Prognostic factors in Hodgkin's disease: multivariate analysis of 327 patients from a single institution.

On the basis of a retrospective study of 327 patients with Hodgkin's disease (HD), the prognostic significance of several factors, accepted previously and recently proposed, has been analyzed with regard to response to treatment and the survival time. Multivariate regression analysis strongly decreased the number of potentially prognostic parameters. The only independent, pretreatment factors negatively influenced by either time of survival or response to treatment were the following: age at diagnosis of more than 45 years, advanced (IIIB/IV) clinical stage, poor clinical status according to Karnofsky's scale (score less than 70), presence of systemic symptoms, mixed cellularity/lymphocyte depletion histological type, multisite peripheral nodal localization of the disease, abdominal lymphadenopathy, and large primary tumor mass (bulky disease). Short time to achieve complete remission (during the first four courses of chemotherapy) has proven to be significantly positive predictive factor. Cumulative dose of cytostatics lower than programmed was a significantly negative prognostic factor that correlated with a shorter time of survival. Lack of or a too-low dose of radiotherapy had the same predictive value. High activity of serum lactate dehydrogenase correlated moderately with poor response to the first-line treatment but did not influence the survival time. Other clinical, morphological, and biochemical parameters influenced neither the prognosis nor the response to treatment. Additionally, immunohistochemical examinations for proliferating cell nuclear antigen and the protein products of the p53 and bcl-2 genes were performed on the lymph nodes obtained from the patients with HD. High expression of proliferating cell nuclear antigen, p53, and BCL-2 correlated with poor response to the treatment and/or short time of survival. Statistical analysis has led us to the conclusion that the pretreatment expression of these oncoproteins can be taken into consideration as a new prognostic factor in HD.     

Profiles and prognostic values of serum LDH isoenzymes in patients with haematopoietic malignancies

Serum lacticodehydrogenase (LDH) is commonly increased in patients with haematopoietic malignancies and has been shown to be a prognostic factor in patients with non-Hodgkin's lymphoma (NHL) and myeloma. We have examined the LDH isoenzyme content in serum of 326 patients, including 252 patients with NHL (202 at diagnosis and 50 at relapse), 28 patients with Hodgkin's disease, 17 patients with CLL, 16 patients with myeloproliferative syndromes and 13 patients with multiple myeloma. Among these, 160 pts (49%) had increased serum LDH. The analysis of LDH isoenzyme profiles in all patients showed increased percentages of isoenzyme 2 in patients with NHL, CLL and myeloproliferative syndromes, but not in samples from patients with myeloma or Hodgkin's disease. Isoenzyme alterations were then analyzed for their prognostic value in patients with NHL. In univariate analyses, increased isoenzyme 2 percentages, increased isoenzyme 3 values, total serum LDH, performance status, stage and tumour aggressiveness were prognostic variables for survival. In a multivariate analysis increased LDH isoenzyme 3 values, high isoenzyme 2 percentages and the performance status, but not total serum LDH, were independent prognostic factor for survival. High isoenzyme 3 values were predictive of early death in NHL patients. In patients with relapsing NHL, the overall survival was 12 months in patients with normal isoenzyme 3 but only 2 months in patients with increased isoenzyme 3 values. We conclude that there are characteristic alterations in serum LDH profiles in patients with haematopoietic malignancies and that some of these may be more interesting in terms of prognostic value than total serum LDH.     

The clinical significance of serum CD8 antigen levels in adult patients with Hodgkin's disease.

