Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Allografting

Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after allogeneic stem cell transplantation with reduced-intensity conditioning

Bone Marrow Transplantation volume 36, pages 215–225 (2005)Cite this article

Summary:

Children with multisystem Langerhans cell histiocytosis (LCH) and risk organ involvement who fail to respond to conventional chemotherapy have an extremely poor prognosis. Myeloablative stem cell transplantation (SCT) as a possible salvage approach for these patients has been associated with a high risk of transplant-related mortality. Therefore, allogeneic stem cell transplantation following a reduced-intensity conditioning regimen (RIC-SCT) has recently been performed as an alternative salvage approach. We report on the experience with allogeneic RIC-SCT in nine pediatric high-risk LCH patients. Conditioning regimen included fludarabine in all patients, melphalan in eight patients, total lymphoid irradiation in six patients, total body irradiation in two, antithymocyte globulin in five, and Campath in four patients. RIC-SCT was well tolerated with regard to common procedure-related complications. Two patients died 50 and 69 days after RIC-SCT, respectively. Seven out of the nine patients survived and showed no signs of disease activity (including one with nonengraftment and full autologous hematopoietic recovery) after median follow-up of 390 days post-SCT. Based on this observation, we conclude that RIC-SCT is a feasible procedure with low transplant-related morbidity and mortality and a promising new salvage approach for high-risk LCH patients with resistant risk organ involvement.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Arceci RJ . The histiocytoses: the fall of the Tower of Babel. Eur J Cancer 1999; 35: 747–767; discussion 767–769.

    Article  CAS  PubMed  Google Scholar 

  2. Egeler RM, Favara BE, van Meurs M et al. Differential in situ cytokine profiles of Langerhans-like cells and T cells in Langerhans cell histiocytosis: abundant expression of cytokines relevant to disease and treatment. Blood 1999; 94: 4195–4201.

    CAS  PubMed  Google Scholar 

  3. Favara BE, Jaffe R, Egeler RM . Macrophage activation and hemophagocytic syndrome in langerhans cell histiocytosis: report of 30 cases. Pediatr Dev Pathol 2002; 5: 130–140.

    Article  CAS  PubMed  Google Scholar 

  4. Gadner H, Heitger A, Grois N et al. Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group. Med Pediatr Oncol 1994; 23: 72–80.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  7. Gadner H . Langerhans' cell histiocytosis – still an unsolved problem. Pediatr Hematol Oncol 1999; 16: 489–493.

    Article  CAS  PubMed  Google Scholar 

  8. Minkov M, Grois N, Broadbent V et al. Cyclosporine A therapy for multisystem langerhans cell histiocytosis. Med Pediatr Oncol 1999; 33: 482–485.

    Article  CAS  PubMed  Google Scholar 

  9. Ringden O, Ahstrom L, Lonnqvist B et al. Allogeneic bone marrow transplantation in a patient with chemotherapy-resistant progressive histiocytosis X. N Engl J Med 1987; 316: 733–735.

    Article  CAS  PubMed  Google Scholar 

  10. Stoll M, Freund M, Schmid H et al. Allogeneic bone marrow transplantation for Langerhans' cell histiocytosis. Cancer 1990; 66: 284–288.

    Article  CAS  PubMed  Google Scholar 

  11. Greinix HT, Storb R, Sanders JE, Petersen FB . Marrow transplantation for treatment of multisystem progressive Langerhans cell histiocytosis. Bone Marrow Transplant 1992; 10: 39–44.

    CAS  PubMed  Google Scholar 

  12. Frost JD, Wiersma SR . Progressive Langerhans cell histiocytosis in an infant with Klinefelter syndrome successfully treated with allogeneic bone marrow transplantation. J Pediatr Hematol Oncol 1996; 18: 396–400.

    Article  CAS  PubMed  Google Scholar 

  13. Conter V, Reciputo A, Arrigo C et al. Bone marrow transplantation for refractory Langerhans' cell histiocytosis. Haematologica 1996; 81: 468–471.

    CAS  PubMed  Google Scholar 

  14. Broadbent V, Ladisch S . Results of the Histiocyte Society BMT salvage therapy questionnaire. Med Pediatr Oncol 1998; 31: 45 (abstr.).

    Article  Google Scholar 

  15. Egeler RM, Anderson RA, Wolff JEA et al. Allogeneic peripheral blood stem cell transplantation in Langerhans cell histiocytosis. Med Pediatr Oncol 1999; 32: 238 (abstr.).

    Google Scholar 

  16. Ayas M, Mustafa M, Al-Mahr M, Solh H . Bone marrow transplantation as a salvage therapy for refractory disseminated Langerhans histiocytosis. Med Pediatr Oncol 1999; 32: 238 (abstr.).

    Google Scholar 

  17. Kinugawa N, Imashuku S, Hirota Y et al. Hematopoietic stem cell transplantation (HSCT) for Langerhans cell histiocytosis (LCH) in Japan. Bone Marrow Transplant 1999; 24: 935–938.

    Article  CAS  PubMed  Google Scholar 

  18. Suminoe A, Matsuzaki A, Hattori H et al. Unrelated cord blood transplantation for an infant with chemotherapy-resistant progressive Langerhans cell histiocytosis. J Pediatr Hematol Oncol 2001; 23: 633–636.

