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Allogeneic hematopoietic stem-cell transplantation for adult and adolescent hemophagocytic lymphohistiocytosis: a single center analysis

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Abstract

Myeloablative conditioning-based allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the treatment of adult and adolescent hemophagocytic lymphohistiocytosis (HLH) is rarely reported. We conducted a retrospective study of 30 adult and adolescent HLH transplanted for primary HLH (n = 4), tumor-HLH (n = 8), EBV-HLH (n = 14), and underlying disease-unknown (UDU)-HLH (n = 4). Peripheral blood stem cells (PBSCs) were the stem-cell source in all patients. Twenty-three patients were transplanted from HLA-haploidentical family donors, six from HLA-identical sibling donors, and one from a matched unrelated donor. Four patients appeared with mixed chimerism (MC), and no patient presented with graft failure. There was a high risk for EBV reactivation with an incidence of 47 %. Two patients developed post-transplant lymphoproliferative disorder (PTLD) and three were considered primary disease recurrent. With a median follow-up of 26 months, 19 patients survived and 11 patients died. The estimated 2-year overall survival (OS) was 63.3 ± 8.8 % in all patients, 100 % in primary HLH, 64.3 ± 12.8 % in EBV-HLH, 50.0 ± 17.7 % in tumor-HLH, and 50.0 ± 25.0 % in UDU-HLH. Myeloablative conditioning-based allo-HSCT is an effective treatment for adult and adolescent HLH to achieve complete remission and long-term survival.

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References

  1. Chandrakasan S, Filipovich AH. Hemophagocytic lymphohistiocytosis: advances in pathophysiology, diagnosis, and treatment. J Pediatr. 2013;163:1253–9.

    Article  PubMed  Google Scholar 

  2. Zur Stadt U, Beutel K, Kolberg S, Schneppenheim R, Kabisch H, Janka G, et al. Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Hum Mutat. 2006;27:62–8.

    Article  CAS  PubMed  Google Scholar 

  3. Janka GE, Lehmberg K. Hemophagocytic lymphohistiocytosis: pathogenesis and treatment. Hematol Am Soc Hematol Educ Progr. 2013;2013:605–11.

    Google Scholar 

  4. Janka GE. Familial hemophagocytic lymphohistiocytosis. Eur J Pediatr. 1983;140:221–30.

    Article  CAS  PubMed  Google Scholar 

  5. Henter JI, Samuelsson-Horne A, Aricò M, Egeler RM, Elinder G, Filipovich AH, et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002;100:2367–73.

    Article  CAS  PubMed  Google Scholar 

  6. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–31.

    Article  PubMed  Google Scholar 

  7. Henter JI, Aricò M, Egeler RM, Elinder G, Favara BE, Filipovich AH, et al. HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. HLH study Group of the Histiocyte Society. Med Pediatr Oncol. 1997;28:342–7.

    Article  CAS  PubMed  Google Scholar 

  8. Wang Y, Huang W, Hu L, Cen X, Li L, Wang J, et al. Multi-center study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis. Blood. 2015;126:2186–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Marsh RA, Allen CE, McClain KL, Weinstein JL, Kanter J, Skiles J, et al. Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab. Pediatr Blood Cancer. 2013;60:101–9.

    Article  CAS  PubMed  Google Scholar 

  10. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:825–8.

    CAS  PubMed  Google Scholar 

  11. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945–56.

    Article  PubMed  Google Scholar 

  12. Rasche L, Kapp M, Einsele H, Mielke S. EBV-induced post transplant lymphoproliferative disorders: a persisting challenge in allogeneic hematopoetic SCT. Bone Marrow Transplant. 2014;49:163–7.

    Article  CAS  PubMed  Google Scholar 

  13. Styczynski J, Reusser P, Einsele H, de la Camara R, Cordonnier C, Ward KN, et al. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplant. 2009;43:757–70.

    Article  CAS  PubMed  Google Scholar 

  14. Horne A, Janka G, Maarten Egeler R, Gadner H, Imashuku S, Ladisch S, et al. Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis. Br J Haematol. 2005;129:622–30.

