This was a single-center, retrospective study conducted at the Department of Hematology, Huadong Hospital affiliated with Fudan University (Shanghai, China). Clinical records of patients diagnosed with peripheral T-cell lymphoma from January 2013 to April 2019 were collected and analyzed. The study was approved by the Huadong Hospital ethics committee (2024K150). Clinical variables included gender, age, clinical presentation, pathological type, clinical stage, Eastern Cooperative Oncology Group (ECOG) score, International Prognostic Index (IPI), Epstein-Barr virus(EBV) infection status, hemophagocytic lymphohistiocytosis (HLH), treatment regimen, response, adverse effects, progression-free survival (PFS), and overall survival (OS).

All patients were diagnosed following the 2008 WHO classification criteria for lymphoma hematopoietic tissue tumors (10). Inclusion criteria were as follows: 1) clear diagnosis of PTCL by histopathology, including peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), anaplastic large-cell lymphoma [ALCL, with or without expression of the anaplastic lymphoma kinase (ALK+, ALK-)], angioimmunoblastic T-cell lymphoma (AITL), hepatosplenic T-cell lymphoma; 2) received standard treatment at our hospital and achieved complete response (CR) or partial response (PR) to induction therapy. All patients who underwent upfront transplantation were required to be younger than 65 years old and must have an Eastern Cooperative Oncology Group performance status score of <2; 3) complete clinical data, including staging assessment tests at the time of consultation, evaluation of efficacy during treatment, and regular follow-up examinations. Exclusion criteria were as follows: patients with other malignant tumors, those with active infections, or patients with vital organ dysfunctions such as abnormal liver, kidney, and heart functions. Patients were also excluded if they had severe concomitant medical or psychiatric illnesses or if they were seropositive for human immunodeficiency virus.

Patients were treated based on the NCCN guidelines by pathological staging, stage, and general condition. The dose of chemotherapy drugs or dosing cycles could be adjusted depending on treatment toxicities and patient tolerance. The first-line treatment regimen for T-cell lymphoma in our hospital is CHOP (doxorubicin 50 mg/m2 d1, cyclophosphamide 750 mg/m2 d1, vincristine 1.4 mg/m2 d1, prednisone 100mg d1-5) regimen and CDOP (cyclophosphamide 750 mg/m2 d1, pegylated liposomal doxorubicin (PLD, Shanghai Fudan-Zhangjiagang Bio-Pharmaceutical Co., Ltd, China), 20-40 mg/m2 d1, vincristine 1.4 mg/m2 d1, prednisone 100mg d1-5). We chose pegylated liposomal doxorubicin (PLD) or traditional doxorubicin according to the patient’s willingness, economic situation, and presence of chronic disease, especially heart function failure.

After standardized chemotherapy treatment with at least 4–6 cycles and remission (CR+PR) evaluated by 18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), patients were divided into two groups based on whether they underwent ASCT. The choice of ASCT depended on the patient’s age, physical status, disease status, and willingness: (1) the non-ASCT group (62 patients); (2) the ASCT group (30 patients).

All patients in this study in our center received HSCT with a conditioning regimen: Chemo-mobilization (cyclophosphamide(CTX) 30mg/kg + Etoposide(VP-16) 15mg/kg) according to institutional standards of care. G-CSF mobilization was given to patients during the beginning of myelosuppression recovery, with 5ug/kg G-CSF administered daily for 6 days. BEAM (carmustine, 300 mg/m2, -7d; etoposide, 200 mg/m2/d, -6d~-3d; cytarabine, 200 mg/m2/d, -6d~-3d; melphalan 140 mg/m2, -2d) was used as high-dose therapy (HDT) for patients. And in our center, the graft source is PBSC. Collection of blood grafts: Apheresis was initiated from the fifth day and continued daily for 2 days until the predetermined minimal target yield (mononuclear cells ≥2.0 × 10^8/kg and CD34+ cells ≥1.0 × 10^6/kg) was achieved. The apheresis was carried out initially with the Spectra AutoPBSC (Terumo BCT, Lakewood, Colorado) apheresis machine. The number of CD34+ cells in each apheresis bag was measured by flow cytometry using an International Society of Hemotherapy and Graft Engineering protocol with a single platform method at the stem cell laboratory of each apheresis center. The antibodies against the following cell surface markers were used: CD34, CD38, CD133, and CD45. All antibodies were provided by Beckman Coulter. The graft was infused on Day 0 without freezing. Filgrastim was administered after the graft infusion.

