Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: A systematic scoping review

Blood Rev. 2016 Nov;30(6):411-420. doi: 10.1016/j.blre.2016.05.001. Epub 2016 May 20.


Most knowledge of hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) is derived from pediatric studies; literature on adult HPS/HLH predominantly consists of small retrospective studies with clinical and methodological heterogeneity. The aims of this systematic scoping review were to provide an overview of existing literature on adult HPS/HLH, describe current practices in diagnosis and treatment, and propose priorities for future research. Articles from Ovid Medline, Embase and Pubmed (1975-2015) describing 10 or more unique adults (age>15years) with HPS/HLH were included. 82 publications were eligible: 10 were prospective and 72 were retrospective. Of the six distinct diagnostic criteria, the HLH-2004 criteria were by far the most commonly used. A minority of studies tested for genetic abnormalities (12), soluble interleukin-2 receptor (11), and/or NK function (11) in a subset of patients. Most centers used steroids and either etoposide-based (HLH-94/HLH-2004) or doxorubicin-based (CHOP) initial therapy regimens. Allogeneic hematopoietic cell therapy for treatment of adult HLH has rarely been reported. Mortality in larger treatment focused studies ranged from 20 to 88%. Developing adult-specific diagnostic criteria based on widely evaluable features of secondary HPS/HLH and establishing standard initial therapies are priorities for future research.

Keywords: Adults; Hematophagic histiocytosis; Hemophagocytic lymphohistiocytosis; Hemophagocytic syndromes; Hyperferritinemia; Macrophage activation syndromes.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Combined Modality Therapy
  • Disease Susceptibility
  • Humans
  • Lymphohistiocytosis, Hemophagocytic / diagnosis*
  • Lymphohistiocytosis, Hemophagocytic / epidemiology
  • Lymphohistiocytosis, Hemophagocytic / etiology
  • Lymphohistiocytosis, Hemophagocytic / therapy*
  • Practice Guidelines as Topic
  • Prognosis
  • Treatment Outcome