High-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of non-Hodgkin's lymphoma

Findings for 41 patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and/or autologous peripheral blood stem cell transplantation (PBSCT) are reported. Two of the 41 patients were treated with HDC alone without PBSCT. At transplant, 20 patients were in complete remission, while 19 had resistant NHL and had failed to achieve a complete remission (CR) after several courses of conventional chemotherapy. The conditioning regimens used were mainly ACE (cytarabine, cyclophosphamide, etoposide) and MEAC (MCNU, etoposide, cytarabine, cyclophosphamide). The treatment-related mortality rate was 4.9%. Two patients treated with MEAC died from intractable congestive heart failure. Nine of the 19 patients with resistant NHL achieved CR, and at a median follow-up of 26 months (range, 3 to 93 months) the estimated two-year disease-free survival rate for these patients was 44.4%. Four patients in CR at present were in partial remission before HDC and PBSCT. Fifteen of the 20 patients in CR before HDC were transplanted in first CR and 5 in 2nd CR. At a median follow-up of 49 months (range, 3 to 96 months), the estimated 3-year DFS for the group of all patients was 73.7%. Five relapses occurred between 5 and 35 months post-transplantation. In conclusion, HDC and PBSCT as induction therapy was only effective for patients with resistant NHL who responded to conventional chemotherapy, and may improve the survival of patients in CR as consolidation therapy.     

自体干细胞移植支持下的大剂量化疗一线治疗恶性淋巴瘤

背景与目的:目前自体干细胞移植(autologous stem cell transplantation,ASCT)支持下的大剂量化疗(high-dose chemotherapy,HDC)已成为复发或难治性恶性淋巴瘤(malignant lymphoma,ML)的标准治疗方法,但是对于一些选择的ML是否可作为一线治疗方案目前尚不明确.本文旨在通过回顾性分析探讨HDC/ASCT作为一线方案治疗ML的疗效.方法:自2000年9月至2007年6月, 连续收治28例ML患者,中位年龄32岁(8～60岁),其中男性17例,女性11例.组织学类型包括24例非霍奇金淋巴瘤,4例霍奇金淋巴瘤.自体外周血干细胞动员采用化疗药物联合重组人粒细胞集落刺激因子方案.HDC方案采用BEAC(BCNU、CTX、Ara-C 、VP-16)方案.随访日期自干细胞回输之日期开始,末次随访日期为2007年7月30日.结果:28例患者均移植成功,重建造血功能.移植前CR 14例,PR 14例,移植后CR 22例,PR 6例.随访截止日期为2007年7月30日,中位随访时间为28个月(1.5～82个月),移植后4例病情进展,其中2例死亡,3年生存率及无进展生存率分别为89%和76%.大剂量化疗期间不良反应均可耐受,无移植相关死亡.结论:HDC/ASCT作为一线方案治疗ML是安全、可行及有效的治疗方法.     

大剂量化疗联合自体造血干细胞移植治疗淋巴瘤59例回顾性分析

目的:通过分析大剂量化疗(HDT)联合自体造血干细胞移植(ASCT)治疗淋巴瘤的临床体会,探究安全合理的动员和预处理方案,以进一步提高治疗的安全性和疗效.方法:对59例接受HDT联合ASCT治疗的淋巴瘤患者的资料进行回顾分析.结果:59例患者采集到足够数量的造血干细胞,预处理后接受ASCT并成功恢复造血.随访1～88个月(中位数26.3个月),47例患者无病生存1～88个月(中位数28.5个月),10例在移植后2～37个月死于肿瘤复发,1例移植后16个月死于深部霉菌感染.1例移植后9个月死于爆发性肝炎.结论:HDT联合ASCT与常规化疗有机结合可能是治疗淋巴瘤安全、有效的方法.     

