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Alemtuzumab as a bridge to allogeneic SCT in atypical hemophagocytic lymphohistiocytosis

Nature Reviews Clinical Oncology volume 7, pages 415–420 (2010)Cite this article

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Abstract

Background. A 39-year-old woman with no relevant medical or family history was admitted to hospital with episodic fever, which persisted despite antibiotic therapy. Other notable findings at admission were splenomegaly, pancytopenia, hyponatremia, elevated levels of liver enzymes, hyperferritinemia and hypofibrinogenemia.

Investigations. Physical examination, laboratory tests, rheumatic marker serology, pathogen detection assays, complete blood counts, measurement of levels of ferritin, fibrinogen, triglycerides and soluble CD25, natural killer cell functional studies, PRF1 mutation analysis, renal biopsy, bone marrow biopsy, CT imaging of the chest and abdomen.

Diagnosis. Idiopathic, atypical hemophagocytic lymphohistiocytosis.

Management. Initial treatment with antibiotics was followed by immunosuppressive therapy (including intravenous immunoglobulin, ciclosporin, infliximab, corticosteroids and etoposide). Remission was achieved by treatment with the anti-CD52 monoclonal antibody, alemtuzumab, after which allogeneic stem-cell transplantation (with reduced-intensity conditioning treatment and graft-versus-host disease prophylaxis) resulted in a definitive cure.

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Figure 1: Changes in white blood cell counts and ferritin levels during the patient's treatment.
Figure 2: Chest and abdominal CT images of the patient at diagnosis.
Figure 3: Histology of the patient's bone marrow biopsy sample at diagnosis.

References

  1. Henter, J. I. et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr. Blood Cancer 48, 124–131 (2007).

    Article  Google Scholar 

  2. Henter, J. I. et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood 100, 2367–2373 (2002).

    Article  CAS  Google Scholar 

  3. Arceci, R. J. When T cells and macrophages do not talk: the hemophagocytic syndromes. Curr. Opin. Hematol. 15, 359–367 (2008).

    Article  Google Scholar 

  4. Filipovich, A. H. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am. Soc. Hematol. Educ. Program 127–131 (2009).

    Article  Google Scholar 

  5. Janka, G. E. Familial and acquired hemophagocytic lymphohistiocytosis. Eur. J. Pediatr. 166, 95–109 (2007).

    Article  Google Scholar 

  6. Grunebaum, E., Zhang, J., Dadi, H. & Roifman, C. M. Hemophagocytic lymphohistiocytosis in X-linked severe combined immunodeficiency. Br. J. Hematol. 108, 834–837 (2000).

    Article  CAS  Google Scholar 

  7. Haliotis, T. et al. Chediak–Higashi gene in humans. I. Impairment of natural-killer function. J. Exp. Med. 151, 1039–1048 (1980).

    Article  CAS  Google Scholar 

  8. Stepp, S. E. et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science 286, 1957–1959 (1999).

    Article  CAS  Google Scholar 

  9. Feldmann, J. et al. Munc13–14 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell 115, 461–473 (2003).

    Article  CAS  Google Scholar 

  10. Zur Stadt, U. et al. Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Hum. Mutat. 27, 62–68 (2006).

    Article  CAS  Google Scholar 

  11. Busemann, C. et al. Erdheim–Chester disease with hemophagocytosis. Ann. Hematol. 86, 847–849 (2007).

    Article  Google Scholar 

  12. Henter, J. I. et al. HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. HLH Study Group of the Histiocyte Society. Med. Pediatr. Oncol. 28, 342–347 (1997).

    Article  CAS  Google Scholar 

  13. Ostronoff, M. et al. Hemophagocytic syndrome after autologous peripheral blood stem cell transplantation for multiple myeloma: successful treatment with high-dose intravenous immunoglobulin. Bone Marrow Transplant. 37, 797–798 (2006).

    Article  CAS  Google Scholar 

  14. Mahlaoui, N. et al. Immunotherapy of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins: a single-center retrospective report of 38 patients. Pediatrics 120, e622–e628 (2007).

    Article  Google Scholar 

  15. Makay, B. et al. Etanercept for therapy-resistant macrophage activation syndrome. Pediatr. Blood Cancer 50, 419–421 (2008).

    Article  Google Scholar 

  16. Hu, Y. et al. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology 128, 260–270 (2009).

    Article  CAS  Google Scholar 

  17. Alinari, L. et al. Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia. Oncogene 26, 3644–3653 (2007).

    Article  CAS  Google Scholar 

  18. Horne, A. et al. Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis. Br. J. Hematol. 129, 622–630 (2005).

    Article  Google Scholar 

  19. Cooper, N. et al. The use of reduced-intensity stem cell transplantation in hemophagocytic lymphohistiocytosis and Langerhans cell histiocytosis. Bone Marrow Transplant. 42 (Suppl. 2), S47–S50 (2008).

    Article  Google Scholar 

Download references

Acknowledgements

M. P. Strout is a Fellow of the Leukemia and Lymphoma Society and a Scholar of the American Society of Hematology. Written consent for publication was obtained from the patient.

Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. Section of Hematology, Yale Cancer Center and Smilow Cancer Hospital at Yale–New Haven, Yale University School of Medicine, 333 Cedar Street, New Haven, 06520, CT, USA

    Matthew P. Strout & Stuart Seropian

  2. Department of Internal Medicine, Division of Hematology, Brigham and Women's Hospital, 75 Francis Street, Boston, 02115, MA, USA

    Nancy Berliner

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Correspondence to Matthew P. Strout.

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Strout, M., Seropian, S. & Berliner, N. Alemtuzumab as a bridge to allogeneic SCT in atypical hemophagocytic lymphohistiocytosis. Nat Rev Clin Oncol 7, 415–420 (2010). https://doi.org/10.1038/nrclinonc.2010.40

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