Lymphoma-Associated Bone Marrow Hemophagocytosis (LA-BMHPC): A Retrospective, Single-Center Study of 67 Patients

Objective: To investigate the clinical characteristics, management strategies, and prognostic outcomes of patients with lymphoma-associated bone marrow hemophagocytosis (LA-BMHPC). Methods: This retrospective, single-center cohort study enrolled patients diagnosed with LA-BMHPC between June 1, 2020, and June 30, 2023. We analyzed the clinical characteristics, treatment approaches (hemophagocytic lymphohistiocytosis [HLH]-directed therapy alone [HT], lymphoma-directed therapy alone [LT], simultaneous HLH and lymphoma therapy [HLT], no specific treatment [NST]), and overall survival (OS). Patients meeting the inclusion criteria (n=67) were categorized based on the HLH-2004 criteria into lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH; n=50) and lymphoma-associated hemophagocytosis without fulfilling the HLH criteria (LA-HPC; n=17). Survival was monitored until November 30, 2023. Results: The median overall survival (OS) of the entire LA-BMHPC cohort (n=67) was 3 months (range, 0-40 months), with 3-month, 1-year, and 3-year OS rates of 44.6%, 31.0%, and 22.7%, respectively. Significant differences between LA-HLH and LA-HPC groups were observed in the prevalence of fever, cytopenias (≥2 lineages), hypofibrinogenemia, hyperferritinemia and hypoalbuminemia (all P < 0.05). Receiver operating characteristic analysis identified elevated triglyceride and soluble CD25 levels as strong predictors of progression to LA-HLH, with optimal predictive cut-offs of 1.405 mmol/L and 1352.74 U/L, respectively. Multivariate Cox regression analysis revealed that LDH (hazard ratio [HR] 5.991,95% confidence interval [CI], 1.401-25.614; P=0.016), being treatment-naïve at the time of LA-BMHPC diagnosis (HR 2.537, 95% CI, 1.398-4.604; P=0.002), and treatment strategy (overall P=0.001) were independent prognostic factors. Compared to NST, both LT (HR 0.138, 95% CI, 0.046-0.414; P<0.001) and HLT (HR 0.117, 95% CI, 0.069-0.453; P<0.001) were associated with a significantly better survival benefit, whereas HT alone was not (HR 0.450, 95% CI, 0.172-1.180; P=0.104). Patients who received any form of lymphoma-directed therapy (LT or HLT) had significantly better OS than patients who did not (HT or NST; HR = 0.301, 95% CI, 0.160-0.568; P < 0.001). Patients with LA-HPC exhibited a significantly better OS (median, 17 months;1-year rate, 63.7%) than those with LA-HLH (median, 2 months;1-year rate, 20.6%; P=0.015). Conclusions: LA-BMHPC defines a spectrum of diseases ranging from a high-risk precursor state (LA-HPC) to fulminant LA-HLH. Progression to LA-HLH is associated with fever, cytopenias (≥2 lineages), hypofibrinogenemia, hyperferritinemia, hypoalbuminemia, and elevations in triglyceride (≥1.405 mmol/L) or soluble CD25 (≥1352.74 U/L) levels. Effective treatment of the underlying lymphoma is the most critical determinant of survival. An integrated strategy (HLT) represents a rational approach, potentially serving as a "bridge" by controlling hyperinflammation to enable definitive anti-lymphoma therapy.