Descriptive statistics were used to present patient and treatment characteristics. Categorical variables were presented as n (%) and continuous variables were presented as mean ± standard deviations or median (interquartile range, IQR). A comparison of the characteristics of the two groups was performed using Fisher’s exact test or Pearson’s chi-squared test for categorical variables and Student’s t-test for continuous variables. Kaplan-Meier survival analysis was used to evaluate the OS and PFS, with the log-rank test used to compare the survival rates between the two groups. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were derived from Cox proportional-hazard regression models. To investigate the prognostic factors of PFS and OS, univariate and multivariate Cox analyses were conducted. A two-tailed p-value < 0.05 was considered statistically significant. SPSS 19.0 software was utilized for data comparison between the two groups, and graphs were drawn using Prism Version 8.0.1 (San Diego, CA, USA).

Out of the 92 patients included in this analysis, 30 were in the ASCT group and 62 were in the non-ASCT group. The median age for all patients was 49.5 years (range: 18–83) for the entire cohort. The clinical characteristics of patients in the two groups are summarized in Table 1 . The median age of patients in the ASCT group was younger than that in the non-ASCT group (36 vs. 52 years; p<0.001), and a higher proportion of patients with HLH(p<0.001) was observed in the ASCT group compared to the non-ASCT group. However, there were no significant differences in gender, IPI score, EBV infection rate, the presence of elevated lactate dehydrogenase (LDH), B2 microglobulin, or bone marrow involvement between the two groups.

Regarding the induction treatment regimen, 13 patients (43.4%) in the ASCT group and 30 patients (48.4%) in the non-ASCT group received the CHOP regimen, and no significant difference was observed (p=0.777). All patients achieved complete remission (CR) or partial remission (PR) after receiving chemotherapy.

With a median follow-up time of 41 months (range: 1–217), the median overall survival (OS) was 103.0 months (95% confidence interval [95%CI]: 0.0-223.2), with a 5-year OS rate of 62.1%. The median progression-free survival (PFS) was 18.0 months (95%CI: 0.00-50.749), with a 3-year PFS rate of 54.3% (as shown in Figure 1 ) in the entire cohort.

We then investigated the impact of ASCT on survival. At the end of the follow-up time, the disease relapse rate following transplant is 33.3%; NRM after ASCT is 1 case. A significantly higher OS rate at 5 years was observed in the ASCT group [80.5% (95%CI: 80.3%-80.7%) vs 52.2% (95%CI: 52.0%-52.4%), Figure 1 ], with a median OS not reached (95%CI: not estimated) in the ASCT group compared to 87.0 months (95%CI: 3.6-202.4) in the non-ASCT group (p=0.003). The PFS was also significantly better in the ASCT group [59.8% (95%CI: 59.6%-60.0%) vs 38.2% (95%CI: 38.1%-38.3%)] at 3 years, with a median PFS of 77.0 months (95%CI: 0.1-153.9) in the ASCT group compared to 13.0 months (95%CI: 5.1-20.9) in the non-ASCT group (p=0.015).

In the univariate analysis ( Table 2 ), IPI score (p=0.014), LDH elevation (p=0.024), B2-MGs elevation (p=0.009), bone marrow involvement (p=0.002), combination with HLH (p<0.001), and upfront auto-HSCT (p=0.007) were significantly associated with OS (p<0.05). Additionally, B2-MGs elevation (p=0.047), bone marrow involvement (p=0.002), combination with HLH (p=0.001), and ASCT consolidation therapy (p=0.020) were significantly associated with PFS (p<0.05).