Increased suppressor T-cell activity has been observed in patients with Hodgkin's disease. In order to evaluate the clinical significance of soluble CD8 antigen (sCD8), which is released from CD8+ suppressor/cytotoxic T-lymphocytes, we determined sCD8 levels in the sera of 82 consecutive patients with newly diagnosed untreated Hodgkin's lymphoma who were entered into prospective trials of the German Hodgkin's Disease Study Group. sCD8 levels were significantly higher (p less than 0.01) in stage IV (781 U/ml, n = 19) than in stages I-IIIB (443 U/ml; n = 63). Patients with B-symptoms (n = 36) had slightly higher levels (611 U/ml) than patients without (n = 46) systemic symptoms (447 U/ml; p = 0.08). In 77 patients evaluable for response, the complete remission (CR) rate of patients with sCD8 less than 750 U/ml was higher (54/60 or 90%) than that of patients with sCD8 greater than 750 U/ml 11/17 or 65%; p = 0.01). The time to treatment failure was significantly longer in patients with sCD8 less than 750 U/ml (p = 0.008), even among the group with stages IIIB/IV only (p = 0.04). Our data suggest that the pretreatment levels of sCD8 in adult patients with Hodgkin's lymphoma have prognostic relevance, and that they should be determined especially in patients with advanced disease. Increased understanding of the role of sCD8 may shed light on the pathogenesis of Hodgkin's disease.     

Serum CEA and CA 15-3 as prognostic factors in primary breast cancer

In the present study, we investigated the association of the serum levels of the tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free survival and death from disease in 1046 women with breast cancer without metastases at the time of primary diagnosis in relation to age and the established prognostic factors tumour size, lymph node status, histological grading and hormone receptor status. We found that elevated pre-operative serum marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003) and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001 both) in univariate analyses. By comparing pre- and post-operative values we found a decline in values post-surgery. In those patients where marker levels of carcinoembryonic antigen decreased more than 33%, a significantly higher risk for relapse and death from disease (both P=0.0001) in univariate analyses was observed. In multivariate analysis this decrease of carcinoembryonic antigen proved to be an independent prognostic factor. The results for cancer antigen 15-3 were comparable to carcinoembryonic antigen in univariate analyses but showed no significance in multivariate analysis. In this study the post-operative decrease of the serum tumour marker carcinoembryonic antigen was a strong independent prognostic factor for disease free survival and death from disease in breast cancer patients.     

Prognostic significance of mediastinal mass in adult Hodgkin's disease

The authors analyzed the prognostic significance of mediastinal involvement with Hodgkin's disease in 169 pathologically stage adults (greater than or equal to 17 years) treated at the Mayo Clinic between 1974 and 1978. Sixty percent of the patients presented with mediastinal disease, evenly divided between those with a mediastinal to thoracic ratio (MTR) less than 0.33 and greater than or equal to 0.33. They were of younger average age and were more likely to have nodular sclerosis histologic subtype than those patients without a mediastinal mass. The median follow-up from diagnosis was 4.1 years with 90% of the patients being followed for 2 or more years. The 5-year disease-free survival (DFS) for the radiation only group was 70% in patients without mediastinal disease, 53% in the less than 0.33 MTR group and 44% in the greater than or equal 0.33 MTR group (P = 0.25). The 5-year survival was 92% in the patients without mediastinal disease, 88% in the less than 0.33 MTR group and 90% in the greater than or equal to 0.33 MTR group (P = 0.70). This lack of significant difference both in the 5-year DFS and survival between the three groups was also seen in the patients taken in toto (169) and in those receiving combined modality treatment (36). However, in early stage (I and II) patients, treated with radiation only, those with a large mediastinal mass had a 5-year DFS (33%) that was significantly worse than both the small mass patients (71%) and those with no mediastinal mass (87%) P less than 0.005). The pattern of relapse in the 40 patients who failed following treatment by radiation only was not affected by an increasing size of mediastinal involvement. At the time of this analysis 27 of the 40 patients who had relapsed following treatment by radiation only (all stages) had remained free from second relapse. The authors do not believe that the current data either support or negate the use of a combined modality approach in the initial treatment of Hodgkin's disease patients presenting with a large mediastinal mass. Only further follow-up will establish whether the treatment of patients, who have relapsed following radiation only, is durable and results in an overall survival comparable to that obtained by using combined modality initially.     

