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目的 分析原发系统性间变性大细胞淋巴瘤( ALCL)的临床病理特征和免疫组织化学特点,提高诊治水平。方法选取22例ALCL患者,均进行分期、国际预后指数(IPI)、乳酸脱氢酶(LDH)检测,应用免疫组织化学SP法检测间变性淋巴瘤激酶(ALK)、Ki-67、Caspase-3、CD30、EMA、Granzyme B等,回顾性分析患者临床、病理形态学资料、免疫表型及生物学特性,并进行预后分析。结果22例均为原发系统性ALCL,ALK+ 15例(68.2%),ALK-7例(31.8%);AILK+患者发病年龄、Ki-67增殖指数较ALK-患者低,Caspase-3表达率高,差异有统计学意义(x2 =4.618,P= 0.032);15例ALK+ALCL均表达CD30和EMA。ALCL中ALK的表达与Ki-67、Caspase-3的表达呈负相关(r= -0.581,P= 0.006;r=0.458,P=0.032)。ALK+病例较ALK-病例GranzymeB(x2=0.11,P=0.74)、TIA-1( x2= 0.01,P=0.92)的表达率高,但差异无统计学意义(P>0.05)。有效率为54.5%(12/22),其中完全缓解率为18.2%(4/22);全组中位生存期12个月,1年生存率为59.1%( 13/22),2年生存率为50.0%(11/22)。Ann Arbor分期、LDH及IPI与疾病预后相关。结论ALK+较ALK-ALCL患者核增殖低,恶性程度低,临床特征和免疫表型具有一定的特征性;ALK、Ki-67、Caspase-3、分期、血清LDH及IPI对预测ALCL患者的生存和指导治疗有帮助。 相似文献
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目的 探讨系统型间变性大细胞淋巴瘤(S-ALCL)的临床特征和预后相关因素.方法 回顾性分析30例S-ALCL患者的临床资料.30例患者均以联合化疗为主,配合局部病灶野放疗8例.化疗方案主要为CHOP、EPOCH、Hyper-CVAD,以CHOP方案为主.结果 30例S-ALCL患者中位年龄36岁,男女比例为1.5∶1,有B症状、Ⅲ~Ⅳ期和结外侵犯者分别占60.0%(18/30)、73.3%(22/30)和60.O%(18/30);乳酸脱氢酶(LDH)升高者占46.7%(14/30);间变性大细胞淋巴瘤激酶(ALK)+18例(60.0%),其发病年龄小于ALK-者(u=3.92,P=0.001).单因素分析显示ALKˉ及LDH升高是重要的预后不良因素.结论 S-ALCL患者发病年龄较轻,预后较好.但ALK-、LDH升高者预后不良.治疗以联合化疗为主,对于有不良预后因素的患者,大剂量治疗可能获益. 相似文献
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I Simonitsch ER Panzer-Gruemayer DW Ghali A Zoubek T Radaszkiewicz H Gadner H Kovar 《Canadian Metallurgical Quarterly》1996,92(4):866-871
The chromosomal aberration t(2:5) resulting in the juxtaposition of NPM and ALK genes is a well-known feature of several Ki-1+ anaplastic large cell lymphomas (ALCL) of the T-cell type. However, conflicting results have been reported concerning the presence of this gene rearrangement in other ALCL and Hodgkin's disease (HD), respectively. We performed NPM/ALK RT-PCR on 14 cases of ALCL expressing distinct myelomonocytic markers, e.g. CD11c, CD13, CD14 or CD68, but neither T-cell nor B-cell associated antigens (null cell phenotype). The specific translocation was found exclusively in six childhood tumours previously diagnosed as malignant histiocytosis (MH), whereas all adult lymphomas (three ALCL without characteristics of MH, three secondary ALCL following HD) and two paediatric cases of secondary ALCL following HD did not show NPM/ALK gene fusion products. By Southern blotting, the status of T-cell receptor (TCR) and immunoglobulin heavy chain genes (IgH) were investigated; two patients with initially diagnosed MH had the TCRdelta-chain gene rearranged (Ddelta2-Ddelta3 and Vdelta1-Jdelta1, respectively). IgH rearrangements were detected in only one patient with secondary ALCL. Our data indicate a high association of previously diagnosed MH and NPM/ALK gene rearrangements. In one case, this specific translocation was demonstrated at an early stage of development; in another, a mature TCRdelta-chain gene rearrangement was detected. These data support the hypothesis of a lymphoid origin of this subgroup of Ki-1 positive ALCL previously diagnosed as MH. 相似文献
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S Culine M Bekradda A Kramar A Rey B Escudier JP Droz 《Canadian Metallurgical Quarterly》1998,83(12):2548-2553
BACKGROUND: Patients presenting with brain metastases from renal cell carcinoma portend a poor prognosis, with a reported median survival of 4-6 months. Given their short life expectancy, these patients generally have been excluded from clinical trials that assess the efficacy of medical treatments. However, clinical impression suggests that some patients may achieve long term palliation. METHODS: The clinical features of 68 patients who were treated at the Institut Gustave Roussy for brain metastases from renal cell carcinoma were collected retrospectively. Using univariate and multivariate analyses, a prognostic model based on independent prognostic factors was established. An external data set of 57 patients was