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.     

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.     

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。     

High-dose chemotherapy followed by autologous stem cell transplantation for relapsed or refractory Hodgkin lymphoma: prognostic features and outcomes

Between January 1990 and April 2001, 115 patients received high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) for relapsed or refractory Hodgkin lymphoma (HL). With a median follow-up of 58 months (range, 1 - 175 months), 5-year progression-free survival (PFS) and overall survival (OS) were 46% and 58%, respectively. Twelve patients with primary refractory disease had a 5-year PFS of 41% and OS of 58%, not significantly different from those of the remaining cohort. Early and overall regimen related mortality were 7% and 16%, respectively. Male gender (P = 0.04) and a time to relapse (TTR) < 12 months (P = 0.03) were associated with decreased OS by univariate analysis. In multivariate analysis, TTR < 12 months remained statistically significant (P = 0.04). We have confirmed that HDT and ASCT result in long-term survival for a proportion of patients with relapsed or refractory HL. All patients, including those with primary refractory disease, benefited from HDT and ASCT.     

High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed/refractory lymphoma

Although high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), more than 50% of patients will experience relapse following ASCT. High-dose sequential chemotherapy (HDSC) can intensify the conventional salvage treatment and improve the outcome of ASCT by maximal debulking of the tumor load with the use of non-cross resistant drugs, each at their maximal tolerated doses. We conducted a phase II study in 40 patients with relapsed/refractory HD (n = 18) and NHL (n = 22) using HDSC followed by ASCT. Only patients sensitive to salvage chemotherapy were eligible for the protocol, consisting of three phases. Phase I consisted of cyclophosphamide (4.5 g/m²) followed by G-CSF and peripheral blood stem cell (PBSC) collection. Phase II consisted of etoposide (2 g/m²). The transplant phase consisted of mitoxantrone (60 mg/m²) and melphalan (180 mg/m²) followed by PBSC infusion. Eleven out of nineteen patients with B-cell lymphoma received rituximab. Prior to HDSC, 45% of the patients were in complete remission (CR) and 55% were in partial remission (PR). After completion of all phases of the protocol, 35 out of 39 evaluable patients achieved CR (90%) and this was durable in 30 (75%) patients with a projected progression-free survival (PFS) rate at 4 years of 71.7%. Treatment-related mortality rate at day +100 was 2.5% (n = 1). At a median follow-up of 32 months (range, 3 - 61), nine patients relapsed/progressed and eleven patients died. The estimated 4-year PFS and overall survival (OS) were 72.2% and 47.6% in HD patients and 70.3% and 69.4% in NHL patients, respectively. Factors predicting OS were response to conventional salvage therapy and stage prior to salvage therapy. When compared to patients achieving PR, patients who attained CR prior to HDSC had a significantly higher probability of 4-year OS (78.4% vs 31.3%, p = 0.02). Three prognostic subgroups were defined according to the score determined by stage prior to initiation of salvage chemotherapy, remission duration prior to salvage (refractory/early relapse vs. late relapse) and response to salvage. Prognostic score was found to predict OS, PFS and event free survival (EFS). In conclusion, HDSC followed by ASCT is an effective salvage therapy with acceptable toxicity, allowing further consolidation of response attained by conventional salvage therapy.     

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.     

Primary mediastinal large cell lymphoma (PMBL): frontline treatment with autologous stem cell transplantation (ASCT). The GEL-TAMO experience

Given the excellent results obtained with present new induction regimens in PMBL, the role of frontline ASCT is controversial. We present 71 patients with PMBL receiving induction chemotherapy, followed by ASCT as frontline therapy from the GEL-TAMO registry. Most patients presented with high-risk clinical features. At transplant, 49% of patients were in CR, 32% in PR and 18% failed induction therapy; 53% received radiotherapy. After the transplant 75% of patients achieved CR. With a median follow-up of 52.5 months, the OS, PFS and DFS at 4 years from diagnosis were, respectively, 84%, 81% and 81% for the first CR patients and 49%, 42% and 82% for the induction failure (PR and refractory) patients. Disease progression was the main cause of death (79%). By multivariate survival analysis the tumour score, refractory disease at transplant and radiotherapy were independent variables associated with OS and PFS. Our experience, with a prolonged follow-up, shows that patients with PMBL presenting at diagnosis with high-risk features or PR response to induction therapy have an encouraging survival with frontline ASCT. However, patients who received the transplant after failing the induction regimen have a very poor prognosis and should be tested with other innovative approaches. Finally, only a randomized trial could prove the value of ASCT as frontline therapy and also must be considered that addition to Rituximab to induction treatments could make ASCT unnecessary.     

