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Treatment outcome and efficacy of therapeutic plasma exchange for transplant-associated thrombotic microangiopathy in a large real-world cohort study

Bone Marrow Transplantation volume 57, pages 554–561 (2022)Cite this article

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Abstract

The efficacy and outcome of therapeutic plasma exchange (TPE) for transplant-associated thrombotic microangiopathy (TA-TMA) remain controversial. We therefore sought to evaluate the outcome and efficacy of TPE in patients with TA-TMA and to identify TA-TMA patients who would benefit from TPE management. Eighty-two patients with TA-TMA were treated with TPE. We reported a response rate of 52% and overall survival rates of 20% and 15% at 100 days and 1 year after TA-TMA, respectively, in TPE-treated patients, with a significantly lower survival in gastrointestinal (GI) bleeding patients (5% vs. 41% in non-GI bleeding patients, P = 0.003). Multivariate analysis revealed that patients with GI bleeding, grade III-IV aGVHD, severe anemia, and a lower cumulative volume of TPE were less likely to respond to TPE. GI bleeding, a lower initial volume of TPE, and elevated total bilirubin were independently associated with 100-day mortality. The leading causes of death were infection, active TA-TMA, and MODS. The results of this large cohort of real-world practice indicate that the efficacy and outcome of TPE for TA-TMA patients without GI bleeding are encouraging, and a higher volume of TPE is warranted to achieve favorable outcomes.

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Fig. 1: Overall survival in TA-TMA patients treated with TPE.

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References

  1. Laskin BL, Goebel J, Davies SM, Jodele S. Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood. 2011;118:1452–62. https://doi.org/10.1182/blood-2011-02-321315.

    Article  CAS  PubMed  Google Scholar 

  2. Jodele S, Davies SM, Lane A, Khoury J, Dandoy C, Goebel J, et al. Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults. Blood. 2014;124:645–53. https://doi.org/10.1182/blood-2014-03-564997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ho VT, Cutler C, Carter S, Martin P, Adams R, Horowitz M, et al. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005;11:571–5. https://doi.org/10.1016/j.bbmt.2005.06.001.

    Article  PubMed  Google Scholar 

  4. Jodele S, Licht C, Goebel J, Dixon BP, Zhang K, Sivakumaran TA, et al. Abnormalities in the alternative pathway of complement in children with hematopoietic stem cell transplant-associated thrombotic microangiopathy. Blood. 2013;122:2003–7. https://doi.org/10.1182/blood-2013-05-501445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jodele S, Zhang K, Zou F, Laskin B, Dandoy CE, Myers KC, et al. The genetic fingerprint of susceptibility for transplant-associated thrombotic microangiopathy. Blood. 2016;127:989–96. https://doi.org/10.1182/blood-2015-08-663435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ricklin D, Cines DB. TMA: beware of complements. Blood. 2013;122:1997–9. https://doi.org/10.1182/blood-2013-07-512707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Seaby EG, Gilbert RD. Thrombotic microangiopathy following haematopoietic stem cell transplant. Pediatr Nephrol. 2018;33:1489–1500. https://doi.org/10.1007/s00467-017-3803-4.

    Article  PubMed  Google Scholar 

  8. Jodele S, Laskin BL, Dandoy CE, Myers KC, El-Bietar J, Davies SM, et al. A new paradigm: diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev. 2015;29:191–204. https://doi.org/10.1016/j.blre.2014.11.001.

    Article  PubMed  Google Scholar 

  9. Jodele S, Laskin BL, Pinkard SL, Carey PM, Goebel J, Davies SM. Does early initiation of therapeutic plasma exchange affect outcome in pediatric stem cell transplant-associated thrombotic microangiopathy? Biol Blood Marrow Transplant. 2011;17:S258.

    Article  Google Scholar 

  10. Kennedy GA, Kearey N, Bleakley S, Butler J, Mudie K, Durrant S. Transplantation-associated thrombotic microangiopathy: effect of concomitant GVHD on efficacy of therapeutic plasma exchange. Bone marrow Transplant. 2010;45:699–704. https://doi.org/10.1038/bmt.2009.233.

