Adverse Factors in Clinical Outcomes of T-Cell Large Granular Lymphocyte Leukemia.

Abstract 1086

Poster Board I-108

T-cell large granular lymphocyte (LGL) leukemia is a rare clonal lymphoproliferative disorder derived from cytotoxic T-lymphocytes (CTL) associated mostly with lineage-restricted cytopenias. While the clinical course is often indolent, some patients exhibit severe morbidities due to transfusion dependence, infections or thrombocytopenia. Intuitively, the level of the aberrant CTL clone as expressed by high LGL count or TCR Vβ clonal expansion by flow cytometry, the severity of neutropenia, pancytopenia, or the association with clonal myeloid disorders such as myelodysplastic syndromes (MDS) should herald a worse clinical outcome. Moreover, expression of CD56 has been established as an adverse marker for morbidity and mortality in number of hematological malignancies. In addition, rare cases of aggressive T-cell LGL leukemia were reported to display a CD3+/CD56+ immunophenotype.

Based on the availability of a large, well characterized cohort of patients with T-cell LGL leukemia (n=86), we studied features associated with a poor clinical outcome and perceived need for aggressive therapy, including histomorphologic parameters, immunophenotype (CD56 expression). Both clinical response and overall survival (OS) were analyzed by means of categorical and survival statistical methods.

The median patient age was 64 years (range, 15–80), and 55% were males. Rheumatoid arthritis was present in 14% of patients, 47% of patients had splenomegaly and 43% of those underwent splenectomy. Concomitant hematologic malignancies (5 cases of plasma cell dyscrasia, 8 with B-cell malignancies, and 3 with MDS/sAML) were found in 18% of patients, whereas solid cancers accounted for 15%. Neutropenia, anemia, and thrombocytopenia were seen in 63%, 50%, and 24%, respectively. Overall clinical response to a variety of therapies given was observed in 60% of patients. CD56 expression on the LGL clone was found in 15 patients (21%). Cases expressing CD56 were enriched among females (p=.005). CD56-positive cases were less likely to have neutropenia (p=.03) or thrombocytopenia (p=.03). In contrast to aggressive NK-cell lymphoma, the CD56 phenotype in T-cell LGL leukemia did not negatively impact OS (p=.85). However, increasing number of cytopenias (p=.006) were associated with poor survival. A dose-response pattern of association with OS was detected for pancytopenia (hazard ratio [HR]=9.9, p=.002) vs. bicytopenia (HR=4, p=.06) vs. single/none (reference) cytopenia. Similar results were obtained from logistic regression of factors associated with clinical response to therapeutic intervention. Neutropenia (p=.004) and thrombocytopenia (p=.02), but not anemia were associated with poorer clinical responses. All 5 patients with plasma cell dyscrasia had a complete response to the therapies targeting LGL (p=.01). Similarly, patients who underwent splenectomy tended to have a more favorable clinical response (p=.045).

Multiple lineage cytopenias adversely affect both clinical outcomes and OS of T-cell LGL leukemia. In contrast to other diseases (T-cell acute lymphoblastic leukemia, AML, and multiple myeloma) a CD56+ immunophenotype was not associated with poor outcome in our cohort. Thus, as opposed to other studies, we would not suggest aggressive systemic chemotherapy in management of patients with T-cell LGL leukemia based purely on CD56 expression.