Background: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive non-Hodgkin lymphoma. Currently, high-dose methotrexate (HD-MTX)-based chemotherapy remains the standard first-line treatment. Previous clinical trials have reported that fotemustine-containing regimens offer promising efficacy and tolerability as an alternative option. Objectives: To compare the efficacy, safety, and feasibility of fotemustine-containing regimens with HD-MTX-containing regimens for newly diagnosed PCNSL. Design: A single-center, retrospective cohort study. Methods: We retrospectively analyzed 114 newly diagnosed PCNSL patients treated between April 2011 and December 2021. Patients were classified into two cohorts: those receiving fotemustine-containing regimens ( n = 72) and those receiving HD-MTX-containing regimens ( n = 42). The primary efficacy endpoint was the objective response rate (ORR). Secondary endpoints included complete response rate, progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: No significant difference in ORR was observed between the fotemustine-containing group and HD-MTX-containing group (68% vs 67%, p = 0.879). At a median follow-up of 28.5 months, the survival outcomes were comparable, with no statistically significant differences in either PFS (hazard ratio (HR) = 0.887, 95% confidence interval (CI): 0.522–1.508; p = 0.654) or OS (HR = 0.966, 95% CI: 0.494–1.888; p = 0.918). Notably, fotemustine-based therapy was associated with significantly fewer AEs, including leukopenia, thrombocytopenia, digestive tract toxicity, and mucositis (all p < 0.05). Conclusion: Fotemustine-containing chemotherapeutics appear to confer a safer profile with comparable efficacy relative to HD-MTX-based regimens in newly-diagnosed PCNSL patients.

Background: Approximately 60% of patients with large B-cell lymphoma (LBCL) achieve cure with standard first-line (1L) therapies, such as R-CHOP or DA-EPOCH-R. However, 10% of patients remain refractory to 1L treatment, and 30% of responders experienced relapse within two years. Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, is approved for the treatment of patients with relapsed/refractory LBCL. Furthermore, ZUMA-12, a multicenter phase 2 study investigating axi-cel as part of 1L treatment of high-risk LBCL patients, demonstrated high and durable response rates. With a median follow-up of 40.9 months, axi-cel achieved an objective response rate (ORR) of 92%, complete response (CR) rate of 86%, with responses ongoing in 73% of response-evaluable patients. This study aims to explore the efficacy and safety of CAR-T as consolidation in 1L treatment responders with high risk of relapse. Methods: This real-world case series study enrolled patients with B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), who received axi-cel as consolidation therapy after achieving CR or partial response (PR) to 1L treatment. Efficacy endpoints included complete metabolic response (CMR), 18-month overall survival (OS) rate, and progression-free survival (PFS) rate. Safety endpoints comprised the incidence of adverse events (AEs) including cytokine release syndrome (CRS), leukopenia, thrombocytopenia, and abnormal liver function. Additionally, this study explored the impact of post-infusion maintenance therapy on CAR-T cell expansion. Results: A total of 5 patients were enrolled in this study, with a median age of 66 years and a male-to-female ratio of 3:2. The lymphoma subtypes included 2 cases of non germinal center B-cell-like DLBCL (DLBCL-non-GCB), 2 cases of germinal center B-cell-like DLBCL (DLBCL-GCB), and 1 case of MCL. DLBCL patients had at least one of the following high-risk factors: International Prognostic Index (IPI) score≥4 /age-adjusted IPI (aaIPI) ≥2, double expression, or Ki-67 >90%. High-risk features in the MCL patient included advanced age and Ki-67 >30%. All 4 DLBCL patients received R-CHOP or R-CHOP-like regimens as 1L therapy, while the MCL patient received bendamustine and rituximab (BR) as 1L therapy. Leukapheresis was performed prior to initiation of 1L chemotherapy in the MCL patient and 2 DLBCL patients, while the remaining two underwent leukapheresis after 3 and 4 cycles of chemotherapy, respectively. Before lymphodepletion, 2 patients had achieved CR and 3 achieved PR, and the median time from leukapheresis to infusion was 95 days. With a median follow-up of 21 months since infusion, the best CMR rate was 100 %, and all patients achieved CMR within one month after infusion. The 18-month OS and PFS rates were both 100%. The median peak CAR-T cell counts were 74.65 cells/μL, and the median CAR-T cell counts at 30 days post-infusion were 7.26 cells/μL. Following infusion, 3 patients received IL-2 monotherapy (n=1) or PD-1 inhibitor combined with IL-2 (n=2). At 6 months post-infusion, CAR-T cells were detectable in the peripheral blood of all 3 treated patients, whereas only one of the 2 patients who did not receive PD-1 inhibitor or IL-2 had detectable CAR-T cells. CRS of any grade occurred in 100% of patients (including 1 case of capillary leak syndrome), with no grade ≥3 CRS and no incidence of immune effector cell-associated neurotoxicity syndrome (ICANS). The median time from CAR-T cell infusion to the onset of CRS was 4 days, and the median time from CRS onset to resolution was 3 days. After infusion, the incidence rates of grade ≥3 leukopenia, grade ≥3 thrombocytopenia, and liver dysfunction were 60%, 20%, and 60%, respectively. Conclusions: Consolidation therapy with CAR-T following 1L treatment demonstrated encouraging rates of CMR, PFS, and OS in B-cell lymphoma patients with high risk of relapse. Administration of PD-1 inhibitors and/or IL-2 post-infusion may support sustained expansion and persistence of CAR-T cells. The safety profile was manageable: all CRS were mild, and no ICANS were observed, providing a valuable insight for CAR-T consolidation following 1L treatment. However, the small sample size of this study warrants validation in a larger cohort study.