    Article  PubMed  Google Scholar 

  15. Baker KS, Filipovich AH, Gross TG, Grossman WJ, Hale GA, Hayashi RJ, et al. Unrelated donor hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Bone Marrow Transplant. 2008;42:175–80.

    Article  CAS  PubMed  Google Scholar 

  16. Ouachée-Chardin M, Elie C, de Saint Basile G, Le Deist F, Mahlaoui N, Picard C, et al. Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients. Pediatrics. 2006;117:e743–50.

    Article  PubMed  Google Scholar 

  17. Sparber-Sauer M, Hönig M, Schulz AS, zur Stadt U, Schütz C, Debatin KM, et al. Patients with early relapse of primary hemophagocytic syndromes or with persistent CNS involvement may benefit from immediate hematopoietic stem cell transplantation. Bone Marrow Transplant. 2009;44:333–8.

    Article  CAS  PubMed  Google Scholar 

  18. Jing-Shi W, Yi-Ni W, Lin W, Zhao W. Splenectomy as a treatment for adults with relapsed hemophagocytic lymphohistiocytosis of unknown cause. Ann Hematol. 2015;94:753–60.

    Article  PubMed  Google Scholar 

  19. Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118:4041–52.

    CAS  PubMed  Google Scholar 

  20. Marsh RA, Jordan MB, Filipovich AH. Reduced-intensity conditioning haematopoietic cell transplantation for haemophagocytic lymphohistiocytosis: an important step forward. Br J Haematol. 2011;154:556–63.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kasahara Y, Yachie A, Takei K, Kanegane C, Okada K, Ohta K, et al. Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection. Blood. 2001;98:1882–8.

    Article  CAS  PubMed  Google Scholar 

  22. Fox CP, Shannon-Lowe C, Gothard P, Kishore B, Neilson J, O’Connor N, et al. Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults characterized by high viral genome load within circulating natural killer cells. Clin Infect Dis. 2010;51:66–9.

    Article  CAS  PubMed  Google Scholar 

  23. Yoon HS, Im HJ, Moon HN, Lee JH, Kim HJ, Yoo KH, et al. The outcome of hematopoietic stem cell transplantation in Korean children with hemophagocytic lymphohistiocytosis. Pediatr Transplant. 2010;14:735–40.

    Article  PubMed  Google Scholar 

  24. Cooper N, Rao K, Gilmour K, Hadad L, Adams S, Cale C, et al. Stem cell transplantation with reduced-intensity conditioning for hemophagocytic lymphohistiocytosis. Blood. 2006;107:1233–6.

    Article  CAS  PubMed  Google Scholar 

  25. Cooper N, Rao K, Goulden N, Webb D, Amrolia P, Veys P. The use of reduced-intensity stem cell transplantation in haemophagocytic lymphohistiocytosis and Langerhans cell histiocytosis. Bone Marrow Transplant. 2008;42:S47–50.

    Article  PubMed  Google Scholar 

  26. Marsh RA, Vaughn G, Kim MO, Li D, Jodele S, Joshi S, et al. Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood. 2010;116:5824–31.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Beijing Natural Science Foundation (7132087).

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Authors and Affiliations

  1. Department of Hematology, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, Xicheng District, Beijing, 100050, China

    Li Fu, Jingshi Wang, Na Wei, Lin Wu, Yini Wang, Wenqiu Huang, Jia Zhang, Jinli Liu & Zhao Wang

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  1. Li Fu
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  2. Jingshi Wang
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  3. Na Wei
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  4. Lin Wu
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  5. Yini Wang
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  6. Wenqiu Huang
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  7. Jia Zhang
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  8. Jinli Liu
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  9. Zhao Wang
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Correspondence to Zhao Wang.

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Fu, L., Wang, J., Wei, N. et al. Allogeneic hematopoietic stem-cell transplantation for adult and adolescent hemophagocytic lymphohistiocytosis: a single center analysis. Int J Hematol 104, 628–635 (2016). https://doi.org/10.1007/s12185-016-2062-7

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  • DOI: https://doi.org/10.1007/s12185-016-2062-7

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