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Histiocytic Disorders

Allogeneic bone marrow transplantation for children with histiocytic disorders: use of TBI and omission of etoposide in the conditioning regimen

Bone Marrow Transplantation volume 31, pages 981–986 (2003)Cite this article

Summary:

The histiocytoses are rare disorders of antigen-processing phagocytic or antigen-presenting cells. Allogeneic bone marrow transplantation (BMT) can be curative of these disorders. We report a series of five children with Langerhans cell histiocytosis (n=2) or hemophagocytic lymphohistiocytosis (n=3), who received allogeneic BMT with a total body irradiation (TBI)-containing regimen (TBI, cytarabine, and cyclophosphamide) at our institution between 1995 and 2000. One of these patients received busulfan, cyclophosphamide, and etoposide for the first of two BMTs. All grafts except one (a matched sibling-donor graft) were T-cell-depleted grafts from unrelated donors. All received cyclosporine graft-versus-host disease (GvHD) prophylaxis; the recipient of the matched sibling graft also received methotrexate. Three patients engrafted at a median of 24 days after transplantation. The patient who did not receive TBI experienced primary graft failure and recurrent disease. After the TBI-containing conditioning regimen was given, a second transplant engrafted on day +17. One patient with concurrent myelodysplastic syndrome died of toxicity on day +33 without evidence of engraftment. No acute or chronic GvHD was observed. Four patients survive disease-free, a median of 63 months after transplantation, all with Lansky performance scores of 100. We conclude that a conditioning regimen containing TBI but not etoposide is effective in allogeneic BMT for children with histiocytic diseases.

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References

  1. Stephan JL . Histiocytoses. Eur J Pediatr 1995; 154: 600–609.

    Article  CAS  Google Scholar 

  2. Henter JI, Arico M, Elinder G et al. Familial hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am 1998; 12: 417–433.

    Article  CAS  Google Scholar 

  3. Janka GE . Familial hemophagocytic lymphohistiocytosis. Eur J Pediatr 1983; 140: 221–230.

    Article  CAS  Google Scholar 

  4. Dufourcq-Lagelouse R, Pastural E, Barrat FJ et al. Genetic basis of hemophagocytic lymphohistiocytosis syndrome. Int J Mol Med 1999; 4: 127–133.

    CAS  PubMed  Google Scholar 

  5. Gadner H, Heitger A, Grois N et al. Treatment strategy for disseminated Langerhans cell histiocytosis. Med Pediatr Oncol 1994; 23: 72–80.

    Article  CAS  Google Scholar 

  6. Titgemeyer C, Grois N, Minkow M et al. Pattern and course of single-system disease in Langerhans cell histiocytosis data from the DAL-HX 83- and 90-study. Med Pediatr Oncol 2001; 37: 108–114.

    Article  CAS  Google Scholar 

  7. Morgan G . Myeloablative therapy and bone marrow transplantation for langerhans' cell histiocytosis. Br J Cancer 1994; 23 (Suppl): S52–S53.

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Ringden O, Lonnqvist B, Holst M . 12-year follow-up of allogeneic bone-marrow transplant for Langerhans’ cell histiocytosis. Lancet 1997; 349: 476.

    Article  CAS  Google Scholar 

  10. 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 

  11. 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  Google Scholar 

  12. 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  Google Scholar 

  13. Arico M, Janka G, Fischer A et al. Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. Leukemia 1996; 10: 197–203.

    CAS  Google Scholar 

  14. Blanche S, Caniglia M, Girault D 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 

  15. Favara BE, McCarthy RC, Mierau GW, Histiocytosis X . In: Finegold MJ (ed.) Pathology of Neoplasia in Children and Adolescents, Vol. 196. WB Saunders: Philadelphia, 126pp.

  16. Harrist TJ, Bhan AK, Murphy GF et al. Histiocytosis-X: in situ characterization of cutaneous infiltrates with monoclonal antibodies. Am J Clin Pathol 1983; 79: 294–300.