OBJECTIVE:To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS:Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS:The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION:The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.

The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456-2.785; P = 0.456, HR 0.685, 95%CI 0.256-1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188-11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163-1.117; P = 0.014, HR 0.317, 95%CI 0.113-0.887). By COX analysis, poor baseline performance status (ECOG-PS >= 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.

Background: High-dose methotrexate (HD-MTX)-based chemotherapy followed by whole-brain radiotherapy is the most commonly used approach for patients with newly diagnosed Primary central nervous system lymphoma (PCNSL). However, HD-MTX is a hospital-based drug requiring adequate fluid management and may not be well tolerated in elderly patients with an increased prevalence of comorbid illness. Fotemustine is a third-generation nitrosourea, which is easily penetrated through the blood-brain barrier (BBB) due to its high fat-soluble and low molecular weight, and is indicated for primary brain tumors and disseminated malignant melanoma. Our Center has innovatively conducted three prospective clinical trials using fotemustine-based regimens for the treatment of newly diagnosed PCNSL patients (Wu J et al, J Neurooncol 2018, Wu J et al, Cancer Biol Med 2021, Zhang X et al, ASH 2022), the results of the above studies suggest that the fotemustine-containing regimen has efficacy in the treatment of newly diagnosed PCNSL and has few toxic side effects. Therefore, this study increased the sample size, extended the follow-up time and set up a control group to analyze the efficacy and safety of fotemustine-containing regimens compared with HD-MTX-containing regimens in the treatment of newly diagnosed PCNSL patients. Methods: From April 2011 to December 2021, 114 patients with newly diagnosed PCNSL who received HD-MTX-containing regimens (HD-MTX plus cytarabine [HD-MA], rituximab, HD-MTX plus temozolomide [R-MT]) or fotemustine-containing regimens (fotemustine, teniposide plus dexamethasone [FTD], fotemustine, temozolomide plus dexamethasone [FVD], rituximab, fotemustine, pemetrexed plus dexamethasone [RFPD]) were retrospectively analyzed in this study. Among them, 27 and 15 patients received the HD-MA and R-MT protocol, respectively; 15, 12, and 45 patients received the FTD, FVD and R-FPD protocol, respectively. Results: Of the 114 patients, the objective response rate (ORR) did not differ significantly between the HD-MTX-containing group and the fotemustine-containing group (67% vs 68%, P=0.879). The median follow-up time for 114 patients was 28.5 months (range 2-122 months). Neither the progression free survival (PFS) (P=0.783) nor the overall survival (OS) (P=0.918) exhibited remarkably difference between HD-MTX-containing group and fotemustine-containing group. Notably, we noted that patients treated with HD-MTX-containing regimens experienced more serious adverse events, including leukopenia, anemia, thrombocytopenia, digestive tract toxicity, and mucosis (all P < 0.05) than those undergoing fotemustine-containing therapeutics. Conclusion: Fotemustine-based chemotherapeutics conferred a safer effect on newly-diagnosed PCNSL patients compared with HD-MTX-containing regimens together with comparable efficiency.

