乙型肝炎病毒感染与弥漫大B细胞淋巴瘤临床、病理及预后的关系

目的探讨乙型肝炎病毒(HBV)感染与弥漫大B细胞淋巴瘤(DLBCL)临床、病理及预后的关系。方法采用酶联免疫吸附试验(ELISA)检测2004年1月至2013年1月该院收治的150例DLBCL患者的乙肝5项和肝功能,并选取同期住院的其他肿瘤患者150例及门诊健康体检者150例作为对照。结果 DLBCL患者乙型肝炎表面抗原(HBs Ag)的阳性率(22.7%)显著高于其他肿瘤组患者(9.3%)和健康对照组(8.0%)(P<0.05)。HBs Ag阳性组及HBs Ag阴性组DLBCL临床分期、肝脾受累、乳酸脱氢酶(LDH)含量、结节外受累区域和国际预后指数评分(IPI)差异具有统计学意义(P<0.05),且二组患者化疗前后肝功能损伤情况比较亦有统计学差异(P<0.05)。HBs Ag阴性组治疗完全缓解率及生存期均显著高于HBs Ag阳性组(P<0.05)。结论 DLBCL患者HBs Ag阳性率显著高于其他恶性肿瘤患者及健康对照,且HBV感染与DLBCL患者临床病理特征及预后相关。     

复发难治弥漫大B细胞淋巴瘤的二线治疗：自体造血干细胞移植或嵌合抗原受体T细胞治疗?

摘要 弥漫性大B细胞淋巴瘤（DLBCL）是最常见的侵袭性淋巴瘤亚型。一线规范的治疗后,60%的患者可以实现治愈,但是仍有40%的患者复发或者难治,预后不佳。挽救性化疗联合自体造血干细胞移植（ASCT）是化疗敏感患者的标准二线治疗方案。然而,伴随着新的治疗方式,如嵌合抗原受体T细胞疗法、双特异性抗体、靶向药物等的出现,标准二线治疗方案受到一定的挑战,尤其对于挽救性化疗不够敏感的患者。本文对目前复发难治DLBCL的二线治疗的安全性和疗效及适应证进行综述,以探讨复发难治DLBCL的最佳治疗选择。     

自体造血干细胞移植治疗血管内大B细胞淋巴瘤1例

目的探讨血管内大B细胞淋巴瘤（IVLBCL）的诊治。方法报告经自体造血干细胞移植治疗的1例女性IVLBCL患者的诊治经过,并复习相关文献。结果患者经肺活检及肾脏活检病理诊断为IVLBCL。经过R-CHOP方案6个疗程治疗后取得完全缓解,再经R-CHOPE方案1个疗程并动员采集自体外周血干细胞,行R-CBV方案为预处理方案的自体外周血干细胞移植,之后用利妥昔单抗巩固及维持治疗。术后随访25个月,患者持续完全缓解状态。结论本例IVLBCL患者采用R-CHOP联合自体外周血干细胞移植治疗及利妥昔单抗巩固维持取得满意疗效。     

自体移植联合抗CD19 CAR-T治疗难治性弥漫大B细胞淋巴瘤的临床观察研究

目的:评估难治性弥漫大B细胞淋巴瘤(DLBCL)患者接受自体移植和靶向CD19的嵌合抗原受体T细胞(抗CD19 CAR-T)治疗后的疗效和安全性.方法:纳入7例疾病进展的难治性ⅣB期DLBCL患者进行自体移植,自体干细胞回输后第4天回输自体共刺激因子为4-1BB的抗CD19 CAR-T细胞2.0×106/kg(1.0×...     

自体造血干细胞移植治疗恶性淋巴瘤

自体造血干细胞移植（Auto－HSCT）包括外周血和骨髓移植，发展极为迅速，目前已成为治疗有预后不良因素的恶性淋巴瘤（ML）的主要方法。我院1997年8月至今为2名ML患者分别予以自体骨髓移植（ABMT）、自体外周血于细胞移植（APBSCT）＋激活骨髓（ABM）治疗，取得良好疗效。1对象和方法1．1病例介绍例1男，30岁，体重65kg，体表面积1．65m2。因颈部、腹股为淋巴结肿大，诊断为NHLⅢA。组织病理学为弥漫小裂细胞型B细胞性，先后经CHt）P＋Bel、COP、CHOP＋VP－16、HDMTX等轮替化疗7个疗程，并辅赛诺金（a－Zb；干扰素）、…     

