利妥昔单抗治疗非霍奇金淋巴瘤20例

目的 探讨利妥昔单抗治疗B细胞非霍奇金淋巴瘤(NHL)的疗效、安全性.方法 共20例患者,初治18例,复治2例.利妥昔单抗单用1例;应用利妥昔单抗联合化疗19例,其中用于自体造血干细胞移植(APBSCT)体内净化治疗8例,维持治疗4例.结果 初治者单药治疗完全缓解1例,利妥昔单抗联合化疗完全缓解(CR)率82.4%(14/17),2例部分缓解(PR),总有效率94.1%;复治组中1例CR,1例PR;移植组中未观察到利妥昔单抗对采集的干细胞质量和数量以及移植后造血恢复有不良影响;维持治疗组4例全部生存,最长随访57个月.结论利妥昔单抗治疗NHL安全、有效,不论单用还是联合化疗对B细胞NHL均有良好疗效,可作为APBSCT的体内净化药物.     

套细胞淋巴瘤治疗进展

 套细胞淋巴瘤是一种难以治愈的非霍奇金淋巴瘤亚型。对加用利妥昔单抗高剂量化疗、放射免疫治疗、自体干细胞移植、异基因干细胞移植以及靶向治疗进展进行了综述。常规化疗疗效差,加用利妥昔单抗联合化疗方案大剂量治疗能够提高疗效,放射免疫治疗有一定潜力。自体干细胞移植能够改善生存,复发患者可以考虑行非清髓异基因移植。多种靶向治疗进入临床试验,具有一定疗效。     

利妥昔单抗净化动员B细胞非霍奇金淋巴瘤外周血干细胞的初步研究

 目的 观察利妥昔单克隆抗体（Rituximab,利妥昔单抗）对B细胞非霍奇金淋巴瘤（NHL）患者外周血干细胞（PBSCs）净化动员的作用。方法 8例CD+20 B细胞NHL患者,在应用CHOP类化疗±利妥昔单抗4～6疗程诱导／巩固治疗后进行大剂量环磷酰胺（HD-CTX）+粒细胞集落刺激因子（G-CSF）联合利妥昔单抗（375 mg·m-2·d-1,第-1,7天）体内净化动员PBSCs。观察利妥昔单抗副反应、骨髓抑制期及相关并发症、PBSCs采集时间、数量以及采集物肿瘤标志物基因等。结果 在外周血干细胞动员过程中仅1例患者发生轻度利妥昔单抗相关的皮疹。PBSCs平均采集时间为CTX应用后（11.6±1.0）d,中位采集次数2（1～3）次。采集物平均单个核细胞（MNC）（3.4±1.0）×108／kg,平均CD+34细胞数（3.6±1.7）×106／kg。5例完成移植患者中3例移植后IgH／TCR转为阴性,1例治疗前后均为阴性,1例早期复发。4例无病生存。结论 利妥昔单抗不影响B细胞NHL患者PBSCs的动员效果,安全性好,并能加强体内净化作用。     

自体造血干细胞移植联合利妥昔单抗治疗CD+20B细胞淋巴瘤

 采用自体造血干细胞移植（AHSCT）治疗中,高危侵袭性淋巴瘤已获得了较好疗效,但仍有部分移植患者因复发而死亡。复发的根源主要为微小残留病变,包括体内残留的肿瘤细胞和移植物中的肿瘤细胞污染。利妥昔单抗可靶向性清除CD+20 B细胞,因此,对CD+20 B细胞淋巴瘤患者,移植前后应用利妥昔单抗可起到体内净化和清除残留病灶作用,AHSCT联合利妥昔单抗有望进一步提高CD+20 B细胞淋巴瘤的疗效。     

利妥昔单抗治疗弥漫大B细胞淋巴瘤诱发急性肿瘤溶解综合征一例并文献复习

目的 提高对利妥昔单抗诱发急性肿瘤溶解综合征（ATLS）的认识.方法 回顾性分析1例利妥昔单抗治疗弥漫大B细胞淋巴瘤诱发ATLS患者的临床资料并复习相关文献.结果 患者ATLS确诊后,立即暂缓化疗,补液、碱化尿液,但患者肾功能持续恶化,后经血液透析,肾功能逐渐恢复正常.2周后患者再次接受R-CHOP方案化疗,未再发生ATLS.经外周血造血干细胞移植,患者淋巴瘤完全缓解.结论 在应用利妥昔单抗治疗血液系统恶性肿瘤时需警惕肿瘤溶解综合征的发生,及时诊治可使患者获得较好预后.     