Objective To retrospectively evaluate the clinical efficacy and safety of brentuximab vedotin(BV) combined with chemotherapy in the treatment of malignant lymphoma. Methods We collected the data of 32 lymphoma patients with CD30-positive status, including 14 cases of Hodgkin's lymphomas, 2 cases of diffuse large B-cell lymphomas, and 16 cases of mature T/NK cell lymphomas. Chemotherapy combined with BV was administered to all patients for a minimum of two cycles. The efficacy of the treatment was evaluated according to Lugano criteria every two cycles. Results Complete response rate and overall response rate after four cycles of treatment were 22% and 50%, respectively. Sixteen cases (50.0%) had grades 1 and 2 toxicity, and 16 cases (50.0%) had grade 3 toxicity or higher. The most common adverse events were neutropenia (50.0%), pneumonia (46.9%), and anemia (43.8%). The most common grade 3 or higher adverse events were pneumonia (18.8%) and febrile neutropenia (12.5%). Four patients discontinued brentuximab vedotin because of severe adverse events. Conclusion BV is effective in treating relapsed and refractory CD30- positive Hodgkin's lymphoma and peripheral T-cell lymphoma, and its overall safety is acceptable.

Background: Extranodal Natural Killer/T Cell Lymphoma (ENKTL) is a highly aggressive form of non-Hodgkin lymphoma (NHL), primarily found in Asia and commonly linked to Epstein-Barr virus (EBV) infection. Despite the treatment efficacy for early stage ENKTL has been improved in recent years, there is no consistent approach for clinical treatment. Current guidelines includes radiotherapy (RT) alone, concurrent chemoradiation therapy (CCRT), sequential chemoradiation, and sandwich chemoradiation. Here we present the final results of the efficacy and safety of sequential therapies of DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen or VIPD (etoposide, ifosfamide, cisplatin and dexamethasone) regimen combined with RT, and RT alone. M ethods: We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of sequential chemotherapy (DDGP vs VIPD regimen) followed by RT, sequential RT followed by chemotherapy, and RT alone in eligible patients with newly diagnosed stage I/II ENKTL. Upon study entry, patients were randomized 1:1:1:1:1 to receive either DDGP regimen followed by RT (DDGP+RT), or VIPD regimen followed by RT (VIPD+RT), or RT followed by DDGP regimen (RT+DDGP), or RT followed by VIPD (RT+VIPD), or RT alone. Patients assigned to the DDGP group were administered cisplatin (20 mg/m 2, intravenous, days 1-4), dexamethasone (15 mg/m 2, intravenous, days 1-5), gemcitabine (800 mg/m 2, intravenous, on days 1 and 8), and pegaspargase (2500 IU/m 2, intramuscular, on day 1). Those in the VIPD group received etoposide (100 mg/m 2, intravenous, days 1-3), ifosfamide (1.2 g/m 2, intravenous, days 1-3), cisplatin (33 mg/m 2, intravenous, days 1-3), and dexamethasone (40mg, intravenous, days 1-4). Both the DDGP and VIPD regimens were repeated every 21 days. For the sequential chemotherapy followed by RT group, patients underwent 3 cycles of either DDGP or VIPD regimen, followed by 50 Gy (2 Gy * 25 times) of intensity modulated radiotherapy (IMRT). In the sequential RT followed by chemotherapy group, patients were first given 50 Gy (2 Gy * 25 times) of IMRT and then sequential either DDGP or VIPD regimen. Meanwhile, the RT alone group received 50 Gy (2 Gy * 25 times) of IMRT only. The primary end point of our study was progression free survival (PFS), with secondary end points including complete remission rate (CRR), objective response rate (ORR), overall survival (OS). R esults: Our study, spanning January 2011 to August 2020, involved 244 patients from 22 centers across China, with 200 randomly assigned to receive treatment (40 in each group). Both the demographic and disease characteristics of the patients at baseline were generally consistent across all treatment groups. During a median follow-up of 72.1 months, the median PFS (mPFS) was not reached in neither the DDGP + RT nor RT + DDGP groups, compared to 36.3 months in the VIPD + RT group, 78.3 months in the RT + VIPD group, and 89.6 months in the RT alone group. The 5-year PFS rates for the DDGP + RT, VIPD + RT, RT + DDGP, RT + VIPD, and RT alone groups were 81.5%, 46.1%, 79.8%, 53.1%, and 57.5% respectively. Similarly, the 10-year PFS rates were 81.5%, 42.8%, 74.1%, 45.9%, and 45.7% respectively. Compared with RT alone, PFS was improved in DDGP + RT group (p = 0.006) and RT + DDGP group (p = 0.024). Compared with VIPD + RT, PFS was improved in DDGP + RT group (p = 0.006) and RT + DDGP group (p = 0.026). Either between DDGP +RT and RT + DDGP group or between VIPD +RT and RT +VIPD group, PFS showed no differences. Median OS was not reached in 5 groups. OS showed no differences in 5 groups (p = 0.27). The patients who failed from either VIPD regimen or RT alone received DDGP regimen. This might be the reason why the OS showed no differences between 5 groups. The CRRs of 5 groups (DDGP + RT, VIPD +RT, RT + DDGP, RT +VIPD, RT alone) were 87.5%, 57.5%, 82.5%, 69.2%, and 67.5%, respectively. Similarly, the ORRs were 97.5%, 77.5%, 90.0%, 74.4%, and 87.5%, respectively. Conclusions: The DDGP regimen exhibited promising outcomes in this randomized clinical trial for newly diagnosed early-stage ENKTL patients. The sequential therapies with DDGP regimen could improve the efficacy compared with RT alone. Patients could also benefit more from therapies with DDGP regimen than those with VIPD regimen. The order in which chemotherapy and RT were applied has no fatal impact on the prognosis of early-stage ENKTL.