Prognostic markers in malignant lymphoma: an analysis of 1,198 patients treated at a single centre.

The prognostic significance of 20 putative markers has been assessed in a consecutive series of 1,198 patients with malignant lymphoma seen by the Sheffield Lymphoma Group over three decades. Univariate analysis disclosed that ten factors for both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) Grade I, and twelve factors for NHL Grade II had prognostic significance. However, multivariate analysis selected only three (age, serum albumin and lymphocyte count) for HD, one (serum albumin) for NHL Grade I and five (age, stage, erythrocyte sedimentation rate, serum albumin and serum lactate dehydrogenase) for NHL Grade II as independent predictors for survival. Risk adjusted prognostic models were derived for Hodgkin's disease and NHL Grade II. For Hodgkin's disease the presence of 3 risk factors predicted for only 35% long-term survival for this group of patients. For NHL Grade II the group with 3-5 risk factors present had a median survival of less than 2 years compared to a 9-year median survival in patients with 1 risk factor present. Whilst these models are being validated on a larger series of patients and will also be tested prospectively, new markers are needed to facilitate decisions on treatment for individual patients.     

Treatment outcomes of small cell carcinoma of the prostate: a single-center study

BACKGROUND: The current study was conducted to determine the clinical characteristics and prognostic features associated with prostatic small cell carcinoma (SCC). METHODS: Between January 1985 and May 2005, 83 patients with SCC of the prostate were identified. Univariate and multivariate Cox proportional hazards modeling were used to assess the prognostic significance of the clinical parameters associated with disease-specific outcomes. RESULTS: Twenty-one patients had no evidence of distant metastasis at the time of the diagnosis of SCC, with the remaining patients demonstrating radiologic or biopsy-proven evidence of metastatic disease. Compared with patients with metastases, patients without metastases at the time of diagnosis were older (P = .001) and had a lower serum lactate dehydrogenase (LDH) level at the time of diagnosis (P = .002). On multivariate analysis, an elevated serum LDH level and low serum albumin at the time of SCC diagnosis was found to be predictive of inferior progression-free survival (P = .02 and P = .008, respectively) and inferior disease-specific survival (DSS) (P = .02 and P = .01, respectively). At the time of last follow-up, 72 patients (87%) had died of disease, with a median DSS duration of 13.1 months (range, 10.7-17.1 months). There was a statistically significant difference noted with regard to the median DSS of patients with nonmetastatic versus those with metastatic SCC (17.7 months [95% confidence interval (95% CI), 12.1-39.2 months] vs 12.5 months [95% CI, 8.1-16.1 months], respectively; P = .03). CONCLUSIONS: SCC of the prostate is a highly aggressive tumor, with serum LDH and albumin levels at the time of diagnosis believed to be predictive of disease-related outcomes. Although palliative, current systemic therapy does not result in cure and does not provide long-term survival for patients with metastases. For patients with nonmetastatic disease, a strategy utilizing systemic and local therapies should be evaluated further.     

Clinical importance of serum vascular endothelial and basic fibroblast growth factors in children with acute lymphoblastic leukemia.

The aim of this study is to evaluate, for the first time serum levels of vascular endothelial growth factor (s-VEGF), and basic fibroblast growth factor (s-b FGF) in children with acute lymphoblastic leukemia (ALL), and its relation to clinical manifestations of the disease. Although VEGF and b FGF have been suggested to be reliable prognostic indicators and important tools for treatment approach in malignant haematopoietic and solid tumours, experience in childhood ALL has been limited to only one study on angiogenesis and urine b FGF. All 31 ALL patients included in the present study at the time of diagnosis and in remission, and all 10 control children had detectable serum levels of VEGF and b FGF. The median level of s-VEGF at the time of diagnosis was significantly lower than in the control group and at the time of remission (respectively p = 0.005, p = 0.0001). Twenty six of 31 patients had an increasing trend of s-VEGF levels in remission reaching control values compared with the levels obtained at diagnosis. S-b FGF median levels at the time of diagnosis were the same as those of the control group, significantly lower than the median s-b FGF values in remission (p = 0.001). In patients with lower platelet counts (< 50 x 10(9)/L) growth factors (VEGF and b FGF) were lower than in patients with higher platelet counts (p = 0.0009 and p = 0.002 respectively). In patients with hepatosplenomegaly (longitudinal size > 3 cm) b FGF levels were higher than patients without hepatosplenomegaly (P = 0.003). We concluded that the increment in both s-VEGF and s-b FGF in patients in remission may be related to the renewal of normal haematopoiesis. The increase in s-VEGF values in 26 out of 31 patients in remission compared to normal control values, may also suggest that there is clinical significance in ALL patients.     