High-dose chemotherapy with tandem autologous transplantation as part of the initial therapy for aggressive non-Hodgkin's lymphoma

The purpose of the present study was to evaluate the feasibility and the efficacy of employing a high-dose chemotherapy (HDT) regimen with tandem peripheral blood progenitor cells (PBPC) supported transplantation in the initial treatment of aggressive non-Hodgkin's lymphoma (NHL). HDT was preceded by a standard course of conventional dose chemotherapy in 17 out of the 25 patients treated, while in 8 cases it was delivered after only one or two cycles. HDT was a three-step procedure which included high-dose (6-7 g/m2) cyclophosphamide (CY) supported by haematopoietic growth factors, the first myeloablative course with mitoxantrone (NOV) 60, 75 or 90 mg/m2 plus melphalan (L-PAM) 140-180 mg/m2 with haematopoietic rescue, and the second myeloablative course with etoposide (VP) and carboplatin (CARBO) given at 1.5 g/m2 each with haematopoietic rescue. PBPC were collected after CY administration. Twenty-two patients (88%) completed the HDT, haematological reconstitution was rapid and complete at each step and there were no toxic deaths. The activity of the treatment was high with a CR rate over 90% in the entire patient population. The 2-year overall survival (OS) and failure-free survival (FFS) rates of patients in both Age-Adjusted International Prognostic Index (A-AIPI) groups 2 and 3 are 79% and the disease-free survival (DFS) rate for the CRs is 85%. In A-AIPI group 1 the 2-year OS and FFS rates are both 91%.     

High-dose chemotherapy and autologous hematopoietic progenitor cell transplantation for non-Hodgkin's lymphoma in patients >65 years of age

Patients and methodsWe present a retrospective analysis of 99 consecutive patients with relapsed non-Hodgkin's lymphomas who were older than 65 years at the time of high-dose chemotherapy and autologous progenitor cell transplantation.ResultsMedian age at transplant was 68 years (range 65–82). Thirty-six percent of patients had a hematopoietic cell transplantation comorbidity index of >2 at the time of transplantation. The cumulative nonrelapse mortality was 8% [95% confidence interval (CI) 4–17] at 26 months and the 3-year overall survival (OS) was 61% (95% CI 49–71). On multivariate analysis, disease status at transplant and lactate dehydrogenase (LDH) > normal were significant predictors for OS (P = 0.002). Comorbidity index of >2 did not impact OS but did predict for higher risk of developing grade 3–5 toxicity (P = 0.006). Eight patients developed secondary myelodysplastic syndrome/acute myelogenous leukemia after transplantation (cumulative incidence 16%).ConclusionsPatients with relapsed lymphomas who are >65 years of age should be considered transplant candidates, particularly if they have chemosensitive disease and normal LDH levels at the time of transplantation. Patients with comorbidity index of >2 can also undergo transplantation with acceptable outcomes but may be at higher risk for developing toxicity.     

High-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with multiple myeloma

Multiple myeloma, for all practical purposes, remains an incurable malignancy; however, 5-year survival has improved substantially during the past 30 years. A major contribution to improved outcome is the use of high-dose chemotherapy and stem cell transplantation. This multifaceted approach to therapy requires an understanding of appropriate induction therapy, techniques for stem cell mobilization, appropriate conditioning and supportive care. Also of importance are prognosis, features that predict outcome, the suitability of transplant candidates, and post-transplantation maintenance therapy.     

High-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with multiple myeloma

Multiple myeloma, for all practical purposes, remains an incurable malignancy; however, 5-year survival has improved substantially during the past 30 years. A major contribution to improved outcome is the use of high-dose chemotherapy and stem cell transplantation. This multifaceted approach to therapy requires an understanding of appropriate induction therapy, techniques for stem cell mobilization, appropriate conditioning and supportive care. Also of importance are prognosis, features that predict outcome, the suitability of transplant candidates, and post-transplantation maintenance therapy.     

