PB2011 UNDERSTANDING CIRCULATING LARGE GRANULAR LYMPHOCYTIC PROLIFERATIONS IN CUTANEOUS T‐CELL LYMPHOMA
Authors: Zhang Y. , Hussaini M. , Sokol L. 
Published: June 2019

Background:T‐cell large granular lymphocytic leukemia(T‐LGLL) is a rare hematologic malignancy most frequently from CD8+ T cells. Reactive clonal LGL expansions have been described in elderly and post viral infections. Cutaneous T cell lymphoma (CTCL) is derived from mature CD4+ T cells presenting with cutaneous lesions. Both disorders share common pathogenic pathways such as IL‐15/IL‐15R. We have recently reported a case of Mycosis Fungoides with CD4+ large granular lymphocytic proliferation mimicking Sezary syndrome.Aims:The study was to understand the role of LGL proliferations in CTCL.Methods:We searched MCC CTCL databases for patients with pathologically confirmed diagnosis CTCL associated with LGL proliferations. A retrospective chart review was performed. Clinical, laboratory and pathology data were collected and analyzed using descriptive statistical methods.Cox proportional hazard model was used to test if the presence of LGL proliferation improves survival in patients with Sezary syndrome (SS) as compared to our institutional cohort.Results:Seventeen patients (N = 17) were identified. Median age was 55 years (range 22‐82), M:F ratio 0.88, 71% (12) Caucasian, 18% (3) African‐American and 11% (2) Hispanic. 76% (13) had MF, 6% (1) had SS. 88% (15) had early stage (I/IIA) disease. LGL proliferations were identified after CTCL diagnosis in all patients with a median time of 4 years. Median absolute LGL count was 0.148x109/L. 94% (16/17) revealed characteristic LGLL immune‐phenotype. 30% (5) showed the second CD4+/CD57+ LGL populations. 35% (6) showed resolution of LGL population during follow‐up. Median time to resolution was 146 days. 76% (13) had TCR gene rearrangement studies on bone marrow with 60% (10) positive. All 10 showed identical TCR gene peaks in bone marrow and peripheral blood. 35% (6) were diagnosed with other malignancies including 18% (3) with LGL leukemia. None with LGL proliferations developed cytopenia requiring therapy. 35% (6) had hepatomegaly, splenomegaly, or lymphadenopathy including 3 LGL leukemia. 5 pts had available TCR gene rearrangement of both skin and blood. Two showed identical TCR peaks.On separate analysis, four patients with SS and LGL were identified. When compared to our institutional cohort of SS, the presence of LGL is a potential favorable prognostic factor with the hazard ratio of 0.485 (p = 0.195) (see attached graph). Statistical insignificance is likely due to small samples and that all patients with LGL were still alive as of 1/1/2019. Longer follow‐up and larger cohort are needed to confirm this trend.Summary/Conclusion:Clonal LGL proliferations in CTCL are heterogeneous ranging from benign transient reactive clones to LGLL. None required therapy for LGL proliferations suggests a benign course. Interestingly, 2 patients revealed identical TCR gene rearrangement peaks in MF and LGL cells suggesting the possibility of common putative mutation in progenitor T‐cell such as JAK/STAT pathway. The separate analysis of patients with SS also suggests that the presence of LGL is a potential favorable prognostic factor.image