Extranodal natural killer (NK)/T-cell lymphoma (NKTL) is a rare non-Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5-year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T-cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected.

目的 探讨多学科综合治疗联合三轨教学法在肿瘤内科临床教学中的使用效率及其可操作性.方法选取2020 年 8 月至2023 年4 月在郑州大学第一附属医院肿瘤内科轮转的研究生、留学生、进修生及规培生 60名作为研究对象,随机均分为观察组和对照组,每组 30 名.教学时长 12 学时,教学内容为肿瘤内科诊断与治疗.观察组实施MDT联合三轨教学法,对照组实施传统教学法,随后进行临床考核及问卷调查,比较 2 组考试成绩和对教学质量的评价.结果 观察组基础理论、病例分析、综合评分成绩均高于对照组(t=3.764,P＜0.001;t= 8.667,P＜0.001;t=9.941,P＜0.001).观察组课堂气氛活跃、自主学习能力提高、理论知识增加、理论联系实际能力提高、培养临床思维、文献检索与分析能力提高、获得与理解信息能力提高、团队协作能力提升、满意目前教学模式、继续接受该教学模式的满意度均高于对照组(χ2 =13.871,P＜0.001;χ2 =18.373,P＜0.001;χ2 =14.067,P＜0.001;χ2 =11.915,P＜0.001;χ2 =8.531,P＜0.001;χ2 =15.152,P＜0.001;χ2 =11.915,P＜0.001;χ2 =21.991,P＜0.001;χ2 =24.754,P＜0.001;χ2 =30.240,P＜0.001).结论 在肿瘤内科临床教学中应用MDT联合三轨教学法,提高了教学质量和效果,可行性强,值得推广.

To investigate the efficacy and safety of the FEAC (fotemustine, etoposide, cytarabine, and cyclophosphamide) conditioning regimen for the treatment of lymphoma, we retrospectively analyzed the records of 76 Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent autologous stem cell transplantation (ASCT) after the FEAC conditioning regimen. Their survival, as well as the clinical efficacy, hematopoietic engraftment time, and toxicity, were analyzed. One patient died of severe pulmonary infection, and the transplant-related mortality (TRM) was 1.3% (1/76). Hematopoietic engraftment was achieved successfully in the remaining 75 patients. The median times of neutrophil and platelet engraftment were 11 d (6-21 d) and 13 d (8-24 d), respectively. The 2-year progression-free survival (PFS) rate was 69.1%, and the 2-year overall survival (OS) rate was 84.2%. FEAC conditioning regimen has acceptable toxicity, and the prognosis of patients is good, making it a feasible alternative to the BEAM regimen for ASCT.

