Outcome and prognostic factors in advanced Hodgkin's disease treated with high-dose chemotherapy and autologous stem cell transplantation: a study of 341 patients.

BACKGROUND: The reported probability of survival of patients with Hodgkin's disease (HD) following high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT) is 35-65% at 5 years. The Polish Lymphoma Research Group investigated retrospectively prognostic factors for overall survival (OS) and event-free survival (EFS), and the risk of secondary malignancies in a large series of patients who underwent HDC/ASCT. PATIENTS AND METHODS: The data of 341 consecutive patients treated in 10 centers from 1990 to 2002 were collected and analyzed. RESULTS: The actuarial 5-year OS and EFS were 64% [95% confidence interval (CI) 57% to 71%] and 45% (95% CI 39% to 51%), respectively. In the multivariate model, unfavorable prognostic factors for EFS were less than partial response at the time of ASCT [relative risk (RR), 2.92 (95% CI 1.68-5.08); P<0.001] and three or more previous chemotherapy lines (RR, 2.16; 95% CI 1.42-3.30; P<0.001). These two factors were also associated with unfavorable OS (RR, 3.32; 95% CI 1.90-5.79; P<0.001 and RR, 2.34, 95% CI 1.51-3.64; P<0.001). Five-year cumulative risk of secondary malignancy was 8.4% (95% CI 2% to 13%) and the only identified risk factor was splenectomy (P=0.02). CONCLUSIONS: HDC/ASCT should be considered early in the course of disease for patients with a response after standard therapy.     

Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Espa?ol de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group.

PURPOSE: To analyze clinical outcome and significant prognostic factors for overall (OS) and time to treatment failure (TTF) in a group of 494 patients with Hodgkin's disease (HD) undergoing autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Detailed records from the Grupo Espa?ol de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group Database on 494 HD patients who received an ASCT between January 1984 and May 1998 were reviewed. Two hundred ninety-eight males and 196 females with a median age of 27 years (range, 1 to 63 years) received autografts while in complete remission (n = 203) or when they had sensitive disease (n = 206) or resistant disease (n = 75) at a median time of 26 months (range, 4 to 259 months) after diagnosis. Most patients received high-dose chemotherapy without radiation for conditioning (n = 443). The graft consisted of bone marrow (n = 244) or peripheral blood (n = 250). RESULTS: The 100-day mortality rate was 9%. The 5-year actuarial TTF and OS rates were 45.0% (95% confidence interval [CI], 39.5% to 50.5%) and 54.5% (95% CI, 48.4% to 60.6%), respectively. In multivariate analysis, the presence of active disease at transplantation, transplantation before 1992, and two or more lines of therapy before transplantation were adverse prognostic factors for outcome. Sixteen patients developed a secondary malignancy (5-year cumulative incidence of 4.3%) after transplantation. Adjuvant radiotherapy before transplantation, the use of total-body irradiation (TBI) in the conditioning regimen, and age > or = 40 years were found to be predictive factors for the development of second cancers after ASCT. CONCLUSION: ASCT achieves long-term disease-free survival in HD patients. Disease status before ASCT is the most important prognostic factor for final outcome; thus, transplantation should be considered in early stages of the disease. TBI must be avoided in the conditioning regimen because of a significantly higher rate of late complications, including secondary malignancies.     

Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin's lymphoma autografted after a first relapse.

