Skip to main content

Advertisement

SpringerLink
Log in

IgM anti-recipient ABO antibodies predict acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Passenger lymphocyte syndrome (PLS) presents as transient immune hemolysis due to anti-recipient ABO antibodies produced by donor B-lymphocytes accompanying minor or bidirectional ABO incompatible allogeneic hematopoietic stem cell transplantation (HSCT). We monitored both IgM and IgG type anti-recipient ABO antibodies in 18 consecutive HSCT recipients with hematological malignancies. Five of these patients (28 %) developed transient immune hemolysis due to PLS after a median of 19 days post-HSCT. This response was associated with the detection of IgM and IgG anti-recipient ABO antibodies after a median of 16 and 22 days post-HSCT, respectively. All five patients subsequently developed acute graft-versus-host disease (GVHD) grades II–IV, and three died due to transplant-related mortality (TRM) within 1 year after HSCT, while in contrast, of the 13 patients without PLS, three (23 %) developed grades II–IV acute GVHD (p < 0.01) and the 1-year TRM was 8 % (p = 0.03). Thus, patients with PLS had a significantly lower 1-year overall survival than those without PLS (20 vs. 75 %, p = 0.03). These findings suggest that the IgM anti-recipient ABO antibody may be an early predictor of acute GVHD and poor survival after minor or bidirectional ABO incompatible HSCT.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Takasaki H, Tanaka M, Tachibana T, Numata A, Fujimaki K, Sakai R, Fujisawa S, et al. Prognostic factors in patients aged 50 years or older undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancy. Int J Hematol. 2012;95:291–8.

    Article  PubMed  Google Scholar 

  2. Bensinger WI, Buckner CD, Thomas ED, Clift RA. ABO-incompatible marrow transplants. Transplantation. 1982;33:427–9.

    Article  PubMed  CAS  Google Scholar 

  3. Hows J, Beddow K, Gordon-Smith E, Branch DR, Spruce W, Sniecinski I, Krance RA, et al. Donor-derived red blood cell antibodies and immune hemolysis after allogeneic bone marrow transplantation. Blood. 1986;67:177–81.

    PubMed  CAS  Google Scholar 

  4. Bolan CD, Childs RW, Procter JL, Barrett AJ, Leitman SF. Massive immune haemolysis after allogeneic peripheral blood stem cell transplantation with minor ABO incompatibility. Br J Haematol. 2001;112:787–95.

    Article  PubMed  CAS  Google Scholar 

  5. Gajewski JL, Petz LD, Calhoun L, O’Rourke S, Landaw EM, Lyddane NR, Hunt LA, et al. Hemolysis of transfused group O red blood cells in minor ABO-incompatible unrelated-donor bone marrow transplants in patients receiving cyclosporine without posttransplant methotrexate. Blood. 1992;79:3076–85.

    PubMed  CAS  Google Scholar 

  6. Hazlehurst GR, Brenner MK, Wimperis JZ, Knowles SM, Prentice HG. Haemolysis after T-cell depleted bone marrow transplantation involving minor ABO incompatibility. Scand J Haematol. 1986;37:1–3.

    Article  PubMed  CAS  Google Scholar 

  7. Hoffman PC. Immune hemolytic anemia—selected topics. ASH Educ Program Book. 2009;2009:80–6.

    Google Scholar 

  8. Snell M, Chau C, Hendrix D, Fox R, Downes KA, Creger R, Meyerson H, et al. Lack of isohemagglutinin production following minor ABO incompatible unrelated HLA mismatched umbilical cord blood transplantation. Bone Marrow Transplant. 2006;38:135–40.

    Article  PubMed  CAS  Google Scholar 

  9. Worel N, Greinix HT, Keil F, Mitterbauer M, Lechner K, Fischer G, Mayr W, et al. Severe immune hemolysis after minor ABO-mismatched allogeneic peripheral blood progenitor cell transplantation occurs more frequently after nonmyeloablative than myeloablative conditioning. Transfusion. 2002;42:1293–301.

