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Outcomes of combination therapy including rituximab for antibody-mediated rejection after lung transplantation

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Abstract

Objectives

This study assessed the outcomes of combination therapy including rituximab for antibody-mediated rejection after lung transplantation.

Methods

Retrospective chart reviews were performed for all patients who received combination therapy including rituximab for post-lung transplantation antibody-mediated rejection between June 2008 and October 2018.

Results

Among the 196 consecutive patients undergoing lung transplantation during the study period, eight (4.1%) were eligible for this study. Two patients (25.0%) were classified as having clinically definite antibody-mediated rejection and six (75.0%) as having possible antibody-mediated rejection. Prior to treatment, four patients (50.0%) met the definition of chronic lung allograft dysfunction; seven of the eight patients (87.5%) remained alive at 6 months and four (50.0%) at 12 months after antibody-mediated rejection. All patients identified as having chronic lung allograft dysfunction, prior to the treatment, died of allograft failure, or underwent re-transplantation. Decreases in the mean fluorescence intensities of the major donor-specific antibodies were observed in three patients. One patient, diagnosed with clinical antibody-mediated rejection but without pre-treatment chronic lung allograft dysfunction, began treatment relatively soon after lung transplantation, and demonstrated improved respiratory function at the 3-year follow-up.

Conclusions

Our experience suggests that multimodality therapy that includes rituximab is feasible and may prevent progression of antibody-mediated rejection after lung transplantation in selected patients.

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References

  1. Date H. Current status and problems of lung transplantation in Japan. J Thorac Dis. 2016;8(Suppl 8):S631–S636636.

    Article  Google Scholar 

  2. Miyoshi R, Chen-Yoshikawa TF, Hijiya K, Motoyama H, Aoyama A, Menju T, et al. Significance of single lung transplantation in the current situation of severe donor shortage in Japan. Gen Thorac Cardiovasc Surg. 2016;64:93–7.

    Article  Google Scholar 

  3. Sato M, Okada Y, Oto T, Minami M, Shiraishi T, Nagayasu T, et al. Registry of the Japanese Society of Lung and Heart-Lung Transplantation: official Japanese lung transplantation report, 2014. Gen Thorac Cardiovasc Surg. 2014;62:594–601.

    Article  Google Scholar 

  4. Yusen RD, Edwards LB, Dipchand AI, Goldfarb SB, Kucheryavaya AY, Levvey BJ, et al. The Registry of the International Society for Heart and Lung Transplantation: thirty-third adult lung and heart-lung transplant report-2016; focus theme: primary diagnostic indications for transplant. J Heart Lung Transplant. 2016;35:1170–84.

    Article  Google Scholar 

  5. Hachem RR, Yusen RD, Meyers BF, Aloush AA, Mohanakumar T, Patterson GA, et al. Anti-human leukocyte antigen antibodies and preemptive antibody-directed therapy after lung transplantation. J Heart Lung Transplant. 2010;29:973–80.

    Article  Google Scholar 

  6. Lobo LJ, Aris RM, Schmitz J, Neuringer IP. Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation. J Heart Lung Transplant. 2013;32:70–7.

    Article  Google Scholar 

  7. Levine DJ, Glanville AR, Aboyoun C, Belperio J, Benden C, Berry GJ, et al. Antibody-mediated rejection of the lung: a consensus report of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2016;35:397–406.

    Article  Google Scholar 

  8. Hachem RR. Acute rejection and antibody-mediated rejection in lung transplantation. Clin Chest Med. 2017;38:667–75.

    Article  Google Scholar 

  9. Vacha M, Chery G, Hulbert A, Byrns J, Benedetti C, Finlen Copeland CA, et al. Antibody depletion strategy for the treatment of suspected antibody-mediated rejection in lung transplant recipients: does it work? Clin Transplant. 2017. https://doi.org/10.1111/ctr.12886.

    Article  PubMed  Google Scholar 

  10. Muller YD, Aubert JD, Vionnet J, Rotman S, Sadallah S, Aubert V, et al. Acute antibody-mediated rejection 1 week after lung transplantation successfully treated with eculizumab, intravenous immunoglobulins, and rituximab. Transplantation. 2018;102:e301–e303303.

    Article  Google Scholar 

  11. Date H, Sato M, Aoyama A, Yamada T, Mizota T, Kinoshita H, et al. Living-donor lobar lung transplantation provides similar survival to cadaveric lung transplantation even for very ill patients. Eur J Cardiothorac Surg. 2015;47:967–72.

    Article  Google Scholar 

  12. Verleden GM, Raghu G, Meyer KC, Glanville AR, Corris P. A new classification system for chronic lung allograft dysfunction. J Heart Lung Transplant. 2014;33:127–33.

    Article  Google Scholar 

  13. Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. Am J Transplant. 2006;6(5 Pt 1):859–66.

    Article  CAS  Google Scholar 

  14. Le Pavec J, Suberbielle C, Lamrani L, Feuillet S, Savale L, Dorfmuller P, et al. De-novo donor-specific anti-HLA antibodies 30 days after lung transplantation are associated with a worse outcome. J Heart Lung Transplant. 2016;35:1067–77.