大剂量化疗联合自体造血干细胞移植治疗复发、难治性边缘区非霍奇金淋巴瘤疗效观察

 【摘要】　目的　评价大剂量化疗联合自体造血干细胞移植治疗复发、难治性边缘区淋巴瘤的价值。方法　回顾性分析12例接受大剂量化疗或放化疗联合自体造血干细胞移植治疗的复发、难治性边缘区淋巴瘤患者的临床资料。结果　12例患者中,1例发生治疗相关性死亡,1例在移植后出现复发, 4例死于非肿瘤相关性疾病;中位无进展生存期104个月,中位总生存期117个月;6例患者尚无病生存。结论　大剂量化疗联合自体造血干细胞移植治疗复发、难治性边缘区淋巴瘤有效,尤其适用于对利妥昔单抗联合化疗不敏感的患者。     

High-dose therapy/autologous hematopoietic stem cell transplantation in relapsed or refractory marginal zone non-Hodgkin lymphoma

The optimal therapy for patients who have relapsed or refractory marginal zone lymphoma has not been defined. We analyzed the clinical outcomes of 14 patients who had relapsed or refractory marginal zone lymphomas and underwent high-dose therapy/autologous hematopoietic stem cell transplantation (HDT/AHSCT) at the University of Nebraska from August 1992 to August 2008. The median age of patients was 48 years (range, 29 to 62 years). All patients had relapsed or refractory disease. There were three treatment-related deaths within 100 days of transplantation. With a median follow-up of 138 months, the median duration of failure-free survival is 108 months, and the median duration overall survival is 120 months. Only two patients have relapsed. Secondary malignancies were seen in three patients (myelodysplastic syndrome, n = 2; gastric carcinoma. n = 1). We conclude that HDT/AHSCT is feasible in patients who have relapsed/refractory marginal zone lymphomas. Approximately one- third of patients can achieve long-term disease-free survival.     

High-dose therapy with autologous transplantation for aggressive non-Hodgkin's lymphoma: the Bologna experience

Patients with aggressive non-Hodgkin's lymphoma (NHL) who relapse after initial therapy have a poor prognosis and with standard dose salvage therapy the outlook remains poor. In this work we examine the patient characteristics and outcome of patients with aggressive NHL treated with HDT and autologous transplantation at our Institute from 1982 to 1999. A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for hematopietic recovery, complications of transplantation, response rates, overall survival (OS) and relapse-free survival (RFS). One hundred and thirty-four patients with aggressive NHL were treated with estimated 10-year OS and RFS rates of 50% and 66%, respectively. Disease status (sensitive vs. refractory) pre-HDT was the most powerful predictive parameter for OS and RFS, at both univariate and multivariate analysis. For the entire cohort, transplant-related mortality was only 3.5% without evidence of second malignancies. Our results confirm that HDT with autologous transplantation is associated with a durable RFS in a remarkable proportion of aggressive NHL patients with very low global early and late toxicity. Improved patient selection, transplant timing, ongoing improvements in supportive care, and selected phase III trials should increase outcomes further.     

High-dose chemotherapy with hematopoietic stem cell transplantation for the treatment of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare B-cell lymphoid neoplasm for which current regimens utilizing standard-dose chemotherapy and/or radiation therapy lead to high relapse rates and/or unacceptable neurologic sequelae. High-dose chemotherapy followed by hematopoietic stem cell transplantation may overcome limitations of current treatment schemas. A search was performed of all English-language literature (1968 to June 2009) within the MEDLINE, EMBASE and Cochrane Library databases to identify relevant clinical trials using the terms stem cell transplantation, bone marrow transplantation, primary central nervous system lymphoma, and PCNSL. Bibliographies were reviewed to extract other relevant articles. Use of high-dose chemotherapy followed by hematopoietic stem cell transplantation for the treatment of PCNSL in a predominantly elderly population is feasible. Use of this treatment modality for newly diagnosed and recurrent or relapsed disease is burdened by a paucity of data guiding patient selection, optimal induction regimen, stem cell mobilization and conditioning chemotherapy. Data are also sparse and confounding regarding timing of initiation of this procedure relative to the natural history of the disease and timing of each chemotherapy regimen relative to each other. High-dose chemotherapy followed by hematopoietic stem cell transplantation remains an experimental procedure with insufficient data to guide clinicians. However, the data are encouraging and merit continued research to guide patient selection and treatment regimens which may produce optimal outcomes.     