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.     

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。     

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.     

High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy.

PURPOSE: To determine whether high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT) should be included in the initial consolidative treatment of patients with advanced, unfavorable Hodgkin's lymphoma (HL). PATIENTS AND METHODS: One hundred sixty-three patients achieving complete remission (CR) or partial remission (PR) with four initial courses of doxorubicin, bleomycin, vinblastine, and dacarbazine, or other doxorubicin-containing regimens, were randomly assigned to receive HDT plus ASCT (83 patients) versus four courses of conventional chemotherapy (80 patients). Unfavorable HL was defined as the presence of at least two of the following poor prognostic factors: high lactate dehydrogenase level, large mediastinal mass (greater than at least 33% of the thoracic diameter), more than one extranodal site, low hematocrit level, and inguinal involvement. RESULTS: At the end of the treatment program, 92% of patients in arm A and 89% in arm B achieved a CR (P =.6). After a median follow-up of 48 months, the 5-year failure-free survival rates were 75% (95% confidence interval [CI], 65 to 85) in arm A and 82% (95% CI, 73 to 90) in arm B (P =.4). The 5-year overall survival rates were 88% (95% CI, 80 to 96) in arm A and 88% (95% CI, 79 to 96) in arm B (P =.99). The 5-year relapse-free survival rates were 88% in arm A (95% CI, 80 to 96) and 94% in arm B (95% CI, 88 to 100), and the difference was not significant (P =.3). CONCLUSION: Patients with advanced unfavorable HL achieving CR or PR after four courses of doxorubicin-containing regimens have a favorable outcome with conventional chemotherapy. No benefit from an early intensification with HDT and ASCT was shown.     

自体造血干细胞移植可使中国高危多发性骨髓瘤患者获益更多

目的 评价自体造血干细胞移植（ASCT）对初治多发性骨髓瘤（MM）的疗效.方法 选取诱导治疗后获得部分缓解（PR）及以上疗效的42例初治MM患者进行ASCT,中位随访34.2个月后,观察患者的疗效、无进展生存（PFS）和总生存（OS）.选择同时期的49例诱导治疗后获得PR及以[上疗效的初治MM患者,进入非移植组（non-ASCT）,经巩固维持治疗后观察疗效、PFS和OS,比较两组的差异,分析ASCT在MM中的作用.结果 与non-ASCT组相比,ASCT可明显延长患者的OS（未达到/37.2个月,P=O.000）,而且对PFS也有延长趋势（33.9个月/39.8个月,P=0.133）.ASCT可明显改善DSⅢ期（P=0.009）和ISSⅢ期（P=0.049）患者PFS,但对DSⅠ /Ⅱ期和ISS Ⅰ/Ⅱ期患者的PFS改善不明显.ASCT可明显改善诱导治疗后获得CR患者的PFS（P=0.016）,对非常好的PR （VGPR） /PR患者的PFS改善不明显;不同年龄患者OS均明显改善（≤55岁,P=0.039;＞ 55岁,P=0.000）.ASCT可明显改善不同ISS分期患者的OS（Ⅰ/Ⅱ期,P=0.003;Ⅲ期,P=0.012）,对DSⅢ期患者的OS也有明显改善作用（P=0.000）,但对DSⅠ/Ⅱ期患者OS的作用不明显（P=0.446）.诱导治疗后获得CR和VGPR/PR的患者进行移植后,OS可进一步得到改善（CR,P=0.004; VGPR/PR,P=0.004）.结论 ASCT可明显改善初治MM患者的生存,使高龄和分期预后不良的MM患者获益更多.     