利妥昔单抗联合化疗治疗弥漫型大B细胞淋巴瘤的临床观察

目的: 探讨利妥昔单抗联合化疗治疗弥漫型大B细胞淋巴瘤患者的临床疗效和安全性.方法: 回顾性分析100例病理确诊为弥漫型大B细胞淋巴瘤患者的临床资料.所有患者均接受2～8次的利妥昔单抗治疗,利妥昔单抗的平均治疗次数为5.8次.同时,所有患者均接受了化疗.评价疗效和不良反应.结果: 100例患者中达完全缓解者46例(46%).达部分缓解者37例(37%),总有效率(完全缓解+部分缓解)为83%(83/100).红细胞沉降率、国际预后指数评分、是否为初治患者、B症状以及利妥昔单抗治疗周期数对疗效有显著影响(P<0.05),而性别、年龄、原发部位和功能状态评分对疗效无影响(P>0.05).1、2、3和5年生存率分别为87.5%、72.8%、60.8%和60.8%.COX回归模型多因素分析发现,国际预后指数评分、利妥昔单抗治疗周期数和治疗后的疗效对生存的影响有统计学意义(P<0.05).100例患者中共有11例因静脉输注利妥昔单抗而发生输液不良反应.结论: 利妥昔单抗联合化疗治疗弥漫型大B细胞淋巴瘤的临床缓解率较高,患者酎受良好且生存时间较长.     

自体干细胞移植联合利妥昔单抗治疗弥漫大B细胞淋巴瘤八例

目的观察自体干细胞移植（Auto—SCT）联合利妥昔单抗治疗弥漫大B细胞淋巴瘤（DLBCL）疗效。方法对Auto—SCT联合利妥昔单抗治疗DLBCL患者的疗效进行分析。8例CD;0DLBCL患者,化疗达CR后经巩固治疗,用环磷酰胺＋G—CSF动员后进行Auto—SCT,造血功能重建后予利妥昔单抗500mg静脉滴注,每周1次,连续2次,2个月后重复一次。出院后定期随访,用Karnosky评分标准评价生活质量。结果8例患者造血功能完全重建。予利妥昔单抗后除2例白细胞及1例血小板减少外,均无其他不良反应。随访2～6年,8例患者均无病生存,Karnosky评分100分。结论Auto—SCT联合利妥昔单抗是治疗DLBCL的有效方法,可降低移植后复发,提高长期生存率。     

利妥昔单抗联合CHOP方案治疗B细胞非霍奇金淋巴瘤的临床分析

目的 观察利妥昔单抗联合CHOP方案治疗CD20阳性B细胞非霍奇金淋巴瘤的临床疗效及毒副反应.方法 8例B细胞非霍奇金淋巴瘤均采用利妥昔单抗联合化疗,利妥昔单抗375 ms/m2于每1周期化疗前1天静脉滴注,每3周为1疗程,4～6周期后评价疗效及毒副反应.结果 8例患者中,CR 7例,PR 1例,总有效率100%.主要...     