PURPOSE: To analyse outcome and prognostic factors for overall survival (OS) and time to treatment failure (TTF) in 357 patients with Hodgkin's lymphoma (HL) undergoing an autologous stem cell transplantation (ASCT) after a first relapse and reported to the The Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea (GEL/TAMO) Cooperative Group. METHODS: Two hundred and twenty males and 137 females with a median age of 29 years were autografted in second remission (n=181), first sensitive relapse (n=148) and first resistant relapse (n=28). RESULTS: Five-year actuarial TTF and OS were of 49% +/- 3% and 57% +/- 3%. Advanced stage at diagnosis, complementary radiotherapy before ASCT, a short first complete response (CR) and detectable disease at ASCT adversely influenced TTF. Year of transplant < or =1995, bulky disease at diagnosis, a short first CR, detectable disease at ASCT and > or =1 extranodal areas involved at ASCT were adverse factors for OS. CONCLUSIONS: ASCT constitutes a therapeutic option for HL patients after a first relapse. Promising results are observed in patients with low tumour burden at diagnosis, autografted after a long CR and without detectable disease at ASCT. Innovative approaches should be pursued for patients with risk factors at relapse.     

Clinical characteristics and outcomes of relapsed follicular lymphoma after autologous stem cell transplantation in the rituximab era

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a therapeutic option for patients with relapsed follicular lymphoma (FL). The clinical characteristics and outcomes of FL relapse after ASCT in the rituximab era have not yet been fully elucidated. We retrospectively reviewed 414 FL patients treated with ASCT between 2000 and 2014 in four hematology departments. All patients received rituximab as a first-line treatment. We specifically analyzed the clinical characteristics, treatment strategies at relapse, and outcomes of 95 patients (23%) who relapsed after ASCT. The patients (median age, 57 y) received a median of two lines of therapy (range, 2-6) prior to ASCT, with 92% in complete response (CR) or partial response (PR) before ASCT. Histological transformation at relapse after ASCT was observed in 20% of the patients. Treatment at relapse after ASCT consisted of chemotherapy with or without rituximab (n = 45/90, 50%), targeted agents (18%), rituximab monotherapy (14%), or consolidation allogeneic transplantation after induction chemotherapy (12%) and radiotherapy (6%). After relapse, the median progression-free survival (PFS) and overall survival (OS) were 1 year (95% CI, 0.541-1.579) and 5.5 years (95% CI, 1.910-9.099), respectively. In the multivariate analysis, histological transformation (HT) was associated with OS (P = .044; HR 2.439; 95% CI, 1.025-5.806), and a high FLIPI score at relapse was associated with PFS (P = .028; HR 2.469; 95% CI, 1.104-5.521). This retrospective study showed that the period of PFS of patients who relapsed after ASCT is short. A biopsy should be performed for these patients to document the HT. Our results indicate that new treatment strategies will need to be developed for these patients.     

Management of adult patients with acute lymphoblastic leukemia in first complete remission

BACKGROUND:

The optimal postremission therapy in adults with acute lymphoblastic leukemia (ALL) is still a matter of debate. The objective of this study was to compare the various potential therapeutic options for patients who achieved first complete remission.

METHODS:

The authors conducted a systematic review and meta‐analysis of randomized trials, including patients with standard‐risk (SR) All and high‐risk (HR) ALL who received first postremission therapy. Outcomes assessed were all‐cause mortality (ACM), disease recurrence (relapse), and nonrelapse mortality (NRM). Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled.

RESULTS:

Overall, there was a significant reduction in ACM in the allogenic stem cell transplantation (alloSCT) arm (RR, 0.88; 95% CI, 0.8‐0.97) compared with autologous stem cell transplantation (ASCT) or chemotherapy. Subgroup analyses revealed a similar pattern among SR patients (RR, 0.8; 95% CI, 0.68‐0.94) but a nonsignificant advantage for alloSCT among HR patients (RR, 0.88; 95% CI, 0.76‐1.01). There was an increase in NRM (RR, 2.99; 95% CI, 1.37‐6.53) and a decrease in the relapse rate in the alloSCT arm (RR, 0.52; 95% CI, 0.33‐0.83). There was no difference in ACM or the relapse rate between the ASCT and chemotherapy arms.

CONCLUSIONS:

Overall, alloSCT was superior to ASCT or chemotherapy for patients with ALL in first complete remission. The survival advantage was of greater statistical significance for patients with SR ALL than for patients with HR ALL. Cancer 2010. © 2010 American Cancer Society.     

