donor platelets in patients refractory to platelet transfusion. Blood 70: 1433, 1987.

    PubMed  CAS  Google Scholar 

  30. Zeigler ZR, Shadduck RK, Rosenfeld CS, et al. Intravenous gammaglobulin decreases platelet-associated IgG and improves transfusion responses in platelet refractory states. Am J Hematol 38: 15, 1991.

    Article  PubMed  CAS  Google Scholar 

  31. Schiffer CA, Hogge DE, Aisner J, et al. High-dose intravenous gamma globulin in alloimmunized platelet transfusion recipients. Blood 64: 937, 1984.

    PubMed  CAS  Google Scholar 

  32. Bensinger WI, Buckner CD, Clift RA, et al. Plasma exchange for platelet allo-immunization. Transplantation 41: 602, 1986.

    Article  PubMed  CAS  Google Scholar 

  33. Christie DJ, Howe RB, Lennon SS, Souro SC. Treatment of refractoriness to platelet transfusion by protein A column therapy. Transfusion 33: 234, 1993.

    Article  PubMed  CAS  Google Scholar 

  34. Sniecinski I, Delaney G. Response to therapy with Protein-A column in alloimmunized patients (Abstract). Proceedings of International Society of Hematology, Blackwell Scientific Publications, p. 17, 1992.

    Google Scholar 

  35. Slichter SJ, Deeg HJ, Kennedy MS. Prevention of platelet alloimmunization in dogs with systemic cyclosporine and UV irradiation of cyclosporine loading of donor platelets. Blood 69: 414, 1987.

    PubMed  CAS  Google Scholar 

  36. Slichter SJ, Weiden PL, Kane PJ, Storb RF. Approaches to preventing or reversing platelet alloimmunization using animal models. Transfusion 28: 103, 1988.

    Article  PubMed  CAS  Google Scholar 

  37. Gmur J, Burger J, Schanz U, Fehr J, Schaffner A. Safety of stringent prophylactic platelet transfusion policy for patients with acute leukemia. Lancet 338: 1223, 1991.

    Article  PubMed  CAS  Google Scholar 

  38. Slichter SJ, O’Donnell MR, Weiden PL, Storb R, Schroeder ML. Canine platelet alloimmunization: The role of donor selection. Br J Haematol 63: 713, 1986.

    Article  PubMed  CAS  Google Scholar 

  39. Sintnicolaas K, Vriesendorp HM, Sizoo W, et al. Delayed alloimmunization by random single donor platelet transfusions. Lancet 1: 750, 1981.

    Article  PubMed  CAS  Google Scholar 

  40. Gmur J, von Felten A, Osterwalder B, Scali G, Sauter Chr, Frick P. Delayed allo-immunization using random single donor platelet transfusions: A prospective study in thrombocytopenic patients with acute leukemia. Blood 61: 473, 1983.

    Google Scholar 

  41. Kakaiya RM, Hezzey AJ, Bove JR, et al. Alloimmunization following apheresis platelets vs pooled platelet concentrate transfusion - a prospective randomized study (abstract). Transfusion 21: 600, 1981.

    Google Scholar 

  42. Lee EJ, Schiffer CA. ABO compatibility can influence the results of platelet transfusion. Results of randomized trial. Transfusion 29: 384, 1989.

    Article  PubMed  CAS  Google Scholar 

  43. Carr R, Hutton JL, Jenkins JA, Lucas GF, Amphlett NW. Transfusion of ABO mismatched platelets leads to early platelet refractoriness. Br J Haematol 75: 408, 1990.

    Article  PubMed  CAS  Google Scholar 

  44. Messerschmidt G, Makuch R, Appelbaum F, et al. A prospective randomized trial of HLA-matched versus mismatched single-donor platelet transfusions in cancer patients. Cancer 62: 795, 1988.

    Article  PubMed  CAS  Google Scholar 

  45. Murphy MF, Metcalfe P, Thomas H, et al. Use of leukocyte-poor blood components and HLA-matched-platelet donors to prevent HLA alloimmunization. Br J Haematol 62: 529, 1986.

    Article  PubMed  CAS  Google Scholar 

  46. Kao KJ. Effects of leukocyte depletion and UVB irradiation on alloantigenicity of major histocompatibility complex antigens in platelet concentrate: A comparative study. Blood 80: 2931, 1992.

    Google Scholar 

  47. Blajchman MA, Bardossy L, Carmen RA, Goldman M, Heddle NM, Singal DP. An animal model of allogeneic donor platelet refractoriness: The effect of pre-storage leukodepletion. Blood 79: 1371, 1992.