自体造血干细胞移植治疗小细胞肺癌

小细胞肺癌（ＳＣＬＣ）对化疗有较高的敏感性，常规化疗有效率为７０％～８０％，但几乎没有被治愈者。现已证明，强烈的化疗可有更高的疗效。自体造血干细胞移植能有效地克服化疗药物所致的造血系统毒性，使ＳＣＬＣ的超大剂量化疗成为可能。１　移植时机与类型为了减少耐药的产生，ＳＣＬＣ患者在化疗（或放疗）获完全缓解（ＣＲ）或部分缓解（ＰＲ）后，应尽早进行干细胞移植治疗。因为此时除了肿瘤细胞易被杀灭外，而且造血干细胞受损伤小，质量佳，移植后造血恢复快，而且患者的一般情况和重要脏器功能好、耐受性强，更易度过造血干细…     

老年弥漫大B细胞淋巴瘤50例患者的临床特征和预后分析

目的 探讨老年弥漫大B细胞淋巴瘤（DLBCL）患者的临床特征及预后因素。方法 回顾性分析2010年1月至2013年1月,第四军医大学西京医院血液内科收治的50例年龄≥70岁的老年DLBCL患者,收集整理年龄、Ann-Arbor分期、B症状、国际预后指数（IPI）、乳酸脱氢酶（LDH）、β2?微球蛋白、Ki-67等资料进而分析临床特点;采用Kaplan-Meier法进行生存分析,并进行单因素分析评估预后。结果 50例初发老年DLBCL患者中,60%患者为Ⅲ～Ⅳ期,54% IPI评分为3～5分,52%有B症状,75%原发部位为结外。在老年患者中,调整剂量的化疗疗效优于放疗及对症支持治疗。利妥昔单抗联合剂量调整化疗（R-CHOP）组完全缓解（CR）率优于不包括利妥昔单抗的剂量调查化疗（CHOP/COP）组。患者中位生存时间为 8个月,1、2、3年总生存率分别为48.5%、30.8%、11.5%。生存分析发现Ki-67对患者生存有显著的影响,尤其是Ki-67＞80%患者预后差。结论 老年患者以疾病分期晚,易合并其他系统疾病,生存期短为特征,具有更高的DLBCL发病率,Ki-67是一个重要的不良预后指标。R-CHOP方案可明显提高CR率,并且足够疗程的化疗将显著改善超高龄患者的生存期。     

弥漫大B细胞淋巴瘤的预后及分层治疗

弥漫大 B 细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤（NHL）,占成人 NHL 的30％～40％。尽管淋巴瘤的治疗已经有很大的进步,仍然有40％的 DLBCL患者死于疾病复发。随着对 DLBCL 临床、病理及分子病理研究的深入,新药物引入 DLBCL 的治疗,需要大样本的随机临床研究来评估新方案的疗效。目前国际预后指数（IPI,表1）已经不能满足临床预后评估。我们将近年来新的对临床及预后有重要影响的预后因素进行概述,以更好地指导临床治疗。     

自体造血干细胞移植治疗老年恶性血液病的疗效和安全性

目的 自体造血干细胞移植是血液系统肿瘤的有效治疗选择,但在老年患者中的应用仍有争议,本文旨在分析自体造血干细胞移植在老年患者中的疗效和安全性。方法 回顾性分析2016年1月—2022年12月在华东医院血液科接受自体造血干细胞移植的患者数据,根据患者年龄分为老年组(≥60岁,n=25)和中青年组(<60岁,n=174),比较2组的外周造血干细胞动员效果、造血重建效果、肿瘤复发率、不良反应发生率和长期预后。结果 与中青年组比较,老年组的造血干细胞动员效果和重建速率差异均无统计学意义(P>0.05),且不加重移植相关的不良反应。长期预后分析显示2组均未达到中位总生存期和中位无进展生存期,2组5年生存率和5年无进展生存率无差异,多因素分析表明年龄不是影响自体造血干细胞移植预后的独立危险因素。结论 自体造血干细胞移植对于体能良好的老年恶性血液病患者是安全有效的治疗选择。     

乙型肝炎病毒感染患者进行异基因造血干细胞移植的安全性评价

目的:对伴有乙型肝炎病毒(HBV)感染的恶性血液病患者抗病毒治疗后进行异基因造血干细胞移植(allo- HSCT)的安全性进行评价.方法:allo- HSCT患者45例,均为HBV感染的恶性血液病患者,移植前感染HBV的患者和供者均给予拉米夫定和(或)阿德福韦/恩替卡韦抗病毒治疗;移植前对HBV-DNA的拷贝数进行评估...     