    Article  Google Scholar 

  15. Czuczman MS, Grillo-Lopez AJ, White CA, Saleh M, Gordon L, LoBuglio AF, et al. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999;17:268–76.

    Article  CAS  Google Scholar 

  16. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.

    Article  CAS  Google Scholar 

  17. Igarashi T, Kobayashi Y, Ogura M, Kinoshita T, Ohtsu T, Sasaki Y, et al. Factors affecting toxicity, response and progression-free survival in relapsed patients with indolent B-cell lymphoma and mantle cell lymphoma treated with rituximab: a Japanese phase II study. Ann Oncol. 2002;13:928–43.

    Article  CAS  Google Scholar 

  18. Chen F, Miyagawa-Hayashino A, Yurugi K, Chibana N, Yamada T, Sato M, et al. Redo living-donor lobar lung transplantation for bronchiolitis obliterans associated with antibody-mediated rejection. Transpl Int. 2014;27:e8–12.

    Article  Google Scholar 

  19. Chen F, Chibana N, Kanematsu A, Takakura S, Yurugi K, Hishida R, et al. Antibody-mediated rejection of a unilateral donor lung in bilateral living-donor lobar lung transplantation: report of a case. Surg Today. 2012;42:808–11.

    Article  Google Scholar 

  20. Petit LM, Rabant M, Canioni D, Suberbielle-Boissel C, Goulet O, Chardot C, et al. Impacts of donor-specific anti-HLA antibodies and antibody-mediated rejection on outcomes after intestinal transplantation in children. Pediatr Transplant. 2017. https://doi.org/10.1111/petr.12847.

    Article  PubMed  Google Scholar 

  21. Demetris AJ, Bellamy C, Hubscher SG, O'Leary J, Randhawa PS, Feng S, et al. 2016 Comprehensive update of the Banff working group on liver allograft pathology: introduction of antibody-mediated rejection. Am J Transplant. 2016;16:2816–35.

    Article  CAS  Google Scholar 

  22. Mittal S, Page SL, Friend PJ, Sharples EJ, Fuggle SV. De novo donor-specific HLA antibodies: biomarkers of pancreas transplant failure. Am J Transplant. 2014;14:1664–711.

    Article  CAS  Google Scholar 

  23. Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12:388–99.

    Article  CAS  Google Scholar 

  24. Kfoury AG, Renlund DG, Snow GL, Stehlik J, Folsom JW, Fisher PW, et al. A clinical correlation study of severity of antibody-mediated rejection and cardiovascular mortality in heart transplantation. J Heart Lung Transplant. 2009;28:51–7.

    Article  Google Scholar 

  25. Pineiro GJ, De Sousa-Amorim E, Sole M, Rios J, Lozano M, Cofan F, et al. Rituximab, plasma exchange and immunoglobulins: an ineffective treatment for chronic active antibody-mediated rejection. BMC Nephrol. 2018;19:261.

    Article  Google Scholar 

  26. Parajuli S, Joachim E, Alagusundaramoorthy S, Blazel J, Aziz F, Garg N, et al. Subclinical antibody mediated rejection after kidney transplantation: treatment outcomes. Transplantation. 2018. https://doi.org/10.1097/TP.0000000000002566.

    Article  Google Scholar 

  27. Moreso F, Crespo M, Ruiz JC, Torres A, Gutierrez-Dalmau A, Osuna A, et al. Treatment of chronic antibody mediated rejection with intravenous immunoglobulins and rituximab: a multicenter, prospective, randomized, double-blind clinical trial. Am J Transplant. 2018;18:927–35.

    Article  CAS  Google Scholar 

  28. Macklin PS, Morris PJ, Knight SR. A systematic review of the use of rituximab for the treatment of antibody-mediated renal transplant rejection. Transplant Rev (Orlando). 2017;31:87–95.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Thoracic Surgery, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Keiji Yamanashi, Toyofumi Fengshi Chen-Yoshikawa, Masatsugu Hamaji, Satona Tanaka, Yojiro Yutaka, Yoshito Yamada, Daisuke Nakajima, Akihiro Ohsumi & Hiroshi Date

  2. Department of Transfusion Medicine and Cell Therapy, Kyoto University, Kyoto, Japan

    Kimiko Yurugi

Authors
  1. Keiji Yamanashi
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  2. Toyofumi Fengshi Chen-Yoshikawa
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  3. Masatsugu Hamaji
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  4. Kimiko Yurugi
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  5. Satona Tanaka
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  6. Yojiro Yutaka
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  10. Hiroshi Date
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Correspondence to Hiroshi Date.

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Yamanashi, K., Chen-Yoshikawa, T.F., Hamaji, M. et al. Outcomes of combination therapy including rituximab for antibody-mediated rejection after lung transplantation. Gen Thorac Cardiovasc Surg 68, 142–149 (2020). https://doi.org/10.1007/s11748-019-01189-1

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  • DOI: https://doi.org/10.1007/s11748-019-01189-1

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