Malignancy‐associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes

Abstract

Background Malignancy-associated hemophagocytic lymphohistiocytosis (HLH) in adults is a highly lethal disorder. Knowledge gaps have resulted in under-diagnosis or delayed diagnosis. Patients and Methods The University of Texas MD Anderson Cancer Center pathology database (1991–2014) was retrospectively interrogated for the keywords “hemophagocytosis” and/or “lymphohistiocytosis”. 77 adult patients were identified. All had an underlying malignancy. 16 patients with insufficient documentation were excluded. Results The majority of patients with pathologic evidence of hemophagocytosis/lymphohistiocytosis had incomplete work-up to confirm or refute HLH using the HLH-2004 criteria (HLH-2004 = 8 variables) and this is a common problem in adult HLH. Only 13/61 (21%) patients met the HLH-2004 diagnostic criteria based on available retrospective data. To identify potentially missed cases of HLH we reviewed published literature and selected additional variables known to be associated with adult HLH resulting in an extended diagnostic criteria of 18 variables. 35 patients met the extended criteria and 33 had follow-up data. The median OS of the 13 patients who met both the extended criteria and the HLH-2004 criteria was similar to the 20 patients who met the extended criteria but NOT the HLH-2004 criteria (1.43 vs 1.76 months, P=0.34) indicating similar underlying aggressive systemic process. 26 patients did not meet either criteria and 17 had follow-up data. The median OS of the 17 patients who had pathologic hemophagocytosis or lymphohistiocytosis but met neither criteria was significantly superior to those who met both the extended criteria and the HLH-2004 criteria or those who met the extended criteria but NOT the HLH-2004 criteria (17.27 vs 1.43 vs 1.76, P=0.002). Conclusion Addition of diagnostic laboratory variables that are more easily and rapidly available in smaller institutions and primary care settings than the HLH-2004 variables may be a good surrogate to raise early suspicion of malignancy-associated HLH. Prospective validation is warranted.

Hemophagocytic Lymphohistiocytosis in Adults with Intraocular Involvement: Clinicopathologic Features of 3 Cases

“…The term familial hemophagocytic reticulosis was then changed to primary or familial HL and subsequently, nongenetic causes were recognized (i.e., secondary HLH) [1,4]. While primary HLH consists of different monogenic alterations that derive from impaired cytotoxicity of natural killer cells (NK) and CD8+ cytotoxic T lymphocytes (CTL), secondary HLH presents as an acquired complication in several contexts such as infections, malignant neoplasms, autoimmune diseases, post-transplantation, or is iatrogenically induced (Table 1) [8,9,10,11,12,13,14,15]. Regardless of the etiology, HLH is characterized by an uncontrolled activation of NK/CTL that provokes the release of large amounts of proinflammatory cytokines such as IFN-γ, TNF-α, GM-CSF, M-CSF, and IL-2, resulting in hyperstimulation and systemic infiltration by macrophages which, in turn, phagocytose blood cells, mostly red blood cell precursors, and secrete other cytokines responsible for myelosuppression, endothelial damage with coagulopathy, tissue injury, and NK/CTL incessant activation (IL-1, IL-6, and TNF-α) (Fig.…”

Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia

“…Laboratory findings associated with the activation of macrophages include high ferritin levels, elevated C-reactive protein, d-dimer, transaminases and triglycerides, and hypofibrinogenemia. These cases are observed in about 1% of all patients treated with CAR T-cells [69] and are associated with high mortality in absence of prompt treatment [81]. The goal of therapy is theoretically to suppress overactive CD8 + T cells and macrophages responsible for the immunological syndrome.…”

Limited Role of Random Skin Biopsy in the Diagnosis of Intravascular Lymphoma in Adult Patients with Hemophagocytic Lymphohistiocytosis

“…Though the HLH-2004 criteria were developed in the pediatric population, their use has been extended to the adult patient population in clinical practice empirically [17]. Tamamyan et al [16] proposed additional criteria for adult patients with malignancy-associated HLH in whom a partial laboratory evaluation may preclude the diagnosis of HLH. The lab values taken closest to the date of the initial dermatology consultation and skin biopsy were selected.…”

“…Lab results were reviewed for each patient, including the 8 criteria defined by the HLH-2004 criteria [15] (Table 1) and the 18 extended criteria defined by Tamamyan et al [16] (see online suppl. Table S1; for all online suppl.…”