自体造血干细胞移植一线巩固治疗高危弥漫大B细胞淋巴瘤的效果

目的探讨利妥昔单抗治疗时代自体造血干细胞移植一线巩固治疗高危弥漫大B细胞淋巴瘤(DLBCL)的远期疗效。方法纳入2010年1月至2017年6月河南省肿瘤医院收治的113例经利妥昔单抗联合化疗获完全缓解的高危DLBCL患者, 其中40例化疗后行自体造血干细胞移植一线巩固治疗(移植组), 73例化疗后未接受造血干细胞移植一线巩固治疗(非移植组)。对113例患者的临床资料进行回顾性分析, 采用Kaplan-Meier法分析两组总生存(OS)和无进展生存(PFS)并进行比较。结果移植组与非移植组患者2年OS率分别为90.0%、91.8%, 3年OS率分别为84.9%、80.1%, 5年OS率分别为80.9%、72.8%, 两组OS差异无统计学意义(P=0.457);2年PFS率均为85.0%, 3年PFS率分别为82.2%、61.8%, 5年PFS率分别为82.2%、60.0%, 两组PFS差异有统计学意义(P=0.046)。移植组无一例发生早期移植相关死亡。结论在利妥昔单抗治疗时代, 自体造血干细胞移植一线巩固治疗能改善化疗敏感的高危DLBCL患者的PFS, 并可能改善OS, 且安全可靠。     

自体造血干细胞移植治疗复发难治非霍奇金淋巴瘤

目的探讨高剂量放化疗联合自体造血干细胞移植治疗复发、耐药侵袭性和高度侵袭性非霍奇金淋巴瘤(NHL)的疗效和安全性。方法23例复发和11例耐药的NHL患者接受了解救化疗和自体造血干细胞采集,采集后进行了自体造血干细胞支持下的高剂量放化疗。结果采集到的全部患者干细胞数均达到了移植要求,CD34+细胞中位数为6.06×106/kg。接受移植的患者经高剂量放化疗治疗后全部出现Ⅳ度骨髓抑制,出现1例移植相关死亡。移植后23例完全缓解,6例部分缓解,5例进展。缓解的患者中,10例复发,中位疾病进展时间(TTP)为7.9个月,复发患者中7例死亡。1例发生第二肿瘤。5年总生存率为60.5%,5年无复发总生存率为58.2%。结论高剂量放化疗联合自体造血干细胞移植治疗复发耐药的侵袭和高度侵袭性NHL疗效高、安全性好,但对于预后差的患者尚需探讨新的方法。     

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。     

自体外周血造血干细胞移植治疗非霍奇金淋巴瘤疗效分析

目的观察高剂量化疗联合自体造血干细胞移植治疗复发和难治性非霍奇金淋巴瘤的疗效。方法1995年至2005年采用大剂量化疗联合自体外周血造血干细胞移植治疗非霍奇金淋巴瘤30例。外周血干细胞动员方法为将常规剂量CHOP方案中CTX增至2500mg/m2,化疗后予G-CSF3.5~5μg/kg的动员方案,当骨髓功能恢复WBC计数达(2~5)×109/L,外周血单核细胞(MNC)计数达20%~30%时分离外周血造血干细胞。预处理方案为异环磷酰胺(IFO)12g/m2,阿糖胞苷(Ara-c)4.5g/m2,足叶乙甙(Vp-16)0.75g/m2。结果30例患者移植后缓解时间为1~108个月,中位缓解期42个月。其中1年无病生存25例(83%),2年22例(73%),3年20例(66.7%)。最长存活9年。全组无移植相关死亡。结论高剂量化疗联合自体造血干细胞移植治疗复发和难治性恶性淋巴瘤的疗效优于常规化疗。     