Allogeneic hematopoietic stem cell transplantation in patients with diffuse large B cell lymphoma relapsed after autologous stem cell transplantation: A GITMO study

Patients who relapse after an autologous hematopoietic stem cell transplantation (SCT) have a very poor prognosis. We have retrospectively analyzed diffuse large B cell lymphoma patients who underwent an allo-SCT after an auto-SCT relapse reported in the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) database. From 1995 to 2008, 3449 autologous transplants were reported in the GITMO database. Eight hundred eighty-four patients relapsed or progressed after transplant; 165 patients, 19% of the relapsed patients, were treated with allo-transplant. The stem cell donor was related to the patient in 108 cases. A reduced intensity conditioning regimen was used in 116. After allo-SCT, 72 patients (43%) obtained a complete response and 9 obtained a partial response with an overall response rate of 49%; 84 patients (51%) experienced rapid progression of disease. Ninety-one patients died, 45 due to disease and 46 due to treatment-related mortality. Acute graft-versus-host disease was recorded in 57 patients and a chronic GvHD in 38 patients. With a median follow-up of 24 months (2-144) after allo, overall survival (OS) was 39%, and after a median of 21 months (2-138) after allo, progression-free survival (PFS) was 32%. Multivariate analysis indicated that the only factors affecting OS were status at allo-SCT, and those affecting PFS were status at allo-SCT and stem cell donor. This retrospective analysis shows that about one-fifth of patients with diffuse large B cell lymphoma who experience relapse after autologous transplantation may be treated with allogeneic transplantation. Moreover, the only parameter affecting either OS or PFS was the response status at the time of allo-SCT.     

Comparison of outcomes after allogeneic hematopoietic stem cell transplantation in patients with follicular lymphoma, diffuse large B-cell lymphoma associated with follicular lymphoma, or de novo diffuse large B-cell lymphoma

The outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT) for diffuse large B-cell lymphoma (DLBCL) associated with follicular lymphoma (FL), which includes DLBCL with pre- or co-existing FL, remains controversial, and few previous reports have compared the outcomes after allo-HCT for FL, DLBCL associated with FL, and de novo DLBCL. We retrospectively analyzed 97 consecutive patients with FL (n = 46), DLBCL associated with FL (n = 22), or de novo DLBCL (n = 29) who received allo-HCT at our institute between 2000 and 2010. With a median follow-up of 53 months, the 5-year overall survival (OS) and progression-free survival (PFS) were, respectively, 77% and 70% for FL, 62% and 57% for DLBCL associated with FL, and 26% and 23% for de novo DLBCL. The 5-year cumulative incidences of non-relapse mortality and disease progression/relapse were, respectively, 16% and 15% for FL, 19% and 24% for DLBCL associated with FL, and 36% and 41% for de novo DLBCL. By a multivariate analysis, the OS and PFS for DLBCL associated with FL were significantly better than those for de novo DLBCL, whereas they were not significantly different from those for FL. These results suggest that allo-HCT may be a promising option for patients with not only advanced FL but also DLBCL associated with FL.     

High-dose therapy and autologous stem cell transplantation for follicular lymphoma undergoing transformation to diffuse large B-cell lymphoma

The transformation of follicular lymphoma (FL) to high-grade histology occurs in up to 70% of patients. The role of hematopoietic stem cell transplantation (HSCT) in transformed FL is poorly defined. Twenty-four FL patients with histologically confirmed transformation to diffuse large B-cell lymphoma underwent unpurged autologous HSCT at our institution. Their median age was 56 yr. The median number of prior chemotherapies was 2 (range 1-6). Thirteen patients had residual nodal disease measuring more than 2 cm and four patients had bulky disease at the time of HSCT. Six patients had refractory disease at transplantation. At a median follow-up of 38 months, 3-yr progression-free survival following autologous HSCT was 40%. The 3-yr overall survival was 52%. The cumulative incidence of relapse and non-relapse mortality rate was 41% and 25%, respectively.     