利妥昔单抗联合化疗治疗弥漫大B细胞淋巴瘤临床分析

 目的　观察利妥昔单抗（商品名：美罗华）联合化疗治疗弥漫大B细胞淋巴瘤（DLBCL）的临床疗效及淋巴瘤国际预后指数（IPI）评分对预后的影响;探讨利妥昔单抗在DLBCL自体外周血干细胞移植（APBSCT）中的应用。方法　DLBCL 患者21例,IPI评分低危和中低危（0～2分）14例,中高危和高危（3～5分）7例。采用利妥昔单抗联合CHOP（环磷酰胺、多柔比星、长春新碱、泼尼松）方案4～8个疗程,其中有5例接受APBSCT,动员方案为利妥昔单抗联合环磷酰胺加依托泊苷,预处理方案为CBV （环磷酰胺、卡莫司汀、依托泊苷）方案。结果　21例患者中CR 13例（61.9 %）,总有效率90.5 %（19／21）;2年疾病无进展生存率为（69.74±10.43）%,2年总生存率为（84.44±8.35）%。IPI评分0～2分患者CR率92.9 %,总有效率100 %,3～5分患者CR率0,总有效率71.4 %,IPI 0～2分患者CR率高于3～5分患者（P＜0.01）;5例接受APBSCT的患者采集的中位单个核细胞（MNC）为7.34×108／kg,中位CD+34细胞为8.82×106／kg,造血恢复中性粒细胞＞0.5×109／L的中位时间＋9天,血小板＞20×109／L的中位时间＋12天;主要不良反应是输注相关的不良反应（14.3 %）以及化疗相关的血液学不良反应。结论　利妥昔单抗联合化疗治疗DLBCL疗效满意,IPI 0～2分患者的完全缓解率明显高于3～5分患者;利妥昔单抗不影响外周造血干细胞的采集及造血重建;利妥昔单抗应用安全性较好。     

抗CD20单克隆抗体联合自体外周血干细胞移植治疗非霍奇金淋巴瘤的临床研究

 目的　探讨抗CD20单克隆抗体（利妥昔单抗,商品名：美罗华）联合自体外周血干细胞移植（APBSCT）治疗B细胞非霍奇金淋巴瘤（NHL）的疗效。方法　21例CD20阳性的NHL患者,经过前期治疗,5例达完全缓解（CR）,难治性病例为16例,包括11例部分缓解（PR）和5例疾病进展（PD）。在自体造血干细胞动员的第1、8天及预处理的-1、＋7天每天应用利妥昔单抗375 mg／m2。结果　移植前疾病达到CR的5例患者,无一例复发;移植前处于PR的11例患者,仅1例在移植后6个月疾病复发,其余均无病生存;移植前处于PD的5例患者,2例无病生存。21例患者中位随访24（1～68）个月,复发、死亡4例（19 %）,其余17例均无病生存,2年无病生存（EFS）和总生存（OS）率均为81.0 %。未观察到利妥昔单抗对采集所得干细胞的质量和数量以及移植后造血恢复有不良影响。结论　APBSCT联合利妥昔单抗做体内净化治疗B细胞NHL疗效与移植前状态有关,作为巩固治疗,能使移植前达CR的患者获得长期生存,提高治愈率;作为强化治疗,可提高缓解率,延长PR患者的EFS及OS。利妥昔单抗的加入不影响造血干细胞采集和移植后造血重建。     

Rituximab,Dexamethasone, Cytarabine,and Oxaliplatin (R-DHAX) Is an Effective and Safe Salvage Regimen in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

BackgroundSalvage therapy for patients with refractory/relapsed B-cell non-Hodgkin lymphoma (NHL) is based on polychemotherapy, followed by high-dose therapy and autologous stem cell transplantation in eligible patients (HDT/ASCT). R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone.Patients and MethodsWe substituted cisplatin with oxaliplatin to avoid nephrotoxicity and retrospectively analyzed a large series of 91 patients with refractory/relapsed B-cell NHL to evaluate toxicities, response rates (RRs), and survival. Median age at R-DHAX (rituximab/dexamethasone/cytarabine/oxaliplatin) treatment was 60 years (range, 28-82 years). Renal insufficiency was present in 18 patients. The most frequent histologic subtypes were diffuse large B-cell lymphoma (n = 42) and follicular lymphoma (n = 30). Seventeen patients (19%) were naive to rituximab at time of R-DHAX.ResultsGrade III/IV toxicities were mainly hematologic, including anemia (n = 9), neutropenia (n = 44), and thrombocytopenia (n = 47). Grade I/II neurologic toxicities, sensitive or motor, were observed, and these were mainly transient except for 3 cases of motor neuropathy associated with previous exposure to vincristine. Neither renal toxicities nor degradation of previous renal insufficiency were observed. The overall RR was 75%, with a complete RR of 57%, with no statistical difference between patients previously treated with rituximab versus without rituximab. At a median follow-up of 23 months, 2-year probability rates of overall survival and progression-free survival were 75% and 43%, respectively, with a significant difference between patients treated with HDT/ASCT and patients not eligible for HDT/ASCT.ConclusionR-DHAX is an efficient regimen in patients with relapsed/refractory B-cell NHL even in elderly patients if hematologic toxicities are closely managed.     