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.     

High-dose therapy and autologous stem-cell transplantation versus conventional-dose consolidation/maintenance therapy as postremission therapy for adult patients with lymphoblastic lymphoma: results of a randomized trial of the European Group for Blood and Marrow Transplantation and the United Kingdom Lymphoma Group.

PURPOSE: To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission therapy in adults with lymphoblastic lymphoma. PATIENTS AND METHODS: One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT. In some centers, patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation (BMT) without randomization. RESULTS: Of the 119 patients entered, 111 were assessable for response to induction therapy. The overall response rate was 82% (56% complete response, 26% partial response). Of the 98 patients eligible for randomization, 65 were randomized, 31 to ASCT and 34 to CC. Reasons for failure to randomize included patient refusal (12 patients), early progression or death on induction therapy (eight patients), excessive toxicity of induction regimen (six patients), and elective allogeneic BMT (12 patients). With a median follow-up of 37 months, the actuarial 3-year relapse-free survival rate is 24% for the CC arm and 55% for the ASCT arm (hazards ratio = 0.55 in favor of the ASCT arm; 95% confidence interval [CI], 0.29 to 1.04; P =.065). The corresponding figures for overall survival are 45% and 56%, respectively (hazards ratio = 0.87 in favor of the ASCT arm; 95% CI, 0.42 to 1.81; P =.71). CONCLUSION: The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial.     

A meta-analysis and systematic review of thalidomide for patients with previously untreated multiple myeloma

A systematic review and meta-analysis was performed to determine the efficacy and toxicity of thalidomide in previously untreated patients with myeloma. Medline, Embase, Cochrane Controlled Trials Register, and abstracts from the American Society of Hematology and the American Society of Clinical Oncology were searched for randomized controlled trials (RCTs) of either induction or maintenance thalidomide in adults with previously untreated myeloma. Nine RCTs of induction thalidomide, three RCTs of maintenance thalidomide, and one RCT of induction and maintenance thalidomide were identified, involving a total of 4144 subjects. When thalidomide was added to standard, non-transplantation myeloma therapy, overall survival (OS) improved (HR 0.67; 95% CI 0.56-0.81). When thalidomide was given as maintenance following autologous transplantation (ASCT), there was a trend to improved OS (HR 0.61, 95% CI 0.37-1.01); when the only trial which combined induction and maintenance thalidomide was excluded from this analysis, a significant survival advantage emerged (HR 0.49, 95% CI 0.32-0.74). The relative risk of venous thromboembolism (VTE) with induction thalidomide was 2.56 (95% CI 1.88-3.49). A meta-analysis of trials/sub-groups administering low molecular weight heparin (LMWH) as VTE prophylaxis, suggested a persistently increased relative risk of VTE with induction thalidomide (RR 1.54, 95% CI 1.07-2.22). The relative risk of VTE was substantially lower, but still elevated, when thalidomide was given as maintenance therapy following ASCT (RR 1.95, 95% CI 1.15-3.30). In summary, thalidomide appears to improve the overall survival of patients with newly diagnosed myeloma both when it is added to standard, non-transplantation therapy, and when it is given as maintenance therapy following ASCT. However, thalidomide is associated with toxicity, particularly a significantly increased risk of VTE.     

Long-term follow-up after high-dose chemotherapy and autologous stem-cell transplantation for high-grade B-cell lymphoma suggests an improved outcome for high-risk patients with respect to the age-adjusted International Prognostic Index.

