Background:
Although many patients with Large granular lymphocytic leukemia present with cytopenias at diagnosis, the necessity for targeted treatment is not universally indicated. The diagnostic landscape is complicated by the coexistence of factors including autoimmune conditions, clonal hematopoiesis (CH), monoclonal gammopathy (MG) and myelodysplastic syndrome (MDS).
Methods:
We performed a retrospective review of 558 LGLL pts diagnosed from 2 institutions. A random forest model was developed to identify predictors for treatment requirements with area under the curve used to compare the random forest vs multivariate logistic regression model.
Results:
Of 558 pts, the median age was 64 years with 58% females. 123 (32%) pts had concurrent MG, 99 (38%) had STAT3MT, and 4 (2%) had STAT5bMT. Splenomegaly was present in 101 (19%) pts. 202 (38%) pts had clinical manifestations requiring LGLL directed therapy. Indications for treatment were anemia (84%) or neutropenia (72%). Clonal Vβ/TCR (64% vs. 44%, p< 0.001), splenomegaly (30% vs. 12%, p< 0.001), RA (24% vs. 11%, p< 0.001), and STAT3MT (52% vs. 25%, p< 0.001) were more prevalent in treated pts. In univariate analysis, splenomegaly (OR=3, p< 0.001), RA (OR=2.6, p=0.03), STAT3MT (OR=3.2, p< 0.001), and clonal Vβ/TCR (OR=2.3, p< 0.001) were associated with treatment requirement. In multivariate regression, splenomegaly (OR=2.7, p=0.002), RA (OR=4.8, p< 0.001), hemoglobin (OR=0.7, p< 0.001), CD7 (OR=3, p=0.001), CD16 (OR=2.5, 0.04), and CD4 (OR=0.4, p=0.03) were associated with need for treatment. Random forest model had AUC of 0.99 vs 0.85.
Conclusions:
Applying machine learning, the study revealed that splenomegaly, RA, clonal Vβ/TCR, MG, specific CD markers, and STAT3MT are associated with cytopenias and treatment need in LGLL pts.