Autologous hematopoietic stem cell transplantation for aggressive B-cell non-Hodgkin's lymphoma

To evaluate the results of high-dose chemotherapy (HDT) and autologous hematopoietic stem cell transplantation (ASCT) in patients with diffuse B-cell aggressive non-Hodgkin's lymphoma(NHL). Between 1991 and 2004, 25 patients who did not achieve complete remission and 26 in complete remission from conventional chemotherapy received HDC-ASCT. Of 25 patients with refractory NHL,14 were chemotherapy-sensitive before HDT-ASCT and 11 were chemotherapy-resistant. CR was achieved after HDC-ASCT in 50% of 14 chemotherapy sensitive patients and in none of 11 chemotherapy-resistant patients. The 5-year probability of event-free survival for chemotherapy-sensitive and chemotherapy-resistant patients was 51.3% and 20.8%, respectively (p<0.05, log-rank test). Moreover, the 5-year probability of event-free survival for patients in the low-risk group with International Prognostic Index (IPI) and in the high-risk group with IPI was 75.0% and 16.3%, respectively (p<0.05, log-rank test). HDT-ASCT should be considered for patients with refractory aggressive NHL who are chemotherapy-sensitive rather than chemotherapy-resistant. Twenty-six patients in complete remission received consolidation therapy with HDT-ASCT. The 5-year probability of disease-free survival for patients in the low-risk group and in the high-risk group was 68.8% and 60.0%,respectively (p = 0.9 6). HDT-ASCT should be considered for patients at high risk who achieve complete remission after induction treatment. In future, HDT-ASCT combined with rituximab as induction therapy or as consolidation therapy is needed for patients with aggressive NHL in the high-risk group.     

High-dose therapy and transplantation in non-Hodgkin's lymphoma

High-dose therapy and transplantation have been explored as a therapeutic option for patients with non-Hodgkin's lymphomas (NHLs) for the past two decades, in an effort to improve the long-term outcome of this spectrum of disorders. Although a plethora of pilot and phase II studies in the various subtypes of NHL have been reported, there is a problematic lack of randomized phase III trials that would aid in answering important questions regarding the role of transplantation in these disease processes. The results of transplantation trials for these patients are also confounded by the relatively short follow-up intervals in low-grade NHL and small patient numbers in studies of transplantation for less common NHL subtypes, such as lymphoblastic, Burkitt's, and mantle cell lymphomas. The emerging late toxicities of transplantation are of increasing concern and underscore the need for more studies that address questions of relative therapeutic benefits. Fortunately, the limitations of these existing studies are recognized, and new transplantation trials presently underway or in development are beginning to address these concerns. As clinical transplantation moves into a more mature phase, these phase III studies should provide more definitive answers as to the specific role of transplantation in specific subtypes of NHL.     

高剂量化放疗联合造血干细胞移植治疗霍奇金病

高剂量化放疗联合造血干细胞移植是近20年来肿瘤治疗领域的一个研究热点,已成为霍奇金病(HD)复发与耐药患者标准的解救治疗模式,但对于初治晚期患者的作用,特别是在初治患者综合治疗中的应用价值还不完全明确.进一步探讨其移植适应证的选择、移植时机的确定以及移植的利弊,具有重要意义.     

High-dose chemotherapy and autologous hematopoietic stem cell transplantation: the lymphoma experience and its potential relevance to solid tumors

Lymphomas, which are frequently subdivided into Hodgkin's disease and non-Hodgkin's lymphoma, represent one of the more curable cancers that present as a solid tumor. Unfortunately, most patients cannot be cured with conventional chemotherapy, therefore new techniques have been developed including high-dose chemotherapy and autotransplantation. Non-Hodgkin's lymphoma was one of the first illnesses to be tested using the new methods and initial encouraging results in relapsed lymphoma led to the testing of high-dose chemotherapy with autotransplantation as a primary therapy for patients with lymphomas. Encouraging results have been obtained in several randomized trials. Studies of the treatment of lymphoma have identified several principles related to the application of autotransplantation, which may be relevant to other solid tumors. Autotransplantation is likely to be of benefit only when using active chemotherapeutic agents that can be escalated in dose and when myelosuppression is the dose-limiting toxicity. Chemotherapy-responsive tumors are obvious targets for autotransplantation, whereas chemotherapy-resistant tumors are unlikely to benefit. Other factors that should be taken into account when selecting patients for high-dose chemotherapy regimens include the extent of disease, preceding therapy and the performance status of the patient.