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Successful correction of familial hemophagocytic lymphohistiocytosis using prenatal genetic testing and preemptive hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 53, pages 223–224 (2018)Cite this article

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Hemophagocytic lymphohistiocytosis (HLH) is a dysregulated immune condition causing widespread organ damage and cytopenias secondary to excessive inflammation and hemophagocytosis. The disease may be primary in nature resulting from a genetic cause or may be secondary to another clinical process, such as a rheumatologic, autoimmune, infectious or malignant disorder. Familial hemophagocytic lymphohistiocytosis (FHL) can be sub-divided into FHL-1 through FHL-5, with a yet to be determined genetic mutation causing FHL-1 but PFR-1, UNC13D, STX11 and STXBP2 gene defects causing FHL-2 through FHL-5, respectively. While treatment of secondary HLH primarily involves controlling the triggering condition, allogeneic hematopoietic stem cell transplantation (HSCT) is essential to the survival of FHL patients.1 Symptoms of HLH may begin in early infancy and in utero on occasion.2, 3

Here we review the cases of two brothers with genetically defined HLH. The first was managed with conventional dose medical therapy followed by allogeneic HSCT to correct the underlying immune disorder. The second case was recognized in utero using prenatal diagnosis and managed in a more novel manner with preemptive protective isolation and allogeneic HSCT prior to the onset of clinical HLH. Both siblings were treated on a prospective, IRB-approved clinical trial of unrelated cord blood HSCT.

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Authors and Affiliations

  1. Children’s Hospital Colorado, Pediatric Bone Marrow Transplant Program, University of Colorado School of Medicine, Aurora, CO, USA,

    T F Michniacki, J M Mulcahy Levy, R R Quinones & R H Giller

  2. Department of Pediatric Hematology/Oncology, CS Mott Children’s Hospital, University of Michigan Medical School, Ann Arbor, MI, USA,

    T F Michniacki

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  1. T F Michniacki
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  2. J M Mulcahy Levy
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  3. R R Quinones
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  4. R H Giller
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Correspondence to R H Giller.

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Michniacki, T., Mulcahy Levy, J., Quinones, R. et al. Successful correction of familial hemophagocytic lymphohistiocytosis using prenatal genetic testing and preemptive hematopoietic stem cell transplantation. Bone Marrow Transplant 53, 223–224 (2018). https://doi.org/10.1038/bmt.2017.219

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