Bone marrow hemophagocytosis in patients with hematological malignancies and COVID-19 infections: mimicry or secondary HLH?

BACKGROUND

Severe coronavirus disease 2019 (COVID-19) and secondary hemophagocytic lymphohistiocytosis (sHLH) share overlapping pathogenesis, symptoms, and ultimately fatal outcomes unless prompt early interventions are undertaken. The excessive immune response in COVID-19 may increase hemophagocytes in bone marrow aspirate (BMA), which could mimic sHLH.

PURPOSE: We aimed to assess hemophagocytic cells in the BM of COVID-19 patients with hematological neoplasms and examine their link to sHLH.

METHODS

BMAs from 44 living COVID-19-positive patients with hematological neoplasms were examined, focusing on the presence of hemophagocytic cells. Alongside clinical and laboratory data, patients were classified into two groups according to the HLH-2004 diagnostic criteria: those meeting ≥ 4 criteria (n = 23) and those meeting < 4 criteria (n = 21). BMAs from 44 COVID-19-negative patients with similar hematological malignancies were also analyzed for comparison.

RESULTS

Hemophagocytic cells were present in 33/44 (75.0%) COVID-19-positive patients and were associated with normal and increased erythropoiesis (p = 0.044). Hemophagocytosis was significantly more frequent in COVID-19-positive than in COVID-19-negative patients (p < 0.001). Meeting ≥ 4 HLH-2004 criteria was significantly more prevalent in newly diagnosed patients than in those during follow-up/relapse (p = 0.004). Significantly higher H-scores were also observed in newly diagnosed patients compared with those in follow-up (p < 0.001). Patients with severe/critical COVID-19 or intensive care unit (ICU) admission had higher H-scores; however, the differences were not statistically significant (p = 0.509 and 0.246, respectively).

CONCLUSION

Hemophagocytic cells are significantly observed in COVID-19 patients with hematological neoplasms, but are insufficient to support a classic diagnosis of concurrent sHLH. These findings suggest that COVID-19-associated hyperinflammation may contribute to BM hemophagocytosis in this vulnerable population.