used to validate the model. RESULTS: The median survival was 7 months. On univariate analysis survival was related significantly to the following adverse prognostic factors: no initial nephrectomy, left side and temporal location of brain metastases, presence of fever or weight loss, erythrocyte sedimentation rate > 50 mm/h, and time from initial diagnosis to brain metastases < or = 18 months. Multivariate analyses identified the previous variable as well as the presence of other visceral metastases as independent prognostic factors. Forty-four patients (65%) with no or 1 adverse prognostic factor (average risk group) had a median survival of 8 months and a 26% 1-year survival rate. Twenty-four patients (35%) with 2 adverse prognostic factors (poor risk group) had a median survival of 3 months and a 1-year survival rate of 9%. This model proved to be discriminant in an external data set; the median survival of patients assigned to the average risk group was 11 months (46% 1-year survival rate) compared with 4 months (9% 1-year survival rate) for patients assigned to the poor risk group. CONCLUSIONS: Patients presenting with brain metastases from renal cell carcinoma and poor risk prognostic factors are highly unlikely to benefit from medical treatments except symptomatic procedures. Conversely, the enrollment of patients with average risk prognostic factors into clinical trials dealing with chemotherapy or immunotherapy may be considered. 相似文献
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H Tilly P Gaulard E Lepage C Dumontet J Diebold I Plantier F Berger M Symann T Petrella P Lederlin J Brière 《Canadian Metallurgical Quarterly》1997,90(9):3727-3734
Anaplastic, CD30+, large-cell lymphoma is now a well-recognized pathologic entity that accounts for 2% to 8% of all lymphomas. Recent progress has been made in the understanding of certain biologic features found in anaplastic large-cell lymphoma, but information about its clinical behavior, in comparison to other large-cell lymphomas, is limited. The pathologic review of a large multicenter study of the treatment of aggressive lymphoma identified 146 cases of anaplastic large-cell lymphoma (ALCL) on the basis of morphology and CD30 expression. We compared initial presentation, immunophenotype, and clinical outcome of these cases with those of the 1,695 nonanaplastic diffuse large-cell lymphomas (non-ALCL) included in the same trial. Patients with ALCL were more likely to be male (P = .018) and were younger (P < .0001) than those with non-ALCL. B symptoms were more frequent in ALCL (P = .006). Skin (P < .0001) and lung (P < .05) involvement was also more frequent in ALCL, but frequency of bone marrow involvement was identical (P = . 5). Tumor cell phenotype was B in 56 cases (38%), T in 49 cases (34%), and null in 33 cases (22%). Response to chemotherapy (P = . 001), event-free survival (P = .006), and overall survival (P = . 0004) were better for ALCL than for non-ALCL. Multivariate analyses identified anaplastic character as an independent factor that predicted a longer survival. Tumor cell phenotype did not influence event-free survival (P = .72) or overall survival (P = .83). ALCL in adults is a clinicopathologic entity which, independent of its phenotypic characteristics, has a better outcome than other diffuse large-cell lymphomas. 相似文献
