An analysis of veterans diagnosed with large granular lymphocytic disorders at the national Veteran Affairs Healthcare System

Abstract: This is a retrospective, secondary analysis of electronic health records of a VA cohort of patients diagnosed with LGL leukemia from January 1, 1998 to December 31, 2020 using the VA informatics infrastructure.3 The VA is the largest integrated healthcare system in the United States with sites also in American Samoa, Guam, Philippines, Puerto Rico, and the Virgin Islands. The diagnosis of LGL leukemia was made by the detection of monoclonal population of at least 0.5 × 109/L cells with the expression of CD3+CD8+CD16+/−CD57+/− and a T-cell receptor gamma gene rearrangement as T-cell LGL leukemia, and CD3-CD16+CD56+ as NK-cell LGL leukemia. If the LGL cell count was <0.5 × 109/L by peripheral blood flow cytometry, then this was deemed to be precursor state. Transformation was defined as an aggressive progression of disease with lymphocytosis. Descriptive data summarized patient and disease characteristics. Treatments were categorized as methotrexate-based, cyclophosphamide-based, cyclosporine A-based, growth factors, or other immunosuppression, which included steroids and mycophenolate. Response rates were evaluated by blood counts and organ response after four 28-day cycles of therapy. A complete response (CR) was defined as improvement of hemoglobin >11 g/dL, platelets >100 × 109/L, ANC >1.5 × 109/L, and lymphocyte count <4 × 109/L; a partial response defined as improvement in counts without meeting CR, stable disease as no response within 4 months, and progressive disease (PD) as worsening cytopenias or organomegaly.4 Multivariate hazard ratios were calculating with the Cox proportional hazard model. Overall survival (OS) was defined as the time from date of diagnosis to death from any cause. Disease specific survival (DSS) was defined as the time from date of diagnosis to death from hematologic malignancy. Patients who were alive were censored at the date of last contact (data cutoff December 31, 2020). Kaplan–Meier curves were used to estimate survival and compared by log-rank tests. Causes and dates of death were confirmed by using data from the National Death Index through December 31, 2020.5 p-values were reported for two-sided tests. This study was approved by the Institutional Review Boards at the VA Long Beach Healthcare System and the University of California, Irvine and was conducted in accordance with the principles of the Declaration of Helsinki.