    Article  PubMed  Google Scholar 

  10. Oziel-Taieb S, Faucher-Barbey C, Chabannon C, Ladaique P, Saux P, Gouin F, Gastaut JA, et al. Early and fatal immune haemolysis after so-called ‘minor’ ABO-incompatible peripheral blood stem cell allotransplantation. Bone Marrow Transplant. 1997;19:1155–6.

    Article  PubMed  CAS  Google Scholar 

  11. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    Google Scholar 

  12. Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706.

    Article  PubMed  CAS  Google Scholar 

  13. Ludajic K, Balavarca Y, Bickeböller H, Rosenmayr A, Fischer GF, Faè I, Kalhs P, et al. Minor ABO-mismatches are risk factors for acute graft-versus-host disease in hematopoietic stem cell transplant patients. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplant. 2009;15:1400–6.

    Article  Google Scholar 

  14. Resnick IB, Tsirigotis PD, Shapira MY, Aker M, Bitan M, Samuel S, Abdul-Hai A, et al. ABO incompatibility is associated with increased non-relapse and GVHD related mortality in patients with malignancies treated with a reduced intensity regimen: a single center experience of 221 patients. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplant. 2008;14:409–17.

    Article  CAS  Google Scholar 

  15. Kimura F, Sato K, Kobayashi S, Ikeda T, Sao H, Okamoto S, Miyamura K, et al. Impact of ABO-blood group incompatibility on the outcome of recipients of bone marrow transplants from unrelated donors in the Japan Marrow Donor Program. Haematologica. 2008;93:1686–93.

    Article  PubMed  Google Scholar 

  16. Stussi G, Seebach L, Muntwyler J, Schanz U, Gmür J, Seebach JD. Graft-versus-host disease and survival after ABO-incompatible allogeneic bone marrow transplantation: a single-centre experience. Br J Haematol. 2001;113:251–3.

    Article  PubMed  CAS  Google Scholar 

  17. Bacigalupo A, Van Lint MT, Occhini D, Margiocco M, Ferrari G, Pittaluga PA, Frassoni F, et al. ABO compatibility and acute graft-versus-host disease following allogeneic bone marrow transplantation. Transplantation. 1988;45:1091–4.

    Article  PubMed  CAS  Google Scholar 

  18. Klumpp TR, Fairclough D, Ritz J, Soiffer R. The effect of minor ABO mismatches on the incidence of graft-versus-host disease after allogeneic bone marrow transplantation. Transplantation. 1994;57:780.

    Article  PubMed  CAS  Google Scholar 

  19. Keever-Taylor CA, Bredeson C, Loberiza FR, Casper JT, Lawton C, Rizzo D, Burns WH, et al. Analysis of risk factors for the development of GVHD after T cell-depleted allogeneic BMT: effect of HLA disparity, ABO incompatibility, and method of T-cell depletion. Biol Blood Marrow Transplant. 2001;7:620–30.

    Article  PubMed  CAS  Google Scholar 

  20. Seebach JD, Stussi G, Passweg JR, Loberiza FR Jr, Gajewski JL, Keating A, Goerner M, et al. ABO blood group barrier in allogeneic bone marrow transplantation revisited. Biol Blood Marrow Transplant. 2005;11:1006–13.

    Article  PubMed  Google Scholar 

  21. Benjamin RJ, Antin JH. ABO-incompatible bone marrow transplantation: the transfusion of incompatible plasma may exacerbate regimen-related toxicity. Transfusion. 1999;39:1273–4.

    Article  PubMed  CAS  Google Scholar 

  22. Stussi G, Muntwyler J, Passweg JR, Seebach L, Schanz U, Gmur J, Gratwohl A, et al. Consequences of ABO incompatibility in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2002;30:87–93.

    Article  PubMed  CAS  Google Scholar 

  23. Kanda J, Ichinohe T, Matsuo K, Benjamin RJ, Klumpp TR, Rozman P, Blumberg N, et al. Impact of ABO mismatching on the outcomes of allogeneic related and unrelated blood and marrow stem cell transplantations for hematologic malignancies: IPD-based meta-analysis of cohort studies. Transfusion. 2009;49:624–35.