BACKGROUND: To evaluate the long-term benefit from high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT), as part of the initial treatment for patients with chemosensitive, high-grade B non-Hodgkin's lymphoma (hg B-NHL), stratified according to the age-adjusted International Prognostic Index (aaIPI). PATIENTS AND METHODS: Eligible patients were 33 consecutive hg B-NHL patients responding to first-line chemotherapy and fulfilling at least one of the following criteria: stage III or IV, bulky disease, elevated lactate dehydrogenase or failure to achieve complete remission (CR). Twenty-two of 33 patients (67%) had two or three risk factors with respect to the aaIPI. All patients received HDCT with ASCT after a minimum of 6 weeks of VACOP-B standard therapy and VIP-E for mobilization. RESULTS: After ASCT, 31 patients (94%) achieved CR. No treatment-related death occurred. The cumulative incidence of relapse at a medium follow-up of 10 years is 16% for 31 of 33 patients achieving CR. Twenty-five of 33 patients are in sustained CR with a disease-free survival of 76% [95% confidence interval (CI) 67% to 86%]. The overall survival at a median follow-up of 122 months (range 86-148) is 79% (95% CI 68% to 89%). CONCLUSIONS: The results suggest that up-front HDCT with ASCT may improve long-term outcome in high-risk patients with chemotherapy-sensitive hg B-NHL when compared to historic populations treated solely with dose-intense chemotherapy. We observed that long-term survival of high-risk (two to three risk factors) patients is comparable to low-risk (zero to one risk factor) patients after HDCT and ASCT with a low incidence of late relapse.     

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。     

Similar response rates and superior early progression-free survival with gemcitabine, dexamethasone, and cisplatin salvage therapy compared with carmustine, etoposide, cytarabine, and melphalan salvage therapy prior to autologous stem cell transplantation for recurrent or refractory Hodgkin lymphoma

BACKGROUND: The objective of this study was to compare the response rates, ability to mobilize autologous hematopoietic (peripheral blood) stem cells (PBSCs), and progression-free survival (PFS) after second-line chemotherapy with either gemcitabine, dexamethasone, and cisplatin (GDP) or carmustine, etoposide, cytarabine, and melphalan (mini-BEAM) followed by high-dose therapy and hematopoietic stem cell transplantation (ASCT) for patients with recurrent or refractory Hodgkin lymphoma. METHODS: The outcomes of 68 consecutive patients who were referred for salvage therapy (34 patients received mini-BEAM, and 34 patients received GDP) were compared retrospectively. Patients received mini-BEAM as inpatient treatment every 3-4 weeks, whereas GDP was administered on an outpatient basis every 3 weeks. Responding patients proceeded to stem cell mobilization, followed by high dose etoposide and melphalan, and ASCT. Patients who had disease bulk at recurrence that measured > 5 cm received involved-field radiation post-ASCT. RESULTS: The response rate to GDP prior to ASCT (complete responses, unconfirmed complete responses, and partial responses) was 62% (95% confidence interval [95% CI], 45-78%) compared with 68% (95% CI, 52-83%) for mini-BEAM (P = 0.61). After mobilizing chemotherapy, the proportion of patients for whom the target PBSC number of > or = 5 x 10(6) CD34-positive cells/kg was obtained was 97% after GDP and 57% after MB (P = 0.0003). More patients completed collection with a single apheresis procedure after GDP than after mini-BEAM (73% vs. 36%; P = 0.004), and fewer patients in the GDP group required bone marrow harvesting to proceed to ASCT. After a median follow-up of 1.8 years after ASCT, PFS was significantly better for patients who received GDP compared with patients who received mini-BEAM (74% vs. 35% at 1.5 yrs, respectively; P = 0.005). Overall survival at 1.5 years was 91% after GDP and 82% after mini-BEAM (P = 0.23). CONCLUSIONS: Although this was a retrospective analysis, response to GDP and early PFS after ASCT compared favorably with mini-BEAM salvage chemotherapy. Based on these data, the authors believe that a Phase III trial comparing GDP with mini-BEAM or other platinum-containing regimens is warranted.     