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We determined the proportion of survival variability explained by the usual prognostic factors in childhood acute lymphoblastic leukaemia (ALL) during a prognostic study of 1552 patients enrolled in three consecutive Fralle group protocols (Fralle 83, Fralle 87 and Fralle 89). The event-free survival rates at 5 years were 54.8% (SD 1.9), 43.1%) (SD 2.7) and 55.6% (SD 2.2), respectively. In the univariate analysis the following variables were predictive of poor outcome: male gender, elevated leucocytosis (> 50 x 10(9)/l), circulating blastosis. haemoglobin >12 g/dl, platelet count <100 x 10(9)/l, age under 1 year or over 9 years, enlarged mediastinum, nodes, spleen and liver, T phenotype, absence of CD10+ cells; testicular and meningeal involvement, poor response to induction therapy (CCSG M3), and LDH >400 U/l. Among the cytogenetic features, hyperdiploidy had a protective effect, whereas hypodiploidy, translocation and other structural abnormalities had a negative influence, particularly in cases of t(9;22) or t(4;11). Multivariate analysis summarized the prognostic information in terms of four variables: age, gender, leucocytosis and cytogenetic features. Missing data had little influence on the results. However, despite their significance in the multivariate analysis, these four variables each had very low predictive power (1.1% for gender, 2.0% for age, 3.5% for leucocytosis, and 1.6% for cytogenetic features). Thus, the most significant prognostic factors in childhood ALL each explain no more than 4% of the variability in prognosis. This may explain the disappointing practical value of these factors and underlines the need for prognostic tools in childhood ALL. 相似文献
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I Wlodarska C De Wolf-Peeters B Falini G Verhoef SW Morris A Hagemeijer H Van den Berghe 《Canadian Metallurgical Quarterly》1998,92(8):2688-2695
Recently, a distinctive entity characterized by expression of the anaplastic lymphoma kinase (ALK) protein [most frequently due to the t(2;5)(p23;q35)-associated NPM-ALK fusion] has emerged within the heterogenous group of non-Hodgkin's lymphomas (NHL) classified as anaplastic large-cell lymphoma (ALCL). Sporadic variant 2p23/ALK abnormalities identified in ALK-positive ALCL indicate that genes other than NPM may also be involved in the deregulation of ALK and lymphomagenesis. We report here three cases with an inv(2)(p23q35) detected by fluorescence in situ hybridization (FISH) in young male patients with ALK-positive ALCL. In contrast to ALCL cases with the classical t(2;5)(p23;q35) that usually show both cytoplasmic and nuclear or predominantly nuclear alone localization of the NPM-ALK chimeric product, in all three cases with an inv(2)(p23q35) the ALK protein accumulated in the cytoplasm only, supporting the previous assumption that the oncogenic potential of ALK may not be dependent on its nuclear localization. As the first step to identify the ALK partner gene involved in the inv(2)(p23q35), we performed extensive FISH studies and demonstrated that the 2q35 breakpoint occurred within the 1,750-kb region contained within the 914E7 YAC. Moreover, a striking association of the inv(2)(p23q35) with a secondary chromosomal change, viz, ider(2)(q10)inv(2)(p23q35), carrying two additional copies of the putative ALK-related fusion gene, was found in all three patients, suggesting that, in contrast to the standard t(2;5)/NPM-ALK fusion, multiple copies of the putative 2q35-ALK chimeric gene may be required for efficient tumor development. In summary, we demonstrate that the inv(2)(p23q35), a variant of the t(2;5)(p23;q35), is a recurrent chromosomal abnormality in ALK-positive ALCL, the further characterization of which should provide new insight into the pathogenesis of these lymphomas. 相似文献
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SA Pileri K Pulford S Mori DY Mason E Sabattini G Roncador M Piccioli C Ceccarelli PP Piccaluga D Santini O Leone H Stein B Falini 《Canadian Metallurgical Quarterly》1997,150(4):1207-1211