Efficacy of up-front treatment with a double stem cell transplantation in multiple myeloma

BACKGROUND: We report the outcome of 53 patients with multiple myeloma (MM), who received autologous stem cell transplantation (ASCT) from April 1996 to September 2004 at our institution and who survived for more than 3 months after the transplant. METHODS: Following the first ASCT, 36 patients underwent an up-front second SCT, which consisted of either an ASCT (n = 24) or a reduced-intensity conditioning allogeneic stem cell transplant (RIST) (n = 12). Seventeen patients were given maintenance treatment. RESULTS: Seventy-seven percent of the patients (n = 41) showed an objective response to the initial therapy prior to the first ASCT. Overall, 60.4% (32 out of 53) and 32.1% (17 out of 53) of the patients had a complete response (CR) and partial response (PR) after the first ASCT, respectively. At the time of analysis, 34 patients (64.2%) were still alive. With a median follow-up of 32 months (range 9-98), the estimated progression-free survival (PFS) and overall survival (OS) at 5 years were 17.0 and 34.9%, respectively. Multivariate analysis revealed that the second SCT, normal hemoglobin and <50% marrow plasma cells were associated with an improved PFS. A second SCT, CR to the first SCT, female gender and an absence of advanced bone lesions were associated with a better OS. CONCLUSIONS: A second SCT is the most significant factor for an improved PFS and OS after the first ASCT (P < 0.001, respectively). Up-front double SCT is needed to improve the OS and PFS in patients with MM.     

The results of consolidation with autologous stem-cell transplantation in patients with peripheral T-cell lymphoma (PTCL) in first complete remission: the Spanish Lymphoma and Autologous Transplantation Group experience.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas associated with poor prognosis with standard chemotherapy. Consolidation with autologous stem-cell transplantation (ASCT) may improve survival. We present 74 patients transplanted in first complete response (CR) from the Spanish Lymphoma and Autologous Transplantation Group cooperative group. PATIENTS AND METHODS: Median age was 46 years. Eighty-eight percent presented advanced (III-IV) Ann Arbor stage; 53% had B symptoms; 52% had high lactate dehydrogenase; 65% had two or three risk factors of the adjusted-International Prognostic Index; 58% presented a high Tumor score and in 14% more than two adverse factors of the Prognostic Index for peripheral T-cell lymphoma (PIT) were observed. RESULTS: With a median follow-up of 67 months from diagnosis, the 5-year overall survival (OS) was 68% and progression-free survival (PFS) reached 63%. The multivariate analysis showed that the only factor associated with a shorter OS and PFS was the presence of more than two risk factors from the PIT risk system. CONCLUSIONS: In a retrospective study with a prolonged follow-up, consolidation with ASCT in CR patients who had presented unfavorable prognostic factors at diagnosis substantially increased the OS and PFS when compared with conventional chemotherapy. The PIT risk system identified 14% of patients without benefit from ASCT consolidation. Thus, other innovative therapies are still necessary in certain cases.     

自体造血干细胞移植治疗多发性骨髓瘤的疗效及预后影响因素分析

目的:探讨自体造血干细胞移植治疗多发性骨髓瘤（MM）的疗效和影响MM患者预后的因素。方法:回顾性分析我院2012年01月至2019年12月37例接受自体造血干细胞移植的MM患者的临床资料,中位随访时间为55（1～91）个月。对37例患者的反应深度、无进展生存时间（PFS）、总生存时间（OS）和影响预后的相关因素进行分析。结果:移植后3月内疗效达到完全缓解率和深度缓解率均优于移植前（P＜0.01,P＜0.05）,移植前后总有效率（ORR）比较无统计学意义（P＞0.05）。患者3年、5年OS率为97.0%、81.4%;3年、5年PFS率为62.7%、51.0%;中位PFS和OS均未获得。单因素分析结果表明移植后3月内疗效获得深度缓解较未获得患者无论是OS 还是PFS均较优 (P均＜0.01);诱导化疗后获得深度缓解可明显延长OS（P＜0.05）;DS分期Ⅰ-Ⅱ期、mSMART3.0危险分层标危患者相比DS分期Ⅲ期、高危患者PFS均有明显优势(P＜0.05)。Cox 多因素回归分析显示,移植后3月内疗效达深度缓解是PFS和OS的独立预后因素,mSMART3.0危险分层也是PFS的独立预后因素。结论:自体造血干细胞移植可以提高 MM 患者的反应深度。移植前后疗效、DS分期和mSMART3.0危险分层均可影响MM患者生存率。移植后3月内疗效达深度缓解是PFS 和OS的独立预后因素,mSMART3.0危险分层也是PFS的独立预后因素。     

