D-二聚体水平与非霍奇金淋巴瘤患者预后关系的研究

  目的  本研究拟探讨D-二聚体升高与非霍奇金淋巴瘤（Non-Hodgkin Lymphoma NHL）患者总生存之间的关系。  方法  回顾性分析2000年1月至2009年12月天津医科大学附属肿瘤医院收治的经病理证实的NHL 425例,分析患者临床病理特征、D-二聚体及国际预后指数（the International prognostic index,IPI）对总生存的影响。  结果  血浆D-二聚体水平与IPI评分明显相关。低、中、高水平D-二聚体组5年生存率分别为97.4%,86.1%,35.0%（P < 0.05）。与IPI为0或1的患者相比,IPI≥4分者预后较差（P < 0.05）。Ann Arbor分期、病理类型、D-二聚体水平以及IPI评分是影响总生存的主要因素,多元分析表明IPI评分、血浆D-二聚体水平是独立预后因子。  结论  高水平的D-二聚体是NHL患者预后差的标志物。      

Hepatitis C infection and B-cell non-Hodgkin's lymphoma in British Columbia: A cross-sectional analysis

Objectives: To determine the prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (NHL) in British Columbia.Design: A cross-sectional analysis.Setting: The British Columbia Cancer Agency (BCCA), a Canadian provincial tertiary oncology referral center.Subjects: Consecutive patients with B-cell NHL registered onto the BCCA lymphoma database in 1996 and part of 1997 and a control group of patients with T-cell NHL registered on the database from 1995 through 1997. Patients with HIV infection were excluded from the analysis. A second control group (n = 1085) consisted of health-care workers tested for HCV infection following a needle-stick injury.Interventions: Stored sera from patients with B-cell NHL (n= 88) and T-cell NHL (n = 37), identified from the database, were tested for the presence of HCV infection with commercially available serologic tests.Main outcome measures: HCV seropositivity in the B-cell lymphoma group compared to the control groups (T-cell NHL and health-care workers).Results: 2.3% of the B-cell NHL group, none of the T-cell NHL group and 1% of the health-care worker control group were positive for HCV infection. These results were not statistically significantly different.Conclusion: Patients in British Columbia with B-cell NHL do not have an increased prevalence of HCV infection. These data suggest that the lymphotrophism of HCV may differ by regional, racial and genotypic variations around the world.     

Exercise preferences among a population-based sample of non-Hodgkin's lymphoma survivors

In the present study, we examined the exercise preferences of a population-based sample of non-Hodgkin's lymphoma (NHL) survivors. A secondary purpose was to explore the association between various demographic, medical, and exercise behaviour variables and elicited exercise preferences. Using a retrospective survey design, 431 NHL survivors residing in Alberta, Canada completed a mailed questionnaire designed to assess exercise preferences, past exercise behaviour, and various demographic variables. Overall, 77% of participants preferred or maybe preferred to receive exercise counselling at some point after their NHL diagnosis. An overwhelming majority indicated that they would possibly be interested (81%) and able (85%) to participate in an exercise programme designed for NHL survivors. The majority of participants (55%) listed walking as their preferred choice of exercise. Logistic regression analyses indicated that NHL survivors' exercise preferences were influenced by body mass index (BMI), exercise behaviour, and gender. Eliciting exercise preferences from the population in question yields important information for cancer care professionals designing exercise programmes for NHL survivors. Furthermore, tailoring exercise programmes to the preferences of NHL survivors may be one method to potentially enhance exercise adherence in this population both inside and outside of clinical trials.     

Critical review of epidemiological studies of the association between smoking and non-Hodgkin's lymphoma.

Smoking has been suggested to increase the risk of non-Hodgkin's lymphoma (NHL) but the results of epidemiological studies have been inconsistent. The aim of this work was to assess whether the findings of individual studies might have arisen by chance, bias or confounding and whether any associations found between smoking and NHL represent cause-and-effect. Reports of the association between smoking and NHL were identified from Medline. Confidence intervals on relative risks and odds ratios, use of multiple comparisons, and information on source, direction, actual existence and size of potential biases and confounding and features of any associations were abstracted. Four out of five cohort studies found no association between current smoking and NHL but three may have been biased against doing so. One found an association with follicular lymphoma but without a convincing exposure-risk gradient. The fifth found a strong association and an exposure-response gradient with ever smoking but excluded living cases from the end-point. Only one study found an association with past smoking which lacked features of causality. Eight out of 14 case-control studies found no association between current and/or past smoking and NHL but five may have been biased against doing so. Of six positive studies, three involved multiple comparisons, the association of one became non-significant after eliminating bias, four did not explore features of causality and one found an association only in heavy smokers, particularly under 45 years old. There are no grounds to reject the null hypothesis but associations should continue to be sought particularly in subgroups of smokers and with NHL subtypes.     

