Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a rare, highly fatal disorder of uncontrolled inflammation, usually affecting infants. Significant progress in the treatment of this disorder has been achieved during the last decade, and outcomes for larger series of patients have been reported in recent years. Although medical therapy has advanced, hematopoietic cell transplantation remains the only curative therapy for patients with the familial form of this disorder. Unfortunately, these patients have demonstrated relatively poor post-transplant outcomes for a nonmalignant disorder, with approximately 30% mortality in the first 100 days. Early deaths were attributable to infection, GVHD, and unusually high rates of primary nonengraftment, venoocclusive disease and pneumonitis. In addition, a significant number of deaths were due to HLH reactivation, a unique complication seen in this patient group. In contrast, late complications were relatively infrequent and essentially all patients with durable engraftment remained in remission indefinitely. In this review, we will discuss recent progress in the transplant management of patients with HLH and potential future strategies, including the use of reduced intensity conditioning regimens.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Scott R, Robb-Smith A . Histiocytic medullary reticulosis. Lancet 1939; 2: 194–198.
Stepp SE, Dufourcq-Lagelouse R, Le Deist F, Bhawan S, Certain S, Mathew PA et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science 1999; 286: 1957–1959.
Jordan MB, Hildeman D, Kappler J, Marrack P . An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. Blood 2004; 104: 735–743.
Henter JI, Horne A, Arico 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.
Billiau AD, Roskams T, Van Damme-Lombaerts R, Matthys P, Wouters C . Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-gamma-producing lymphocytes and IL-6- and TNF-alpha-producing macrophages. Blood 2005; 105: 1648–1651.
Henter JI, Elinder G, Soder O, Hansson M, Andersson B, Andersson U . Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. Blood 1991; 78: 2918–2922.
Henter JI, Arico M, Elinder G, Imashuku S, Janka G . Familial hemophagocytic lymphohistiocytosis. Primary hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am 1998; 12: 417–433.
Clementi R, Emmi L, Maccario R, Liotta F, Moretta L, Danesino C et al. Adult onset and atypical presentation of hemophagocytic lymphohistiocytosis in siblings carrying PRF1 mutations. Blood 2002; 100: 2266–2267.
Santoro A, Cannella S, Bossi G, Gallo F, Trizzino A, Pende D et al. Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. J Med Genet 2006; 43: 953–960.
Henter JI, Elinder G, Soder O, Ost A . Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis. Acta Paediatr Scand 1991; 80: 428–435.
Janka GE . Familial hemophagocytic lymphohistiocytosis. Eur J Pediatr 1983; 140: 221–230.
Henter JI, Samuelsson-Horne A, Arico M, Egeler RM, Elinder G, Filipovich AH et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood 2002; 100: 2367–2373.
Mahlaoui N, Ouachee-Chardin M, de Saint Basile G, Neven B, Picard C, Blanche S et al. Immunotherapy of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins: a single-center retrospective report of 38 patients. Pediatrics 2007; 120: e622–e628.
Horne A, Janka G, Maarten Egeler R, Gadner H, Imashuku S, Ladisch S et al. Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis. Br J Haematol 2005; 129: 622–630.
Baker KS, Filipovich AH, Gross TG, Grossman WJ, Hale GA, Hayashi RJ et al. Unrelated donor hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Bone Marrow Transplant 2008; 42: 175–180.
Ouachee-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.
Cooper N, Rao K, Gilmour K, Hadad L, Adams S, Cale C et al. Stem cell transplantation with reduced-intensity conditioning for hemophagocytic lymphohistiocytosis. Blood 2006; 107: 1233–1236.
Schaer DJ, Schleiffenbaum B, Kurrer M, Imhof A, Bachli E, Fehr J et al. Soluble hemoglobin–haptoglobin scavenger receptor CD163 as a lineage-specific marker in the reactive hemophagocytic syndrome. Eur J Haematol 2005; 74: 6–10.
Klangsinsirikul P, Carter GI, Byrne JL, Hale G, Russell NH . Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution. Blood 2002; 99: 2586–2591.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Jordan, M., Filipovich, A. Hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis: a journey of a thousand miles begins with a single (big) step. Bone Marrow Transplant 42, 433–437 (2008). https://doi.org/10.1038/bmt.2008.232
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2008.232
Keywords
This article is cited by
-
Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome
Pediatric Rheumatology (2019)
-
Primary hemophagocytic lymphohistiocytosis in adults: the utility of family surveys in a single-center study from China
Orphanet Journal of Rare Diseases (2018)
-
Infusion of leukocytes from HLA haplo-identical familial donors as an adjuvant in the HLH-2004 protocol to treat the virus-associated adult hemophagocytic lymphohistiocytosis: a retrospective study of 26 patients
Annals of Hematology (2018)
-
Adult-Onset Still’s Disease and Macrophage-Activating Syndrome Progressing to Lymphoma
HSS Journal ® (2018)
-
Haplo-identical Hematopoietic Stem Cell Transplant is a Possible Cure in a Patient with Relapsed Hemophagocytic Lymphohistiocytosis Syndrome
Indian Journal of Hematology and Blood Transfusion (2018)