Overall survival of breast cancer patients in relation to preclinically determined total serum cholesterol,body mass index,height and cigarette smoking: a population-based study

Mean overall 5-year survival related to preclinically determined total serum cholesterol, body mass index (BMI), height and cigarette smoking has been analysed among 242 incident cases of breast cancer aged 36–63 years that developed in a population of 24 329 Norwegian women during a mean follow-up of 12 years (range 11–14). The study factors were ascertained at least 1 year prior to diagnosis (mean = 8 years), and the cases have been followed up with respect to death for a mean time of approximately 5 years after diagnosis. Patients whose preclinical total serum cholesterol values were within the highest quartile (≥7.52 mmol/l, mean = 8.58 mmol/l) of the underlying population had a hazard ratio of dying of 2.0 (95% confidence limits, 1.1 and 3.7) compared to cases with cholesterol values in the lowest quartile (mean = 5.28 mmol/l), after adjustment for age at diagnosis, clinical stage, and body mass index. In relation to BMI (Quetelet's index: weight/height²) patients who were obese prior to diagnosis were at higher risk of dying than those who were lean. Compared to patients in the lowest quartile of BMI (mean Quetelet = 21), the hazard ratio was 2.1 (95% confidence limits, 1.2 and 3.8) for patients in the highest quartile (mean Quetelet = 30), after adjustment for age at diagnosis, clinical stage, and total serum cholesterol. For height and for cigarette smoking, no relation with survival was observed. A potential problem of this study might be insufficient information about other well known prognostic factors, but the results suggest that preclinical total serum cholesterol and BMI are positively associated with the risk of dying among women who develop breast cancer.     

Comparison of high-dose therapy and autologous stem-cell transplantation with conventional therapy for Hodgkin's disease induction failure: a case-control study. Société Francaise de Greffe de Moelle.

PURPOSE: To determine the prognostic factors and outcome of first-line induction failure Hodgkin's disease patients who were treated with a salvage regimen of high-dose chemotherapy and autologous stem-cell transplantation, and to compare them with matched, conventionally treated patients. PATIENTS AND METHODS: We retrospectively analyzed data relating to 86 Hodgkin's disease patients who underwent autologous stem-cell transplantation after failure of the first chemotherapy regimen, either because they did not enter a complete remission and experienced progression of disease less than 3 months after the end of their first-line treatment or because they showed evidence of disease progression during first-line therapy. Graft patients were matched with 258 conventionally treated patients (three controls per case) for age, sex, clinical stage, B symptoms, and time at risk; patient data were obtained from international databases. RESULTS: Among the 86 graft patients, the median age at diagnosis was 29 years (range, 14 to 57 years). Thirty-nine percent of patients had stage II disease, 23% had stage III disease, and 38% had stage IV disease. Seventy percent of the patients received chemotherapy and 30% received combined modality therapy; 60% of the patients received a seven- or eight-drug regimen. After this first-line treatment, 91% had disease progression and 9% had a brief partial response. Eighty patients received a second-line treatment; pretransplantation status was as follows: 24% of patients had a complete remission, 38% had a partial remission (PR), 14% had stable disease, and disease progression occurred in 24%. With a median follow-up of 22 months (range, 4 to 105 months) from diagnosis, the 5-year event-free survival and overall survival rates from transplantation were 25% and 35% (95% confidence intervals, 15 to 36 and 23 to 49), respectively. In multivariate analysis, the pretransplantation disease status after salvage therapy was the only significant prognostic factor for survival (PR: relative risk = 2.8, P = .017; progressive disease: relative risk (RR) = 5.26, P < .001). From diagnosis, the 6-year overall survival rates of the graft patients and 258 matched conventionally treated patients were 38% and 29%, respectively (P = .058). CONCLUSION: Autologous stem-cell transplantation represents the best therapeutic option currently available for patients with primary induction failure and is associated with acceptable toxicity. Response to second-line treatment before high-dose chemotherapy is the only prognostic factor that can be correlated with survival.     

