Objective:To evaluate the efficacy and safety of the pegaspargase, etoposide, methotrexate, and dexamethasone (PEMD) regimen in patients with early-stage nonupper respiratory digestive tract or advanced extranodal natural killer/T-cell lymphoma (ENKTL) .Methods:This retrospective analysis included 38 patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL who received PEMD regimen for induction chemotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2022. Survival outcomes and prognostic factors were examined by Kaplan-Meier, and the Log-rank test was used to compare survival.Results:The study population had a median age of 48 years (range, 26-72 years) and included 30 males (78.9%) and 8 females (21.1%). 7 patients’ age >60 years (18.4%). The Eastern Cooperative Oncology Group (ECOG) performance score was >1 in 7 patients (18.4%) ; 20 patients (52.6%) had elevated lactate dehydrogenase levels; and 37 patients (97.4%) exhibited extranodal involvement. Using the Ann Arbor staging system, 37 patients (97.4%) were classified as stage Ⅲ-Ⅳ. The median number of treatment cycles was 5 (1-6), and the median follow-up duration was 60 months (24 - 101 months). Interim efficacy assessment revealed an overall response rate of 52.7%. At 2 and 4 years, the progression-free survival (PFS) rates were 34.2% (95% CI 22.0%-53.2%) and 25.5% (95% CI 14.7%-44.4%), respectively, and the overall survival rates were 50.0% (95% CI 36.4%-68.7%) and 45.5% (95% CI 31.4%-65.7%), respectively. The risk factors for worse PFS were ECOG performance score >1 [ HR=3.711 (95% CI 1.494-9.218), P=0.005]; bone marrow infiltration [ HR=2.251 (95% CI 1.026 - 4.938), P=0.043]; and Prognostic Index for Natural Killer/T-Cell Lymphoma score of 3 - 5 [ HR=2.350 (95% CI 1.009 - 5.476), P=0.048]. Multivariate analysis identified ECOG performance score >1 as an independent risk factor for PFS [ HR=7.971 (95% CI 2.222 - 28.591), P=0.001]. The main adverse effect was anemia in 31 patients (81.6%) . Conclusion:The PEMD regimen was safe and effective for patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL.

Objective:To evaluate the efficacy and safety of the Chi-BEAM regimen (chidamide combined with carmustine, etoposide, cytarabine, and melphalan) followed by autologous hematopoietic stem cell transplantation (ASCT) in patients with high-risk or relapsed/refractory lymphoma.Methods:This retrospective case series included 78 patients with newly treated high-risk or relapsed/refractory lymphoma who underwent ASCT with the Chi-BEAM conditioning regimen in the Department of Hematology, the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), from June 2021 to May 2024. Descriptive statistics were employed to evaluate clinical characteristics, efficacy, and adverse events. The Kaplan-Meier method was applied to calculate cumulative progression-free survival (PFS) and overall survival (OS) rates.Results:The median age of the 78 evaluable patients was 47 years (range 16-68), with 8 patients (10.3%) aged ≥60 years. At the first post-transplant assessment (3 months), the objective response rate was 94.9% (74/78). The median follow-up was 20.1 months (range 2.9-44.9). The median PFS time was 20.1 months (range 1.6-45.1), with a 2-year cumulative PFS rate of 81.8%. The median OS time was 20.6 months (range 3.1-45.1), with a cumulative 2-year OS rate of 93.2%. The regimen was well-tolerated; mild-to-moderate hypocalcemia within 1 week post-infusion and transient mild erythrocyturia on the infusion day were the primary adverse reactions.Conclusion:The Chi-BEAM regimen combined with ASCT demonstrates both safety and clinical benefit in patients with high-risk or relapsed/refractory lymphoma.

Objective:To evaluate the efficacy and safety of the pegaspargase, etoposide, methotrexate, and dexamethasone (PEMD) regimen in patients with early-stage nonupper respiratory digestive tract or advanced extranodal natural killer/T-cell lymphoma (ENKTL) .Methods:This retrospective analysis included 38 patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL who received PEMD regimen for induction chemotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2022. Survival outcomes and prognostic factors were examined by Kaplan-Meier, and the Log-rank test was used to compare survival.Results:The study population had a median age of 48 years (range, 26-72 years) and included 30 males (78.9%) and 8 females (21.1%). 7 patients’ age >60 years (18.4%). The Eastern Cooperative Oncology Group (ECOG) performance score was >1 in 7 patients (18.4%) ; 20 patients (52.6%) had elevated lactate dehydrogenase levels; and 37 patients (97.4%) exhibited extranodal involvement. Using the Ann Arbor staging system, 37 patients (97.4%) were classified as stage Ⅲ-Ⅳ. The median number of treatment cycles was 5 (1-6), and the median follow-up duration was 60 months (24 - 101 months). Interim efficacy assessment revealed an overall response rate of 52.7%. At 2 and 4 years, the progression-free survival (PFS) rates were 34.2% (95% CI 22.0%-53.2%) and 25.5% (95% CI 14.7%-44.4%), respectively, and the overall survival rates were 50.0% (95% CI 36.4%-68.7%) and 45.5% (95% CI 31.4%-65.7%), respectively. The risk factors for worse PFS were ECOG performance score >1 [ HR=3.711 (95% CI 1.494-9.218), P=0.005]; bone marrow infiltration [ HR=2.251 (95% CI 1.026 - 4.938), P=0.043]; and Prognostic Index for Natural Killer/T-Cell Lymphoma score of 3 - 5 [ HR=2.350 (95% CI 1.009 - 5.476), P=0.048]. Multivariate analysis identified ECOG performance score >1 as an independent risk factor for PFS [ HR=7.971 (95% CI 2.222 - 28.591), P=0.001]. The main adverse effect was anemia in 31 patients (81.6%) . Conclusion:The PEMD regimen was safe and effective for patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL.