High-dose therapy and autologous stem cell transplantation in patients with diffuse large B-cell lymphoma in first complete or partial remission

Improved survival has been observed in poor-risk diffuse large B-cell lymphoma (DLBCL) patients treated with high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in first complete remission. Retrospective studies have suggested that HDT with ASCT can improve survival also in partial responders but some doubts about the advantage of intensive therapy in such patients still remain. We evaluated retrospectively the results of HDT and ASCT in 55 patients with confirmed DLBCL treated between May 1999 and July 2006. Thirty-six patients (65%) showed partial remission (PR) and 19 patients (35%) reached complete remission (CR) after induction treatment with (44%) or without (56%) concomitant rituximab (R) immunotherapy. After HDT and ASCT, 69% of patients fulfilled the criteria of CR, 22% had unconfirmed CR (CRu), 7% remained in PR and 1 patient (2%) relapsed. Twenty patients in PR after the induction treatment reached CR after ASCT, 12 other PR patients achieved CRu. The 5-year event-free survival (EFS) of the 55 transplanted patients was 76% (95% confidence interval /CI/, 63% to 89%) and the 5-year overall survival (OS) was 85% (95% CI, 73% to 97%). The EFS and OS rates differed significantly only between patients younger than 40 years and older groups (p=0.022 and p=0.046, respectively). On univariate analysis of prognostic factors, EFS and OS were not affected by any of the following: age, sex, stage, subtype of DLBCL, initial lactate dehydrogenase, beta-2-microglobulin and serum thymidine kinase levels, International Prognostic Index (IPI) and age-adjusted IPI scores, induction treatment with or without rituximab and type of primary therapeutic response (CR vs PR). These results show that first-line HDT and ASCT for adults up to the age of 65 years with poor-risk DLBCL is a feasible and effective treatment option even in the era of R-chemotherapy in CR as well as for patients in PR.     

Dendritic cells in autologous hematopoietic stem cell transplantation for diffuse large B-cell lymphoma: graft content and post transplant recovery predict survival

Allograft dendritic cell (DC) content has been identified as a predictor of relapse and event-free survival after allogeneic bone marrow transplantation. However, the prognostic importance of DCs has not been evaluated in the setting of autologous hematopoietic stem cell transplantation (HSCT). We prospectively determined pre-transplant and post transplant DC levels, including DC1 and DC2 subset levels, in 53 patients with diffuse large B-cell non-Hodgkin's lymphoma (DLBC NHL) undergoing autologous HSCT. Pre-transplant DCs were measured in the collected stem cell products and were therefore indicative of cell numbers infused directly into patients; post transplant analysis of DCs was performed on the peripheral blood of patients 6 weeks after the infusion of autologous stem cells. Higher pre-transplant levels of DC1 cells and total DCs were significantly associated with improved survival. Similarly, greater post transplant levels of total DCs and both subsets were significantly associated with survival. These findings suggest a relationship between DC reconstitution and survival following autologous HSCT for DLBC NHL. Strategies to increase autograft DC content or accelerate DC recovery after autologous HSCT might improve outcomes in this setting.     

Role of hematopoietic stem cell transplantation for advanced-stage diffuse large cell B-cell lymphoma-B

