A Case of T-Cell Large Granular Lymphocytic Leukemia in a Patient with Longstanding Rheumatoid Arthritis and Neutropenic Sepsis

Introduction/Background/Significance: T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder characterized by the clonal expansion of cytotoxic T-cells. It often presents with neutropenia and is associated with autoimmune diseases, particularly rheumatoid arthritis (RA). Prompt recognition is critical, as complications such as severe infections can occur. This case highlights the diagnostic challenges and clinical course of T-LGLL in a patient with a complex immunosuppressive and infectious history.

Materials and Methods/Case Presentation/Objective: A 57-year-old male with longstanding seropositive RA and recent EBV infection presented with chills and sepsis. He had developed a sacral decubitus ulcer and had been severely neutropenic for several months, despite cessation of immunosuppressive medications. On arrival, he was febrile, tachycardic, and ill-appearing. Laboratory workup showed an absolute neutrophil count of 0, anemia, and mild splenomegaly. Empiric broad-spectrum antibiotics and antifungals were initiated for neutropenic sepsis.

Results/Description/Main Outcome Measures: The patient's infection source was localized to his sacral ulcer. Infectious and nutritional workups were unrevealing. Given persistent neutropenia and serologies suggestive of active RA, a hematologic malignancy was suspected. Flow cytometry identified a clonal CD8+, CD3+, CD57+ T-cell population expressing NK-cell associated antigens. A bone marrow biopsy confirmed hypercellular marrow with 40% atypical lymphocytes (CD8+, CD3+, CD57+, TIA-1+, granzyme B+) and a STAT3 mutation, consistent with T-LGLL. The patient was started on methotrexate for dual treatment of RA and T-LGLL. He subsequently experienced clinical improvement and neutrophil count recovery.

Conclusions: This case underscores the importance of considering T-LGLL in patients with longstanding RA and unexplained neutropenia, especially when immunosuppression has been withheld, and other etiologies have been ruled out. Timely diagnosis through immunophenotyping and bone marrow biopsy can guide effective immunosuppressive therapy. The course is generally indolent, and many cases may be observed without treatment. Treatment is indicated in cases of severe neutropenia, transfusion-dependent anemia, or autoimmune disorders such as rheumatoid arthritis and Sjögren's syndrome. Methotrexate remains a first-line agent in symptomatic T-LGLL, particularly in those with concurrent RA. Other first line treatment options include cyclophosphamide and cyclosporine. For patients with relapsed or refractory T-LGLL, alternative therapies include alemtuzumab or pentostatin.