2.1 CASE 1
A 34-year-old male with refractory T-cell rich DLBCL with associated
HLH/MAS at diagnosis, underwent Tisa-Cel therapy in 2019. High tumor
burden with progressive disease was documented after bridging therapy.
During lymphodepletion with cyclophosphamide and fludarabine, persistent
fever with neutropenia was treated with empiric broad-spectrum
antimicrobials agents, without resolution.
On day +1, he presented with grade 1 CRS, managed with tocilizumab on
days +15 and +20, achieving partial response. However, high grade fever
followed with hyperferritinemia (peak 50,000ng/ml on day +23), severe
cytopenias, altered liver function, coagulopathy and high values of
IL-15, IL-1β, GM-CSF and IL-6. HLH/MAS was suspected and bone marrow
aspiration was performed on day +22, showing hemophagocytosis and no
evidence of infiltration by lymphoma.
In order to distinguish between CAR-T cell related and malignancy
associated HLH/MAS, a PET-CT was performed on day +25, showing
paradoxical response. Concurrently, CAR-T cells expansion in peripheral
blood (PB) was detected by flow cytometry and polymerase chain reaction
(PCR). Furthermore, a lymph node biopsy was performed where CAR-T cells
were detected, with only 4% of neoplastic lymphocytes (Figure
1).
Subsequently, high dose corticosteroids, siltuximab, anakinra and
cyclophosphamide were administered. Hemoadsorption with extracorporeal
cytokine adsorber (CytoSorb®) was initiated on day
+35. Etoposide was not considered due to severe liver function
impairment.
Patient showed no response to treatment, and died from multiorgan
failure on day +36. Tumor necrosis was the predominant finding in
necropsy, with an estimated 15% of residual tumor.