Hyper-CVAD方案治疗侵袭性T细胞淋巴瘤的效果和安全性

目的 评价Hyper-CVAD化疗方案治疗侵袭性T细胞淋巴瘤的效果和安全性.方法 对2009年9月至2010年12月在北京协和医院接受Hyper-CVAD方案诱导化疗的34例初诊侵袭性T细胞淋巴瘤患者的疗效和不良反应等资料进行回顾性分析,并进行生存分析.结果 34例患者接受Hyper-CVAD方案诱导化疗后,28例(82.4％)有治疗反应,其中10例(29.4％)获得完全缓解(CR);11例接受造血干细胞移植(包括1例同胞全合异基因造血干细胞移植).中位随访时间16个月(1～82个月),1、3年总生存(OS)率分别为70.2％、41.1％;1、3年无进展生存(PFS)率分别为49.3％、31.6％.化疗不良反应主要为骨髓抑制,18例(52.9％)发生Ⅳ级骨髓抑制;3例因严重感染死亡.Cox多因素分析显示,化疗能否达到CR是PFS的独立影响因素(HR=6.118,95％CI 1.327～28.206,P=0.020);骨髓是否受累(HR=0.270,95％CI 0.101～0.722,P=0.009)和化疗能否达到CR(HR=6.669,95％CI 1.754～25.354,P=0.005)是OS的独立影响因素.结论 Hyper-CVAD方案诱导化疗治疗侵袭性T细胞淋巴瘤的反应率高,但有效持续时间短,远期疗效不佳,同时骨髓抑制严重,感染发生率高.缓解后行自体造血干细胞移植可能提高侵袭性T细胞淋巴瘤的疗效.     

化疗序贯自体造血干细胞移植治疗淋巴瘤的疗效评价及影响因素分析

目的:探讨化疗序贯自体造血干细胞移植(auto-HSCT)对淋巴瘤患者的疗效及影响因素.方法:回顾性分析2015年09月至2020年12月于我科接受大剂量化疗(HDC)序贯自体外周血造血干细胞移植治疗的患者,并进行疗效及不良反应评价.结果:40例患者,其中非霍奇金淋巴瘤34例,霍奇金淋巴瘤6例;男性27例,女性13例,...     

自体造血干细胞移植治疗高侵袭性淋巴瘤的临床疗效及影响因素

目的:探讨自体造血干细胞移植(autologous hematopoietic stem cell transplantation, Auto-HSCT)治疗高侵袭性淋巴瘤的临床疗效和相关因素分析。方法:回顾性分析了2011年7月至2021年8月我院88例高侵袭性淋巴瘤患者的临床资料。伯基特淋巴瘤(Burkitt lymphoma, BL)患者33例,移植组13例,单纯化疗组20例。T淋巴母细胞淋巴瘤(T-lymphoblastic cell lymphoma, T-LBL)患者53例,移植组25例,单纯化疗组28例。B淋巴母细胞淋巴瘤(B-lymphoblastic cell lymphoma, B-LBL)患者2例,移植组2例。结果:BL移植组12例无进展生存,1例复发,所有患者均存活。单纯化疗组15例无进展生存,5例复发,16例存活,4例死亡。移植组1、3年PFS率为92%、53%,单纯化疗组1、3年PFS率为65%、10%,两组PFS无统计学意义(P=0.167)。移植组1、3年OS率为100%、61%,单纯化疗组1、3年OS率为70%、10%,两组OS无统计学意义(P=0.0...     

大剂量化疗联合自体造血干细胞移植治疗淋巴瘤的疗效

目的:观察大剂量化疗联合自体造血干细胞移植治疗恶性淋巴瘤的疗效。方法:选择2009年12月－2015年12月于我科住院治疗的恶性淋巴瘤病例30例,均接受大剂量化疗联合自体造血干细胞移植治疗。结果:1例患者造血干细胞回输后因严重肺部感染死亡,其余均成功植入并快速重建造血;随访至2016年3月1日,有22例存活,无病生存19例,9例复发,中位复发时间为4.5(1~15)个月,其中6例复发后3年内死亡,2例治疗后重新评估为CR随访至今未再复发,1例为单一椎体复发至今仍存活。移植相关死亡率为6.7%。结论:大剂量化疗联合自体造血干细胞移植能很快重建造血,是治疗恶性淋巴瘤安全有效的方法。     

