Malignancy-Associated Hemophagocytic Lymphohistiocytosis: Clinical Characteristics, Treatment Patterns, and Survival Outcomes in a Tertiary Care Center Cohort
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Published on: September 30, 2021
Ricardo Kosch1, Winfried Alsdorf1, Paymon Ahmadi1
1Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Background:
Malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH) carries a poor prognosis and is often complicated by overlapping infection, cytopenias, organ failure, and progressive disease.
Methods:
We retrospectively analyzed 49 adults with M-HLH at a single tertiary cancer center (2013-2026), summarizing malignancy spectrum, diagnostic features, treatment, and survival outcomes. HLH probability was assessed by HScore and modified HLH-2004 criteria.
Results:
Lymphoma was the main underlying disease (34/49; 69.4%), led by aggressive B-cell (17/49; 34.7%) and T-cell NHL (12/49; 24.5%). HLH coincided with initial malignancy recognition in 17 of 49 patients (34.7%). The median HScore was 231 (IQR 202-256); 44 of 49 patients (89.8%) met the ≥ 169 threshold, and 42 of 49 patients (85.7%) fulfilled ≥ 5 of 7 modified HLH-2004 criteria. HLH-directed therapy included corticosteroids (41/49; 83.7%), etoposide (21/49; 42.9%), and anakinra (16/49; 32.7%); 21 of 49 patients (42.9%) received concurrent malignancy-directed chemotherapy. Mortality was 59.2% (29/49) with a median overall survival of 56 days (median follow-up 612 days for the cohort; 574 days among survivors, n = 20). De novo presentation carried substantially lower mortality than HLH in previously known malignancy (23.5% vs. 78.1%; hazard ratio [HR] 5.38, 95% confidence interval [CI], 1.85-15.61; P = .002). Malignancy-directed chemotherapy was associated with lower mortality than HLH-directed therapy alone (HR 3.11, 95% CI, 1.36-7.09; P = .007). All 6 patients with invasive mold infection died.
Conclusions:
M-HLH was predominantly lymphoma-associated, met diagnostic criteria with high probability, and carried poor short-term survival. De novo presentation had better outcomes, likely because lymphoma-directed chemotherapy can simultaneously address the underlying malignant trigger and the hyperinflammatory state. Invasive mold infection was uniformly fatal, illustrating the lethal combination of profound immunosuppression and uncontrolled opportunistic infection in this setting.