Objective:To evaluate the efficacy and safety of the Chi-BEAM regimen (chidamide combined with carmustine, etoposide, cytarabine, and melphalan) followed by autologous hematopoietic stem cell transplantation (ASCT) in patients with high-risk or relapsed/refractory lymphoma.Methods:This retrospective case series included 78 patients with newly treated high-risk or relapsed/refractory lymphoma who underwent ASCT with the Chi-BEAM conditioning regimen in the Department of Hematology, the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), from June 2021 to May 2024. Descriptive statistics were employed to evaluate clinical characteristics, efficacy, and adverse events. The Kaplan-Meier method was applied to calculate cumulative progression-free survival (PFS) and overall survival (OS) rates.Results:The median age of the 78 evaluable patients was 47 years (range 16-68), with 8 patients (10.3%) aged ≥60 years. At the first post-transplant assessment (3 months), the objective response rate was 94.9% (74/78). The median follow-up was 20.1 months (range 2.9-44.9). The median PFS time was 20.1 months (range 1.6-45.1), with a 2-year cumulative PFS rate of 81.8%. The median OS time was 20.6 months (range 3.1-45.1), with a cumulative 2-year OS rate of 93.2%. The regimen was well-tolerated; mild-to-moderate hypocalcemia within 1 week post-infusion and transient mild erythrocyturia on the infusion day were the primary adverse reactions.Conclusion:The Chi-BEAM regimen combined with ASCT demonstrates both safety and clinical benefit in patients with high-risk or relapsed/refractory lymphoma.

Objective:This study aimed to assess the efficacy and safety of thioamide as a maintenance therapy for peripheral T-cell lymphoma (PTCL) .Methods:This study retrospectively analyzed the data from 58 patients with PTCL who were treated in the Department of Hematology at the First Affiliated Hospital of Nanjing Medical University from January 2015 to July 2022. Chidamide was orally administered as a maintenance therapy after first-line or salvage treatment. Progression-free survival (PFS), overall survival (OS), and safety were analyzed.Results:Among the 58 patients with PTCL, 43 were males and 15 were females, and the median age was 66 (range: 29-83) years. Thirty-nine patients received thioamide as first-line maintenance therapy, and 19 patients received thioamide as maintenance therapy after salvage treatment. The median maintenance therapy duration was 16 months (range: 1-72 months), with a median PFS time of 33 (2-74) months, and the median OS time had not been reached. Patients who received first-line maintenance therapy with thioamide demonstrated superior PFS and OS outcomes compared with patients who received thioamide maintenance therapy after salvage treatment (median PFS time: not reached vs 7 months, P<0.001; median OS time: not reached vs 67 months, P=0.009). The most prevalent adverse reaction was a hematologic adverse reaction (77.6%). Twelve (20.7%) patients underwent a dose reduction and three patients discontinued treatment. Conclusion:Patients receiving thioamide maintenance therapy demonstrated a promising PFS and OS with a manageable safety profile, especially as the first-line maintenance therapy.

Objective:To assess the efficacy, safety, and related prognostic factors associated with the P-GemDOx regimen as a first-line treatment for patients with early-stage extranodal natural killer (NK) /T cell lymphoma (ENKTL) .Methods:A retrospective analysis was performed on sixty early-stage ENKTL patients treated with the P-GemDOx regimen who were admitted to the First Affiliated Hospital of Nanjing Medical University between August 2015 and May 2021. The Chi-square test or Fisher's exact test was used to compare group differences, and the Log-rank test was used to compare the differences in survival. Survival outcomes and prognostic factors were examined.Results:After completing 4 to 6 cycles of P-GemDOx chemotherapy, the overall response rate (ORR) was 88.3%, with forty-six patients (76.7% ) achieving complete response (CR). The 4-year progression-free survival (PFS) and overall survival (OS) rates were (66.3±7.1) % and (79.5±6.0) %, respectively. According to the PINK/PINK-E model, there was no significant difference in survival outcomes among risk groups. 23.3% of patients experienced progression of disease within 24 months (POD<24). OS estimates differed significantly ( P<0.001) between the POD<24 group ( n=14) and the POD≥24 group ( n=46). Analysis showed that SUVmax > 12.8 at diagnosis, non-single nasal cavity infiltration, and response less than CR after 4–6 cycles all had a significant association with POD24. We used these data as the basis for predicting POD<24 international prognostic index (POD24-IPI). Patients were stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high risk (two or three risk factors). These groups were associated with 4-year OS rate of 100%, (85.6±9.7) %, and (65.0±10.2) %, respectively ( P=0.014). The P-GemDOx regimen was well tolerated, with hematological toxicity being the main side effect. Conclusion:This study demonstrated that the P-GemDOx regimen is effective and safe in the first-line treatment of early-stage ENKTL, and POD24-IPI is a promising prognostic model.

