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The use of reduced-intensity stem cell transplantation in haemophagocytic lymphohistiocytosis and Langerhans cell histiocytosis

Bone Marrow Transplantation volume 42, pages S47–S50 (2008)Cite this article

Abstract

Allogeneic stem cell transplant is curative for haemophagocytic lymphohistiocytosis (HLH) and refractory Langerhans cell histiocytosis (LCH). However, patients frequently have significant pre-transplant morbidity and there is high TRM. Because HLH is caused by immune dysregulation, we surmised that a reduced-intensity conditioned (RIC) regimen might be sufficient for cure, while decreasing the TRM. In 2006, we reported the outcome of 12 patients treated with RIC SCT from a matched family/unrelated or haploidentical donor. Here we discuss the update of these patients, including a total of 25 patients treated with RIC SCT for HLH and three for LCH. Twenty-one of the twenty-five patients with HLH (84%) are alive and well with remission at a median of 36 months from SCT. Mortality included pneumonitis (n=3) and hepatic rupture (n=1). All three patients treated with RIC SCT for LCH remain alive and in remission at a median of 5.1 years from SCT. Seven of twenty-four survivors (one with LCH) have mixed chimerism but remain disease-free. These data are supported by other groups including 100% survival in seven patients with HLH and 78% survival of nine patients with LCH. In summary, RIC compares favourably with conventional SCT with long-term disease control in surviving patients with both HLH and LCL, despite a significant incidence of mixed chimerism.

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References

  1. Janka GE . Familial hemophagocytic lymphohistiocytosis: diagnostic problems and differential diagnosis. Pediatr Hematol Oncol 1989; 6: 219–225.

    Article  CAS  Google Scholar 

  2. Arico M, Janka G, Fischer A, Henter JI, Blanche S, Elinder G et al. Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society. Leukemia 1996; 10: 197–203.

    CAS  PubMed  Google Scholar 

  3. Eife R, Janka GE, Belohradsky BH, Holtmann H . Natural killer cell function and interferon production in familial hemophagocytic lymphohistiocytosis. Pediatr Hematol Oncol 1989; 6: 265–272.

    Article  CAS  Google Scholar 

  4. Osugi Y, Hara J, Tagawa S, Takai K, Hosoi G, Matsuda Y et al. Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis. Blood 1997; 89: 4100–4103.

    CAS  PubMed  Google Scholar 

  5. Egeler RM, Shapiro R, Loechelt B, Filipovich A . Characteristic immune abnormalities in hemophagocytic lymphohistiocytosis. J Pediatr Hematol Oncol 1996; 18: 340–345.

    Article  CAS  Google Scholar 

  6. Arico M, Imashuku S, Clementi R, Hibi S, Teramura T, Danesino C et al. Hemophagocytic lymphohistiocytosis due to germline mutations in SH2D1A, the X-linked lymphoproliferative disease gene. Blood 2001; 97: 1131–1133.

    Article  CAS  Google Scholar 

  7. Ericson KG, Fadeel B, Andersson M, Gudmundsson GH, Gürgey A, Yalman N et al. Sequence analysis of the granulysin and granzyme B genes in familial hemophagocytic lymphohistiocytosis. Hum Genet 2003; 112: 98–99.

    Article  CAS  Google Scholar 

  8. Feldmann J, Callebaut I, Raposo G, Certain S, Bacq D, Dumont C et al. Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell 2003; 115: 461–473.

    Article  CAS  Google Scholar 

  9. Goransdotter Ericson K, Fadeel B, Nilsson-Ardnor S, Söderhäll C, Samuelsson A, Janka G et al. Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis. Am J Hum Genet 2001; 68: 590–597.

    Article  CAS  Google Scholar 

  10. Henter JI . Biology and treatment of familial hemophagocytic lymphohistiocytosis: importance of perforin in lymphocyte-mediated cytotoxicity and triggering of apoptosis. Med Pediatr Oncol 2002; 38: 305–309.