Combined chemoradiation vs radiation therapy alone in stage-II nasopharyngeal carcinoma: A meta-analysis of the published literature

The aim of this meta-analysis was to evaluate the efficacy and toxicity of adding chemotherapy to radiotherapy (RT) in the treatment of stage-II nasopharyngeal carcinoma (NPC). We searched Pubmed, Cochrane Library, Embase, China National Knowledge Internet, China Biology Medicine, VIP, and Wanfang database for studies of the RT with or without chemotherapy in patients with stage-II NPC that were published in any language. Analyses were carried out using RevMan 5.3 software. The relative risk was used to evaluate the data, the I² test was used to compare heterogeneity, sensitivity analysis was used to evaluate the stability and reliability of the results. There were 16 studies with 3038 patients that were included in this analysis. Risk ratios (RR) of 1.04 (95% CI: 1.01-1.06), 1.05 (95% CI: 1.00-1.10), 1.05 (95% CI: 1.02-1.07), and 1.00 (95% CI: 0.97-1.03) were observed for overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS). Subgroup analysis showed that compared with conventional RT alone, chemoradiation (CRT) could significantly improve OS (RR = 1.09, 95% CI: 1.03-1.15), PFS (RR = 1.20, 95% CI: 1.08-1.35), and LRFS (RR = 1.09, 95% CI: 1.04-1.14), but did not significantly improve the rate of DMFS (RR = 1.03, 95% CI: 0.94-1.12). However, compared with intensity modulated radiation therapy alone, CRT did not significantly improve the rate of OS (RR = 1.01, 95% CI: 0.99-1.03), PFS (RR = 0.99, 95% CI: 0.95-1.03), LRFS (RR = 1.02, 95% CI: 0.99-1.05), and DMFS (RR = 0.99, 95% CI: 0.96-1.01). Compared with conventional RT alone, CRT could significantly improve patients’ prognoses in terms of OS, PFS, and LRFS for stage-II NPC, but not DMFS, and CRT can provide greater benefits from concurrent chemotherapy than neoadjuvant chemotherapy. With intensity modulated radiation therapy, the stage-II NPC patients did not benefit from the addition of chemotherapy.     

Treatment of stage I and II Hodgkin's disease with NOVP (mitoxantrone, vincristine, vinblastine, prednisone) and radiotherapy.

We investigated the effectiveness of a new treatment regimen termed NOVP in early Hodgkin's disease, which reportedly has lower toxicity. Thirty-four patients were treated with three cycles of NOVP (mitoxantrone, vinblastine, vincristine, prednisone) and radiotherapy, 40% of them had unfavourable prognostic factors. All patients obtained complete remission. With a median follow up of 5 years, the overall survival (OS) and time to treatment failure (TTF) was 95% (95% confidence interval [CI], 87 to 103) and 89% (95% CI, 78 to 100), respectively. The presence of either B symptoms or pulmonary hilar involvement was associated with a significant decrease in TTF (91% VS 50% p=0.003 and 92% VS 30% p=0.02, respectively) but do not correlate with OS. The tolerance to NOVP was excellent with minimal toxicity. In conclusion, this regimen is associated with a favourable outcome and low toxicity in stage I and II Hodgkin's disease, although patients with B symptoms and pulmonary hilar involvement have a higher risk of relapse.     

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.     

WT1基因 rs16754位点多态性与急性髓系白血病预后关系的 Meta 分析

目的：采用 Meta 分析总结 WT1基因 rs16754位点多态性与急性髓系白血病（AML）预后的关系。方法以英文检索词“WT1”“polymorphism”“Leukemia,Myeloid,Acute”检索 PubMed 数据库,同时以中文检索词“WT1”“多态性”“急性髓系白血病”检索中国知网、万方数据库和中国生物医学文摘数据库,时限截至2015年12月1日。结果共纳入11篇英文文献,样本量共计2789例。 Meta 分析结果显示, WT1基因 rs16754位点多态性与 AML 患者化疗完全缓解情况无相关性（RR＝1.02,95% CI 0.99～1.06, P＝0.20）,与总体生存（OS）（HR＝0.68,95% CI 0.45～1.02,P＝0.06）、5年 OS（RR＝1.10,95% CI 0.90～1.34,P＝0.37）及无复发生存期（RFS）（HR＝0.80,95% CI 0.54～1.19,P＝0.27）也无相关性。结论 WT1基因 rs16754位点多态性与 AML 预后各指标无相关性。     

