Proliferation through activation

hemophagocytic lymphohistiocytosis in hematologic malignancy

Eric J. Vick, Kruti Patel, Philippe Prouet, Michael Martin

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of cytokine-driven immune activation. Cardinal features include fever, hemophagocytosis, hepatosplenomegaly, lymphocytic infiltration, and hypercytokinemia that result in multisystem organ dysfunction and failure. Familial HLH is genetically driven, whereas secondary HLH (SHL) is caused by drugs, autoimmune disease, infection, or cancer. SHL is associated with worse outcomes, with a median overall survival typically of less than 1 year. This reflects difficulty in both diagnostic accuracy and in establishing reliable treatments, especially in cases of malignancy-induced SHL, which have significantly worse outcomes. Malignancy-induced HLH is seen almost exclusively with hematologic malignancies, constituting 97% of cases in the literature over the past 2 years. In these situations, the native immune response driven by CD8 T cells produces an overabundance of T helper 1 cytokines, notably interferon-γ, tumor necrosis factor-α, and interleukin-6, which establish a positive feedback loop of inflammation, enhancing replication of hematologic malignancies while leaving the host immune system in disarray. In this paper, we present 2 case studies of secondary HLH driven by HM, followed by a review of the literature discussing the cytokines driving HLH, diagnostic criteria, and current treatments used or undergoing investigation.

Original languageEnglish (US)
Pages (from-to)779-791
Number of pages13
JournalBlood advances
Volume1
Issue number12
DOIs
StatePublished - May 9 2017

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Hemophagocytic Lymphohistiocytosis
Hematologic Neoplasms
Cytokines
Neoplasms
Interferons
Autoimmune Diseases
Immune System
Interleukin-6
Fever
Tumor Necrosis Factor-alpha
Inflammation
T-Lymphocytes
Therapeutics
Infection
Pharmaceutical Preparations

Cite this

Proliferation through activation : hemophagocytic lymphohistiocytosis in hematologic malignancy. / Vick, Eric J.; Patel, Kruti; Prouet, Philippe; Martin, Michael.

In: Blood advances, Vol. 1, No. 12, 09.05.2017, p. 779-791.

Research output: Contribution to journalReview article

Vick, Eric J. ; Patel, Kruti ; Prouet, Philippe ; Martin, Michael. / Proliferation through activation : hemophagocytic lymphohistiocytosis in hematologic malignancy. In: Blood advances. 2017 ; Vol. 1, No. 12. pp. 779-791.
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