自体造血干细胞移植治疗难治复发霍奇金淋巴瘤、灰区淋巴瘤的疗效及预后分析

 目的　评价自体外周血干细胞移植（APBSCT）对霍奇金淋巴瘤（HL）及灰区淋巴瘤患者的缓解率和生存率的作用。方法　回顾性分析30例接受APBSCT的HL及灰区淋巴瘤患者临床资料,中位移植年龄30岁（13～55岁）,病理类型以结节硬化型HL为主,占19例;临床分期以Ⅲ～Ⅳ期为主;分析APBSCT治疗HL及灰区淋巴瘤患者的疗效及生存情况,并探讨了相关影响因素。结果　30例患者均成功采集干细胞,采集单个核细胞中位数为6.8×108／kg（1.0×108／kg～13.8×108／kg）,CD+34 细胞中位数为6.3×106／kg（0.6×106／kg～20.6×106／kg）。中性粒细胞中位植入时间9 d（8～12 d）。28例可评估患者,中位随访时间为18.5个月（2.5～95.0个月）,18例（64.3 %）获完全缓解（CR）,7例（25.0 %）部分缓解（PR）,总反应率（RR）89.3 %。预计5年总生存（OS）率、无进展生存（PFS）率分别为78 %、58 %。7例未缓解患者在移植前更换化疗方案为利妥昔单抗联合化疗后3例获得CR,2例PR。单因素分析提示移植前疾病状态及更换化疗种类数影响OS,移植前放疗史影响PFS。结论　APBSCT可提高HL及灰区淋巴瘤患者CR率,改善患者的OS及PFS;移植前挽救化疗采用利妥昔单抗联合化疗有助于改善移植前疗效;移植前化疗敏感性影响生存,过多化疗种类更换不利生存,移植前放疗史有影响患者PFS的趋势。     

42例原发性中枢神经系统淋巴瘤患者预后影响因素分析

背景与目的：原发性中枢神经系统淋巴瘤（primary central nervous system lymphoma,PCNSL）是发生在脑、脊髓、脑膜或眼的罕见侵袭型非霍奇金淋巴瘤,无CNS之外的部位累及。PCNSL与其他类型淋巴瘤相比,患者生存期短,预后差,且复发率高,未经治疗的患者的中位生存期仅为3个月。近年来研究发现C-MYC、BCL-2、BCL-6、Ki-67等指标在一定程度上影响PCNSL患者预后。因此,通过分析PCNSL相关蛋白表达、治疗方式及其他临床因素对患者预后的影响, 希望为该病的临床治疗及预后评价进一步积累资料。方法：回顾性分析自2013年6月—2021年5月于大连医科大学附属第二医院治疗的42例经病理学检查明确诊断为原发性中枢神经系统弥漫大B细胞淋巴瘤患者的临床资料,包括性别、年龄、病灶数量、美国东部肿瘤协作组（Eastern Cooperative Oncology Group,ECOG）评分、血清乳酸脱氢酶（lactate dehydrogenase,LDH）、病灶是否累及深部脑组织、治疗方案、病理学Hans分型及C-MYC、BCL-2、BCL-6、Ki-67等生物标志物,结合随访调查,了解患者生存时间及生存状况,应用Kaplan-Meier法及log-rank检验分析影响患者无进展生存期（progression-free survival,PFS）和总生存期（overall survival,OS）的预后相关因素,多因素分析采用COX回归模型。结果：42例PCNSL患者中位发病年龄61岁,男女比例为1.33∶1.00,颅脑增强MRI病灶多呈均匀明显强化。所有患者均接受含有大剂量甲氨蝶呤（high-dose methotrexate,HD-MTX）方案化疗,治疗后评价完全缓解（complete response,CR）20例、部分缓解（partial response,PR）5例,疾病稳定（stable disease,SD）11例,疾病进展（progressive disease,PD）6例。中位PFS为21个月,中位OS为34个月,1年PFS率为63.7%,2年PFS率为47.0%;1年OS率为70.8%,2年OS率为55.6%。单因素分析结果显示,影响PFS的因素是HD-MTX多药联合化疗、鞘内化疗及联合利妥昔单抗。影响OS的因素是ECOG评分≥2、C-MYC（+）、BCL-2及C-MYC双表达、HD-MTX多药联合化疗、鞘内化疗及联合利妥昔单抗。多因素分析结果显示：利妥昔单抗治疗是影响PFS的独立预后因素（P=0.020）,ECOG评分、利妥昔单抗是影响OS的独立预后因素（P=0.007;P=0.046）。与未接受巩固治疗的患者相比,接受巩固治疗患者的中位PFS及OS较高;进一步的亚组分析显示,自体干细胞移植（autologous stem cell transplantation,ASCT）组的中位PFS及OS较全脑放疗（whole brain radiation therapy,WBRT）组高,但差异无统计学意义。结论：PCNSL多发于中老年人,男性多于女性,影像学缺乏特异性。ECOG评分≥2与PCNSL患者较差的OS相关。C-MYC（+）、BCL-2及C-MYC双表达可作为指导危险分层的预后标志物。以HD-MTX为基础的多药联合化疗已经成为PCNSL的首选治疗手段,利妥昔单抗的应用可延长生存期。在全身化疗的基础上,联合局部鞘内化疗可以改善预后。进一步的巩固治疗主要包括ASCT及WBRT,可延长PFS及OS,ASCT可以取得与WBRT相似的疗效,且可避免WBRT的晚期神经毒性,但本研究中因样本量及随访时间的限制,未得出明确的统计学结果。     