自体造血干细胞移植治疗多发性骨髓瘤

 自体造血干细胞移植（ASCT）治疗多发性骨髓瘤进展较大。与常规方案相比，ASCT提高了患者的完全缓解（CR）、无事件生存（EFS）和总生存率（OS）。高龄、肾衰竭并非ASCT的禁忌证。双次ASCT可提高CR率，对长期EFS率、OS率影响仍需观察。改进预处理方案、选择移植时机、改进移植后巩固治疗可以提高疗效。     

自体造血干细胞移植治疗中、高度恶性淋巴瘤

背景与目的:自体造血干细胞移植(autologoushemotopoieticstemcelltransplantation,ASCT)支持下的大剂量化疗目前已成为治疗对化疗敏感的淋巴瘤最有效的手段之一。本研究评价自体造血干细胞移植支持下的大剂量化疗加放疗治疗预后差的中、高度恶性淋巴瘤的疗效。方法:1995年11月～2001年5月收集到的13例病例中,非霍奇金淋巴瘤(non-Hodgkinslymphoma,NHL)11例,复发霍奇金淋巴瘤(Hodgkinsdisease,HD)2例。移植前首次完全缓解(firstcompleteremission,CR1)8例,第二次完全缓解(secondcompleteremission,CR2)4例,第二次部分缓解(secondpartialremission,PR2)1例。预处理方案:单纯化疗4例;化疗加受累区放疗6例;全身放疗加化疗3例。2例采用自体骨髓移植,11例行自体外周血干细胞移植。结果:本组病例回输单核细胞(mono-nuclearcell,MNC)和粒-巨细胞系祖细胞(granulocyte-macrophagecolony-formingcells,CFU-GM)的均数(范围)分别为2.55(2.07～3.31)×109/L和1.43(0.6～2.36)×109/L。随访到2001年10月,所有患者造血功能都获得重建。白细胞恢复到≥1.0×109/L和血小板>50×109/L的中位时间(范围)分别为6(7～35)天和8(6～32)天。CR持续时间为4～57个月,中位时间为16个月,1年生存率76.9%,3年生存率46.2%。结论:自体造     

Phase I/II trial of total lymphoid irradiation and high-dose chemotherapy with autologous stem-cell transplantation for relapsed and refractory Hodgkin's lymphoma.

BACKGROUND: The standard approach to treatment of relapsed/refractory Hodgkin's lymphoma (HL) is high-dose chemotherapy conditioning followed by autologous hematopoietic stem-cell transplantation (aHSCT). We report the results of a prospective phase I/II clinical trial of accelerated hyperfractionated total lymphoid irradiation (TLI) immediately followed by high-dose chemotherapy for relapsed/refractory HL. PATIENTS AND METHODS: Forty-eight patients underwent aHSCT with either sequential TLI/chemotherapy (n = 32) or chemotherapy-alone conditioning (n = 16), based on prior radiation exposure. The first 22 patients enrolled on trial received escalating doses of etoposide (1600-2100 mg/m(2)) with high-dose carboplatin and cyclophosphamide. RESULTS: No dose-limiting toxicity was seen and TLI/chemotherapy was well tolerated. The 5-year event-free survival (EFS) estimate for all patients was 44% with overall survival (OS) of 48%. Five-year EFS and OS for the TLI/chemotherapy group was 63% and 61%, respectively, compared with 6% and 27%, respectively, for the chemotherapy-alone group (P < 0.0001 and P = 0.04, respectively). Patients with primary induction failure HL who received TLI/chemotherapy had 5-year EFS and OS rate of 83%. The 100-day treatment-related mortality was 4.2% and two secondary cancers were seen. Significant factors predicting survival by multivariate analysis included TLI/chemotherapy conditioning and B symptoms at relapse. CONCLUSIONS: Sequential TLI/chemotherapy conditioning for relapsed/refractory HL is safe and associated with excellent long-term survival rates.     

Romidepsin treatment for relapsed or refractory peripheral and cutaneous T‐cell lymphoma: Real‐life data from a national multicenter observational study

Romidepsin is a class I selective histone deacetylase (HDAC) inhibitor approved by the Food and Drug Administration (FDA) for relapsed/refractory (R/R) cutaneous T‐cell lymphoma (CTCL) and peripheral T‐cell lymphoma (PTCL), treated with at least one prior systemic therapy. Currently, there is paucity of real‐life data on the efficacy and safety of romidepsin in R/R T‐cell lymphoma. This national, multicenter study presents real‐life data on the efficacy and safety of romidepsin in R/R T‐cell lymphoma. Patients diagnosed and treated with romidepsin for R/R CTCL or PTCL between 2013 and 2018 were retrospectively reviewed. Outcomes included overall survival (OS), event‐free survival (EFS), overall response rate (ORR), complete response (CR), and adverse events. Fifty‐three patients with R/R PTCL (n = 42) or CTCL (n = 11) were included. Among CTCL patients, median OS was not reached, ORR was 25%, and none achieved CR. Among PTCL patients, median OS was 7.1 months, EFS was 1.9 months, ORR rate was 33%, and 12.5% achieved CR. In a univariate analysis, predictors for longer EFS include any response to therapy, number of previous lines, and PTCL subclass (with better results for angioimmunobalstic T‐cell lymphoma). In a univariate and multivariate analysis for OS, treatment response was the only factor predicting OS (OR 4.48; CI 95%, 1.57‐12.79; P = .005). Most grade 3 and 4 adverse events were hematological (35%). Infections were reported in 34% of patients. This real‐life experience with romidepsin confirms the results of the pivotal phase II trials. PTCL subtype and the number of previous lines of therapy have an impact on EFS. In addition, patients who had good response to romidepsin benefited most in terms of both EFS and OS. Efforts should be done to identify those patients.     

Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study.

BACKGROUND: We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma. PATIENTS AND METHODS: Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. RESULTS: Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1-69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan-Meier), after HD-BuTT 27 months and "not reached", respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively. CONCLUSION: MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.     

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation.

We report the results of two prospective phase II studies investigating the role of high-dose sequential chemotherapy, followed by autologous stem cell transplantation (ASCT) in 62 patients with advanced stage peripheral T-cell lymphomas (PTCLs) at diagnosis. Conditioning regimen consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) or carmustine, etoposide, Ara-C and melphalan followed by peripheral blood stem cell autografting. In an intent-to-treat analysis, 46 out of 62 patients (74%) completed the whole programme, whereas 16 patients did not undergo ASCT, mainly because of disease progression. At a median follow-up of 76 months, the estimated 12-year overall (OS), disease-free and event-free survival (EFS) were 34, 55 and 30%, respectively. OS and EFS were significantly better in patients with anaplastic lymphoma-kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL), as compared with the remaining PTCL. Multivariate analysis showed that patients attaining complete remission (CR) before ASCT had a statistically significant benefit in terms of OS and EFS (P<0.0001). Overall treatment-related mortality rate was 4.8%. In conclusion, our findings indicate (1) up-front high-dose therapy and ASCT are feasible, but could induce a high rate of long-term CR only in patients with ALK-positive ALCL and (2) the achievement of CR before autografting is a strong predictor of better survival.     

Long-term follow-up of advanced-stage low-grade lymphoma patients treated upfront with high-dose sequential chemotherapy and autograft.

Long-term outcome, after first line intensified high-dose sequential (i-HDS) chemotherapy, was evaluated in 46 patients, aged < or =65 years, with advanced low-grade lymphoma. Seventeen patients had small lymphocytic lymphoma (SLL), 29 had follicular lymphoma (FL), 10 of them with histologic transformation. I-HDS included: (1) tumor debulking, by 2 APO+2 DHAP courses; (2) sequential administration of high-dose (hd) etoposide, methotrexate, and cyclophosphamide, followed by peripheral blood progenitor cell (PBPC) harvest; (3) hd-mitoxantrone + melphalan with PBPC autograft. Ten FL patients had their PBPC immunologically purged ex vivo. There were two treatment-related deaths; five FL patients had short-lasting response followed by disease progression, five SLL reached a stable PR; overall, 34 patients (74%) reached CR. At a median follow-up of 4.3 years, the estimated 9-year OS and EFS were 84% and 45%, respectively. No significant differences were observed in the OS among patients at low, intermediate or high IPI score, with an estimated OS projection of 95%, 78%, and 75%, respectively. FL had longer survival without evidence of residual disease (9-year EFS: 59%) as compared to SLL patients (8.8-year EFS: 17%); however, both groups had prolonged survival and no need of salvage treatment, as shown by the time to disease progression curve, projected to 66% and 62% for SLL and FL, respectively. The results indicate that hd-approach in low-grade lymphoma: (1) is associated with longer progression-free survival as compared to conventional therapies; (2) may imply higher tumor mass reduction in FL as compared to SLL patients; (3) offers long life expectancy, with potential survival benefits at least for patients at intermediate/high IPI score.     

Dexamethasone, carmustine, etoposide, cytarabine, and melphalan (dexa-BEAM) followed by high-dose chemotherapy and stem cell rescue--a highly effective regimen for patients with refractory or relapsed indolent lymphoma

We performed a phase II study to determine the efficacy of maximal cytoreductive therapy with up to five cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) for patients with advanced relapsed or refractory indolent lymphoma. Thirty-two patients with primary refractory or relapsed indolent lymphoma were treated with the Dexa-BEAM regimen. Thirteen patients had primary refractory disease, 4 patients partial remission, and 15 patients first or subsequent relapse. Patients achieving PR or CR received HDCT with ASCT. The conditioning regimen used was BEAM (carmustine [BCNU], etoposide, cytarabine, and melphalan). Twenty-two patients responded to Dexa-BEAM resulting in a response rate of 78%. Maximum response was observed after 3.2 (range 2-5) courses. One patient with progressive disease died in septic shock during neutropenia. Nineteen patients with partial or complete remission after Dexa-BEAM received HDCT. Hematopoietic stem cells (HSC) were collected after two cycles of Dexa-BEAM. The median number of CD34+ HSC reinfused was 3.1 x 10(6)/kg (range 1.6-8.2 x 10(6)/kg). There was no transplantation-related death. All patients receiving HDCT achieved complete remission. Overall survival (OS) and freedom from treatment failure (FFTF) for all patients are estimated to be 68% and 65% at two years, respectively. With a mean follow-up of 20 months (range 8-42 months), 16/19 patients receiving HDCT are in continuous complete remission. The Dexa-BEAM regimen is effective in overcoming drug resistance in patients with indolent lymphoma who failed to respond to conventional treatment or who relapsed. The CR rate of 100% of those patients receiving HDCT and ASCT after maximal cytoreductive treatment with Dexa-BEAM suggests the use of HDCT at the time of maximal response.     

High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma - results of a comprehensive meta-analysis

BACKGROUND: Randomized controlled trials (RCTs) reported conflicting results on the impact of high-dose chemotherapy (HDCT) and autologous stem cell transplantation in the first-line treatment of patients with aggressive non-Hodgkin lymphoma (NHL). METHODS: We performed a systematic meta-analysis to assess the efficacy HDCT compared to conventional chemotherapy in aggressive NHL patients with regard to complete response (CR), overall survival (OS), event-free survival (EFS), toxicity, and impact of the age-adjusted International Prognostic Index (aaIPI) risk factors. We searched the Cochrane Library, MEDLINE and other databases (1/1990 to 1/2005). Hazard ratio (HR), relative risks (RR) and 95% confidence intervals (CIs) were calculated using the fixed effect model. RESULTS: Fifteen RCTs including 2728 patients were identified. HDCT improved CR when compared to conventional chemotherapy (RR 1.11, CI 1.04-1.18). Overall, there was no evidence for HDCT to improve OS (HR 1.05, 95% CI 0.92-1.19) or EFS (HR 0.92, 95% CI 0.80-1.05) when compared with conventional chemotherapy. However, subgroup analysis indicated OS differences (p=0.032) between good (HR 1.46, 95% CI 1.02-2.09) and poor risk (HR 0.95, 95% CI 0.81-1.11) patients. Conflicting results were reported for poor risk patients, where some studies reported improved and others reduced OS and EFS after HDCT. CONCLUSION: There was no evidence that HDCT improved OS and EFS in good risk NHL patients. The evidence for poor risk patients is inconclusive. HDCT should not be further investigated in good risk patients with aggressive NHL but high quality studies in poor risk patients are warranted.     

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.     

Treatment of Relapsed or Refractory Aggressive Non-Hodgkin Lymphoma with Two Ifosfamide-Based Regimens,IMVP and ICE

Abstract

We report the outcomes of 45 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) treated with a combination of ifosfamide, carboplatinum and etoposide (ICE) and 28 patients treated with a combination of ifosfamide, methotrexate and etoposide (IMVP) during two 5-year periods. The response rate (RR) to ICE was 47%, 2-year overall survival (OS) 31% and 2-year event-free survival (EFS) 22%. These results were similar to those obtained with IMVP (RR 39%, 2-year OS 23%, 2-year EFS 13%; p=0.355 for RR, 0.275 for OS, 0.668 for EFS). Higher IPI scores and refractoriness to treatment were negative prognostic factors, immunophenotype (B vs. T) had no influence on prognosis. Changing from IMVP to ICE does not substantially improve the outcome of patients with relapsed or refractory aggressive NHL. Patients with relapsed/refractory aggressive B-NHL do not have a superior out-come in comparison to those with T-NHL if treated with chemotherapy alone.     

High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study.

BACKGROUND: Combination chemotherapy can cure patients with non-Hodgkin's lymphoma (NHL), but those who suffer treatment failure or relapse still have a poor prognosis. High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) can improve the outcome of these patients. We evaluated an intensified high-dose sequential chemotherapy program with a final myeloablative course. PATIENTS AND METHODS: Inclusion criteria were age 18-65 years, histologically proven primary progressive or relapsed aggressive NHL and eligibility for HDCT. The therapy consists of two cycles DHAP: dexamethasone 40 mg (day 1-4), high-dose cytarabine 2 g/m2 12q (day 2), cisplatin 100 mg/m2 (day 51); patients with partial (PR) or complete remission (CR) received cyclophosphamide 4 g/m2 (day 37), followed by peripheral blood stem cell (PBSC) harvest; methotrexate 8 g/m2 (day 1) plus vincristine 1.4 mg/m2 (day 51); and etoposide 500 mg/m2 (day 58-62). The final myeloblative course was BEAM: cytarabine 200 mg/m2 12q (day 81-84), etoposide 150 mg/m2 12q (day 81-84), melphalan 140 mg/m2 (day 80), carmustin 300 mg/m2 (day 80) followed by PBSCT. RESULTS: Fifty-seven patients (median age 43 years, range 24-65) were enrolled: 23 (40%) patients were refractory to primary therapy and 34 (60%) patients had relapsed NHL. The response rate (RR) after 2 cycles of DHAP was 72% (9% CR, 63% PR) and at the final evaluation (100 days post transplantation) 43% (32% CR, 11% PR). Toxicity was tolerable. Median follow-up was 25 months (range 1-76 months). Freedom from second failure (FF2F) and overall survival (OS) at 2 years were 25% and 47% for all patients, respectively. FF2F at 2 years for patients with relapse and for patients refractory to primary therapy were 35% and 9% (P=0.0006), respectively. OS at 2 years for patients with relapse and for patients refractory to primary therapy were 58% and 24% (P=0.0044), respectively. CONCLUSIONS: We conclude that this regimen is feasible, tolerable and effective in patients with relapsed NHL. In contrast, the results in patients with progressive disease are unsatisfactory. This program is currently being modified by addition of rituximab for patients with relapsed aggressive NHL.