自体造血干细胞移植联合大剂量放化疗治疗恶性淋巴瘤32例

目的观察自体造血干细胞移植(AHSCT)治疗恶性淋巴瘤的疗效.方法自1991年6月至2000年4月,用AHSCT治疗恶性淋巴瘤32例.其中非霍奇金淋巴瘤(NHL)23例,霍奇金病(HD)9例;行自体骨髓移植(ABMT)12例,自体外周血干细胞移植(APBSCT)20例.外周血干细胞动员方法均采用常规化疗(CE或CHOP)加细胞集落刺激因子(G-CSF或GM-CSF;或G-CSF+GMCSF)10μg*kg-1*d-1.预处理方案为BEAM方案和MEL140mg/m2(或+Vp-16200mg)+单次全身照射(TBI)8Gy.结果全部患者移植后均重建造血,随访至2000年5月30日,中位随访1020d.处于无病生存者24例(75.0%),1,2年无病生存分别为78.1%(25/32)和46.9%(15/32),最长存活8年.8例(25.0%)复发.全组患者无移植相关死亡.结论AHSCT联合大剂量放化疗对预后不良复发或敏感的恶性淋巴瘤疗效佳,优于常规化疗.APBSCT造血恢复比ABMT快.预处理方案中含TBI的放疗组与单用联合化疗组疗效差异无显著性,但含放疗组副作用大.     

High-dose Thiotepa,Busulfan, Cyclophosphamide,and Autologous Stem Cell Transplantation as Upfront Consolidation for Systemic Non-Hodgkin Lymphoma With Synchronous Central Nervous System Involvement

IntroductionSynchronous involvement of the central nervous system (CNS) at the diagnosis of systemic non-Hodgkin lymphoma (NHL) is associated with an increased risk for relapse despite complete remission to initial therapy. High-dose chemotherapy with a CNS-directed conditioning regimen followed by autologous stem cell transplantation (ASCT) holds promise as a consolidative approach.Patients and MethodsWe conducted a retrospective analysis of all patients with systemic B-cell NHL and synchronous CNS involvement who received upfront consolidation with high-dose chemotherapy with thiotepa, busulfan, cyclophosphamide, and ASCT while in first complete remission between July 2008 and June 2016 at 2 partner academic institutions.ResultsTwenty patients were identified through the transplant database. The median age at diagnosis was 53 years (range, 37-65 years). The majority had diffuse large B-cell lymphoma histology (n = 17; 85%). The sites of CNS involvement were parenchymal (n = 12; 60%) and leptomeningeal disease (n = 9; 45%). All patients received systemic and CNS-directed therapy prior to transplant, with the most common approaches being R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) (n = 13; 65%) and high-dose intravenous methotrexate (n = 16; 80%), respectively. With a median follow up of 4.4 years after ASCT (range, 2 months-8.5 years), the Kaplan-Meier estimates of 4-year progression-free and overall survival were 77% (95% confidence interval, 48%-91%) and 82% (95% confidence interval, 54%-94%), respectively.ConclusionCNS-directed high-dose chemotherapy and ASCT provides durable remission for patients with synchronous aggressive lymphoma and should be strongly considered as consolidative therapy for eligible patients with systemic NHL with CNS involvement in first complete remission.     