Comparison of peripheral T-cell lymphomas and diffuse large B-cell lymphoma

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are a biologically heterogeneous subgroup of lymphomas with poor prognosis. In this study, the authors analyzed the clinical behaviors of PTCLs and diffuse large B-cell lymphoma (DLBCL). METHODS: The authors compared the characteristics and outcomes of 59 patients with PTCLs, including 33 angioimmunoblastic T-cell lymphomas and 26 unspecified peripheral T-cell lymphomas, with the characteristics and outcomes of 193 patients with DLBCLs who were treated in the era before rituximab. RESULTS: Based on the clinical characteristics, elevated lactate dehydrogenase (LDH), poor PS, advanced stage, higher International Prognostic Index score, and B symptoms were more common in patients with PTCLs, and bulky mass was more common in patients with DLBCL. The rates of complete response (CR) or an unconfirmed CR (CRu) were higher in patients with DLBCL (72%) than in patients with PTCLs (56%; P = .03). The 5-year overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) rates were 31%, 26%, and 47%, respectively, in patients with PTCLs and 59%, 55%, and 73%, respectively, in patients with DLBCL (P = .001, P < .001, and P = .003, respectively). Although multivariate analysis identified several risk factors that were significant in PTCLs, but not in DLBCLs, for the CR/CRu, OS, PFS, and DFS rates, the immunophenotype was not identified as a risk factor. CONCLUSIONS: The poor response and survival of patients who had PTCLs, compared with patients who had DLBCL, was caused by numerous initial risk factors. T-cell phenotype itself did not appear to have a significant impact on either response or survival.     