Breast cancer in Hodgkin's disease and non-Hodgkin's lymphoma survivors.

BACKGROUND: Better therapeutic approaches for patients with Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL) resulted in high cure rates, at cost of serious late side effects. Second primary tumours are a major concern for long-term survivors, and breast cancer (BC) is the most common solid tumour among women treated for HD. Materials and methods: Fifty-three women treated for primary BC with previous history of malignant lymphoma were identified in our institution, 35 with HD (66%), 18 (34%) with NHL. A comparison group was randomly selected from our database matching for each patient with previous lymphoma, two patients with primary BC (rate 1 : 2) for age, stage (pathological tumour size [pT] status and nodal status), year of diagnosis, and estrogen and progesterone status (positive versus negative). The primary end points were disease-free survival (DFS) and overall survival (OS). RESULTS: The two groups of patients were compared for biological features: histopathological diagnosis, grading, lymphatic invasion, c-erbB2 overexpression, and Ki-67. Considering these variables, no significant differences were observed between the two groups with the exception of Ki-67, which was found higher in those with previous HD or NHL (65% versus 49%, respectively, P = 0.0526, borderline significant). Comparing the two groups for treatment approach, no differences were found for surgical and medical therapy (endocrine therapy and chemotherapy). However, regarding patients with node-positive disease (14 versus 35 patients), five patients in the lymphoma group (36%), compared with 24 (69%) in the matched group received anthracycline-based therapy (P = 0.0345). As expected, radiotherapy was used very differently in the two groups, with 36% of patients in the study group undergoing intraoperative radiotherapy with electrons versus 10% in the control group (P = 0.0001). Five-year DFS was 54.5% for the study cohort compared with 91% for controls (P < 0.0001). Five-year OS percentages were also statistically different (86.6% and 98.6%, respectively, P = 0.031). CONCLUSIONS: Previous history of malignant lymphoma is a negative prognostic factor for women diagnosed subsequently with BC. Some undertreatment of women with the latter might be hypothesised as the reason for the worse outcome. Influence of other variables, like previous exposure to cytotoxics, or some unknown biological features related to the previous disease and treatment, should still be investigated in the attempt to improve the dire outcome of these patients.     

Primary gastric non-Hodgkin's lymphoma: Clinical features, management, and prognosis of 185 patients with diffuse large B-cell lymphoma

Background: Primary gastric non-Hodgkin's lymphoma (PG-NHL) is common in Saudi Arabia. This has prompted the analysis of a large series of patients with PG-NHL having high-grade diffuse large B-cell lymphoma (DLCL) in order to define the clinical features and outcome of this disease.Patients and methods: The data of all adult patients in the series with PG-NHL having DLCL histology were retrospectively reviewed. Patients were eligible if they had biopsy-confirmed diagnoses obtained by endoscopy or following laparotomy.Results: Over a 16-year period, 185 patients with DLCL PG-NHL were identified and their data were reviewed. Patients had a median age of 54 years. In 53% of them only one initial therapeutic modality was given, while 47% were managed by a multi-modality approach. One hundred forty patients (76%), 19 (10%), and 26 (14%) attained complete remission (CR), partial remission, and no response/progressive disease, respectively. Multivariate analysis showed that poor performance status and advanced stage were negatively associated with the likelihood of attaining CR. Over a median follow-up of 54 months, 118 (64%) of the patients were alive and disease-free, 17 (9%) were alive with evidence of disease, and the remaining 50 (27%) were dead. The projected 5-year and 10-year overall survivals (OS) (± SD) were 68% (± 4%) and 61% (± 6%), respectively. The Cox proportional hazards model identified the same variables of response as adverse prognostic factors of survival. Using the influence of performance status, and stage, a prognostic index was constructed to recognize three prognostically distinctive risk categories with overall survival proportions of 87%, 61%, and 45%, respectively. The unadjusted International Prognostic Index, however, failed to classify patients into prognostically meaningful risk strata. Of the 140 patients who achieved CR, the median disease-free survival (DFS) was not reached, but the predicted 5- and 10-year DFS were 82% and 75%, respectively. A multivariate analysis identified poor performance status as the only independent prognostic covariate that adversely influenced DFS. Our analysis showed that compared with single-modality management, multi-modality strategy attained significantly higher CR, and advantageous OS and DFS.Conclusions: This large series characterized the clinico-pathologic features and outcome of patients with DLCL PG-NHL. Performance status, and stage significantly influenced patient outcome. A prognostic index was developed and it identified three prognostically distinctive risk groups; however, prospective validation is warranted.     