    Article  CAS  PubMed  Google Scholar 

  19. Nagarajan R, Neglia J, Ramsay N, Baker KS . Successful treatment of refractory Langerhans cell histiocytosis with unrelated cord blood transplantation. J Pediatr Hematol Oncol 2001; 23: 629–632.

    Article  CAS  PubMed  Google Scholar 

  20. Hale GA, Bowman LC, Woodard JP et al. Allogeneic bone marrow transplantation for children with histiocytic disorders: use of TBI and omission of etoposide in the conditioning regimen. Bone Marrow Transplant 2003; 31: 981–986.

    Article  CAS  PubMed  Google Scholar 

  21. Akkari V, Donadieu J, Piguet C 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  PubMed  Google Scholar 

  22. Amrolia P, Gaspar HB, Hassan A et al. Nonmyeloablative stem cell transplantation for congenital immunodeficiencies. Blood 2000; 96: 1239–1246.

    CAS  PubMed  Google Scholar 

  23. Jacobsohn DA, Duerst R, Tse W, Kletzel M . Reduced intensity haemopoietic stem-cell transplantation for treatment of non-malignant diseases in children. Lancet 2004; 364: 156–162.

    Article  PubMed  Google Scholar 

  24. Meyer-Wentrup F, Foell J, Wawer A, Burdach S . Unrelated cord blood transplantation in an infant with severe multisystem Langerhans cell histiocytosis: clinical outcome, engraftment and culture of monocyte-derived dendritic cells. Bone Marrow Transplant 2004; 33: 875–876.

    Article  CAS  PubMed  Google Scholar 

  25. Histiocytosis syndromes in children. Writing Group of the Histiocyte Society. Lancet 1987; 1: 208–209.

  26. Broadbent V, Gadner H, Komp DM, Ladisch S . Histiocytosis syndromes in children: II. Approach to the clinical and laboratory evaluation of children with Langerhans cell histiocytosis. Clinical Writing Group of the Histiocyte Society. Med Pediatr Oncol 1989; 17: 492–495.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  28. Slavin S, Nagler A, Naparstek E et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  29. Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  30. Lansky SB, List MA, Lansky LL et al. The measurement of performance in childhood cancer patients. Cancer 1987; 60: 1651–1656.

    Article  CAS  PubMed  Google Scholar 

  31. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  32. Egeler RM, Favara BE, Laman JD, Claassen E . Abundant expression of CD40 and CD40-ligand (CD154) in paediatric Langerhans cell histiocytosis lesions. Eur J Cancer 2000; 36: 2105–2110.

    Article  CAS  PubMed  Google Scholar 

  33. Kannourakis G, Abbas A . The role of cytokines in the pathogenesis of Langerhans cell histiocytosis. Br J Cancer Suppl 1994; 23: S37–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Nezelof C, Basset F . An hypothesis Langerhans cell histiocytosis: the failure of the immune system to switch from an innate to an adaptive mode. Pediatr Blood Cancer 2004; 42: 398–400.

    Article  PubMed  Google Scholar 

  35. Rao K, Nanduri V, Brock P et al. Bone marrow transplant as salvage for multisystem Langerhans cell histiocytosis. Pediatr Blood Cancer 2004; 43: 196 (abstr.).

  36. Matthes-Martin S, Lion T, Haas OA et al. Lineage-specific chimaerism after stem cell transplantation in children following reduced intensity conditioning: potential predictive value of NK cell chimaerism for late graft rejection. Leukemia 2003; 17: 1934–1942.

    Article  CAS  PubMed  Google Scholar 

  37. Jordan MB, McClain KL, Xiaotian Y et al. Anti-CD52 antibody, alemtuzumab, binds to Langerhans cells in Langerhans cell histiocytosis. Pediatr Blood Cancer 2005; 44: 251–254.

    Article  PubMed  Google Scholar 

  38. Henter JI, Karlen J, Calming U et al. Successful treatment of Langerhans'-cell histiocytosis with etanercept. N Engl J Med 2001; 345: 1577–1578.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr G Surico and Dr P Muggeo, II Pediatric Clinic, University of Bari, Italy, and Dr D Koliouskas, Ippokration Hospital, Thessaloniki, Greece, for referring their patients to our institution. We also thank Dr J Foell, University Hospital Halle, Germany, for his assistance.

Author information

Authors and Affiliations

  1. St Anna Children's Hospital, Vienna, Austria

    M Steiner, S Matthes-Martin, A Attarbaschi, M Minkov, N Grois, E Unger & H Gadner

  2. Department of Pediatrics, University Hospital Erlangen, Germany

    W Holter

  3. Department of Pediatrics, University Hospital Muenster, Germany

    J Vormoor

  4. Department of Pediatrics, University Hospital Munich (TUM), Germany

    A Wawer

  5. Department of Pediatrics, Necker Hospital Paris, France

    M Ouachee

  6. Department of Pediatrics, University Hospital Giessen, Germany

    W Woessmann

Authors
  1. M Steiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Matthes-Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Attarbaschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Minkov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Grois
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E Unger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. W Holter
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Vormoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Wawer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Ouachee
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. W Woessmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. H Gadner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H Gadner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steiner, M., Matthes-Martin, S., Attarbaschi, A. et al. Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after allogeneic stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant 36, 215–225 (2005). https://doi.org/10.1038/sj.bmt.1705015

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705015

Keywords

This article is cited by

Search

Advanced search

Quick links