99例结外NK/T细胞淋巴瘤预后分析

背景与目的：结外NK/T细胞淋巴瘤的临床及预后存在明显的异质性,以早期病变为主,常见原发灶局部外侵,早期患者放疗为主要治疗手段。本研究旨在分析早期结外NK/T细胞淋巴瘤患者的临床特征、治疗方案、生存预后及可能影响预后的相关因素。方法：收集河北医科大学第四医院2010年1月—2015年12月病理证实的早期NK/T细胞淋巴瘤患者99例,发病平均年龄45.5岁（6~76岁）,男女发病比例2.1∶1;56.6%患者伴有B症状;单纯放疗7例,单纯化疗29例,放化综合治疗63例;中位放疗剂量52 Gy（34~60 Gy）,含左旋门冬酰胺酶或培门冬酶化疗患者73例,不含19例,中位化疗周期为6个（1~12个）。结果：全组患者中位生存时间59.9个月,中位局控时间73.5个月。全组患者1、2和5年总生存率分别为76.8%、68.8%和61.4%;1、2和5年局控率分别为84.5%、81.6%和78.3%;1、2和5年无远处失败生存率分别为83.4%、83.4%和76.8%。单纯放疗或放化疗与单纯化疗比较,5年总生存率为66.0%和47.3%（χ²=4.782,P=0.029）,5年局控率为85.8%和58.7%（χ²=5.949,P=0.015）。不伴原发肿瘤侵犯（primary tumor invasion,PTI）患者与伴有PTI患者比较,5年总生存率为71.5%和55.5%（χ²=4.950,P=0.026）;5年局控率为81.5%和72.0%（χ²=0.983,P=0.321）。全组近期疗效评价达CR者62例（62.6%）,治疗有效率83.8%,疾病控制率85.8%。评价CR患者与非CR患者5年生存率为84.1%和27.6%（χ²=31.566,P=0.000）;5年局控率为92.2%和52.4%（χ²=18.417,P=0.000）。结论：早期结外NK/T细胞淋巴瘤患者单放或放化综合治疗比单纯化疗疗效好,与生存有关的独立预后因素有Ann Arbor分期和乳酸脱氢酶（lactate dehydrogenase,LDH）,与局控有关的独立预后因素仅有LDH。     

Autologous Stem-Cell Transplantation for Poor-Risk and Relapsed Intermediate- and High-Grade Non-Hodgkin's Lymphoma

The primary objective of this study was to evaluate the outcome of patients treated with high-dose chemo-/radiotherapy or high-dose chemotherapy and autologous stem-cell transplant (ASCT) for relapsed, refractory, or poor-risk intermediate-grade (IG) and high-grade (HG) non-Hodgkin's lymphoma (NHL). The secondary objectives were to determine prognostic factors for relapse and survival. Between February 1987 and August 1998, 264 patients, 169 (64%) IG and 95 (36%) HG, underwent high-dose therapy and ASCT at City of Hope National Medical Center (COHNMC). There were 157 (59%) males and 107 (41%) females with a median age of 44 years (range, 5–69 years). The median number of prior chemotherapy regimens was 2 (range, 1–4), and 71 (27%) had received prior radiation as part of induction or as salvage therapy. The median time from diagnosis to ASCT was 10.8 months (range, 3–158 months). Ninety-four patients (36%) underwent transplantation in first complete/partial remission (CR/PR), 40 (15%) in induction failure, and 130 (49%) in relapse or subsequent remission. Two preparative regimens were used: total body irradiation/high-dose etoposide/cyclophosphamide (TBI/VP/CY) in 208 patients (79%) and carmustine/etoposide/cyclophosphamide (BCNU/VP/CY) in 56 patients (21%). One hundred sixty-three patients (62%) received peripheral blood stem cells (PBSC) and 101 (38%) received bone marrow (BM) alone or BM plus PBSC. At a median follow-up of 4.43 years for surviving patients (range, 1–12.8 years), the 5-year Kaplan-Meier estimates of probability of overall survival (OS), progression-free survival (PFS), and relapse for all patients are 55% (95% confidence interval [CI]: 49%–61%), 47% (95% CI: 40%–53%), and 47% (95% CI: 40%–54%), respectively. There were 27 deaths (10%) from nonrelapse mortality, including seven (3%) patients who developed second malignancies (five with myelodysplasia/acute myelogenous leukemia and two with solid tumors). By stepwise Cox regression analysis, disease status at ASCT was the only prognostic factor that predicted for both relapse and survival. The 5-year probability of PFS for patients transplanted in first CR/PR was 73% (95% CI: 62%–81%) as compared to 30% (95% CI: 16%– 45%) for induction failure and 34% (95% CI: 26%–42%) for relapsed patients. Our results further support the role of high-dose therapy and ASCT during first CR/PR for patients with poor-risk intermediate- and high-grade NHL. Early transplant is recommended for patients failing initial induction therapy or relapsing after chemotherapy-induced remission. Relapse continues to be the most common cause of treatment failure. An alternative approach to prevent relapse, the incorporation of radioimmunotherapy into the high-dose regimen, is being investigated. The development of a second malignancy is a serious complication of high-dose therapy, which requires close surveillance.