In the multivariate analysis, a combination with HLH (p<0.001) and ASCT consolidation therapy (p=0.005) were significantly associated with OS (p<0.05). Furthermore, clinical stage (p=0.014), IPI score (p=0.049), bone marrow involvement (p=0.010), combination with HLH (p<0.001), and ASCT consolidation therapy (p<0.001) were significantly associated with PFS (p<0.05).

Additionally, we conducted univariate analysis to evaluate the impact of ASCT on OS by subgroups ( Table 3 ). A single-factor stratification study revealed that compared with the non-ASCT group, ASCT as a consolidation regimen was beneficial in increasing the long-term OS rate, particularly for males [p = 0.001, HR 0.15 (95% CI: 0.04–0.66)], patients with stage III or IV disease [p = 0.002, HR 0.15 (95% CI: 0.05-0.50)], patients with an IPI score ≥ 3 [p = 0.050, HR 0.13 (95% CI: 0.02-1.00)], those with high LDH [p= 0.024, HR 0.24 (95% CI: 0.07-0.83)] and high B2-MG [p= 0.034, HR 0.21 (95% CI: 0.05-0.89)], patients with bone marrow involvement [p= 0.033, HR 0.20 (95% CI: 0.05-0.88)], and EBV infection [p= 0.033, HR 0.20 (95% CI: 0.05-0.88)]. ASCT demonstrated a tendency to prolong OS in patients with HLH at diagnosis [p=0.052, HR 0.23 (95% CI: 0.05-1.02)]. Details are presented in Table 3 .

For PFS, univariate analysis by subgroups revealed that patients with stage III or IV disease [p= 0.005, HR 0.35 (95% CI: 0.17-0.72)], and those with an IPI score ≥ 3 [p= 0.028, HR 0.20 (95% CI: 0.05-0.84)] and high LDH [p=0.027, HR 0.33 (95% CI: 0.13-0.88)] would benefit from ASCT. Details are presented in Table 4 .

Further analysis was conducted in patients who received ASCT to determine which type of patients could benefit more. Patients treated with the PLD-containing chemotherapy as an induction regimen had significantly higher OS rates at 5 years [91.7% (95%CI: 91.5%-91.9%) vs. 71.4% (95%CI: 71.1%-71.7%)] and PFS rates at 3 years [76.0% (95%CI: 75.8%-76.2%) vs. 45.1% (95%CI: 44.8%-45.4%)] than those treated with traditional doxorubicin (pOS=0.038, pPFS=0.022) ( Figure 2 ).

To further investigate the reasons for these results, we analyzed the overall response rate (ORR) of induction therapy in patients before ASCT. Patients in the PLD–containing chemotherapy regimen group had a higher ORR [82.6% (95%CI: 59.8%-102.7%) vs 60.9% (95%CI: 27.5%-86.8%), p=0.021]. Among them, 7 patients achieved complete remission (CR) in the PLD–containing chemotherapy regimen group, with a CR rate of 50.0%(95%CI: 20.0%-80.0%). In the CHOP group, 3 patients achieved CR with a CR rate of 37.5%(95%CI: -5.80%-80.8%). Although the CR rate of patients in the CDOP group was higher, the difference was not statistically significant (p=0.077), indicating a tendency towards benefit among patients with PTCL in terms of chemotherapy efficacy, resulting in better survival outcomes.

Safety during therapy was assessed for the 30 patients who underwent HSCT. All adverse events are presented in Table 5 . The most common adverse events with grade 3-4 severity were febrile neutropenia (100%) and nausea and vomiting (76.7%). There were no occurrences of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS, 0%). Additionally, no cardiac adverse events were reported in the ASCT group during the long-term follow-up periods, as monitored by myocardial markers and cardiac echography.