Elderly patients with non-Hodgkin's lymphoma: Population-based results in the Netherlands

Background: To compare characteristics, treatment and outcome of patients 70 years with patients <70 years in a population-based non-Hodgkin's lymphoma (NHL) registry.Patients and methods: All new patients with NHL (n = 1168) in a geographically defined region in the western part of The Netherlands were registered during a nearly 10-year period. Patient, tumour and treatment characteristics, response to therapy and survival were analysed for both age groups. An age-adjusted prognostic index was determined for elderly patients with aggressive lymphoma.Results: The elderly comprised 41% of the registered patients. There were significantly more females, a preponderance of intermediate-grade histology (diffuse large B-cell lymphoma) and a lower performance status. Incomplete staging in the elderly was mostly due to the omission of a bone marrow biopsy. With respect to WF grading the complete remission rate (except for patients with low-grade/stage I NHL, patients with extranodal NHL and for patients with intermediate grade/extensive NHL) and overall survival at five years (except for patients with low-grade/stage I NHL and for patients with intermediate-grade/extensive NHL) were significantly inferior in the elderly. With respect to the R.E.A.L. Classification the exceptions were in patients with high grade MALT lymphomas (elderly good) and patients with mantle-cell and peripheral T-cell lymphomas (younger group bad too). However, once complete remission was reached, the disease-free survival did not differ significantly between the two age groups, emphasising the importance of achieving complete remission. Although 65% of the classified elderly patients presented with intermediate-grade NHL, only 26% of the elderly patients treated with chemotherapy received anthracycline-based chemotherapy. In the elderly, lymphoma (treatment-related toxicity included) contributed to death in 70% and concomitant disease (other malignancy included) in 30%, versus 78% and 22%, respectively, for the younger group (P = 0.04). The age-adjusted prognostic index, made up of the factors serum LDH, stage and Karnofsky index, showed a clear distinction between the four risk categories low, low/intermediate, intermediate/high and high, with a median survival time of 43, 20, seven and four months, respectively. For the younger group the respective numbers were 144, 45, 19 and 11 months.Conclusions: In a population-based NHL registry the elderly, predominately female patients, formed a larger proportion of the patient group than the one usually reported in the literature. In this population-based cohort inferior remission and overall survival rates were seen in the elderly. However, obtaining complete remission was beneficial for the prognosis of this disease in the elderly. By the application of the R.E.A.L. Classification important subgroups emerge.     

Systemic Fusarium nygamai infection in a patient with lymphoblastic non-Hodgkin's lymphoma

Summary. We report the case history of a 35-year-old male patient with lymphoblastic non-Hodgkin's lymphoma who acquired a systemic infection with Fusarium nygamai during the granulo-cytopenic phase of cytostatic treatment. The patient survived this infection after haematological recovery and treatment with intravenous amphotericin B (total dose 543 mg). Subsequent chemotherapy courses were not complicated by fungal infections. A recent trip to Egypt and severe chemotherapy-induced mucositis were probably the major causes of this severe infection.
Zusammenfassung. Wir berichten über den Fall eines 35-Jährigen Patienten mit lymphobla-stischem Non-Hodgkin Lymphom, der sich während der granulocytopenischen Phase der zytostatischen Therapie eine systemische Infektion mit Fusarium nygamai zuzog. Der Patient überlebte diese Infektion nach hämatologischer Genesung und intravenöser Behandlung mit Amphotericin B (totale Dosis 543 mg). Die anschließenden chemotherapeutischen Kuren waren nicht durch Pilzinfektionen kompliziert. Eine kürzlich unternommene Reise nach Ägypten und schwere Mucositis, die auf die Chemotherapie zurückzuführen ist, werden als Hauptursachen dieser schweren Infektion betrachtet.     

Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma: a report from the non-Hodgkin's lymphoma co-operative study group

The aim of the study was to determine the safety and efficacy of the combination of fludarabine (FLU), cyclophosphamide (CY) and mitoxantrone (FLU/CY/MITO) in untreated follicular lymphomas (FL). Sixty patients with newly diagnosed stage II bulky to IV FL, median age 59 years (range 36 - 70), received FLU/CY/MITO regimen (FLU 25 mg/m² days 1 - 3, CY 300 mg/m² days 1 - 3, Mito 10 mg/m² day 1). Patients received antibiotic oral prophylaxis during all treatments, and growth factors (G-CSF) when grade III granulocytopenia (WHO) occurred. The overall response rate was 87%: 46 patients achieved complete response (CR) (77%), 6 a partial response (10%) and 8 were non-responders. Fifty patients are surviving with a median observation time of 31 months. The 4-year estimated probability of overall survival and failure-free survival were 78.2% and 45% respectively. Thirty-five patients (58%) are still in CR. Sixty percent of patients experienced grade III-IV granulocytopenia. Two patients suffered grade III pulmonary infection and one grade III liver toxicity. In a subset of 46 patients, bcl-2 translocation was positive in bone marrow (BM) and/or peripheral blood (PB) of 36 patients. At the end of treatment, 25 of these patients had CR and 19 (76%) converted to polymerase chain reaction (PCR) negativity. FLU/CY/MITO regimen showed a high level of activity in follicular lymphoma. Toxicity, mainly hematological, was acceptable and the treatment was made feasible by the use of antibiotic prophylaxis and G-CSF. Significant non-hematological toxicities were seen, but no patients died. The conversion of bcl-2 from positive to negative by PCR in BM and/or PB suggests a possible role for this treatment in clearing minimal residual disease and improving patients' outcome.     

Value of oxaliplatin treatment in heavily pretreated patients with non-Hodgkin's lymphoma

In order to assess the efficacy and toxicity profile of oxaliplatin, a third generation platinum derivate active against several solid tumors, we carried out a study in a group of heavily pretreated patients with non-Hodgkin's lymphoma (NHL). Between August 2003 and May 2004, 19 pretreated patients were enrolled in a phase II trial and were treated with oxaliplatin. The drug was administered intravenously on day 1 of a 21-day schedule, at a dose of 130 mg/m² for a total of 6 cycles. One (5%) patient achieved complete remission (CR) and 5 patients (27%) had partial response (PR), thus giving an overall response rate of 32%. The patient in CR suffered from an aggressive B NHL. One of the 5 patients in PR had an aggressive B NHL, whereas the remaining 4 had an indolent B NHL. The treatment was well tolerated with minimal hematologic and extrahematologic toxicity. These data suggest and confirm the efficacy and low toxicity of oxaliplatin in the treatment of patients with heavily pretreated NHL. Further trials using oxaliplatin alone or in combination with other conventional drugs are needed.     

FMD/R-FMD方案治疗老年复发NHL 17例报告

目的 观察FMD/R-FMD方案治疗老年复发NHL的疗效和不良反应.方法复治的老年NHL患者17例,采用FMD(fludarabine,mitoxantrone and dexamethasone)方案治疗14例,采用Rituximab(美罗华)-FMD方案治疗3例.结果 17例NHL中可评价疗效的有16例,有效率为81.3%,完全缓解率为25%(4/16).主要不良反应为骨髓抑制和轻度胃肠道反应.结论 FMD/R-FMD方案治疗老年复发NHL效果好,不良反应轻,值得进一步研究.     