Effects of radiochemotherapy and splenectomy on cellular immunity in long-term survivors of Hodgkin's disease and non-Hodgkin's lymphoma

Thirty-six patients treated for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) who had been in complete remission and off all therapy for greater than two years were examined for evidence of immunosuppression. All patients were found to have marked depression of their lymphocyte blastogenic response to phytohemagglutinin (PHA) and of their skin test responses. No abnormalities of serum protein or immunoglobulins were found. T cells were significantly lower than normal in patients who had had Hodgkin's disease, but not in those who had had NHL. B cells, on the other hand, were significantly elevated in both groups. Splenectomy elevated the total lymphocyte count, while those who had not had a splenectomy had lower than normal lymphocyte counts. B cells were elevated while T cells tended to be lower in both splenectomy and nonsplenectomy groups, though only in the nonsplenectomized patients did this reach statistical significance. PHA response tended to be higher in patients with less advanced disease and less extensive treatment than in those with more advanced disease and more extensive treatment, although there was no statistically significant difference. Skin test response though, was shown to correlate well with both stage of disease at diagnosis and extent of treatment.     

Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study.

PURPOSE: A total of 2,185 patients with advanced soft tissue sarcomas who had been treated in seven clinical trials investigating the use of doxorubicin- or epirubicin-containing regimens as first-line chemotherapy were studied in this prognostic-factor analysis. PATIENTS AND METHODS: Overall survival time (median, 51 weeks) and response to chemotherapy (26% complete response or partial response) were the two end points. The cofactors were sex; age; performance status; prior therapies; the presence of locoregional or recurrent disease; lung, liver, and bone metastases at the time of entry onto the trial; long time period between the initial diagnosis of sarcoma and entry onto the study; and histologic type and grade. RESULTS: Univariate analyses showed (a) a significant, favorable influence of good performance status, young age, and absence of liver metastases on both survival time and response rate, (b) a significant, favorable influence of low histopathologic disease grade on survival time, despite a significantly lower response rate, (c) increased survival time for patients with a long time period between the initial diagnosis of sarcoma and entry onto the study, despite equivalent response rates, and (d) increased survival time with liposarcoma or synovial sarcoma, a decreased survival time with malignant fibrous histiocytoma, a lower response rate with leiomyosarcoma, and a higher response rate with liposarcoma (P < .05 for all log-rank and chi2 tests). The Cox model selected good performance status (P < .0001), absence of liver metastases (P = .0001), low histopathologic grade (P = .0002), long time lapse since initial diagnosis (P = .0004), and young age (P = .0045) as favorable prognostic factors of survival time. The logistic model selected absence of liver metastases (P < .0001), young age (P = .0024), high histopathologic grade (P = .0051), and liposarcoma (P = .0065) as favorable prognostic factors of response rate. CONCLUSION: This analysis demonstrates that for advanced soft tissue sarcoma, response to chemotherapy is not predicted by the same factors as is overall survival time. This needs to be taken into account in the interpretation of trials assessing the value of new agents for this disease on the basis of response to treatment.     

