UNC13D mutation

HLH was diagnosed and treated with Etoposide and Dexamethasone. While there is not currently a significant body of evidence connecting RB1 mutations and HLH, this case provides a unique situation in which both have occurred. The rarity of these diseases, along with our ever-evolving knowledge of genetics could mean that a link between the two does exist, but is only now starting to come to light. The presence of the UNC13D VUS in our patient also helps to provide data that this variation may be a full disease-causing mutation, or perhaps one that leads to increased HLH risk when present in combination with additional mutations, such as the RB1 mutation.

Compound heterozygous CX3CR1 variants, referred to as pathogenic and risk factors according to the ClinVar database, were enriched in the T-defect group (3 of 26). In summary, the clinical characteristics and T-cell immunodeficiency genetic features may help explain the underlying mechanism of treatment primary resistance and provide novel insights into CAR T-cell immunotherapy.

Repeat bone marrow biopsy was consistent with HSTCL.Chemotherapy with ifosfamide/carboplatin/etoposide (1st line therapy for HSTCL per NCCN guidelines) was given without response. He was subsequently treated with pulse solumedrol for persistent fever and rising HLH markers and 2nd line therapy with EPOCH (etoposide/prednisone/vincristine/cyclophosphamide/doxorubicin)... Individuals with UNC13D mutations have a predisposition to HLH, lymphomas and leukemias. HSTCL is a rare, often fatal lymphoma typically affecting young adult males; sometimes in a setting of long-term immunosuppression. HSTCL can present with clinical findings of HLH in healthy males.