The revised European-American lymphoma classification recognizes a subtype of anaplastic large-cell lymphoma (ALCL), termed lympho-histiocytic because of its peculiar cytological composition. As in the case of classical ALCL, this tumor usually occurs in young patients and shows an excellent response to chemotherapy, but some authors have suggested that in reality this is a nonanaplastic T-cell lymphoma rich in histiocytes. In this paper, we show that three of five cases of lympho-histiocytic ALCL stain with anti-ALK antibodies and can therefore be presumed to express the chimeric NPM/ALK protein secondary to (2;5) translocation. These findings further support the inclusion of this as a type of ALCL and not among the nonanaplastic peripheral T-cell lymphomas. Furthermore, they indicate that staining for ALK proteins is a powerful tool for the diagnosis of lympho-histiocytic ALCL, the recognition of which may be difficult on morphological grounds. 相似文献
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目的 探讨系统性间变性大细胞淋巴瘤(S-ALCL)骨髓累及的临床病理学特点、免疫学表型及临床生物学行为.方法 回顾性分析34例S-ALCL病例资料,进行骨髓活检(19例)或涂片(15例).其中ALK(+)24例,ALK(-)10例.HE染色、免疫组织化学染色观察病理形态及免疫表型,原位杂交法检测EB病毒.结果 6例(17.6%)S-ALCL存在骨髓累及,均经骨髓活检标本确定,15例患者骨髓涂片中均未见肿瘤累及.ALK(+)ALCL和ALK(-)ALCL骨髓累及的发生率分别为16.7%(4/24)和20.0%(2/10),差异无统计学意义(P=0.3555).与无骨髓累及病例比较,骨髓累及病例的年龄、性别分布差异无统计学意义(P值分别为0.8089和0.3085).骨髓累及者肿瘤细胞以间质性分布为主[83.3%(5/6)].生存分析统计提示伴有骨髓累及的患者预后明显差于无骨髓累及者(P=0.0407).结论 S-ALCL骨髓累及发生率低,与患者的发病年龄、性别及ALK蛋白的表达无相关性.伴有骨髓累及的S-ALCL患者临床预后差,骨髓活检在判断S-ALCL预后中有重要意义. 相似文献
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SD Foss? RT Oliver SP Stenning A Horwich P Wilkinson G Read GM Mead JT Roberts G Rustin MH Cullen SB Kaye SJ Harland P Cook 《Canadian Metallurgical Quarterly》1997,33(9):1380-1387
Prognostic factors for 3-year progression-free survival (PFS) were defined in 286 patients with advanced seminoma treated with cisplatin-based chemotherapy at 10 European oncology units (no prior treatment: 236; prior radiotherapy: 50). Previously irradiated patients displayed a 69% PFS as compared to 87% in those presenting with advanced seminoma at the time of diagnosis (P = 0.009). In the univariate analysis, the extent and site of disease before chemotherapy and the level of serum LDH (< 2.0 versus > or = 2.0 x upper limit of normal) correlated with PFS in previously non-irradiated patients, but not in patients with prior radiotherapy. The multivariate analysis was, therefore, restricted to previously non-irradiated patients. The presence of non-pulmonary visceral metastases and a serum LDH level of > or = 2 x normal (N) proved to be independent prognostic factors. Based on these variables, two prognostic models were constructed and validated in an external data set of 166 comparable patients. For clinical use, Model 2 is recommended. The good-prognosis group comprises non-irradiated patients with stage II seminoma and any LDH level at presentation, or stage III and IV patients (with lung metastases only) whose serum LDH level is < 2 x N. These patients display a 94% 3-year PFS. The poor prognosis group includes all other patients with a 56% PFS. With this prognostic model, individualisation of the therapeutic approach may be considered in patients with advanced seminoma and a high risk of chemotherapy-related toxicity. 相似文献
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SH Cheng JJ Jian SY Tsai KY Chan LK Yen NM Chu TD Tan MH Tsou AT Huang 《Canadian Metallurgical Quarterly》1998,41(4):755-762
PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT. METHODS AND MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis-free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI: 65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow-up interval of 29 months (range 15-74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH < or = 410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions. 相似文献
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P Goldstraw GC Mannam DK Kaplan P Michail 《Canadian Metallurgical Quarterly》1994,107(1):19-27; discussion 27-8