国际预后分数预测晚期霍奇金淋巴瘤预后的可行性研究

背景与目的:目前,按标准方案治疗晚期霍奇金淋巴瘤(HodgkinNslymphoma,HL)治愈率可达60%。晚期HL国际预后因素课题组研究总结出晚期初治HL的7个不良预后因素:男性、年龄≥45岁、Ⅳ期、白细胞增高、淋巴细胞减少、低血红蛋白、低白蛋白,并据此提出了国际预后分数(internationalprognosticscore,IPS)的概念。本研究旨在探索应用IPS预测晚期HL预后的价值。方法:回顾性分析1980年1月至2004年12月中山大学肿瘤防治中心初次治疗的141例晚期HL,按照确诊时患者不良预后因素的数目计算IPS。采用Kaplan-Meier法进行生存分析,生存率的比较用log-rank检验,采用Cox部分风险模型进行多因素分析,按IPS分组计算生存率并进行生存率比较。结果:141例晚期HL患者5年无失败生存率(failurefreesurvival,FFS)为57.6%,5年总生存率(overallsurvival,OS)为68.1%。IPS=0～1、2、3和IPS≥4组的5年FFS分别为67.7%、63.2%、61.8%、34.9%;5年OS分别为81.0%、75.5%、70.3%、42.3%。低危患者(IPS0～2)和高危患者(IPS≥3)5年FFS分别为65.4%和48.9%(P=0.012);5年OS分别为78.4%和57.1%(P=0.004)。接受ABVD方案[阿霉素(A)、博来霉素(B)、长春花碱(V)、氮烯咪胺(D)]或MOPP方案[氮芥(M)、长春新碱(O)、甲基苄肼(P)、强的松(P)]治疗的低危患者的5年OS均优于高危患者;接受ABVD治疗的高危晚期HL患者5年FFS和OS均显著优于接受MOPP方案治疗者。多因素分析显示B症状、结外病变、接受MOPP方案化疗为晚期HLFFS和OS独立预后不良因素。结论:IPS对晚期HL的预后有较好的预测价值;高危晚期HL患者接受MOPP方案化疗生存比接受ABVD方案差,推荐接受ABVD方案或更强的方案化疗。     

Analysis of treatment results in advanced Hodgkin's disease: the case for adjuvant radiotherapy

PURPOSE: To assess the treatment results in patients with advanced Hodgkin's disease in a single center and to evaluate the clinical and therapeutic prognostic factors, including verification of the significance of the prognostic score. METHODS AND MATERIALS: Treatment results were analyzed in 133 patients with newly diagnosed Stage IIIB and IV Hodgkin's disease. Treatment consisted of six courses of hybrid chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]/doxorubicin (adriamycin), bleomycin, and vincristine [ABV]) followed by irradiation (RT) in patients with an indication for RT (84 patients). Chemotherapy was then continued for another two cycles. The indications for consolidation RT included bulky disease and/or partial response after six cycles of chemotherapy. In 31 patients, extended-field RT was performed, and in 53, limited fields were irradiated. The median radiation dose was 39 Gy. RESULTS: The median follow-up was 78 months. Complete remission after whole treatment was achieved in 88.7% of patients. The actuarial overall survival rate was 78% and 71%, and relapse-free survival rate was 73% and 65% at 5 and 10 years, respectively. The independent adverse prognostic factors in multivariate analysis appeared to be older age, low serum albumin, low serum gammaglobulin, lower number of chemotherapy cycles, and no RT. The value of the prognostic score was confirmed; the higher the prognostic score, the worse the survival. CONCLUSION: In patients with advanced Hodgkin's disease, consolidation RT improved survival. The best results were achieved with the use of large-volume RT.     

Neurone specific enolase (NSE) in small cell lung cancer: a tumour marker of prognostic significance?