Primary non-Hodgkin's lymphoma of bone: a rare disorder with high frequency of T-cell phenotype in southern Taiwan

Primary non-Hodgkin's lymphoma of bone (PLB) is a rare disorder representing less than 1% of all non-Hodgkin's lymphomas and has rarely been reported in Taiwan. A retrospective clinicopathological study was performed according to the 2002 World Health Organization criteria and identified 14 cases during a 13-year period in 2 medical centers in southern Taiwan. There was male predominance (M:F = 6:1) with a median age of 42 and bone pain (6 patients, 43%) as the most common symptom. Half of the patients had monostotic and the other half polyostotic lesions. Axial skeletons (10 cases, 71%) were the most frequent sites of involvement. The staging results were stage I (9 patients, 64%), stage II (2, 14%) and stage IV (3, 21%). Eight cases (57%) were of B-cell phenotype and the remaining 6 (43%), T-cell. Histologically, 7 (50%) were diffuse large B-cell lymphomas (DLBCLs) and 5 (36%) anaplastic large cell lymphomas. Seven patients received chemotherapy and radiotherapy; 4 chemotherapy and 3 radiotherapy alone. Of the 11 patients with follow-up information, 6 (55%) died of disease within 1 year including 5 with T-cell lymphomas, while all the 5 patients surviving over 1 year were of B-cell phenotype. The overall 1-year survival rate was 45%. The survival of B-cell lymphomas was significantly better than T-cell tumors (p = 0.016, log-rank test). In summary, this study reported the largest series of PBL in Taiwan and confirmed that the majority was DLBCL and B-cell tumors had more favorable prognosis. As compared to the Western series, the cases showed a striking male predominance, higher percentage of axial skeleton involvement, higher relative frequency of T-lineage tumors and poorer prognosis.     

Tobacco and non-Hodgkin's lymphoma: combined analysis of three case-control studies (United States)

The role of tobacco in the etiology of non-Hodgkin's lymphoma (NHL)was evaluated in a combined analysis of data from three population-basedcase-control studies conducted in four midwestern states of the UnitedStates: Nebraska, Iowa, Minnesota, and Kansas. Interviews were obtained from1,177 cases (993 men, 184 women) and 3,625 controls (2,918 men, 707 women )or, if deceased, from their next-of-kin. Overall, there was no associationbetween NHL and tobacco use (odds ratio [OR] = 1.0, 95 percent confidenceinterval [CI] = 0.8-1.1) or cigarette smoking (OR = 1.0, CI = 0.8-1.1). Aslight negative association evident in analyses by intensity and duration ofsmoking was not present when interviews from proxy respondents wereeliminated. There was a suggestion of a positive association between smokingand NHL among women (OR = 1.3, CI = 0.9-1.9), although there was no clearexposure-response relationship. This large case-control analysis provides noevidence that smoking is linked to the development of NHL among men. Thepossible role of smoking in the etiology of NHL among women needs furtherevaluation.     

Adding high-dose tamoxifen to CHOP does not influence response or survival in aggressive non-Hodgkin's lymphoma: an interim analysis of a randomized phase III trial

Purpose CHOP is the standard regimen currently used in the management of the majority of patients with aggressive non-Hodgkin's lymphoma (NHL). However, CHOP only produces 30–35% long-term survival. We hypothesized that adding high-dose tamoxifen, which is known to have multiple drug resistance-modulatory effects, to the CHOP regimen could increase the response rate, and consequently enhance the survival of patients with NHL. Patients and Methods In a prospective, controlled, and randomized study, eligible adult patients with aggressive NHL were randomized between CHOP only (Group I), or CHOP plus high-dose tamoxifen (Group II). The primary aim was to assess the effect of tamoxifen on complete response (CR) rate, with the secondary evaluation of tamoxifen potential impact on survival. The interim analysis of this study is presented. Results Fifty-one and forty-seven evaluable patients were randomized to Group I and Group II, respectively. The median age of all patients was 53y (range 18–78y). The two groups had comparable distributions of the pretreatment prognostic variables. The CR for patients in Group I was 80% (41 patients) as compared with 74% (35 patients) in Group II (P=0.48). Likewise, there was no apparent difference in the partial remission rates between the two groups (6% vs 15%, respectively). Of patients who initially attained CR, 15 (37%) and 10 (29%) subsequently relapsed in Groups II and I respectively (P=0.45). The NHL International Prognostic Index (IPI) was the only factor that predicted attaining CR. At the time of this interim analysis, the actuarial-estimated overall survival (OS) probability (±S.E.) for the entire population at 5 y was 58% (±6) with no survival difference between the two groups (P=0.51). Only attaining CR and the IPI predicted OS probability. The probability of remaining event-free at 5 y (±SE) for those achieving CR was 72% (±9), and there was no significant difference between the two treatment groups (P=0.68). Toxicity profile was similar in the two groups. Conclusion Based on this interim analysis, combining high-dose tamoxifen, as used in this study, with the CHOP regimen has failed to have any favorable effect on the outcome of patients with aggressive NHL, and therefore cannot be recommended for future trials.     