Between 1979 and 1989, 876 patients with non-small-cell lung carcinoma were referred to our unit for surgical treatment. One hundred forty-six patients were judged not suitable for surgical treatment on clinical, radiologic, or bronchoscopic findings. Cervical mediastinoscopy or anterior mediastinotomy (or both) showed that 151 patients had mediastinal involvement by invasion or metastases into the ipsilateral (N2 disease) or contralateral (N3 disease) superior mediastinal lymph nodes and were therefore deemed inoperable. Except for one patient who had involvement of a single nodal station at mediastinoscopy, all other patients (n = 578) undergoing thoracotomy were thought, on the basis of computed tomographic scan or mediastinal exploration (or both) not to have N2 disease. Despite our efforts to avoid surgery on patients with N2 disease, at thoracotomy routine mediastinal node dissection disclosed that 149 patients had unsuspected N2 disease. Resection was possible in 130 (87.3%) by pneumonectomy (n = 72), bilobectomy (n = 7), lobectomy (n = 49), or lesser resection (n = 2). In three patients the resection was incomplete (2.3%), but in 127 a complete resection was performed (85%). Histologic examination in these 149 patients showed that 72 tumors were squamous cell carcinoma, 54 adenocarcinoma, 14 large-cell carcinoma, and 9 of mixed type. Eight patients died in the hospital after thoracotomy. Adjuvant therapy was not used after complete resection. Complete follow-up was obtained in 134 patients and the mean follow-up period was 27.25 months (1 to 116 months). The actuarial 5-year survival for those having complete resection was 20.1%. There was a statistically significant difference favoring long-term survival in those patients with squamous cell carcinoma (p < 0.01) and those in whom only one nodal station was involved (p < 0.05). Neither the extent of resection nor the involvement of any specific nodal station influenced long-term survival. Despite rigorous preoperative investigations, routine mediastinal node dissection demonstrated mediastinal node metastasis for the first time at thoracotomy in 26% of our patients. We believe resection is justified in these patients, who have already necessarily incurred the morbidity and mortality of thoracotomy, so long as complete resection is possible. 相似文献
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S Leyvraz V Spataro J Bauer S Pampallona R Salmon T Dorval R Meuli M Gillet F Lejeune L Zografos 《Canadian Metallurgical Quarterly》1997,15(7):2589-2595
PURPOSE: Ocular melanoma is characterized by a high rate of liver metastases and is associated with a median survival time less than 5 months. There is no standard treatment available. Treatment strategies have, without success, relied on the experience with metastatic cutaneous melanoma. The only effective treatment is chemoembolization using cisplatin and polyvinyl sponge, which has never become accepted on a large scale. The objective of the study was to establish prospectively the efficacy and toxicity of hepatic intraarterial fotemustine, a third-generation nitrosourea, in patients with liver metastases from ocular melanoma. PATIENTS AND METHODS: Thirty-one patients were subjected to laparotomy to place a totally implantable catheter into the hepatic artery and received fotemustine 100 mg/m2 as a 4-hour infusion, first once a week for four times and then, after a 5-week rest period, every 3 weeks until progression or toxicity. Cox regression models were used to assess the prognostic role of patient survival characteristics. RESULTS: Objective responses were observed in 12 of 30 assessable patients (40%; 95% confidence interval, 22% to 59%). The median duration of response was 11 months and the median overall survival time, 14 months. Lactate dehydrogenase (LDH) appeared to be the strongest prognostic factor for survival. Toxicity was minimal and treatment could be administered on an outpatient basis. CONCLUSION: The results of hepatic arterial chemotherapy with fotemustine produced a high response rate and survival similar to chemoembolization therapy. It involves no major toxicity and preserves the quality of life. To assess further its effectiveness, a randomized study to compare hepatic intraarterial versus intravenous chemotherapy is being planned. 相似文献