Pretreatment serum levels of neurone specific enolase (NSE) were measured in patients with small cell lung cancer (SCLC). Median values were significantly higher in patients with extensive compared with limited stage disease (48 ng ml-1 v. 17 ng ml-1: P less than 0.001). Serial NSE levels paralleled the clinical response to treatment. In 37 patients with limited SCLC, receiving identical chemotherapy, the pretreatment NSE level was of prognostic significance: with an approximate reduction in median survival of 10% for each 5 ng ml-1 incremental rise in NSE (P = 0.004).     

Use of carcinoembryonic antigen in small cell lung cancer. Prognostic value and relation to the clinical course 1

Carcinoembryonic antigen (CEA) was measured in 147 patients at diagnosis of small cell lung cancer; 17% of patients with limited disease and 51% with extensive disease had an abnormal CEA level (greater than 10 ng/ml). The median level was higher in extensive than in limited disease (11 ng/ml and 5.8 ng/ml, respectively; P less than 0.001). Multivariate analysis showed CEA level greater than or equal to 50 ng/ml to be an adverse prognostic factor (P = 0.02); median survival at this level was shorter than at less than 50 ng/ml (7 and 46 weeks, respectively; P = 0.002). No consistent directional changes of follow-up CEA values were observed in patients with initially normal CEA levels, but normalization of levels occurred in complete responders. We recommend that CEA be measured in this disease at diagnosis as an additional prognostic factor and that patients with abnormal initial CEA levels have follow-up measurements to aid in evaluating response.     

Serum thymidine kinase in monoclonal gammopathies. A prospective study. The Cooperative Group for Study and Treatment of Multiple Myeloma.

Between January 1986 and March 1990, the serum levels of thymidine kinase (TK) were evaluated at diagnosis in 97 patients with monoclonal gammopathy of undetermined significance (MGUS) and 149 patients with multiple myeloma (MM) enrolled in a prospective protocol for treatment of MM. At presentation, patients with MGUS had lower TK levels than those with Stage I MM (P less than 0.05) and the overall population of those with MM (P less than 0.0005). TK levels were increased in advanced stages in comparison with earlier ones (P less than 0.01). The TK level was related to survival. With a median follow-up of 29 months, patients with TK levels greater than 7.0 U/microliters had shorter survival times than those with lower levels (medians, 23 and 42 months; P less than 0.0001). In a multivariate analysis, TK explained most of the variability of survival (P less than 0.0001), the remaining being accounted for by serum creatinine and beta-2 microglobulin. No changes in TK levels occurred during follow-up of patients with stable MGUS, whereas TK levels increased in two patients at time of progression to overt MM. In patients with MM, TK levels decreased (P less than 0.01) in those who responded to treatment but increased in those having relapses (P less than 0.03) and those with progressive disease (P less than 0.03). These results indicate that TK has clinical and prognostic relevance in monoclonal gammopathies, and additional investigations are warranted to determine whether it is a useful tool for the clinical evaluation, staging, and follow-up of patients with MM.     

Risk of Hodgkin's disease and other cancers after infectious mononucleosis

BACKGROUND: Infectious mononucleosis, which is caused by the Epstein-Barr virus, has been associated with an increased risk for Hodgkin's disease. Little is known, however, about how infectious mononucleosis affects long-term risk of Hodgkin's disease, how this risk varies with age at infectious mononucleosis diagnosis, or how the risk for Hodgkin's disease varies in different age groups. In addition, the general cancer profile among patients who have had infectious mononucleosis has been sparsely studied. METHODS: Population-based cohorts of infectious mononucleosis patients in Denmark and Sweden were followed for cancer occurrence. The ratio of observed-to-expected numbers of cancers (standardized incidence ratio [SIR]) served as a measure of the relative risk for cancer. SIRs of Hodgkin's disease in different subsets of patients were compared with the use of Poisson regression analysis. All statistical tests including the trend tests were two-sided. RESULTS: A total of 1381 cancers were observed during 689 619 person-years of follow-up among 38 562 infectious mononucleosis patients (SIR = 1. 03; 95% confidence interval [CI] = 0.98-1.09). Apart from Hodgkin's disease (SIR = 2.55; 95% CI = 1.87-3.40; n = 46), only skin cancers (SIR = 1.27; 95% CI = 1.13-1.43; n = 291) occurred in statistically significant excess. In contrast, the SIR for lung cancer was reduced (SIR = 0.71; 95% CI = 0.58-0.86; n = 102). The SIR for Hodgkin's disease remained elevated for up to two decades after the occurrence of infectious mononucleosis but decreased with time since diagnosis of infectious mononucleosis (P: for trend <.001). The SIR for Hodgkin's disease tended to increase with age at diagnosis of infectious mononucleosis (P: for trend =.05). Following infectious mononucleosis, the SIR for Hodgkin's disease at ages 15-34 years was 3.49 (95% CI = 2.46-4.81; n = 37), which was statistically significantly higher than the SIR for any other age group (P: for difference =.001). CONCLUSION: The increased risk of Hodgkin's disease after the occurrence of infectious mononucleosis appears to be a specific phenomenon.     