目的 探讨红细胞分布宽度(RDW)、血红蛋白/红细胞分布宽度比值(HRR)与霍奇金淋巴瘤(HL)患者临床特征及预后的关系.方法 回顾性分析2014年1月至2021年1月郑州大学第一附属医院收治的292例HL患者的临床资料.采用受试者工作曲线(ROC)确定RDW、HRR的最佳临界值,比较分析RDW、HRR与HL临床特征的关系,Kaplan-Meier曲线和long rank检验绘制并比较不同水平HRR患者的总生存(OS)和疾病无进展生存(PFS),单因素及多因素Cox比例风险回归模型分析影响HL预后的风险因素.结果 ROC曲线确定RDW、HRR的最佳临界值分别为15.25、8.85.RDW≥15.25、HRR＜8.85与结外侵犯、高IPS评分、低血红蛋白、低淋巴细胞、低白蛋白等预后不良因素密切相关.Kaplan-Meier生存曲线显示RDW≥15.25、HRR＜8.85组的OS、PFS更差.多因素Cox比例风险回归模型分析结果显示,HRR为PFS的独立预测因素.结论 初诊时低HRR与HL患者不良预后密切相关.

Importance The L-asparaginase-based SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen has shown higher response rates and survival benefit over an anthracycline-containing regimen. However, the safety profile was not satisfied. A well-tolerated regimen with promising efficacy is lacking. Objective To compare the efficacy and safety of the DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen with the SMILE regimen in newly diagnosed advanced-stage (III/IV) extranodal natural killer/T-cell lymphoma (ENKL). Design, Setting, and Participants This was an open-label, multicenter, randomized clinical trial that took place across 12 participating hospitals in China from January 2011 to February 2019. Patients were eligible if they were 14 to 70 years old with newly diagnosed ENKL in stages III/IV and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Eligible patients were evenly randomized to either the DDGP or SMILE group. Interventions Patients in each group were treated with the assigned regimen every 21 days for 6 cycles. Main Outcomes and Measures The primary end point was progression-free survival (PFS), and secondary end points included overall response rate and overall survival (OS). The adverse events between the DDGP and SMILE groups were compared. Results Among the 87 randomized patients, 80 received treatment (40 in the DDGP group and 40 in the SMILE group); the median (IQR) age was 43 (12) years, and 51 (64%) were male. The baseline characteristics were similar between the groups. At a median follow-up of 41.5 months, the median PFS was not reached in the DDGP group vs 6.8 months in the SMILE group (HR, 0.42; 95% CI, 0.23-0.77; P = .004), and the median OS was not reached in the DDGP group vs 75.2 months in the SMILE group (HR, 0.41; 95% CI, 0.19-0.89, P = .02). The PFS rate at 3 years and OS rate at 5 years were higher in the DDGP group vs the SMILE group (3-year PFS, 56.6% vs 41.8%; 5-year OS, 74.3% vs 51.7%). The overall response rate was higher in the DDGP group than in the SMILE group (90.0% vs 60.0%; P = .002). Grade 3 and 4 hematologic toxic effects were more frequently reported in the SMILE group vs the DDGP group (leukopenia, 85.0% vs 62.5%; neutropenia, 85.0% vs 65.0%). Conclusions and Relevance In this randomized clinical trial, the DDGP regimen showed promising preliminary results for patients with newly diagnosed local advanced ENKL. A confirmation trial based on larger population is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT01501149.

NK/T cell lymphoma (ENKTCL) is a rare subtype of non-Hodgkin’s lymphoma, and previous studies report that the incidence of central nervous system (CNS) invasion is about 5%-6%. CNS involvement is a critical and fatal complication, however, due to the rarity, the clinical course and treatment strategies are still unclear. This article reports 3 cases of brain metastasis of ENKTCL in our hospital, hoping to provide information for diagnosis and treatment.

