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.

  • Letter to the Editor
  • Published:

Successful haploidentical stem cell transplantation for three adults with primary hemophagocytic lymphohistiocytosis

Bone Marrow Transplantation volume 52, pages 330–333 (2017)Cite this article

Subjects

Hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyper-inflammation syndrome, is classified into primary and secondary forms.1 Primary HLH is caused by gene mutations (PRF1, UNC13D, STX11, STXBP2, RAB27A, LYST and AP3B1) resulting in impaired cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes. HLH also presents in immunodeficiencies driven by uncontrolled EBV infection, which include X-linked lymphoproliferative syndrome (XLP) 1, XLP2, ITK deficiency and CD27 deficiency, caused by defects in SH2D1A, BIRC4, ITK and CD27, respectively. Secondary HLH often occurs in adults and is associated with various conditions. Primary HLH can occur at any age, although it predominately affects pediatric patients. In contrast to the well-documented efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric HLH, the role of HSCT in adult HLH is unclear.2 In particular, few reports address the treatment of adult primary HLH with haploidentical HSCT.

All three patients presented with a high fever as their initial clinical feature. Anti-infection treatments had no effect. HLH was suspected based on laboratory findings including liver and coagulation function abnormalities, elevated serum ferritin and decreased NK-cell activity. Diagnosis of primary HLH was confirmed by mutations detected in HLH-associated genes (Table 1). Representative results from a genetic test for patient 2 and his family are presented in Figure 1. Patients 1 and 2 were found to have an EBV infection on admission. Their blood EBV-DNA load became negative during induction therapy. All patients achieved remission at HSCT. Their clinical features were significantly improved after HSCT (data not shown). All patients demonstrated complete chimerism on day +20. No patient developed graft rejection or underwent a second transplant if donor chimerism remained complete after day +20. The acute GvHD that occurred in patients 2 and 3 resolved after maintaining a CsA blood concentration of 150–250 ng/mL and with methylprednisolone (1–2 mg/kg). As for patient 2, lichenification was found in the mouth 2 months after transplant. This finding was considered a local chronic GvHD with no treatment, and the patient remained well. EBV viremia occurred in patients 2 and 3, and both patients’ results became negative after reducing the immunosuppressors. There was no evidence of EBV disease. At the end of follow-up, all patients remained well with stable engraftment. Post-transplant genetic testing confirmed the mutations in patients were replaced by the donor genotypes.

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

References

  1. Janka GE, Lehmberg K . Hemophagocytic syndromes—an update. Blood Rev 2014; 28: 135–142.

    Article  Google Scholar 

  2. Nikiforow S . The role of hematopoietic stem cell transplantation in treatment of hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am 2015; 29: 943–959.

    Article  Google Scholar 

  3. 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: 124–131.

    Article  Google Scholar 

  4. Henter JI, Samuelsson-Horne A, Aricò M, Egeler RM, Elinder G, Filipovich AH et al. Histocyte Society. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood 2002; 100: 2367–2373.

    Article  CAS  Google Scholar 

  5. Wang Y, Huang W, Hu L, Cen X, Li L, Wang J et al. Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis. Blood 2015; 126: 2186–2192.

    Article  CAS  Google Scholar 

  6. Yan CH, Xu LP, Wang FR, Chen H, Han W, Wang Y et al. Causes of mortality after haploidentical hematopoietic stem cell transplantation and the comparison with HLA-identical sibling hematopoietic stem cell transplantation. Bone Marrow Transplant 2016; 51: 391–397.

    Article  CAS  Google Scholar 

  7. Gluckman E, Jolivet I, Scrobohaci ML, Devergie A, Traineau R, Bourdeau-Esperou H et al. Use of prostaglandin E1 for prevention of liver veno-occlusive disease in leukaemic patients treated by allogeneic bone marrow transplantation. Br J Haematol 1990; 74: 277–281.

    Article  CAS  Google Scholar 

  8. Nikiforow S, Berliner N . The unique aspects of presentation and diagnosis of hemophagocytic lymphohistiocytosis in adults. Hematology Am Soc Hematol Educ Program 2015; 2015: 183–189.

    Article  Google Scholar 

  9. Ueda I, Kurokawa Y, Koike K, Ito S, Sakata A, Matsumora T et al. Late-onset cases of familial hemophagocytic lymphohistiocytosis with missense perforin gene mutations. Am J Hematol 2007; 82: 427–432.

    Article  CAS  Google Scholar 

  10. 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–S50.

    Article  Google Scholar 

  11. Marsh RA, Jordan MB, Filipovich AH . Reduced-intensity conditioning haematopoietic cell transplantation for haemophagocytic lymphohistiocytosis: an important step forward. Br J Haematol 2011; 154: 556–563.

    Article  Google Scholar 

  12. 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–e750.

    Article  Google Scholar 

  13. Ayala E, LaFave D, Nishihori T, Kharfan-Dabaja MA . Haploidentical transplantation as a promising therapy for relapsed hemophagocytic lymphohistiocytosis in an older adult patient. Hematol Oncol Stem Cell Ther (e-pub ahead of print 23 June 2016; doi: 10.1016/j.hemonc.2016.05.005).

  14. Jordan MB, Filipovich AH . Hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis: a journey of a thousand miles begins with a single (big) step. Bone Marrow Transplant 2008; 42: 433–437.

    Article  CAS  Google Scholar 

  15. Bryceson YT, Pende D, Maul-Pavicic A, Gilmour KC, Ufheil H, Vraetz T et al. A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes. Blood 2012; 119: 2754–2763.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Bone Marrow Transplant practitioners at Beijing Friendship Hospital for patient care. This work was supported by a National Natural Science Foundation of China Grant No. 81401627, a Medical Development Research Foundation of the Capital of China Grant 2014-4-2025 and a Beijing Science and Technology Plan Grant Z151100004015172.

Author information

Authors and Affiliations

  1. Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Z Li, Y Wang, J Wang, J Zhang & Z Wang

Authors
  1. Z Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Z Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z Wang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Z., Wang, Y., Wang, J. et al. Successful haploidentical stem cell transplantation for three adults with primary hemophagocytic lymphohistiocytosis. Bone Marrow Transplant 52, 330–333 (2017). https://doi.org/10.1038/bmt.2016.284

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2016.284

This article is cited by

Search

Advanced search

Quick links