Introduction CHOP are mostly planned as the first line therapy for PTCL patients. However, in the current modes of treatment strategy, a high incidence of relapse/disease progression/death was observed in PTCL patients. Methods 64 newly diagnosed PTCL patients (25 AITL, 17 PTCL NOS, 11 ALK ALCL and 11 others) were enrolled between August 2021 and September 2023. Plasma samples were collected at time points of pretreatment, at the end of therapy or PD at any time. Target DNA sequenced on using a panel of 475 lymphoma related genes (Jinhua Liang, Leukemia). Objectives We try analysis molecular features possessed in the dynamic ctDNA to reveal the true culprit for disease progression (PD) and recurrence for PTCL. Results Although 46.9% of patients achieved complete response at the EOT, only 25.9% achieved negative minimal residual disease (MRDend) and demonstrated superior prognosis. The ratio of 1st PD were extremly high in MRDend+ patients among the patients with EOT more than PR. It suggests that EOT MRD status may be a critical factor in PD and recurrence for PTCL. TET2 (66.7%), DNMT3A (48.5%), RHOA (27.3%) and TP53 (15.2%) were the top 5 genes which cannot be cleared based on first line CHOP like regimen. Importantly, almost no clonal evolution was observed during first line induction therapy and follow up across all histological subtypes of PTCL. Conclusions Our finding provides important molecular information for the renewal of the concept of therapy strategy and clear direction of exploration of treatments for PTCL patients particularly those effort to clear TET2/DNMT3A/RHOA/TP53 mutation clones.