初诊伴自身免疫性溶血性贫血的侵袭性非霍奇金淋巴瘤特征分析

  目的  探讨首发伴自身免疫性溶血性贫血（autoimmune hemolytic anemia,AIHA）的侵袭性非霍奇金淋巴瘤（non-Hodgkin's lymphoma,NHL）的临床及实验室特征。  方法  收集2013年9月至2016年7月苏州大学附属第二医院收治的6例首发伴AIHA的侵袭性NHL患者的临床资料,分析患者的发病情况、疾病进展、治疗及预后相关因素。  结果  2013年9月至2016年7月苏州大学附属第二医院收治初发侵袭性NHL 155例,起病伴AIHA为6例（3.9%）,其中男性3例,女性3例;中位年龄67（62~74）岁。首发症状包括:全身多发淋巴结肿大5例、发热3例、多发骨破坏并骨痛1例,均表现血红蛋白进行性下降。6例患者病理类型分别为:弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）3例,其中1例Bcl-2（+）Bcl-6（+）c-myc（+）三表达,1例CD5阳性;1例外周T细胞淋巴瘤-非特指型（peripheral T-cell lymphoma-not otherwise specified,PTCL-NOS）;2例血管免疫母细胞性T细胞淋巴瘤（angioimmunoblastic T-cell lymphoma,AITCL）。色素原位杂交（chromogenic in situ hybridization,CISH）法检测石蜡组织EB病毒基因（Epstein-Barr virus-mRNA,EBV-mRNA）（EBER）的表达:所检测5例均阳性。6例ECOG评分3~4分,Ann-Arbor分期均为Ⅲ~Ⅳ期,IPI评分4~5分,均为高危组。淋巴瘤病理确诊时中位血红蛋白56（34~79）g/L、中位网织红细胞比例6.7（0.2~21.0）%;6例患者Coombs试验均阳性:6例抗C3阳性（1:64~1:2048）、4例抗IgG阳性（±~1:16）;检测3例血浆EBV-DNA拷贝数均增高。6例患者中:1例AITCL确诊后放弃治疗;其余5例应用CHOP样方案±利妥昔单抗联合化疗2~8个疗程（4例化疗间歇期加强的松治疗）,其中2例DLBCL持续完全缓解（complete response,CR）,总生存时间（overall survival,OS）分别为20、14个月,另1例DLBCL及1例PTCL-NOS经2个疗程化疗后骨髓抑制期继发严重肺部感染、心功能衰竭死亡,OS分别为1.5、2个月,1例AITCL化疗4个疗程后疾病快速进展死亡,OS为4.5个月。  结论  侵袭性NHL首发伴AIHA多见于老年患者,EBV感染率高,溶血进展快、程度严重,化疗耐受性差,总体预后差,早期死亡率高。早期诊断及有效化疗可能改善预后。      

Outcome of patients with non-Hodgkin's lymphoma of the stomach after gastrectomy: clinicopathologic study and reclassification according to the revised European-American lymphoma classification

Background. The best treatment for patients with non-Hodgkin's lymphoma (NHL) of the stomach is still uncertain. The revised European-American lymphoma (REAL) classification has helped to define new, potentially more appropriate classification schemes for gastric lymphomas. Methods. Fifty-one resected gastric lymphomas were reclassified according to the REAL classification, and the efficacy of multimodal treatment was examined retrospectively. The principal treatment plan consisted of: (1) surgical resection of the stomach with lymph node dissection, followed by (2) systemic chemotherapy, mainly using the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen. Results. According to the Ann Arbor classification, 27 patients had stage IE, 19 had stage IIE, and 5 had stage IV NHL. Using the REAL classification, we diagnosed diffuse large B-cell lymphoma (DLBL) in 23 patients, marginal zone B-cell (low-grade mucosa-associated lymphoid tissue [MALT]-type) lymphoma in 22, follicle center lymphoma in 4, mantle cell lymphoma in 1, and peripheral T-cell lymphoma in 1 patient. Nine of the 51 patients relapsed, and 8 patients with DLBL died of cancer. Survival rates at 5 years after surgery were 96.0% for stage IE, 83.3% for stage IIE, and 87.0% for all patients. Univariate analysis indicated that the tumor histology (according to the REAL classification), depth of invasion, degree of nodal involvement, Ann Arbor staging, and chemotherapy had an impact on patient outcome (P = 0.0018; P = 0.0002; P = 0.0308; P = 0.0016, and P = 0.0118, respectively). Conclusions. These data reveal that gastric NHL, especially of the low-grade MALT-type, often remains localized and has a good prognosis after surgery. The REAL classification was useful for classifying new categories of NHL, including the MALT-type, in the clinical setting, and for determining the optimal treatment modality for gastric NHL. Received: December 11, 2000 / Accepted: July 18, 2001     