The prognosis of patients with relapsed or refractory diffuse large cell B-cell lymphoma-B (DLCL-B) is poor with conventional salvage chemotherapy; therefore, high-dose therapy (HDT) combined with autologous stem cell transplant (ASCT) has become the treatment of choice for these patients. The outcomes of transplant are better in patients with chemosensitive relapse: those with a longer duration of first remission (>12 month) and those with an age-adjusted low-risk International Prognostic Index (IPI) at relapse. Several high-dose regimens with or without total body irradiation (TBI) have been used with similar outcomes. Relapse remains the most common cause of treatment failure, and thus the use of radioimmunotherapy (RIT) in the high-dose regimens and incorporation of rituximab in the transplant setting have been explored. Several studies have shown that RIT both at conventional dose and at high dose can be given in combination with high-dose chemotherapy regimens without additional toxicity or delay in hematopoietic recovery after ASCT. Additional studies using RIT in combination with high-dose chemotherapy and ASCT are ongoing, and preliminary results suggest that these approaches may be superior to conventional high-dose regimens. Since rituximab is an effective therapy for B-cell non-Hodgkin's lymphoma and given its limited toxicity, rituximab has been incorporated into HDT and ASCT for DLCL-B as in vivo purging, as part of high-dose regimens, and as maintenance therapy to prevent relapse. Preliminary results suggested that rituximab during ASCT and as maintenance therapy post-transplant reduces the risk of relapse and improves survival; however, these results need to be confirmed in phase III randomized trials. The role of ASCT during first remission as consolidative therapy in patients with DLCL-B remains controversial and should not be performed outside of the clinical trial setting. Allogeneic stem cell transplant (allo-SCT) for patients with relapsed DLCL-B is associated with significant toxicity and should be reserved for patients who relapse after ASCT or those with persistent marrow involvement. Innovative approaches are needed for primary refractory and chemoresistant relapsed DLCL-B since these patients have very poor outcomes after ASCT.     

Combination of rituximab with autologous peripheral blood stem cell transplantation for treatment of diffuse large B-cell lymphoma:a single-center experience

Objective To investigate whether incorporation of rituximab into high-dose chemotherapy with autologous peripheral blood stem cell transplantation(auto-PBSCT) could improve the survival of patients with diffuse large B-cell lymphoma(DLBCL),and evaluate the safety of     

Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma

Second-line chemotherapy followed by high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) cures less than half of the patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Prognostic models capable of predicting outcome are essential. In 3 sequential clinical trials, conducted from January 1993 to August 2000, we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease. We evaluated the age-adjusted International Prognostic Index at the initiation of second-line therapy (sAAIPI) as a predictor of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 4 years, the PFS and OS are 28% and 34% by intention to treat and 39% and 45% for only those patients with chemosensitive disease. Three risk groups with different PFS and OS were identified by the sAAIPI: low risk (0 factors), 70% and 74%; intermediate risk (1 factor), 39% and 49%; and high risk (2 or 3 factors), 16% and 18% (P <.001 for both PFS and OS). The sAAIPI also predicts the PFS and OS for patients with ICEchemosensitive disease: low risk, 69% and 83%; intermediate risk, 46% and 55%; and high risk, 25% and 26% (P <.001 PFS and OS). The sAAIPI predicts outcome for patients with relapsed or primary refractory DLBCL in both intent-to-treat and chemosensitive populations. This powerful prognostic instrument should be used to evaluate new treatment approaches and to compare results of different regimens.     

Early-stage splenic diffuse large B-cell lymphoma is highly associated with hepatitis C virus infection

Splenic marginal zone lymphoma (SMZL) and splenic diffuse large B-cell lymphoma (DLBCL) are the most common types of lymphomas involving the spleen. Geographic variation in hepatitis C virus (HCV) seroprevalence is characteristic of splenic lymphomas. In Italy, HCV seroprevalence was higher in patients with SMZL and splenic DLBCL than in patients with all types of lymphoma. In Japan, HCV seroprevalence was higher in patients with splenic DLBCL than in patients with all types of lymphoma; however, HCV seroprevalence in patients with SMZL was similar to that in patients with all types of lymphoma. In this study, clinicopathological data of 74 splenic lymphoma cases between 1988 and 2011 collected from the Department of Pathology at National Taiwan University Hospital were analyzed. Serology for HCV infection was available for 41 cases. Splenic DLBCL and SMZL accounted for 36% (n = 27) and 42% (n = 31) of splenic lymphomas, respectively. Microscopically, most cases of DLBCL (26/27) presented with circumscribed tumor and most cases of SMZL (28/31) presented with white pulp expansion. HCV seroprevalence in patients with DLBCL and SMZL was 44% and 10%, respectively (7/16 vs. 2/20, p = 0.020). The pattern identified in this study is closer to that in Japan than in Italy. HCV seroprevalence in patients with early-stage (I/II) and late-stage (III/IV) DLBCL was 100% and 10%, respectively (6/6 vs. 1/10, p < 0.001). Early-stage DLBCL is clinically considered a form of primary splenic lymphoma rather than a systemic lymphoma with splenic involvement. High HCV seroprevalence in patients with early-stage DLBCL suggests a role of HCV in the pathogenesis of primary DLBCL.