    Article  CAS  Google Scholar 

  17. Rowden G, Connelly EM, Winkelman RK . Cutaneous histiocytosis X: the presence of S-100 protein and its use in diagnosis. Arch Dermatol 1983; 119: 553–559.

    Article  CAS  Google Scholar 

  18. Henter J-I, Elinder G, Ost A . Diagnostic guidelines for hemophagocytic lymphohistiocytosis. Semin Oncol 1991; 18: 29–33.

    CAS  Google Scholar 

  19. Hongeng S, Krance RA, Bowman LC et al. Outcomes of transplantation with matched sibling and unrelated-donor bone marrow in children with leukemia. Lancet 1997; 350: 767–771.

    Article  CAS  Google Scholar 

  20. Baker KS, DeLaat CA, Steinbuch M et al. Successful correction of hemophagocytic lymphohistiocytosis with related or unrelated bone marrow transplantation. Blood 1997; 89: 3857–3863.

    CAS  PubMed  Google Scholar 

  21. Hale GA, Tong X, Benaim E et al. Allogeneic bone marrow transplantation in children failing prior autologous bone marrow transplantation. Bone Marrow Transplant 2001; 27: 15–62.

    Article  Google Scholar 

  22. Rooney CM, Smith CA, Ng C et al. Use of gene-modified virus-specific T lymphocytes to control Epstein–Barr virus-related lymphoproliferation. Lancet 1995; 345: 9–13.

    Article  CAS  Google Scholar 

  23. Phipps S, Dunavant M, Srivastava DK et al. Cognitive and academic functioning in survivors of pediatric bone marrow transplantation. J Clin Oncol 2000; 18: 1004–1011.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Jones RJ, Lee KS, Beschorner WE et al. Veno-occlusive disease of the liver following bone marrow transplantation. Transplantation 1987; 44: 778–783.

    Article  CAS  Google Scholar 

  26. Common Toxicity Criteria- Version 1.0 Official reference of CTC version 1.0: Cancer Therapy Evaluation Program. Common Toxicity Criteria, Version 1.0. DCTD,NCI, NIH,DHHA. March 1998. Publication Date: April 1982.

  27. Bolme P, Henter JI, Winiarski J et al. Allogeneic bone marrow transplantation for hemophagocytic lymphohistiocytosis in Sweden. Bone Marrow Transplant 1995; 15: 331–335.

    CAS  PubMed  Google Scholar 

  28. Durken M, Horstmann M, Bieling P et al. Improved outcome in haemophagocytic lymphohistiocytosis after bone marrow transplantation from related and unrelated donors: a single-centre experience of 12 patients. Br J Haematol 1999; 106: 1052–1058.

    Article  CAS  Google Scholar 

  29. Durken M, Finckenstein FG, Janka GE . Bone marrow transplantation in hemophagocytic lymphohistiocytosis. Leukemia Lymphoma 2001; 41: 89–95.

    Article  CAS  Google Scholar 

  30. Ardeshna KM, Hollifield J, Chessells JM et al. Outcome for children after failed transplant for primary haemophagocytic lymphohistiocytosis. Br J Haematol 2001; 115: 949–952.

    Article  CAS  Google Scholar 

  31. Landman-Parker J, Le Deist F, Blaise A et al. Partial engraftment of donor bone marrow cells associated with long-term remission of haemophagocytic lymphohistiocytosis. Br J Haematol 1993; 85: 37–41.

    Article  CAS  Google Scholar 

  32. Jabado N, de Graeff-Meeder ER, Cavazzan-Calvo M et al. Treatment of familial hemophagocytic lymphohistiocytosis with bone marrow transplantation from HLA genetically nonidentical donors. Blood 1997; 90: 4743–4748.