PURPOSE:To explore the best treatment for early natural killer/T (NK/T)-cell lymphoma, we compared the efficacy and safety of DDGP (pegaspargase, gemcitabine, cisplatin and dexamethasone) followed by radiotherapy (RT) and VIPD (etoposide, ifosfamide, cisplatin, and dexamethasone) followed by radiotherapy for newly diagnosed patients. MATERIALS AND METHODS:40 newly diagnosed patients with stage I-II from January 2011 to November 2016 were treated with DDGP followed by radiotherapy or VIPD followed by radiotherapy. They were assessed in this study. RESULTS:The complete response rate (CRR) and overall response rate (ORR) of the DDGP followed by radiotherapy group were higher than those of the VIPD followed by radiotherapy group (CRR: 85 % vs 50 %, P = 0.018; ORR: 95 % vs 65 %, P = 0.048). The 5-year progression-free survival (PFS) rate was better in the DDGP followed by radiotherapy group (83.3 % vs 44.4 %, χ2 = 7.809, P = 0.005). There was no significant difference in the 5-year overall survival (OS) rate between the two groups (83.0 % vs 72.1 %, χ2 = 0.231, P = 0.631). Treatment method (P = 0.011) and IPI score (P = 0.027) were independent risk factors for PFS. The DDGP followed by radiotherapy group was more prone to grade I-II clotting dysfunction (P = 0.004). CONCLUSIONS:In patients newly diagnosed with early NK/T-cell lymphoma, those treated with DDGP followed by radiotherapy had a higher CRR and ORR and longer PFS than those treated with VIPD followed by radiotherapy, and adverse reactions were tolerable.

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by poor prognosis after frontline immunochemotherapy. This retrospective study investigated the effect of consolidative radiation after systemic treatment in newly diagnosed stage I-II de novo CD5+ DLBCL. In this study, 22 patients received consolidative radiotherapy (RT) after immunochemotherapy (chemotherapy + RT group) and 28 patients received chemotherapy alone. Patients who received chemotherapy alone had a significantly shorter PFS and OS than those who received consolidative radiotherapy. The five-year PFS rates for the chemotherapy + RT and chemotherapy alone groups were 75.1% and 40.5%, respectively. The five-year OS rates for the chemotherapy + RT and chemotherapy alone groups were 84.2% and 50.1%, respectively. Even after receiving consolidation radiotherapy, 2/22 (9.1%) patients experienced CNS relapse. Age >60 years and lack of radiotherapy were independent prognostic factors for PFS and OS. Ki-67 (≥80%) was an independent prognostic factor for poor OS. Consolidative radiotherapy might be a good option for stage I-II CD5+ DLBCL, but further investigation is needed.

The emergence of chimeric antigen receptor (CAR) T cell therapy has shifted the paradigm of malignant tumor treatment, especially the advent of CD19-directed CAR-T cell therapy for the treatment of relapsed/refractory (R/R) B-cell malignancies. Although CAR-T cell therapy has promising effects, some patients are resistant to this treatment, leaving them with limited options. Therefore, strategies to overcome resistance to CAR-T cell therapy are needed. We retrospectively studied three R/R diffuse large B-cell lymphoma patients who were resistant to CAR-T cell therapy and whose disease was controlled after receiving pembrolizumab, 21D4 CAR-T cells, or ibrutinib and venetoclax. Some promising prevention and treatment strategies to overcome treatment resistance are also discussed.

To investigate the clinical characteristics and prognostic factors of natural killer/T-cell lymphoma (NKTCL). We retrospectively reviewed 410 NKTCL patients admitted to our lymphoma center from 2000 to 2019. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan–Meier method, and the differences between the study groups were compared by the log-rank test. The median age of the 410 patients was 44 (range 8–84), and the 5-year OS and PFS were 61.2

Background. Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. Methods. Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators’ assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. Results. A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. Conclusion. Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.

Supplementary Figure from Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma

BACKGROUND CD5 expression in different B-cell lymphomas has different clinicopathological and prognosis and the value of CD5 expression in marginal zone lymphoma is undefined. METHODS Clinicopathological features, survival outcomes of marginal zone lymphoma were retrospectively analyzed in 204 patients. We classified patients into (i) CD5-positive marginal zone lymphoma (ii) CD5-negative marginal zone Lymphoma, Fisher's exact test was used to compare the CD5-positive and CD5-negative marginal zone lymphoma. Progression-free survival (PFS) and overall survival (OS) curves were summarized by Kaplan-Meier method and compared using the log-rank test. RESULTS Of the 204 patients, 48 (23.53%) were CD5-positive. The 5-year PFS and OS rates for CD5-positive marginal zone lymphoma were 64.80% and 84.10%, there was no significant difference between CD5-positive and CD5-negative (P > 0.05). Diffuse large B cell lymphoma (DLBCL) transformation was pathologically indicated in 6 patients, of which 5 (83.33%) patients were CD5-positive marginal zone lymphoma. CONCLUSION CD5 expression in marginal zone lymphoma is not relevant to the prognosis of the patients, but CD5-positive marginal zone lymphoma seems more likely to transformation to diffuse large B-cell lymphoma.