A Review of Autologous Stem Cell Transplantation in Lymphoma

Purpose of Review

Chemotherapy remains the first-line therapy for aggressive lymphomas. However, 20–30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin lymphoma (HL) recur after initial therapy. We want to explore the role of high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients.

Recent Findings

There is some utility of upfront consolidation for-high risk/high-grade B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma, but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL.

Summary

Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high-dose consolidation or in the maintenance setting.

     

Treatment of primary CNS lymphoma (PCNSL) following successful treatment of systemic non-Hodgkin’s lymphoma (NHL): a case series

Management of PCNSL occurring after successful treatment of systemic non-Hodgkin’s lymphoma (NHL) is poorly defined. Illustrate a treatment approach for PCNSL following prior treatment of a systemic NHL. A retrospective case series of 6 patients (mean age 60 years; range 46–65) diagnosed with a diffuse large B cell lymphoma of the CNS following prior successful treatment of a systemic NHL (low-grade in 2; high-grade in 4). Mean interval to diagnosis of PCNSL after diagnosis of systemic NHL was 12 months (range 7–18). In 4/6 patients in whom genetic analysis could be performed, the PCNSL and NHL differed. Treatment utilized high-dose methotrexate and rituximab (immunochemotherapy) followed in patients with a radiographic complete response by autologous peripheral stem cell transplant (ASCT) with total body irradiation (TBI) and multi-agent conditioning chemotherapy (BEAM: carmustine, etoposide, cytarabine, melphalan). 5/6 patients had a radiographic complete response to immunochemotherapy and were treated with ASCT. 4/5 patients were free of disease following ASCT with a mean follow-up of 3 years (range 0.5–4 years). There were no toxic deaths and all patients transplanted successfully engrafted within 28 days (mean 18). Using a treatment paradigm similar to that utilized for recurrent systemic NHL (induction chemotherapy followed by ASCT) for PCNSL occurring metachronously after successful treatment of systemic NHL appears safe and effective.     

Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed aggressive B-cell lymphoma

This study was conducted to evaluate the efficacy and safety of Rituximab, Gemcitabine, Cisplatin, and Dexamethasone (R-GDP) in relapsed or refractory aggressive B-Cell Non-Hodgkin's Lymphoma (NHL). Treatments consisted of rituximab 375?mg/m(2), i.v. on day 1; gemcitabine 1,000?mg/m(2), i.v. on days 1 and 8, dexamethasone 40?mg i.v. on days 1-4, and cisplatin 25?mg/m(2) i.v. on days 1-3, every 21?days. The primary end-points were the overall survival (OS) and progression-free survival (PFS). Secondary endpoints included response rate (ORR; CR) and toxicities. Eligible patients could then proceed to high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) or receive up to six treatment cycles. From January 2005 to December 2010, 50 successive patients at Tianjin cancer hospital lymphoma department were enrolled in this study. All patients were recurrent or refractory aggressive B-cell NHL, including diffuse large B-cell lymphoma (n?=?30) and follicular lymphoma grade 3b (n?=?20). The median follow-up time was 42?months (range, 12-70). After two cycles, the overall response rate was 72.0?%, with a CR/CRu rate of 56?%. The 2-year OS and PFS of all patients were 70.0 and 48.0?%, respectively. Grade III-IV neutropenia and thrombocytopenia occurred in 34 and 40?% of patients, respectively. Twenty-one patients (42?%) proceeded to ASCT. Higher International Prognostic Index and refractory disease were independently associated with worse survival and progression-free survival. R-GDP chemotherapy in patients with refractory or relapsed aggressive B-Cell NHL was effective as a salvage therapy and helpful for HDC/ASCT.     