Mastectomy and oophorectomy by menstrual cycle phase in women with operable breast cancer

BACKGROUND: It is unclear whether the phase of the menstrual cycle in which primary surgical treatment occurs influences disease-free survival (DFS) and overall survival (OS) in premenopausal women with breast cancer. We investigated this question in the context of a clinical trial comparing mastectomy alone with mastectomy plus adjuvant oophorectomy and tamoxifen in premenopausal women with operable breast cancer. METHODS: The date of the first day of the last menstrual period (LMP) was used to estimate the phase of the menstrual cycle when the surgeries were done. Follicular phase was defined as day 1-14 from LMP. Luteal phase was defined as day 15-42 from LMP. DFS and OS statistics were determined and analyzed by Cox proportional hazards ratios and Kaplan-Meier methods. All statistical tests were two-sided. RESULTS: We analyzed results for 565 women who reported an LMP within 42 days before surgery. For women in the mastectomy only arm (n = 289), there were no differences in DFS or OS by menstrual cycle phase. For women in the adjuvant treatment arm (n = 276), those whose surgery occurred during the luteal phase (n = 158) had better DFS (relative risk [RR] = 0.54; 95% confidence interval [CI] = 0.32 to 0.96; P =.02) and OS (RR = 0.53; 95% CI = 0.30 to 0.95; P =.03) than those whose surgery occurred during the follicular phase (n = 118). Moreover, women whose surgery occurred during the luteal phase and who received adjuvant therapy had better 5-year DFS than did women whose surgery occurred during the follicular phase (84%; 95% CI = 78% to 90% versus 67%; 95% CI = 58% to 78%; P =.02); they also had better OS (85%; 95% CI = 78% to 92% versus 75%; 95% CI = 66% to 84%; P =.03). CONCLUSIONS: The phase of the menstrual cycle at which surgery was done had no impact on survival for women who received mastectomy only. However, women who received a mastectomy and surgical oophorectomy and tamoxifen during the luteal phase had better outcomes than women who received surgery during the follicular phase.     

Primary diffuse large B‐cell lymphoma of the tonsil

BACKGROUND: The purpose was to evaluate the prognostic factors and treatment outcome of Indian patients with primary diffuse large B-cell lymphoma (DLBCL) of the tonsil treated at a single institution. METHODS: In all, 121 patients with DLBCL of the tonsil, treated at the Tata Memorial Hospital, Mumbai, India, from January 1990 to December 2002, were included. The median age was 45 years and the majority of patients (68%) were males. Systemic symptoms were present in 12% of patients; 28% presented with stage I and 67% had stage II disease. Treatment consisted of a combination of chemotherapy (CTh) and radiotherapy (RT) for the majority of patients (69.4%). Among those receiving RT, 64% received an RT dose of > or =45 Gy. RESULTS: After a median follow-up of 62 months, disease-free survival (DFS) and overall survival (OS) were 66.4% and 81.6%, respectively. Significant prognostic factors included: WHO performance score > or =2 (OS: 72.1% vs 95.6%, P = .016), bulky tumors (OS: 68.5% vs 86.9%, P = .001), presence of B-symptoms (OS: 36.7% vs 79.6%, P < .001), and Ann Arbor stage. On multivariate analysis; WHO performance score > or =2 (hazard ratio [HR], 4.27; 95% confidence interval [CI], 1.20-15.12), and B symptoms (HR, 6.27; 95% CI, 2.38-16.48), retained statistical significance. CTh + RT resulted in a significantly better outcome than those treated with CTh alone (OS: 85.7% vs 70.7%, P = .008). The complete response (P = .053), DFS (P = .039), and OS (P = .014) rates were significantly better for patients receiving an RT dose > or =45 Gy. CONCLUSIONS: Tumor bulk, WHO performance score, the presence of B symptoms, and Ann Arbor stage significantly influence outcome. A combined modality treatment, consisting of CTh and RT (with an RT dose of > or =45 Gy), results in a satisfactory outcome in patients with this uncommon neoplasm.     