    PubMed  CAS  Google Scholar 

  48. Eernisse JG, Brand A. Prevention of platelet refractoriness due to HLA antibodies by administration of leukocyte-poor blood components. Exp Hematol 9: 77, 1981.

    PubMed  CAS  Google Scholar 

  49. Fisher M, Chapman JR, Ting A, Morris PJ. Alloimmunization to HLA antigens following transfusion with leukocyte-poor and purified platelet suspensions. Vox Sang 49: 331, 1985.

    Article  PubMed  CAS  Google Scholar 

  50. Murphy MF, Metcalfe P, Thomas H, et al. Use of leukocyte-poor blood components and HLA-matched-platelet donors to prevent HLA alloimmunization. Br J Haematol 62: 529, 1985.

    Article  Google Scholar 

  51. Brand A, Claas FH, Voogt PJ, Wasser MN, Eernisse JG. Alloimmunization after leukocyte-depleted multiple random donor platelet transfusions. Vox Sang 54: 160, 1988.

    Article  PubMed  CAS  Google Scholar 

  52. Saarinen UM, Kekomaki R, Silimes M, Myllyla G. Effective prophylaxis against platelet refractoriness in multitransfused patients by use of leukocyte-free blood components. Blood 75: 512, 1990.

    PubMed  CAS  Google Scholar 

  53. Schiffer CA. Management of patients refractory to platelet transfusion-an evaluation of methods of donor selection. Prog Hematol p. 91, 1987.

    Google Scholar 

  54. Sniecinski I, O’Donnell MR, Nowicki B, Hill LR. Prevention of refractoriness and HLA-alloimmunization using filtered blood products. Blood 71: 1402, 1988.

    PubMed  CAS  Google Scholar 

  55. Andreu G, Dewailly J, Leberre C, et al. Prevention of HLA immunization with leukocyte-poor packed red cells and platelet concentrates obtained by filtration. Blood 72: 964, 1988.

    PubMed  CAS  Google Scholar 

  56. van Marwijk Kooy M, van Prooijen HC, Moes M, Bosma-Stants I, Akkerman JW. Use of leukocyte-depleted platelet concentrates for the prevention of refractoriness and primary HLA alloimmunization: A prospective, randomized trial. Blood 77: 201, 1991.

    PubMed  Google Scholar 

  57. Oksanen K, Kekomaki R, Ruutu T, et al. Prevention of alloimmunization in patients with acute leukemia by use of white cell-reduced blood components: A randomized trial. Transfusion 31: 588, 1991.

    Article  PubMed  CAS  Google Scholar 

  58. Handa M, et al. Role of leukocyte depletion from platelet concentrates in reducing HLA alloimmunization and platelet refractoriness in polytransfused patients: A prospective multicenter randomized study in Japan. In: Clinical Application of Leukocyte Depletion. Sekiguchi S [ed ), Blackwell Scientific Publications, 1993.

    Google Scholar 

  59. Heedle N. The efficiency of leukodepletion to improve platelet transfusion response: A critical appraisal of clinical studies. Trans Med Reviews 8: 15, 1994.

    Article  Google Scholar 

  60. Lindahl-Kiessling K, Safwenberg J. Inability of UV-irradiated lymphocytes to stimulate allogeneic cells in mixed lymphocyte culture. Int Arch Allergy 41: 670, 1971.

    Article  PubMed  CAS  Google Scholar 

  61. Deeg HJ, Bazar L, Sigaroudinia M, CottlerFox M. Ultraviolet B light inactivates bone marrow T lymphocytes but spares hematopoietic precursor cells. Blood 73: 369, 1989.

    PubMed  CAS  Google Scholar 

  62. Lau H, Reemtsma K, Hardy MA. Pancreatic islet allograft prolongation by donor-specific blood transfusions treated with ultraviolet irradiation. Science 221: 754, 1983.

    Article  PubMed  CAS  Google Scholar 

  63. Deeg HJ, Aprile J, Graham TV, Appelbaum FR, Storb R. Ultraviolet irradiation of blood prevents transfusion-induced sensitization and marrow graft rejection in dogs. Blood 67: 537, 1986.

    PubMed  CAS  Google Scholar 

  64. Oluwole SF, Iga C, Lau H, Reemtsma K, Hardy MA. Prolongation of rat heart allografts by donor-specific transfusion treated with ultraviolet irradiation. Heart Transplant 4: 385, 1985.

    CAS  Google Scholar 

  65. Slichter SJ, Deeg HJ, Kennedy MS. Prevention of platelet alloimmunization in dogs with systemic cyclosporine and by UV-irradiation or cyclosporine-loading of donor platelets. Blood 69: 414, 1987.

