Large Granular Lymphocytic Leukemia: A Report of Response to Rituximab

Abstract

Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months' duration. A CBC showed that pancytopenia with an absolute neutrophil count (ANC) was 0. Peripheral blood flow cytometry detected increased number of T cell large granular lymphocytes and T cell receptor rearrangement study detected a clonal T cell population. Bone marrow biopsy showed peripheral T cell lymphoma, most consistent with T-large granulocytic leukemia. The patient was treated with prednisone and oral cyclophosphamide for four months with no response. Thereafter, she received four weekly infusions of rituximab with improvement in her blood counts. A response to rituximab in refractory cases such as ours has been reported and may guide us towards exploring other immune-based therapeutics in this rare disease.

Intersection Between Large Granular Lymphocyte Leukemia and Rheumatoid Arthritis

“…Similarly, therapies introduced to treat the RA in patients with LGL leukemia have shown benefit in improving hematological parameters associated with the leukemia, including cytopenias and LGL expansion. In particular, rituximab, a monoclonal antibody therapy targeting CD20, has been shown to induce a remarkable 100% hematological response rate (either complete or partial leukemia remission) in small case series and case reports of refractory LGL leukemia with RA (81)(82)(83)(84), and in one case of refractory LGL leukemia without RA (85). The JAK3 inhibitor tofacitinib has also been shown to induce hematological improvement in some patients with refractory LGL leukemia and RA (86).…”

Inclusion‐body myositis and primary Sjögren syndrome: mechanisms for shared etiologies

“…Among patients with follicular lymphoma, a prospective study showed that rituximab ameliorates the underlying alterations in T‐cell subsets, supporting the notion that anti‐CD20 treatments have diverse consequences on T‐cell immunity. Indeed, successful use of rituximab in T‐LGLL refractory to corticosteroids and cyclophosphamide adds further support to the broader effects of anti‐CD20 therapy beyond B cells, and specifically on T cells. In one report of a patient with rheumatoid arthritis who developed IBM after anti–tumor necrosis‐alpha therapy, rituximab led to improvement of the rheumatoid arthritis but had no effect on muscle strength …”

Rituximab for rheumatoid arthritis-associated large granular lymphocytic leukemia, a retrospective case series

“…Rituximab is a monoclonal antibody targeting CD20 cells, approved for the treatment of [5] with better efficacy in seropositive patients [6]. Seven patients treated by rituximab for RAassociated LGLL experienced significant improvement in blood count and good response for RA [7][8][9][10]. These cases reflects noticeable discrepancy between rheumatologists and hematologists or oncologists therapeutic strategy that might be due to the difference in clinical manifestations and treatment indications.…”