Extended Adjuvant Therapy With Aromatase Inhibitors for Early Breast Cancer: A Meta-analysis of Randomized Controlled Trials

BackgroundAromatase inhibitors (AIs) are widely used for early breast cancer, whereas the efficacy and safety of extended AI adjuvant therapy compared with shorter AI therapy, observation, or placebo remains controversial. We conducted a quantitative meta-analysis to summarize available randomized controlled trials (RCTs) regarding the efficacy and safety of extended AI therapy for early breast cancer.Materials and MethodsWe systematically searched PubMed, EmBase, and the Cochrane library to select studies published through March 2018. Studies designed as RCTs and that investigated overall survival (OS) or disease-free survival (DFS) for extended AI and shorter AI therapy, observation, or placebo were included. Hazard ratio (HR) and relative risk (RR) with 95% confidence intervals (CIs) were employed to pool analysis according to data type.ResultsWe identified 7 RCTs that involved 16,926 patients with early breast cancer. The summary HRs indicated that extended treatment with AIs was not associated with OS (HR, 0.95; 95% CI, 0.82-1.10; P = .488), whereas it could significantly improve DFS as compared with shorter AI therapy, observation, or placebo (HR, 0.75; 95% CI, 0.66-0.86; P < .001). Treatment with extended AIs significantly reduced contralateral breast cancer recurrence (RR, 0.46; 95% CI, 0.34-0.64; P < .001), whereas it has no significant effect on distant metastatic recurrence (RR, 0.80; 95% CI, 0.64-1.00; P = .055), and locoregional recurrence (RR, 0.76; 95% CI, 0.53-1.08; P = .127). There were no significant differences between treatment with extended AIs and control for grade 3 or more adverse events.ConclusionExtended AI therapy could significantly improve DFS, especially for contralateral breast cancer recurrence. There were no significant differences between treatment with AIs and control for OS, distant metastatic and locoregional recurrence, and serious adverse events.     

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature

We performed a meta-analysis of all published studies relating intratumoural microvessel density (MVD) (45 studies) or vascular endothelial growth factor (VEGF) expression (27 studies), both reflecting angiogenesis, to relapse free (RFS) and overall survival (OS) in colorectal cancer (CRC). For each study, MVD impact was measured by risk ratio between the two survival distributions with median MVD as cutoff. Eleven studies did not mention survival data or fit inclusion criteria, six were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients) and 18 for VEGF (2050 patients). Microvessel density was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (seven studies). Vascular endothelial growth factor expression was mostly assessed by immunohistochemistry. Statistics were performed for MVD in 22 studies (the others lacking survival statistics) including nine studies (n = 957) for RFS and 18 for OS (n = 2383) and for VEGF in 17 studies, including nine studies for RFS (n = 1064) and 10 for OS (n = 1301). High MVD significantly predicted poor RFS (RR = 2.32 95% CI: 1.39-3.90; P < 0.001) and OS (RR = 1.44; 95% CI: 1.08-1.92; P = 0.01). Using CD31 or CD34, MVD was inversely related to survival, whereas it was not using factor VIII. Vascular endothelial growth factor expression significantly predicted poor RFS (RR = 2.84; 95% CI: 1.95-4.16) and OS (RR=1.65; 95% CI: 1.27-2.14). To strengthen our findings, future prospective studies should explore the relation between MVD or VEGF expression and survival or response to therapy (e.g. antiangiogenic therapy). Assessment of these angiogenic markers should be better standardised in future studies.