    Article  PubMed  Google Scholar 

  24. Shimabukuro-Vornhagen A, Hallek MJ, Storb RF, von Bergwelt-Baildon MS. The role of B cells in the pathogenesis of graft-versus-host disease. Blood. 2009;114:4919–27.

    Article  PubMed  Google Scholar 

  25. Dominietto A, Tedone E, Soracco M, Bruno B, Raiola AM, Van Lint MT, Geroldi S, et al. In vivo B-cell depletion with rituximab for alternative donor hemopoietic SCT. Bone Marrow Transplant. 2012;47:101–6.

    Article  PubMed  CAS  Google Scholar 

  26. Perruche S, Kleinclauss F, Tiberghien P, Saas P. B Cell allogeneic responses after hematopoietic cell transplantation: is it time to address this issue? Transplantation. 2005;79:S37–9.

    Article  PubMed  Google Scholar 

  27. Tabilio A, Falzetti F, Zei T, De Ioanni M, Bonifacio E, Battelli F, Iacucci Ostini R, et al. Graft engineering for allogeneic haploidentical stem cell transplantation. Blood Cells Mol Dis. 2004;33:274–80.

    Article  PubMed  Google Scholar 

  28. Ravn V, Dabelsteen E. Tissue distribution of histo-blood group antigens. APMIS. 2000;108:1–28.

    Article  PubMed  CAS  Google Scholar 

  29. Igarashi A, Kakihana K, Haraguchi K, Aoki J, Kobayashi T, Okuyama Y, Ohashi K, et al. Anti-host isohemagglutinin production is associated with a higher risk of acute GVHD in ABO-incompatible transplantation. Bone Marrow Transplant. 2012;47:1356–60.

    Article  PubMed  CAS  Google Scholar 

  30. Chung HJ, Lee JH, Kwon SW. Significance of donor-derived isoagglutinins in ABO-Incompatible hematopoietic stem cell transplantation. J Clin Lab Anal. 2008;22:383–90.

    Article  PubMed  CAS  Google Scholar 

  31. Bacigalupo A, Dominietto A, Soracco M, Raiola AM, Van Lint MT, Lamparelli T, Ibatici A, et al. Rituximab prophylaxis of EBV reactivation after alternative donor transplants following anti-thymocyte globulin-based conditioning regimens. ASH Annual Meet Abstr. 2008;112:2232.

    Google Scholar 

  32. Lee HJ, Gulbis A, De Padua Silva L, Hosing C, Khouri I, de Lima M, Champlin RE, et al. Rituximab for passenger lymphocyte syndrome associated with allogeneic SCT. Bone Marrow Transplant. 2008;42:67–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank all the Kanazawa University Hospital HSCT team. This study was supported by grants from the Ministry of Health, Labor and Welfare of Japan, and the Ministry of Education, Culture, Sports and Technology of Japan. This work was supported in part by a Research on Allergic Disease and Immunology (H23-010) in a Health and Labor Science Grant from the Ministry of Health, Labor and Welfare of Japan. The grant sources played no role in the study design, data collection and analysis, the decision to publish or the preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa, 920-8641, Japan

    Yoshitaka Zaimoku, Akiyoshi Takami & Shinji Nakao

  2. Division of Transfusion Medicine, Kanazawa University Hospital, Kanazawa, Japan

    Yoshitaka Zaimoku, Akiyoshi Takami, Hidehiro Sato & Maki Utsumi

Authors
  1. Yoshitaka Zaimoku
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akiyoshi Takami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hidehiro Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maki Utsumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shinji Nakao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akiyoshi Takami.

Additional information

Yoshitaka Zaimoku, Akiyoshi Takami and Hidehiro Sato equally contributed to the study.

About this article

Cite this article

Zaimoku, Y., Takami, A., Sato, H. et al. IgM anti-recipient ABO antibodies predict acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Int J Hematol 98, 96–101 (2013). https://doi.org/10.1007/s12185-013-1360-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-013-1360-6

Keywords

Search

Navigation