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I Sch?nborn W Zschiesche E Spitzer C Minguillon M M?hner K Ebeling R Grosse 《Canadian Metallurgical Quarterly》1994,29(3):287-295
The prognostic value of c-erbB-2 protein overexpression has been evaluated in 463 patients with operable breast cancer after a median follow-up of 66 months. Overexpression was observed in 99/463 (21%) of the breast tumors. It showed significant positive correlation to histological grade (p < 0.0001) and tumor size (p < 0.02). A relationship of borderline significance was observed between c-erbB-2 protein overexpression and negative or low estrogen receptor (ER) content. No significant correlation was found to lymph node involvement or proliferating tumor cell fraction as determined by the proliferating cell nuclear antigen (PCNA). After a median follow-up of 66 months (range 6 to 109 months), the overall survival of all patients amounted to 63%. Multivariate analysis revealed lymph node involvement, tumor size, histological grade, histological type, c-erbB-2 protein overexpression, progesterone receptor (PR) content, and oral contraceptive use as independent prognostic factors. In an univariate analysis, the overall survival amounted to 72% and 38% of tumor patients with negative and positive c-erbB-2 protein overexpression, respectively. The most significant finding is that c-erbB-2 overexpression has been recognized as an independent predictive factor in subsets of tumor patients who would be expected to have a generally poor prognosis, such as those indicating axillary lymph node involvement, large tumor size (> 2 cm), and PR negativity. 相似文献
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C Guglielmi F Gomez T Philip A Hagenbeek M Martelli C Sebban N Milpied D Bron JY Cahn R Somers P Sonneveld C Gisselbrecht H Van Der Lelie F Chauvin 《Canadian Metallurgical Quarterly》1998,16(10):3264-3269
PURPOSE: The purpose of this study was to investigate the prognostic value of time to relapse in 188 adult patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) included on the Parma trial at the time of their first relapse. PATIENTS AND METHODS: The median follow-up of these patients is 102 months after registration onto the Parma study. Time to relapse was calculated from initial diagnosis, and a cutoff of 12 months was used to separate 77 patients defined as early relapse from 111 patients defined as late relapse. RESULTS: Patients with early and late relapses had significantly different overall response rates to salvage therapy with two courses of dexamethasone, high-dose cytarabine, and cisplatin (DHAP; 40% v 69%; P=.00007) and different 8-year survival rates (13% v 29%; P=.00001). Features at relapse with a negative prognostic value in univariate analysis were higher than normal lactic dehydrogenase (LDH) levels, tumor size greater than 5 cm, Ann Arbor stages III to IV, and Karnofsky score less than 80%. Therefore, multivariate analyses were performed. Time to relapse (P=.001) and LDH levels at relapse (P=.003) had independent prognostic value, whereas tumor size did not reach statistical significance in the logistic model that predicted overall response after two courses of DHAP. The study of prognostic factors for overall survival (OS) and progression-free survival (PFS) confirmed the prognostic value of time to relapse (P < .0001 for OS and P=.005 for PFS) independent of response or treatment after two courses of DHAP. CONCLUSION: Time to relapse may be used to stratify patients at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma. 相似文献