Evidence for an association between cutaneous malignant melanoma and lymphoid malignancy: a population-based retrospective cohort study in Scotland

We analysed the risk of cutaneous malignant melanoma (CM) occurring in patients following a diagnosis of non-Hodgkin's lymphoma (NHL) or chronic lymphatic leukaemia (CLL), and of NHL or CLL subsequently developing in CM survivors. Cohorts of patients with CM, NHL or CLL (index cancer) diagnosed between 1975 and 1997 were identified from the Scottish national cancer registry and followed through the registry for subsequent CM, NHL or CLL. The standardised incidence ratio (SIR) for each cancer was calculated and overall risk, risk in relation to gender and age at diagnosis of the index cancers and time from diagnosis of the index cancer to the diagnosis of the second malignancy were measured. There were 9385 CM patients, 4016 CLL patients and 13 857 NHL patients identified with an index cancer with 56 195, 14 450 and 44 999 person-years of follow-up, respectively. There was an increased risk of both CLL and NHL following a diagnosis of CM (SIR 2.3 and 1.5, respectively) and of CM following a diagnosis of CLL and NHL (SIR 2.3 and 2.1, respectively). The risk was statistically significantly increased for CLL developing in CM patients and for CM occurring in NHL survivors (P<0.05). This study supports an association between CM, CLL and NHL developing in the same patient. Immunosuppression, exposure to ultraviolet radiation and genetic factors may lead to a host environment that is conducive to the development of these malignancies.     

High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study.

BACKGROUND: Combination chemotherapy can cure patients with non-Hodgkin's lymphoma (NHL), but those who suffer treatment failure or relapse still have a poor prognosis. High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) can improve the outcome of these patients. We evaluated an intensified high-dose sequential chemotherapy program with a final myeloablative course. PATIENTS AND METHODS: Inclusion criteria were age 18-65 years, histologically proven primary progressive or relapsed aggressive NHL and eligibility for HDCT. The therapy consists of two cycles DHAP: dexamethasone 40 mg (day 1-4), high-dose cytarabine 2 g/m2 12q (day 2), cisplatin 100 mg/m2 (day 51); patients with partial (PR) or complete remission (CR) received cyclophosphamide 4 g/m2 (day 37), followed by peripheral blood stem cell (PBSC) harvest; methotrexate 8 g/m2 (day 1) plus vincristine 1.4 mg/m2 (day 51); and etoposide 500 mg/m2 (day 58-62). The final myeloblative course was BEAM: cytarabine 200 mg/m2 12q (day 81-84), etoposide 150 mg/m2 12q (day 81-84), melphalan 140 mg/m2 (day 80), carmustin 300 mg/m2 (day 80) followed by PBSCT. RESULTS: Fifty-seven patients (median age 43 years, range 24-65) were enrolled: 23 (40%) patients were refractory to primary therapy and 34 (60%) patients had relapsed NHL. The response rate (RR) after 2 cycles of DHAP was 72% (9% CR, 63% PR) and at the final evaluation (100 days post transplantation) 43% (32% CR, 11% PR). Toxicity was tolerable. Median follow-up was 25 months (range 1-76 months). Freedom from second failure (FF2F) and overall survival (OS) at 2 years were 25% and 47% for all patients, respectively. FF2F at 2 years for patients with relapse and for patients refractory to primary therapy were 35% and 9% (P=0.0006), respectively. OS at 2 years for patients with relapse and for patients refractory to primary therapy were 58% and 24% (P=0.0044), respectively. CONCLUSIONS: We conclude that this regimen is feasible, tolerable and effective in patients with relapsed NHL. In contrast, the results in patients with progressive disease are unsatisfactory. This program is currently being modified by addition of rituximab for patients with relapsed aggressive NHL.