Predictive value of the early response to chemotherapy in high-risk stages II and III Hodgkin's disease

A series of 60 patients with "high risk" Stage II and III Hodgkin's disease (B symptoms, or large mediastinal mass, or E lung disease) were staged without laparotomy and treated with combined modality treatment: mechlorethamine, vincristine, procarbazine, and prednisone (6 MOPP) plus radiotherapy. Patients were restaged after the first three courses of MOPP and the status of response to therapy at that time was called early response to chemotherapy (ERC). The rate of nitrogen mustard and procarbazine delivery (MRD) during the first three cycles of chemotherapy also was assessed. At the completion of the therapy patients were restaged and the final response was assessed. Fifty-two (86.7%) patients entered complete remission (CR). Forty-eight percent of the complete responders achieved CR in the first three courses of MOPP. Eight-year survival and disease-free survival (DFS) rates of the patients achieving CR were 71% and 73%, respectively. Survival and DFS were significantly better for the patients who achieved CR in the first three cycles of chemotherapy than for patients who entered CR at a later stage of therapy: 8-year survival 90% versus 55% (P = 0.00); 8-year DFS 87% versus 59% (P = 0.01). The attainment of a complete ERC was adversely affected by lymphocyte depletion (LD) histologic type (P = 0.01) and MRD less than 65% (P = 0.04). However, when a multivariate regression analysis was used, ERC was the only significant prognostic variable for survival and DFS and its predictive value was confirmed even after correction by MRD. These data suggest that the rapidity of response to chemotherapy could be an important prognostic factor in high-risk Stage II and III Hodgkin's disease.     

77例直肠癌伴肝转移患者的预后因素分析

目的 探讨影响直肠癌伴肝转移患者预后的相关因素.方法 回顾性分析77例直肠癌伴肝转移患者的临床病理资料,以Kaplan-Meier法分析患者的总生存率,以Log rank检验和Cox模型对影响患者生存的临床病理因素进行单因素和多因素分析.结果 全组患者的中位生存时间为12个月,1、2、3和5年生存率分别为47.7%、28.0%、13.1%和1.5%.单因素分析结果显示,原发肿瘤的分化程度越低、肠壁浸润程度越深、有淋巴结转移、肝转移灶分布于双叶、肝转移灶数目＞1个、肝转移灶的最大直径＞5 cm、有肝外受侵或转移、确诊时癌胚抗原(CEA)≥5 ng/ml以及未行根治性手术者的预后较差(均P＜0.05).多因素分析结果显示,原发肿瘤的分化程度(P=0.007)、肠壁浸润深度(P=0.027)、肝转移灶的最大直径(P=0.003)以及确诊时的CEA水平(P=0.000)为影响直肠癌伴肝转移患者预后的独立因素.结论 对于直肠癌伴肝转移的患者,原发肿瘤的分化程度越高、肠壁浸润越浅、肝转移灶的最大直径越小以及确诊时CEA水平越低,患者的预后越好.