    CAS  Google Scholar 

  33. Baker K, Gross TG, DeLaat CA et al. Unrelated donor stem cell transplantation for life-threatening hemophagocytic disorders: preliminary results from the National Marrow Donor Program Pilot Study. Biol Blood Marrow Transplant 2002; 8: 97.

    Google Scholar 

  34. Drobyski WB, Potluri J, Sauer D et al. Autoimmune hemolytic anemia following T cell-depleted allogeneic bone marrow transplantation. Bone Marrow Transplant 1996; 17: 1093–1099.

    CAS  Google Scholar 

  35. Horn B, Viele M, Mentzer W et al. Autoimmune hemolytic anemia in patients with SCID after T cell-depleted BM and PBSC transplantation. Bone Marrow Transplant 1999; 24: 1009–1913.

    Article  CAS  Google Scholar 

  36. Adachi S, Kubota M, Akiyama Y et al. Successful bone marrow transplantation from an HLA-identical unrelated donor in a patient with hemophagocytic lymphohistiocytosis. Bone Marrow Transplant 1997; 19: 183–185.

    Article  CAS  Google Scholar 

  37. Chan KW, Mullen CA, Korbling M . Allogeneic peripheral blood stem cell transplantation for active hemophagocytic lymphohistiocytosis. Bone Marrow Transplant 1998; 22: 301–302.

    Article  CAS  Google Scholar 

  38. Surico G, Muggeo P, Rigillo N et al. Concurrent Langerhans cell histiocytosis and myelodysplasia in children. Med Pediatr Oncol 2000; 35: 421–425.

    Article  CAS  Google Scholar 

  39. Giralt S, Estey E, Albitar M et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative chemotherapy. Blood 1997; 89: 4531–4536.

    CAS  Google Scholar 

  40. Khouri IF, Keating M, Korbling M et al. Transplant-Lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998; 16: 2817–2824.

    Article  CAS  Google Scholar 

  41. Sykes M, Preffer F, McAfee S et al. Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone-marrow transplantation. Lancet 1999; 353: 1755–1759.

    Article  CAS  Google Scholar 

  42. 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  Google Scholar 

  43. Handgretinger R, Klingebiel T, Lang P et al. Megadose transplantation of purified peripheral blood CD34 (+) progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant 2001; 27: 777–783.

    Article  CAS  Google Scholar 

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Acknowledgements

We express our appreciation to Frances Curran and Nancy right for data management; Margaret Aymond, Patricia Johnson, and Cynthia Walker for data collection; and Sara Williams for the manuscript preparation This work was supported in part by NIH Cancer Center Support Grant P 30CA 21765 and by the American Lebanese Syrian Associated Charities (ALSAC).

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Author notes

  1. L C Bowman

    Present address: Emory University, Stem Cell Transplantation, 1405 Clifton Road, NE, Atlanta, GA, 30322, USA

  2. H E Heslop & R A Krance

    Present address: Baylor College of Medicine, 6621 Fannin St MC3-3320, Houston, TX, 77030, USA

Authors and Affiliations

  1. The Division of Stem Cell Transplantation, Department of Hematology-Oncology, Memphis, TN, USA

    G A Hale, L C Bowman, J P Woodard, J M Cunningham, E Benaim, E M Horwitz, H E Heslop, R A Krance, W Leung, P D Shearer & R Handgretinger

  2. Division of Experimental Hematology, Department of Hematology-Oncology, Memphis, TN, USA

    J M Cunningham & E M Horwitz

  3. International Outreach Program St Jude Children's Research Hospital, Memphis, TN, USA

    P D Shearer

  4. Department of Pediatrics, Memphis College of Medicine, University of Tennessee, Memphis, TN, USA

    G A Hale, L C Bowman, J P Woodard, J M Cunningham, E Benaim, E M Horwitz, H E Heslop, R A Krance, W Leung, P D Shearer & R Handgretinger

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Hale, G., Bowman, L., Woodard, J. 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 31, 981–986 (2003). https://doi.org/10.1038/sj.bmt.1704056

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