Skip to main content

Advertisement

SpringerLink
Log in

Ruxolitinib treatment for SR-aGVHD in patients with EBV-HLH undergoing allo-HSCT

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

Abstract

Ruxolitinib is a promising option for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we describe ruxolitinib treatment for SR-aGVHD in HSCT patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) to evaluate its effectiveness. We evaluated the outcomes of 12 patients who received ruxolitinib for SR-aGVHD between January 2017 and March 2019. Of the 12 patients who received ruxolitinib, 7 patients achieved a complete response (CR), 3 had a partial response (PR), and 2 experienced treatment failure (TF). OS and CR rates were 83.3% and 58.3%, respectively. Moreover, CR was achieved by the six patients who had aGVHD with skin involvement. The mean time of steroid application in the patients who received ruxolitinib was 28.1 days. Median survival after HSCT was 64.6 weeks. The adverse effects of ruxolitinib included grades 3 to 4 neutropenia (n = 7) and grades 3 to 4 thrombocytopenia (n = 6). Cytomegalovirus reactivation was observed in three patients. A high rate of CR and short steroid application time of ruxolitinib as a salvage treatment were observed in HSCT patients with EBV-HLH. Consequently, from this study, it was determined that ruxolitinib is an optimal choice to treat SR-aGVHD in patients with EBV-HLH.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Spoerl S, Mathew NR, Bscheider M, Schmitt-Graeff A, Chen S, Mueller T, Verbeek M, Fischer J, Otten V, Schmickl M, Maas-Bauer K, Finke J, Peschel C, Duyster J, Poeck H, Zeiser R, von Bubnoff N (2014) Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease. Blood 123(24):3832–3842

    Article  CAS  Google Scholar 

  2. Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lübbert M, Wäsch R, Scheid C, Stölzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Gräff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, du J, Blazar BR, Arnold R, Kröger N, Passweg J, Halter J, Socié G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N (2015) Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia 29(10):2062–2068

    Article  CAS  Google Scholar 

  3. Khandelwal P, Teusink-Cross A, Davies SM, Nelson AS, Dandoy CE, El-Bietar J et al (2017) Ruxolitinib as salvage therapy in steroid-refractory acute graft-versus-host disease in pediatric hematopoietic stem cell transplant patients. Biol Blood Marrow Transplant 23(7):1122–1127

    Article  CAS  Google Scholar 

  4. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, Lerner KG, Thomas ED (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 18(4):295–304

    Article  CAS  Google Scholar 

  5. Greinix HT, Volc-Platzer B, Kalhs P, Fischer G, Rosenmayr A, Keil F, Hönigsmann H, Knobler RM (2000) Extracorporeal photochemotherapy in the treatment of severe steroid-refractory acute graft-versus-host disease: a pilot study. Blood 96(7):2426–2431

    Article  CAS  Google Scholar 

  6. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED (1995) 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant 15(6):825–828

    CAS  PubMed  Google Scholar 

  7. Wang J, Wang Y, Wu L, Zhang J, Lai W, Wang Z (2016) PEG-aspargase and DEP regimen combination therapy for refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Hematol Oncol 9(1):84

    Article  Google Scholar 

  8. Martin PJ, Rizzo JD, Wingard JR, Ballen K, Curtin PT, Cutler C et al (2012) First-and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant 18(8):1150–1163

    Article  Google Scholar 

  9. Arai S, Margolis J, Zahurak M, Anders V, Vogelsang GB et al (2002) Poor outcome in steroid-refractory graft-versus-host disease with antithymocyte globulin treatment. Biol Blood Marrow Transplant 8(3):155–160

    Article  Google Scholar 

  10. Ghez D, Rubio MT, Maillard N, Suarez F, Chandesris MO, Delarue R, Deau-Fischer B, Varet B, Hermine O, Buzyn A (2009) Rapamycin for refractory acute graft-versus-host disease. Transplantation 88(9):1081–1087

    Article  CAS  Google Scholar 

  11. Hoda D, Pidala J, Salgado-Vila N, Kim J, Perkins J, Bookout R et al (2010) Sirolimus for treatment of steroid-refractory acute graft-versus-host disease. Bone Marrow Transplant 45(8):1347–1351

    Article  CAS  Google Scholar 

  12. Kim JG, Sohn SK, Kim DH, Lee NY, Suh JS, Lee KS, Lee KB (2004) Different efficacy of mycophenolate mofetil as salvage treatment for acute and chronic GVHD after allogeneic stem cell transplant. Eur J Haematol 73(1):56–61

    Article  CAS  Google Scholar 

  13. Furlong T, Martin P, Flowers ME, Carnevale-Schianca F, Yatscoff R, Chauncey T, Appelbaum FR, Deeg HJ, Doney K, Witherspoon R, Storer B, Sullivan KM, Storb R, Nash RA (2009) Therapy with mycophenolate mofetil for refractory acute and chronic GVHD. Bone Marrow Transplant 44(11):739–748