    Article  Google Scholar 

  11. Stepp SE, Dufourcq-Lagelouse R, Le Deist F, Certain S, Mathew PA, Henter JI et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science 1999; 286: 1957–1959.

    Article  CAS  Google Scholar 

  12. Stephan JL, Donadieu J, Ledeist F, Blanche S, Griscelli C, Fischer A et al. Treatment of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins, steroids, and cyclosporin A. Blood 1993; 82: 2319–2323.

    CAS  PubMed  Google Scholar 

  13. Blanche S, Caniglia M, Girault D, Landman J, Griscelli C, Fischer A et al. Treatment of hemophagocytic lymphohistiocytosis with chemotherapy and bone marrow transplantation: a single-center study of 22 cases. Blood 1991; 78: 51–54.

    CAS  PubMed  Google Scholar 

  14. Imashuku S, Hibi S, Todo S, Inoue M, Kawa K, Koike K et al. Allogeneic hematopoietic stem cell transplantation for patients with hemophagocytic syndrome (HPS) in Japan. Bone Marrow Transplant 1999; 23: 569–572.

    Article  CAS  Google Scholar 

  15. 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: 622–630.

    Article  Google Scholar 

  16. Minkov M, Grois N, Heitger A, Pötschger U, Westermeier T, Gadner H et al. Response to initial treatment of multisystem Langerhans cell histiocytosis: an important prognostic indicator. Med Pediatr Oncol 2002; 39: 581–585.

    Article  Google Scholar 

  17. Broadbent V, Gadner H . Current therapy for Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1998; 12: 327–338.

    Article  CAS  Google Scholar 

  18. Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A et al. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr 2001; 138: 728–734.

    Article  CAS  Google Scholar 

  19. Akkari V, Donadieu J, Piguet C, Bordigoni P, Michel G, Blanche S et al. Hematopoietic stem cell transplantation in patients with severe Langerhans cell histiocytosis and hematological dysfunction: experience of the French Langerhans Cell Study Group. Bone Marrow Transplant 2003; 31: 1097–1103.

    Article  CAS  Google Scholar 

  20. Rao K, Amrolia PJ, Jones A, Cale CM, Naik P, King D et al. Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen. Blood 2005; 105: 879–885.

    Article  CAS  Google Scholar 

  21. 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: 1233–1236.

    Article  CAS  Google Scholar 

  22. Vaughn G, Bleesing J, Jordan M, Marsh R, Fillipovich A . Hematopoietic cell transplantation with reduced intensity conditioning (RIC HCT) for hemophagocytic lymphohistiocytosis (HLH) and X-linked lymphoproliferative syndrome. Proceedings of the Histiocyte Society Meeting, Cambridge, September 2007, p 20 (abstract).

  23. Steiner M, Matthes-Martin S, Attarbaschi A, Minkov M, Grois N, Unger E et al. Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after allogeneic stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant 2005; 36: 215–225.

    Article  CAS  Google Scholar 

  24. Ardeshna KM, Hollifield J, Chessells JM, Veys P, Webb DK . Outcome for children after failed transplant for primary haemophagocytic lymphohistiocytosis. Br J Haematol 2001; 115: 949–952.

    Article  CAS  Google Scholar 

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  1. Department of Bone Marrow Transplantation, Great Ormond Street Hospital for Children NHS Trust, London, UK

    N Cooper, K Rao, N Goulden, D Webb, P Amrolia & P Veys

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  1. N Cooper
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  2. K Rao
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  3. N Goulden
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Correspondence to P Veys.

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Cooper, N., Rao, K., Goulden, N. et al. The use of reduced-intensity stem cell transplantation in haemophagocytic lymphohistiocytosis and Langerhans cell histiocytosis. Bone Marrow Transplant 42 (Suppl 2), S47–S50 (2008). https://doi.org/10.1038/bmt.2008.283

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