    Article  CAS  PubMed  Google Scholar 

  11. Worel N, Greinix HT, Leitner G, Mitterbauer M, Rabitsch W, Rosenmayr A, et al. ABO-incompatible allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning: close association with transplant-associated microangiopathy. Transfus Apheresis Sci. 2007;36:297–304. https://doi.org/10.1016/j.transci.2007.03.004.

    Article  Google Scholar 

  12. Cho BS, Yahng SA, Lee SE, Eom KS, Kim YJ, Kim HJ, et al. Validation of recently proposed consensus criteria for thrombotic microangiopathy after allogeneic hematopoietic stem-cell transplantation. Transplantation. 2010;90:918–26. https://doi.org/10.1097/TP.0b013e3181f24e8d.

    Article  CAS  PubMed  Google Scholar 

  13. Heybeli C, Sridharan M, Alkhateeb HB, Villasboas Bisneto JC, Buadi FK, Chen D et al. Characteristics of late transplant-associated thrombotic microangiopathy in patients who underwent allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2020. https://doi.org/10.1002/ajh.25922.

  14. Popat U, Mehta RS, Rezvani K, Fox P, Kondo K, Marin D, et al. Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation. Blood. 2015;125:2885–92. https://doi.org/10.1182/blood-2015-01-607366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864–74.

    Article  Google Scholar 

  16. Kroschinsky F, Weise M, Illmer T, Haenel M, Bornhaeuser M, Hoeffken G, et al. Outcome and prognostic features of intensive care unit treatment in patients with hematological malignancies. Intensive Care Med. 2002;28:1294–1300. https://doi.org/10.1007/s00134-002-1420-5.

    Article  PubMed  Google Scholar 

  17. Jodele S, Dandoy CE, Lane A, Laskin BL, Teusink-Cross A, Myers KC, et al. Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab. Blood. 2020;135:1049–57. https://doi.org/10.1182/blood.2019004218.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Vasu S, Wu H, Satoskar A, Puto M, Roddy J, Blum W, et al. Eculizumab therapy in adults with allogeneic hematopoietic cell transplant-associated thrombotic microangiopathy. Bone Marrow Transplant. 2016;51:1241–4. https://doi.org/10.1038/bmt.2016.87.

    Article  CAS  PubMed  Google Scholar 

  19. Konar M, Granoff DM. Eculizumab treatment and impaired opsonophagocytic killing of meningococci by whole blood from immunized adults. Blood. 2017;130:891–9. https://doi.org/10.1182/blood-2017-05-781450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Peffault de Latour R, Xhaard A, Fremeaux-Bacchi V, Coppo P, Fischer AM, Helley D, et al. Successful use of eculizumab in a patient with post-transplant thrombotic microangiopathy. Br J Haematol. 2013;161:279–80. https://doi.org/10.1111/bjh.12202.

    Article  PubMed  Google Scholar 

  21. Yang LP, Liu X, Zhang XH. Advances in the diagnosis and management of transplant-associated thrombotic microangiopathy. Zhonghua xueyexue zazhi. 2021;42:693–9. https://doi.org/10.3760/cma.j.issn.0253-2727.2021.08.018.

    Article  CAS  PubMed  Google Scholar 

  22. Jodele S, Laskin BL, Goebel J, Khoury JC, Pinkard SL, Carey PM, et al. Does early initiation of therapeutic plasma exchange improve outcome in pediatric stem cell transplant-associated thrombotic microangiopathy? Transfusion. 2013;53:661–7. https://doi.org/10.1111/j.1537-2995.2012.03776.x.

    Article  CAS  PubMed  Google Scholar 

  23. Mulay S, Kreuter JD, Bryant SC, Elliott MA, Hogan WJ, Winters JL, et al. Outcomes of plasma exchange in patients with transplant-associated thrombotic microangiopathy based on time of presentation since transplant. J Clin Apheresis. 2015;30:147–53. https://doi.org/10.1002/jca.21352.

    Article  PubMed  Google Scholar 

  24. Uderzo C, Bonanomi S, Busca A, Renoldi M, Ferrari P, Iacobelli M, et al. Risk factors and severe outcome in thrombotic microangiopathy after allogeneic hematopoietic stem cell. Transplant Transplant. 2006;82:638–44. https://doi.org/10.1097/01.tp.0000230373.82376.46.

    Article  Google Scholar 

  25. Zhao P, Wu Y, He Y, Chong S, Qu Q, Deng R et al. A prognostic model (BATAP) with external validation for patients with transplant-associated thrombotic microangiopathy. Blood Adv. 2021. https://doi.org/10.1182/bloodadvances.2021004530.

  26. Schoettler M, Lehmann LE, Margossian S, Lee M, Kean LS, Kao PC, et al. Risk factors for transplant-associated thrombotic microangiopathy and mortality in a pediatric cohort. Blood Adv. 2020;4:2536–47. https://doi.org/10.1182/bloodadvances.2019001242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Siami K, Kojouri K, Swisher KK, Selby GB, George JN, Laszik ZG. Thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation: an autopsy study. Transplantation. 2008;85:22–28. https://doi.org/10.1097/01.tp.0000297998.33418.7e.

    Article  PubMed  Google Scholar 

  28. Elfeky R, Lucchini G, Lum SH, Ottaviano G, Builes N, Nademi Z, et al. New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT. Blood Adv. 2020;4:2418–29. https://doi.org/10.1182/bloodadvances.2019001315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Postalcioglu M, Kim HT, Obut F, Yilmam OA, Yang J, Byun BC, et al. Impact of thrombotic microangiopathy on renal outcomes and survival after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2018;24:2344–53. https://doi.org/10.1016/j.bbmt.2018.05.010.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Martinez MT, Bucher C, Stussi G, Heim D, Buser A, Tsakiris DA, et al. Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants. Bone Marrow Transplant. 2005;36:993–1000. https://doi.org/10.1038/sj.bmt.1705160.

    Article  CAS  PubMed  Google Scholar 

  31. Li A, Wu Q, Davis C, Kirtane KS, Pham PD, Sorror ML, et al. Transplant-associated thrombotic microangiopathy is a multifactorial disease unresponsive to immunosuppressant withdrawal. Biol Blood Marrow Transplant. 2019;25:570–6. https://doi.org/10.1016/j.bbmt.2018.10.015.

    Article  PubMed  Google Scholar 

  32. Matsui H, Arai Y, Imoto H, Mitsuyoshi T, Tamura N, Kondo T, et al. Risk factors and appropriate therapeutic strategies for thrombotic microangiopathy after allogeneic HSCT. Blood Adv. 2020;4:3169–79. https://doi.org/10.1182/bloodadvances.2020002007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Epperla N, Li A, Logan B, Fretham C, Chhabra S, Aljurf M, et al. Incidence, risk factors for and outcomes of transplant-associated thrombotic microangiopathy. Br J Haematol. 2020;189:1171–81. https://doi.org/10.1111/bjh.16457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kraft S, Bollinger N, Bodenmann B, Heim D, Bucher C, Lengerke C, et al. High mortality in hematopoietic stem cell transplant-associated thrombotic microangiopathy with and without concomitant acute graft-versus-host disease. Bone Marrow Transplant. 2019;54:540–8. https://doi.org/10.1038/s41409-018-0293-3.

    Article  PubMed  Google Scholar 

  35. Biedermann BC. Vascular endothelium and graft-versus-host disease. Best Pract Res Clin Haematol. 2008;21:129–38. https://doi.org/10.1016/j.beha.2008.02.003.

    Article  CAS  PubMed  Google Scholar 

  36. Naymagon S, Naymagon L, Wong S, Ko H, Renteria A, Levine J, et al. Acute graft-versus-host disease of the gut: considerations for the gastroenterologist. Nat Rev Gastroenterol Hepatol. 2017;14:711–26. https://doi.org/10.1038/nrgastro.2017.126

    Article  PubMed  PubMed Central  Google Scholar 

  37. Chinese consensus on the diagnosis and management of transplant-associated thrombotic microangiopathy (2021). Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 2021;42:177–84. https://doi.org/10.3760/cma.j.issn.0253-2727.2021.03.001.

  38. Howard MA, Williams LA, Terrell DR, Duvall D, Vesely SK, George JN. Complications of plasma exchange in patients treated for clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Transfusion. 2006;46:154–6. https://doi.org/10.1111/j.1537-2995.2006.00687.x.

    Article  PubMed  Google Scholar 

  39. Batts ED, Lazarus HM. Diagnosis and treatment of transplantation-associated thrombotic microangiopathy: real progress or are we still waiting? Bone Marrow Transplant. 2007;40:709–19. https://doi.org/10.1038/sj.bmt.1705758.

    Article  CAS  PubMed  Google Scholar 

  40. Gavriilaki E, Sakellari I, Anagnostopoulos A, Brodsky RA. Transplant-associated thrombotic microangiopathy: opening Pandora’s box. Bone Marrow Transplant. 2017;52:1355–60. https://doi.org/10.1038/bmt.2017.39.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by National Key Research and Development Program of China (No. 2017YFA0105503), National Natural Science Foundation of China (Nos. 81970113, 81800116), Key Program of National Natural Science Foundation of China (No. 81730004), Beijing Natural Science Foundation (No. H2018206423), and Beijing Municipal Science and Technology Commission (No. Z171100001017084). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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  1. These authors contributed equally: Li-Ping Yang, Peng Zhao, Ye-Jun Wu.

Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing, China

    Li-Ping Yang, Peng Zhao, Ye-Jun Wu, Hai-Xia Fu, Yun He, Xiao-Dong Mo, Meng Lv, Feng-Rong Wang, Chen-Hua Yan, Yu-Hong Chen, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang & Xiao-Hui Zhang

  2. National Clinical Research Center for Hematologic Disease, Beijing, China

    Li-Ping Yang, Peng Zhao, Ye-Jun Wu, Hai-Xia Fu, Yun He, Xiao-Dong Mo, Meng Lv, Feng-Rong Wang, Chen-Hua Yan, Yu-Hong Chen, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang & Xiao-Hui Zhang

  3. Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

    Li-Ping Yang, Peng Zhao, Ye-Jun Wu, Hai-Xia Fu, Yun He, Xiao-Dong Mo, Meng Lv, Feng-Rong Wang, Chen-Hua Yan, Yu-Hong Chen, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang & Xiao-Hui Zhang

  4. Collaborative Innovation Center of Hematology, Peking University, Beijing, China

    Li-Ping Yang, Peng Zhao, Ye-Jun Wu, Hai-Xia Fu, Yun He, Xiao-Dong Mo, Meng Lv, Feng-Rong Wang, Chen-Hua Yan, Yu-Hong Chen, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang & Xiao-Hui Zhang

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Contributions

L-PY and X-HZ contributed to the concept and design. L-PY, PZ, Y-JW, H-XF, YH, X-DM, ML, F-RW, C-HY, and Y-HC collected the data. L-PY, PZ, and Y-JW contributed to the data analysis and interpretation. Y-JC, L-PX, K-YL, X-JH revised the manuscript critically. L-PY wrote the manuscript. X-HZ designed, conceived and supervised the study, analyzed the data, and drafted and revised the manuscript. All authors critically reviewed and approved the final version of the manuscript.

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Correspondence to Xiao-Hui Zhang.

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The study protocol was approved by the central institutional review board of the Peking University People’s Hospital, Beijing, China.

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Yang, LP., Zhao, P., Wu, YJ. et al. Treatment outcome and efficacy of therapeutic plasma exchange for transplant-associated thrombotic microangiopathy in a large real-world cohort study. Bone Marrow Transplant 57, 554–561 (2022). https://doi.org/10.1038/s41409-022-01581-1

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