    Article  CAS  Google Scholar 

  14. Hautmann AH, Wolff D, Hahn J, Edinger M, Schirmer N, Ammer J, Holler B, Landfried K, Hautmann MG, Ahrens N, Ugocsai P, Andreesen R, Holler E (2013) Extracorporeal photopheresis in 62 patients with acute and chronic GVHD: results of treatment with the COBE spectra system. Bone Marrow Transplant 48(3):439–445

    Article  CAS  Google Scholar 

  15. Berger M, Albiani R, Sini B, Fagioli F (2015) Extracorporeal photopheresis for graft-versus-host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome-results from a large single-center study. Transfusion 55(4):736–747

    Article  Google Scholar 

  16. Ballesteros M, Ferrá C, Serrano D, Batlle M, Ribera JM, Díez-Martín JL (2008) Antithymocyte globulin therapy for steroid-resistant acute graft versus host disease. Am J Hematol 83(10):824–825

    Article  Google Scholar 

  17. Schub N, Günther A, Schrauder A, Claviez A, Ehlert C, Gramatzki M, Repp R (2011) Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective. Bone Marrow Transplant 46(1):143–147

    Article  CAS  Google Scholar 

  18. Schnitzler M, Hasskarl J, Egger M, Bertz H, Finke J (2009) Successful treatment of severe acute intestinal graft-versus-host resistant to systemic and topical steroids with alemtuzumab. Biol Blood Marrow Transplant 15(8):910–918

    Article  CAS  Google Scholar 

  19. de Lavallade H, Mohty M, Faucher C, Fürst S, El-Cheikh J, Blaise D (2006) Low-dose methotrexate as salvage therapy for refractory graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation. Haematologica 91(10):1438–1440

    PubMed  Google Scholar 

  20. Modi B, Hernandez-Henderson M, Yang D, Klein J, Dadwal S, Kopp E et al (2019) Ruxolitinib as salvage therapy for chronic graft-versus-host disease. Biol Blood Marrow Transplant 25(2):265–269

    Article  CAS  Google Scholar 

  21. Betts BC, Bastian D, Iamsawat S, Nguyen H, Heinrichs JL, Wu Y, Daenthanasanmak A, Veerapathran A, O'Mahony A, Walton K, Reff J, Horna P, Sagatys EM, Lee MC, Singer J, Chang YJ, Liu C, Pidala J, Anasetti C, Yu XZ (2018) Targeting JAK2 reduces GVHD and xenograft rejection through regulation of T cell differentiation. Proc Natl Acad Sci U S A 115(7):1582–1587

    Article  CAS  Google Scholar 

  22. Gor D, Sabin C, Prentice HG, Vyas N, Man S, Griffiths PD, Emery VC (1998) Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease. Bone Marrow Transplant 21(6):597–605

    Article  CAS  Google Scholar 

  23. Kröger N (2018) Shahnaz Syed Abd Kadir S, Zabelina T, Badbaran a, Christopeit M, Ayuk F, et al. Peritransplantation Ruxolitinib prevents acute graft-versus-host disease in patients with Myelofibrosis undergoing Allogenic stem cell transplantation. Biol Blood Marrow Transplant 24(10):2152–2156

    Article  Google Scholar 

  24. Zandvakili I, Conboy CB, Ayed AO, Cathcart-Rake EJ, Tefferi A (2018) Ruxolitinib as first-line treatment in secondary hemophagocytic lymphohistiocytosis: a second experience. Am J Hematol 93(5):E123–E125

    Article  Google Scholar 

  25. von Bubnoff N, Ihorst G, Grishina O, Röthling N, Bertz H, Duyster J et al (2018) Ruxolitinib in GvHD (RIG) study: a multicenter, randomized phase 2 trial to determine the response rate of Ruxolitinib and best available treatment (BAT) versus BAT in steroid-refractory acute graft-versus-host disease (aGvHD) (NCT02396628). BMC Cancer 18(1):1132

    Article  Google Scholar 

Download references

Acknowledgments

We thank all the patients for their invaluable contribution to this study, also our colleagues in the Beijing Friendship Hospital.

Funding

This work was supported by National Natural Science Foundation of China (No. 81871633); Beijing Natural Science Foundation (No. 7181003); Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (ZYLX201702); Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20180101).

Author information

Authors and Affiliations

  1. Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Guangqiang Meng, Jingshi Wang, Xinkai Wang, Yini Wang & Zhao Wang

Authors
  1. Guangqiang Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jingshi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xinkai Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yini Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhao Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional Ethics Committee and with the 1964 Helsinki Declaration and its later amendments. And informed consent was obtained from all individual in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meng, G., Wang, J., Wang, X. et al. Ruxolitinib treatment for SR-aGVHD in patients with EBV-HLH undergoing allo-HSCT. Ann Hematol 99, 343–349 (2020). https://doi.org/10.1007/s00277-019-03864-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-019-03864-y

Keywords

Search

Navigation