    PubMed  CAS  Google Scholar 

  66. Baadsgaard O, Fox DA, Cooper KD. Human epidermal cells from ultraviolet light exposed skin preferentially activate auto-reactive CDR +2H4 +suppressor-inducer lymphocytes and CD8+ suppressor/cytotoxic lymphocytes. J Immuno 140: 1738, 1988.

    CAS  Google Scholar 

  67. Hersey P, Haran G, Hasic E, Edwards A. Alteration of T cell subsets and induction of suppressor T cell activity in normal subjects after exposure to sunlight. J Immunol 131: 171, 1983.

    PubMed  CAS  Google Scholar 

  68. Ullrich SE. Suppression of the immune response to allogeneic histocompatibility antigens by a single exposure to ultraviolet radiation. Transplantation 42: 287, 1986.

    Article  PubMed  CAS  Google Scholar 

  69. Ullrich SE. The effect of ultraviolet radiation-induced suppressor cells on T-cell activity. Immunology 60: 353, 1987.

    PubMed  CAS  Google Scholar 

  70. Greene MI, SY MS, Kripke M, Benacerraf B. Impairment of antigen presenting cell function by ultraviolet radiation. Proc Natl Acad Sci USA 76: 6591, 1979.

    Article  PubMed  CAS  Google Scholar 

  71. Jakway JP, Shevach EM. Stimulation of T-cell activation by UV-treated, antigen-pulsed macrophages: Evidence for a requirement for antigen processing and interleukin-1 secretion. Cellular Immunol 80: 151, 1983.

    Article  CAS  Google Scholar 

  72. Everson MP, Spalding DM, Koopman WJ. Exquisite sensitivity of dendritic cells to ultraviolet radiation and temperature changes. Transplantation 48: 666, 1989.

    PubMed  CAS  Google Scholar 

  73. Crow NK, Kunkel HG. Human dendritic cells: Major stimulators of the autologous and allogenic mixed leukocyte reactions. Clin Exp Immunol 49: 338, 1982.

    Google Scholar 

  74. Gromo G, Inverardi L, Geller RL, Alter BJ, Bach FH. The step wise activation of cytotoxic T lymphocytes. Immunol Today 8: 259, 1987.

    Article  CAS  Google Scholar 

  75. Tominaga A, Lefort S, Mizel SB, et al. Molecular signals in antigen presentation. I. Effects of interleukin 1 and 2 on radiation treated antigen presenting cells in vivo and in vitro. Clin Immunol Immunolpathol 29: 282, 1983.

    Article  CAS  Google Scholar 

  76. Slater LM, Murray S, Liu J, Hudelson B. Dissimilar effects of ultraviolet light on HLA-D and HLA-DR antigens. Tissue Antigens 15: 431, 1980.

    Article  PubMed  CAS  Google Scholar 

  77. Gruner S, Volk HD, Noack F, Meffert H, von Baehr R. Inhibition of HLA-DR antigen expression and of the allogeneic mixed leukocyte reaction by photochemical treatment. Tissue Antigens 27: 147, 1986.

    Article  PubMed  CAS  Google Scholar 

  78. Czernielewski J, Viagot P, Asselineau D, Prunieras M. In vitro effect of UV radiation on immune function and membrane mark-ers of human Langerhans’ cells. J Invest Dermatol 83:62, 1984.

    Article  PubMed  CAS  Google Scholar 

  79. Aprile J, Deeg HJ. Ultraviolet irradiation of canine dendritic cells prevents mitogeninduced cluster formation and lymphocyte proliferation. Transplantation 42: 653, 1986.

    Article  PubMed  CAS  Google Scholar 

  80. Andre G, Perrot JY, Pirenne F, Bocaccio C. The effect of ultraviolet light on antigen-presenting cells: Implications for transfusion-induced sensitization. Semin Hematol 29: 122, 1992.

    Google Scholar 

  81. Menitove JE, Kagen LR, Aster RH. Alloimmunization is decreased in platelets receiving UV-B irradiated platelet concentrates and leukocyte-depleted red cells. Blood (Suppl 1 ) 76: 1607, 1990.

    Google Scholar 

  82. Pamphillon DH. Personal communication.

    Google Scholar 

  83. Andreu G. Personal communication.

    Google Scholar 

Download references

Authors
  1. Irena Sniecinski
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Sniecinski, I. (1995). Leukodepletion and Alloimmunization. In: Clinical Benefits of Leukodepleted Blood Products. Medical Intelligence Unit. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-26538-3_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-26538-3_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-1-57059-122-8

  • Online ISBN: 978-3-662-26538-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation