High-dose therapy and autologous stem cell transplantation for chemoresistant Hodgkin lymphoma: the Seattle experience

BACKGROUND.: High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the standard treatment for patients with chemosensitive relapsed/refractory Hodgkin lymphoma (HL), but this therapy is commonly denied to patients with resistant disease. We explored the utility of HDT and ASCT for chemoresistant HL because there are few established therapies for these patients. METHODS.: Sixty-four chemoresistant HL patients underwent HDT followed by ASCT at our center. Baseline characteristics included median age = 35 years (range, 14-59 years), stage III/IV = 49 (77%), nodular sclerosis histology = 51 (80%), and prior radiation = 32 (50%). Twenty-six patients (41%) received total body irradiation (TBI)-based regimens, and 38 (59%) underwent non-TBI conditioning. RESULTS.: The estimated 5-year overall survival (OS) and progression-free survival (PFS) were 31% and 17%, respectively (median follow-up = 4.2 years). Multivariate analysis only identified year of transplant as independently associated with improved OS (P = .008) and PFS (P = .04), with patients receiving transplants in later years having better outcome. The probabilities of 3-year PFS for patients receiving transplants during 1986 to 1989, 1990 to July 1993, August 1993 to 1999, and 2000 to 2005 were 9%, 21%, 33%, and 31%, respectively. CONCLUSIONS.: These data suggest that HDT and ASCT may result in prolonged remissions and survival for a subset of chemoresistant HL patients, with improved outcomes in patients receiving transplants more recently. Cancer 2008. (c) 2008 American Cancer Society.     

Chemoresistance can be overcome with high-dose chemotherapy and autologous stem-cell transplantation for relapsed and refractory Hodgkin lymphoma

BackgroundHigh-dose therapy and autologous stem-cell transplant (HDT/ASCT) is the preferred treatment of chemosensitive relapsed/refractory Hodgkin lymphoma (HL). The role for HDT/ASCT in chemoresistant HL is less well defined. We evaluated long-term outcomes of relapsed/refractory HL patients whose disease was refractory to secondary chemotherapy preceding HDT/ASCT.Patients and methodsAll HL patients who underwent HDT/ASCT in British Columbia for primary progression (PP, defined as progression within 3 months of initial therapy completion) or first relapse (REL1) were reviewed. Patients were grouped based on response to secondary chemotherapy as sensitive (S), resistant (R), and untested/unknown (U).ResultsA total of 256 patients underwent HDT/ASCT for PP (35%) or REL1 (65%) between 1985 and 2011. At median follow-up of 11.7 years, 58% were alive without HL, 36% relapsed; 6% died of transplant-related mortality, 3% secondary malignancies, and 3% unrelated causes. For PP/S, PP/R, and PP/U groups, 10-year FFS were 47%, 31%, and 38%; 10-year OS were 52%, 29%, and 37%, respectively. For REL1/S, REL1/R, and REL1/U groups, 10-year FFS were 64%, 51%, and 81%; 10-year OS were 71%, 59%, and 79%, respectively. In multivariate analysis, resistance to secondary chemotherapy predicted for post-transplant mortality in the PP (P = 0.04) but not REL1 (P = 0.16) groups.ConclusionIn this large uniformly treated cohort of HL patients with long-term follow-up, chemoresistance preceding HDT/ASCT was identified as a poor prognostic factor; however, this factor can be partially overcome by HDT/ASCT, resulting in cure in 30%–50% of patients. HDT/ASCT should therefore be considered in all transplant eligible patients, regardless of responsiveness to salvage chemotherapy.     

Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma

BACKGROUND: The objective was to determine the prognostic value of functional imaging (FI) in predicting outcome of patients with recurrent/refractory Hodgkin lymphoma (HL) before undergoing high-dose chemotherapy with autologous stem cell transplantation (ASCT). METHODS: Clinical and imaging data were retrospectively reviewed in 211 consecutive patients treated with ASCT from February 1993 to May 2004. The FI results were correlated with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. RESULTS: Responses were assessed by conventional criteria and evaluated by positron emission tomography (PET) (n = 68) and gallium scans (n = 144) before ASCT. A complete response (CR) or unconfirmed CR (CRu) was seen in 51% of patients, a partial response (PR) in 41% of patients, and stable or progressive disease in 7% of patients. FI was positive in only 6 of 110 (5%) of CR/CRu patients, in 48 of 86 (56%) of PR patients, and in all 3 patients with progressive disease. The 3-year PFS was 69% for patients with negative FI versus 23% for patients with positive FI (P < .0001). The 3-year OS rates were 87% and 58%, respectively (P < .0001). The 3-year PFS for patients in PR with negative FI was 51% comparable to patients in CR (76%) versus 27% for patients in PR with positive FI (P < .0001). In a multivariate model, positive FI was found to be independently prognostic of PFS. CONCLUSIONS: Pretransplant FI status predicts outcome in patients with recurrent/refractory HL. Positive FI confers a poor prognosis, independent of other traditional presalvage prognostic factors.     

Autologous stem cell transplantation for patients with active Hodgkin's lymphoma: long-term outcome of 61 patients from a single institution

Sixty-one patients with refractory or relapsed Hodgkin's lymphoma (HL) underwent high-dose chemotherapy and autologous stem cell transplantation (ASCT). All patients had active HL at the time of ASCT: 13 patients had partial remission, 14 refractory disease, 18 sensitive relapse, 4 resistant relapse, and 12 nontreated relapse. Overall transplant-related mortality (TRM) was 16.4% at 1 year. Twenty-eight patients (46%) achieved complete remission (CR). Actuarial 5-year overall survival (OS) and progression-free survival (PFS) were 51% and 47%, respectively. Patients with positive gallium-67 scintigraphy at 3 - 6 months after transplantation had a worse PFS at 5 years (28%) than those with negative 67Ga scan (80%) (p = 0.016), whereas no statistical differences were observed between patients with residual mass and those in CR according to computed tomography scan. In multivariate analysis, bulky disease at diagnosis, bone marrow stem cells, and stage IV at transplant were the only adverse prognostic factors significantly influencing OS. Bulky disease at diagnosis and stage IV at transplant adversely influenced PFS. Although long-term outcome of patients with active HL at the time of ASCT is poor due to a high TRM and a low CR after transplantation, a subgroup of patients with no adverse prognostic factors at ASCT gain benefit from this treatment.     

Disease characteristics of diffuse large B-cell lymphoma predicting relapse and survival after autologous stem cell transplantation: A single institution experience

While various tools such as the International Prognostic Index (IPI) and its derivatives exist for risk-stratification of diffuse large B-cell lymphoma (DLBCL) at diagnosis, patient and disease characteristics capable of predicting outcome after high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) are not clearly defined. We retrospectively analyzed medical records of 111 DLBCL patients (78 relapsed and 33 refractory) who underwent HDC/ASCT at our institution from 2010-2015. After a median follow-up time of 4.6 years (interquartile range [IQR] 2.2-8.1), the likelihood of 5-year progression-free survival (PFS) was 62.2% (95% CI, 53.4%-72.4%) and the likelihood of 5-year overall survival (OS) was 68.9% (95% CI, 60.7%-78.2%). More than three chemotherapy regimens prior to ASCT was the only variable associated with lower likelihood of PFS (P = .004) and OS (P = 0.026). Male gender and high IPI score at time of ASCT were also associated with lower likelihood of PFS (P = .043; P = .013). NCCN IPI and age-adjusted IPI at time of ASCT were not predictive of outcome following ASCT. Patients with refractory and relapsed disease had similar outcomes post-ASCT (P = .207 for PFS, P = .073 for OS).     

Long-term follow-up of high-dose treatment with autologous haematopoietic progenitor cell support in 693 patients with follicular lymphoma: an EBMT registry study.

To evaluate the outcome of a large series of patients who received high-dose treatment (HDT) for follicular lymphoma (FL), 693 patients undergoing HDT (total-body irradiation (TBI)-containing regimen: 58%; autologous bone marrow (BM)/peripheral blood progenitor cells (PBPCs): 378/285 patients) were included in the study. A total of 375 patients (54%) developed recurrent lymphoma, 10-year progression-free survival (PFS) being 31%. On multivariate analysis, younger age (P=0.003) and HDT in first complete remission (CR1) (P<0.001) correlated with longer PFS. With a median follow-up of 10.3 years, 330 patients died. Ten-year overall survival (OS) from HDT was 52%. Shorter OS was associated on multivariate analysis with older age (P<0.001), chemoresistant disease (P<0.001), BM+PBPC as source of stem cells (P=0.007) and TBI-containing regimens (P=0.004). Thirty-nine patients developed secondary myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), in 34 cases having received TBI as the conditioning regimen. The 5-year non-relapse mortality (NRM) was 9%. On multivariate analysis, older age (P<0.001), refractory disease (P<0.001) and TBI (P=0.04) were associated with a higher NRM. This long follow-up study shows a plateau in the PFS curve, suggesting that a selected group of patients might be cured with HDT. On the downside, TBI-containing regimens are associated with a negative impact on survival.     

Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma

BackgroundThe purpose of this study was to assess prognostic factors and outcome of patients with relapsed/refractory Hodgkin's lymphoma (HL) who received high-dose chemotherapy and autologous stem-cell transplant (ASCT).Patients and methodsData on 195 patients who received ASCT between 1985 and June 2005 were reviewed. Median time from first treatment to ASCT was 2.6 years (0.4–27.3). Demography at ASCT was 61% stage IV, median age 31 years (18–69), median prior treatment (tx) regimens 3 (2–7), median Hasenclever index 3 (0–6); 150 patients had responding disease [54 complete remission (CR), 96 partial remission (PR)], and 45 patients had untested relapse/refractory disease.ResultsPost-ASCT, 61% (119/195) patients attained CR with an overall response (CR + PR) of 85%. Twelve patients had nonrelapse mortality. Of 119 patients attaining CR, 27 relapsed: 3 after attaining CR for >5 years and 1 after attaining CR for >10 years. Median overall survival (OS)/progression-free survival (PFS) from ASCT was 9 years/2.9 years. Five-year OS/PFS was 55% of 44% and 10-year OS/PFS was 49.4% of 37% for whole group. Twenty (10%) patients developed second cancer (seven secondary acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS)). Probability of developing second cancer at 10 years was 14.7% (95% confidence interval 8.9% to 23.8%) and 24.8% at 19 years.ConclusionThese data provide the longest follow-up reported for patients receiving ASCT for relapsed/refractory HL. In addition to previously described prognostic factors, our data show that Hasenclever index <3 influences outcome favorably and attaining CR at ASCT leads to a better outcome.     

霍奇金淋巴瘤复发、难治的相关因素分析

 目的　探讨霍奇金淋巴瘤（HL）复发、难治的相关因素,分析复发、难治性HL患者的生存情况。方法　对62例HL患者的临床资料进行回顾性分析,对其临床特征、治疗方法等与复发、难治的关系进行相关性分析。结果　62例HL患者中,12例（19.35 %）为复发、难治性。病理类型（P＝0.026）、淋巴结区≥3个（P＝0.030）和大包块（P＝0.006）与复发、难治有关。复发、难治性HL患者中位生存时间为69.5个月（27～129个月）,复发、难治性HL及其他HL患者的5年总生存（OS）率分别为66.7 %和88.8 %,二组差异无统计学意义（P＝0.117）,无事件生存（EFS）率分别为52.4 %和87.9 %,差异有统计学意义（P＝0.006）。结论　HL的病理类型、淋巴结区≥3个和大包块与复发、难治关系密切,同时,短期（<1年）内复发是复发、难治性HL患者的不良预后因素,值得关注。     

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.     

LACE‐conditioned autologous stem cell transplantation for relapsed or refractory diffuse large B‐cell lymphoma: treatment outcome and risk factor analysis from a single centre

High‐dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed diffuse large B‐cell lymphoma. We have analysed 51 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara‐C), cyclophosphamide, etoposide) conditioning for relapsed (n = 34, 67%) or primary refractory (n = 17, 33%) diffuse large B‐cell lymphoma. With a median follow‐up of 60 months (range 2–216) the probabilities of overall survival (OS) and progression‐free survival (PFS) at 5 years were 47 and 42%, respectively. The cumulative treatment‐related mortality was 10% (n = 5). Probabilities for OS and PFS at 5 years were 56 and 50% for patients with chemosensitive and 29 and 27% for patients with chemorefractory disease. In multivariate analysis abnormal pre‐ASCT levels of C‐reactive protein (>5 mg/L) were identified as a risk factor for worse OS, whereas abnormal pre‐ASCT levels of C‐reactive protein and chemoresistance predicted inferior PFS. LACE followed by ASCT is an effective treatment for approximately half of patients with chemosensitive relapsed diffuse large B‐cell lymphoma, and a proportion of chemorefractory patients also benefit. Copyright © 2010 John Wiley & Sons, Ltd.     

含利妥昔单抗化疗方案治疗套细胞淋巴瘤效果分析

目的探讨含利妥昔单抗化疗方案治疗套细胞淋巴瘤(MCL)患者效果及预后影响因素。方法回顾性分析2007年6月至2018年11月苏州大学附属第一医院血液科收治的56例≤65岁MCL患者临床资料,化疗方案中均包括利妥昔单抗,观察临床特征、治疗方案及生物学指标对总生存(OS)和无进展生存(PFS)的影响。结果56例患者中位发病年龄57岁,男性43例,女性13例。24例接受R-CHOP方案化疗;29例接受含阿糖胞苷方案化疗,其中15例接受R-hyper CVAD/R-MA方案化疗,14例接受R-CHOP/R-DAHP交替治疗;3例接受其他方案化疗。19例接受自体造血干细胞移植(ASCT)巩固治疗。56例患者中位OS时间74个月,2年OS率83.8%,3年OS率70.9%,2年PFS率72.0%,3年PFS率49.7%。国际预后指数(IPI)评分和治疗中是否接受ASCT是MCL患者OS和PFS的独立影响因素。含阿糖胞苷治疗组总有效率(ORR)93.1%,优于R-CHOP方案组(83.3%),差异无统计学意义(χ²=0.465,P=0.495);两组间OS及PFS差异均无统计学意义(OS:χ²=0.291,P=0.590;PFS:χ²=0.912,P=0.339)。诱导化疗达缓解的MCL患者中,ASCT巩固治疗可延长中位OS时间(72个月比124个月,χ²=3.973,P=0.040)及中位PFS时间(34个月比90个月,χ²=3.984,P=0.046)。简化MCL国际预后指数(sMIPI)评分中高危组患者中接受ASCT巩固治疗患者OS和PFS优于未接受ASCT治疗者(OS:χ²=5.037,P=0.025;PFS:χ²=6.787,P=0.009),而sMIPI评分低危组患者中,是否接受ASCT组间OS、PFS差异均无统计学意义(均P>0.05)。结论含阿糖胞苷的化疗方案对改善MCL患者的预后和生存并不理想。对于诱导化疗达缓解及sMIPI评分中高危组的MCL患者,ASCT巩固治疗可改善其预后,可作为年轻患者的一线巩固治疗方案。     

自体造血干细胞移植治疗霍奇金淋巴瘤38例临床疗效及预后影响因素分析

目的 探讨自体造血干细胞移植（ASCT）治疗霍奇金淋巴瘤（HL）的临床疗效以及影响预后的因素。方法 回顾2007年10月至2021年10月于郑州大学附属肿瘤医院经ASCT治疗的HL38例患者资料,Kaplan-Meier和Cox方法分析移植后疗效以及预后影响因素。结果 38例移植患者均获得造血重建。全组患者移植前后CR率分别为55.3%和81.6%,5年PFS和OS分别为76.1%和79.0%。单因素分析显示B症状、IPS评分、移植前缓解状态、结外受累和预处理方案（均P<0.05）是影响HL患者ASCT预后的因素,多因素分析显示B症状（P<0.05）是影响5年PFS的独立危险因素。结论 ASCT治疗高危、复发难治HL患者的疗效显著,有B症状是影响移植预后的独立危险因素。     

Outcomes Related to FDG-PET-CT Response in Patients With Hodgkin Lymphoma Treated With Brentuximab-Vedotin at Relapse or Consolidation

BackgroundBrentuximab-vedotin (BV) monotherapy has shown high efficacy in heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma (HL) after high-dose chemotherapy or autologous stem cell transplantation (ASCT). We retrospectively analyzed the outcomes of treatment with BV of HL patients and examined the predictive ability of PET-CT for response in this setting.Patients and methodsRecords of 49 HL patients (median age, 39 years, 55% male) treated with BV for relapse (71.4%) or consolidation (28.6%) post-ASCT were analyzed. Patients who did not reach complete response (CR) on PET/CT after 4 cycles (non-responders) discontinued BV and received the next treatment line. Overall survival (OS) and progression-free survival (PFS) were compared between responders and non-responders.ResultsAfter a median follow-up of 19.1 months, all consolidation patients were alive and none progressed. Median OS in 23 relapsed patients that did not achieve CR after 4 cycles and continued to the next treatment was 55.0 months, while all those in CR (n = 24) were alive (P = .0120). No statistically significant differences in OS were observed between responders and non-responders with relapsed HL (P = .1072). Median PFS evaluated after 4 BV cycles was significantly longer in responders compared to non-responders (47.9 vs. 1.5 months, P < .0001). Neuropathy and neutropenia were the main toxicities observed.ConclusionsHL patients treated with BV for relapse or consolidation who achieved CR by PET-CT after 4 cycles showed improved PFS and OS compared to non-responders. Non-responders treated for relapsed HL who proceeded to the next treatment line demonstrated comparable OS to responders.     

Primary refractory and relapsed Hodgkin lymphoma with unfavorable prognosis

In this retrospective clinical study 100 patients with primary unfavorable prognosis stage II Hodgkin lymphoma (HL) (n = 50) or stage IV HL (n = 50). The ABVD chemotherapy allowed to achieve remission in 90% of cases with 5-year relapse-free survival (RFS) and overall survival (OS) of 64% and 92%, the basic BEACOPP regimen lead to the same 90% remission rate with 74% DFS and 94% OS. These results for ABVD and basic BEACOPP regimens are characterized by similar statistic values (p = 1.0; p = 0.6; p = 0.9), although the use basic BEACOPP lead to statically valid decrease of grade III-IV toxicity (p = 0.005). The occurrence of primary refractory HL was slightly higher in basic BEACOPP group (18% versus 10% in ABVD group), although this difference had no statistical value (p = 0.3) and was probably due to higher number of patients with > 1 extranodal localizations. The occurrence of primary refractory HL correlated to disease stage: 6% in stage II and 22% in stage IV (p = 0.04). HL relapse frequency in ABVD and BEACOPP groups was similar (12% and 8%), there was no statistically valid difference (p = 0.5). In ABVD and basic BEACOPP recipients with stage II/IV HL the primary refractory disease rate was 15%, relapse rate was 10%. Five-year OS in primary refractory and relapsed patients was lower, than in general patient population (64% and 70% compared to 80%), although the difference had no statistical significance (p = 0.6, p = 0.7).     

Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma

BackgroundNovel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of risk factors (RFs) for survival after ASCT.MethodsIn this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resulting prognostic score was then validated in an independent clinical sample (part II).ResultsIn part I, we identified 656 patients treated for relapsed/refractory HL between 1993 and 2013 with a median follow-up of 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy [<partial remission by computed tomography (CT)] as significant and non-redundant RFs for PFS. A risk score composed of these equally weighed RFs was significantly prognostic for PFS (HR = 1.67 for each additional RF; P < 0.0001). Validation in an independent sample of 389 patients treated in different clinical settings with evaluation of response to salvage therapy by functional imaging instead of CT confirmed the excellent discrimination of risk groups and significant prognostication of PFS and overall survival (OS) after ASCT (HR = 1.70 and HR = 1.63, respectively; P < 0.0001).ConclusionsBased on this large study (n = 1045), precise and valid risk prognostication in HL patients undergoing ASCT can be achieved with five easily available clinical RFs. The proposed prognostic score hence allows reliable stratification of patients for innovative therapeutic approaches in clinical practice and future trials.Registered trialsGHSG HD10 NCT00265018, HD11 NCT00264953, HD12 NCT00265031, HD13 ISRCTN63474366, HD14 ISRCTN04761296, HD15 ISRCTN32443041 and HDR2 NCT00025636.     

高剂量化放疗联合自体造血干细胞移植治疗霍奇金淋巴瘤11例报告

背景与目的：高剂量化放疗（high dose chemoradiotherapy,HDT)联合自体造血干细胞移植（autologous hemotopoietic stem cell,ASCT)巳成为复发与耐药霍奇金淋巴瘤（HL）患者重要的解救治疗手段之一,但对于初治晚期患者的作用还不明确。本论文的目的是进一步评价HDT联合ASCT在HL综合治疗中的地位,特别是探讨其对于初治晚期具有明显不良预后因素患者的作用。方法：11例复发和具有不良预后因素的晚期HL患者,其中初始9例,复发2例;自体骨髓移植（autologus bone marrow transplantation,ABMT)1例,自体外周血干细胞移植（autologous peripheral bllod stem cell transplantation,APBSCT)10例。诱导治疗后4例完全缓解（CR）,7例部分缓解（PR）。7例采用高剂量化疗联合全身照射（total body irradiation,TBI)或全淋巴结照射（total lymph node irradiation,TLI)/次全淋巴结照射（subtatal lymph node irradiation,STLI)作用预处理方案,4例采用单纯高剂量化疗作为预处理方案。5例患者于移植后进行了原发部位的补量放疗。结果：移植前达CR者为巩固治疗,达PR后移植后2例达CR,1例达PR,4例稳定（SD）;SD者均为骨受侵。中位随访13（1-84）个月,所有患者全部生存。4例无病生存;4例骨受侵者疾病无进展生存;3例复发,其中1例经复发部位放疗后,目前又无瘤生存42个月,另外2例正进一步治疗中;根据寿命表法分析,全组6年累积疾病无进展生存率（progression-free survival,PTS)为55.68%,6年累积总生存率（OS）为100%;初治患者6年PFS为62.5%。移植相关毒性主要为IV度骨髓抑制,未见明显心、肝、肾毒性,无移植相关死亡。结论：HDT联合ASCT是治疗复发和具有不良预后因素的晚期HL的一种值得进一步探讨的方法。     

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.     

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.     

High‐dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors

High‐dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high‐dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high‐dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression‐free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F‐fluoro‐deoxy‐d ‐glucose positron emission tomography (¹⁸FDG‐PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow‐up of 45 months (range 1–164 months), 5‐year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F‐fluoro‐deoxy‐d ‐glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL. Copyright © 2012 John Wiley & Sons, Ltd.     

High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial.

PURPOSE: To determine, in a randomized clinical trial, whether high-dose therapy (HDT) followed by autologous stem-cell transplantation is more effective than standard treatment with regard to progression-free survival (PFS) and overall survival (OS) in patients with relapsed follicular non-Hodgkin's lymphoma; and to assess the additional value of B-cell purging of the stem-cell graft with regards to PFS and OS. PATIENTS AND METHODS: Patients received three cycles of chemotherapy. Responding patients with limited bone marrow infiltration were eligible for random assignment to three further cycles of chemotherapy (C), unpurged HDT (U), or purged HDT (P). RESULTS: Between August 1993 and April 1997, 140 patients were registered from 36 centers internationally, and 89 were randomly assigned. Reasons for not randomizing included patient refusal, early progression, or death on induction therapy. With a 69-month median follow-up, the log-rank P value for PFS and OS were.0037 and.079, respectively. For PFS, the hazard ratios (95% CIs) for U versus C, P versus C, and P versus U were 0.33 (0.16 to 0.70), 0.38 (0.19 to 0.79), and 1.02 (0.51 to 2.05), respectively. The hazard ratio (95% CI) for C versus U + P was 0.30 (0.15 to 0.61). Hazard ratios (95% CIs) for OS were 0.43 (0.18 to 1.06), 0.43 (0.18 to 1.02), and 0.72 (0.32 to 1.63). For C versus U + P, the hazard ratio (95% CI) was 0.40 (0.18 to 0.89). Kaplan-Meier estimates (95% CIs) of 2-year PFS for C, U, and P were 26% (8% to 44%), 58% (37% to 79%), and 55% (34% to 75%), respectively. OS at 4 years for C, U, and P are 46% (25% to 67%), 71% (52% to 91%), and 77% (60% to 95%) respectively. CONCLUSION: HDT significantly improves PFS and OS. There is no clear evidence of benefit through purging.