Objective:To investigate the efficacy and safety of orelabrutinib combined with R-CHOP in the treatment of MCD subtype diffuse large B cell lymphoma (DLBCL) .Methods:Twenty-three MCD subtype patients whose gene-subtype classification was based on baseline tumor tissue and/or baseline plasma using the LymphGen algorithm from June 2022 to June 2023 in the First Affiliated Hospital of Nanjing Medical University were retrospectively enrolled in the analysis. All patients were treated with R-CHOP or R-miniCHOP in Course 1, OR-CHOP or OR-miniCHOP (21 days for one course) in Courses 2-6, and R-monotherapy in Courses 7-8.Results:Of the 23 patients, the median age was 58 years (range: 30-81 years), and 11 (47.8% ) aged >60 years. Fifteen cases (65.2% ) had international prognostic index (IPI) scores of 3 to 5. The top 10 mutated genes in the gDNA tissues were PIM1 (78.3% ), MYD88 (69.6% ), ETV6 (43.5% ), BTG1 (39.1% ), CD79B (43.5% ), HIST1H1E (39.1% ), BTG2 (34.8% ), KMT2D (30.4% ), CD58 (26.1% ), and CDKN2B (21.7% ). The consistency rate of the tissue and plasma mutations was 80%, while the baseline plasma ctDNA burden was closely correlated with the LDH levels and IPI scores ( P<0.05). All patients received 5 courses of OR-CHOP regimens. The mid-term (after 3 courses) evaluation showed that the overall response rate (ORR) was 100% (23/23), with 22 patients (95.65% ) achieving complete remission (CR), and 1 patient (4.35% ) achieving partial remission (PR). The ORR after the end of treatment (EOT) was 95.65% (22/23). Moreover, 21 patients (91.30% ) obtained CR, 1 patient (4.35% ) obtained PR, and 1 patient (4.35% ) obtained progression disease (PD). Of the 21 patients who had the dynamic EOT-ctDNA burden, only four patients (19.0% ) did not achieve EOT-ctDNA clearance, while the other 17 patients (81.0% ) achieved EOT-ctDNA clearance. The median follow-up time was 20.8 (15.3-30.0) months, while the median progression-free survival (PFS) and overall survival (OS) were not reached. The 2-year PFS rate was 71.8% (95% CI 54.7% -94.2% ), while the 2-year OS rate was 91.3% (95% CI 80.5% -100.0% ). Furthermore, the OR-CHOP regimen was generally well tolerated during clinical use, with hematological toxicity being the main adverse effect. Conclusion:This study revealed that the OR-CHOP regimen can be used as an effective and safe first-line treatment for MCD subtype DLBCL.

Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

Objective:This study aimed to assess the efficacy and safety of thioamide as a maintenance therapy for peripheral T-cell lymphoma (PTCL) .Methods:This study retrospectively analyzed the data from 58 patients with PTCL who were treated in the Department of Hematology at the First Affiliated Hospital of Nanjing Medical University from January 2015 to July 2022. Chidamide was orally administered as a maintenance therapy after first-line or salvage treatment. Progression-free survival (PFS), overall survival (OS), and safety were analyzed.Results:Among the 58 patients with PTCL, 43 were males and 15 were females, and the median age was 66 (range: 29-83) years. Thirty-nine patients received thioamide as first-line maintenance therapy, and 19 patients received thioamide as maintenance therapy after salvage treatment. The median maintenance therapy duration was 16 months (range: 1-72 months), with a median PFS time of 33 (2-74) months, and the median OS time had not been reached. Patients who received first-line maintenance therapy with thioamide demonstrated superior PFS and OS outcomes compared with patients who received thioamide maintenance therapy after salvage treatment (median PFS time: not reached vs 7 months, P<0.001; median OS time: not reached vs 67 months, P=0.009). The most prevalent adverse reaction was a hematologic adverse reaction (77.6%). Twelve (20.7%) patients underwent a dose reduction and three patients discontinued treatment. Conclusion:Patients receiving thioamide maintenance therapy demonstrated a promising PFS and OS with a manageable safety profile, especially as the first-line maintenance therapy.

Humans ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Lymphoma, Non-Hodgkin/drug therapy* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols