Abstract Summary
Introduction: LGLL is a rare lymphoproliferative disorder where somatic STAT3 mutation is common. The clinical characteristics and therapeutic response of LGLL−associated PRCA are largely unclear. Methods: STAT3 mutation detection was conducted in 81 LGLL−associated PRCA patients registered in the CECGA database. Comparative analysis was performed on the clinical characteristics, responses to immunosuppressive therapy, and survival outcomes in patients with STAT3 mutation. Results: 21 cases (26%) were STAT3 mutant, and 60 were wild−type. Among patients with STAT3 mutation, 15 (71%) were positive for exon 21 mutation, 4 (19%) for exon 20 mutation, one for dual mutation in exon 20 and 21, and one for exon 13 mutation. The Y640F was the most commonly detected mutation (42.9%). Patients with STAT3 mutations had a higher percentage of reticulocytes (0.88% vs. 0.28%, P=0.039) and RDW-CV (18.8% vs. 15.8%, P=0.008) compared to wild−type. Those with the STAT3 Y640F mutation had a younger median age at onset (44 years vs. 65 years, P=0.007) and a higher peripheral blood lymphocyte ratio (63.7% vs. 34.4%, P=0.033). The complete response rate (CRR) and overall response rate (ORR) showed no statistical difference between STAT3 mutated and wild−type patients, either treated with CsA or with CP regimen. The relapse rate of the CP regimen was lower than CsA in this whole cohort (24.0% vs 68.4%, P=0.001), as well as in the STAT3 mutant group (18.2% vs 77.8%, P=0.022). Conclusions: STAT3 Y640F was the most common hotspot mutation in LGLL−associated PRCA. Patients with STAT3 mutation treated with CsA showed comparable responses to wild−type.