套细胞淋巴瘤治疗进展

套细胞淋巴瘤是具有独特生物学、病理和临床特征的B细胞恶性肿瘤，占非霍奇金淋巴瘤5%~10%，大多数患者诊断时即为晚期。套细胞淋巴瘤具有侵袭性淋巴瘤的侵袭性和惰性淋巴瘤的难治愈性特征，患者预后较差。近年来随着大剂量化疗、自体造血干细胞移植及新药研究的进展，患者生存期得到明显延长。     

年轻高危弥漫大B细胞淋巴瘤患者治疗研究进展

弥漫大B细胞淋巴瘤(DLBCL)是成年人淋巴瘤中最常见的一种类型,约占非霍奇金淋巴瘤(NHL)的30％～ 40％.年轻高危DLBCL患者是临床预后不良的一组特殊人群,目前在临床实践中尚无标准治疗方案,常规化疗、联合利妥昔单抗的R-CHOP、R-CHOP样方案、大剂量化疗及自体造血干细胞移植并未完全扭转其预后不良的现实.文章就年轻高危DLBCL患者的治疗现状及未来的治疗方向进行综述.     

High dose therapy and autologous stem cell transplantation for human immunodeficiency virus-associated non-Hodgkin lymphoma in the era of highly active antiretroviral therapy

BACKGROUND: The advent of highly active antiretroviral therapy (HAART) has allowed the exploration of more dose-intensive therapy such as autologous stem cell transplantation (ASCT) in selected patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL). METHODS: The authors report on the use of myeloablative chemotherapy with ASCT in two HIV positive patients with NHL. The first patient underwent ASCT at the time of first disease remission for poor risk, diffuse, large cell NHL and the second patient had multiply recurrent, chemosensitive Burkitt lymphoma. ASCT was performed in both patients using a transplant conditioning regimen of high dose cyclophosphamide, carmustine, and etoposide (CBV). RESULTS: The target dose of >/= 5 x 10(6)/kg CD34 positive peripheral blood stem cells (PBSC) utilized for ASCT was collected using granulocyte-colony stimulating factor (G-CSF) after chemotherapy for mobilization while both patients were receiving concomitant HAART for HIV infection. HAART was continued during CBV conditioning. Prompt hematopoietic recovery was observed after ASCT. Both patients remained in clinical disease remission from their lymphoma at 28 months and 20 months after transplant, respectively. CONCLUSIONS: ASCT is feasible in patients with HIV-associated NHL. Adequate numbers of CD34 positive PBSC can be procured from patients receiving HAART and chemotherapy for NHL. Selected patients with HIV-related lymphoma can tolerate the high dose CBV myeloablative chemotherapy regimen without increased acute regimen-related toxicity. Reinfusion of G-CSF-mobilized PBSC can lead to rapid recovery of hematologic function and sustained engraftment after ASCT. Given the poor prognosis of patients with HIV-associated NHL treated with conventional chemotherapy, further investigation of this approach should be considered.     

High-dose rituximab does not negatively affect peripheral blood stem cell mobilization kinetics in patients with intermediate-grade non-Hodgkin's lymphoma

Rituximab, an anti-CD20 human-mouse chimeric monoclonal antibody has been shown to improve response rates when it is combined with standard salvage chemotherapy in patients with relapsed or refractory intermediate-grade B-cell non-Hodgkin's lymphoma. A vast majority of these patients subsequently undergo high-dose therapy followed by stem cell transplantation. However, the impact of rituximab on stem cell mobilization kinetics is not well characterized. The purpose of this study was to study the effect of high-dose rituximab given with chemotherapy on stem cell mobilization in patients with intermediate-grade B-cell non-Hodgkin's lymphoma. Thirty-six patients received ifosfamide, etoposide, and rituximab followed by filgrastim for stem cell mobilization. The chemotherapy regimen was well tolerated. Thirty-four of 36 patients (94%) were able to mobilize at least 2 × 10⁶ CD34+ cells/kg body weight after a median of 2 apheresis procedures. The median CD34+ cell dose collected per kilogram of recipient body weight was 6.5 × 10⁶ (range, 4.65-31.15). All patients who subsequently underwent high-dose chemotherapy and stem cell transplantation experienced sustained engraftment. In conclusion, high-dose rituximab given during stem cell mobilization does not negatively affect stem cell mobilization kinetics.