Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas

The Kiel classification provides a new subdivision of non-Hodgkin lymphomas into distinct entities showing different clinical and prognostic properties. In comparison with earlier classifications this system defines additional types of lymphoma (e.g. CC lymphoma, LP immunocytoma) (for abbreviations see text) which are to be considered separate entities also from a clinical point of view. By data derived from a multicenter prospective observation study (1,127 patients recruited from 1975 to 1980, follow-up until 1985) a precise definition of the clinical features of each lymphoma entity (e.g. frequency, age and sex distribution, patterns of initial involvement and spread of disease) was possible. In addition, the effect of radio- and/or chemotherapeutic measures was evaluated. Strictly localized disease (stage I/IE according to the Ann Arbor classification) occurred in 1.5 to 8% of patients with NHL of low-grade malignancy (comprising 69.4% of cases studied) and in 8 to 17% of patients with high-grade malignant NHL (comprising 30.2% of cases studied). Loco-regional irradiation alone was able to induce complete remission in 86 to 89% (CB and IB lymphomas) and in 100% (LP immunocytoma, CB-CC and CC lymphomas), respectively, of stage I/IE patients. Only CC and IB lymphomas showed a relevant risk of relapse (40% and 50%, respectively). Total lymphoid irradiation as able to induce stable complete remissions in about 50% of patients with stage III of CB-CC lymphoma. Probabilities of survival of patients with initial stages III and IV treated by several types of chemotherapy reflect different prognostic features of individual lymphoma entities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Food groups and risk of non-Hodgkin lymphoma: a multicenter, case-control study in Italy

Incidence of non-Hodgkin lymphoma (NHL) has been rising worldwide, but the reasons are undefined. Dietary habits may play a role in the etiology of NHL by influencing the metabolic pathways of several cells of the immune system. This case-control study investigated the relation between food consumption and NHL risk. Between 1999 and 2002, we conducted a hospital-based case-control study on NHL in 2 areas of Italy. Cases were 190 patients (median age 58 years) with incident NHL admitted to specialized and general hospitals. Controls were 484 patients (median age 63 years) with acute non-neoplastic conditions admitted to the same hospitals network of cases. A validated food-frequency questionnaire was used to assess habitual diet 2 years before interview. Unconditional multiple logistic regression was used to estimate the odds ratios (OR) and the corresponding 95% confidence intervals (CI), with allowance for energy intake, according to the residual model. Consumption of highest versus lowest quartile of pasta/rice (OR = 1.87, 95% CI: 1.04-3.36) and cheese (OR = 1.66, 95% CI: 0.98-2.83) were associated with a significantly increased NHL risk. Inverse association was found for vegetables (OR = 0.49, 95% CI: 0.28-0.87), fruits (OR = 0.51, 95% CI: 0.30-0.85), and egg consumption (OR = 0.59, 95% CI: 0.36-0.97). The association of pasta/rice was also supported by an increased risk of high glycemic load levels (OR = 1.86, 95% CI: 1.04-3.32). In conclusion, our results suggested that diet could affect NHL risk.     

Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG)

BackgroundThe nuclear factor-kappa B activation in mucosa-associated lymphoid tissue (MALT) lymphoma pathogenesis provided the rationale for the evaluation of bortezomib in this malignancy.Patients and methodsThirty-two patients with relapsed/refractory MALT lymphoma were enrolled. Thirty-one patients received bortezomib 1.3 mg/m² i.v., on days 1, 4, 8, and 11, for up to six 21-day cycles.ResultsMedian age was 63 years (range, 37–82 years). Median number of prior therapies was 2 (range, 1–4). Nine patients had Ann Arbor stage I, 7 patients had stage II, and 16 patients had stage IV. Primary lymphoma localization was the stomach in 14 patients; multiple extranodal sites were present in 10 patients. Among the 29 patients assessable for response, the overall response rate was 48% [95% confidence interval (CI) 29% to 67%], with 9 complete and 5 partial responses. Nine patients experienced stable disease and six had disease progression during therapy. The most relevant adverse events were fatigue, thrombocytopenia, neutropenia, and peripheral neuropathy. After a median follow-up of 24 months, the median duration of response was not reached yet. Five deaths were reported, in two patients due to disease progression.ConclusionBortezomib is active in relapsed MALT lymphomas. Further investigations to identify optimal bortezomib dose, schedule, and combination regimens are needed since the frequent detection of dose-limiting peripheral neuropathy.     

Impact of Interferon at Induction Chemotherapy and Maintenance Treatment for Multiple Myeloma Preliminary results of a multicenter study by the Italian Non-Hodgkin's Lymphoma Cooperative Study Group (NHLCSG)

In 1990 the Italian Non-Hodgkin's Lymphoma Cooperative Study Group (NHLSG) started a multicenter study on the role of interferon (IFN) in multiple myeloma (MM). The schedule of treatment was based on the assumption that melphalan plus prednisone (MP) would be better for good-prognosis patients, whereas poor-prognosis patients would benefit from polychemotherapy. Accordingly, IFN was included randomly for the induction treatment of good-prognosis patients and randomly as maintenance of the response achieved in both groups. Up to now 78 patients of the 124 enrolled have completed the induction treatment and are evaluable for response and response duration. The overall response rate was 59%. Sixty-two percent of good-prognosis patients obtained objective response, 9/14 (64%) with MP and 9/15 (60%) with MP + IFN. Up to now, with a median follow-up of 9 months from the evaluation of response, no difference has been recorded between the maintenance and no maintenance groups on relapse rate, neither in good- nor in poor-prognosis patients.     

Peripheral T-cell lymphomas: clinical features and prognostic factors of 92 cases defined by the revised European American lymphoma classification

The purpose of this study was to better define the clinical features and natural history of peripheral T-cell lymphomas (PTCL) entities included in the Revised European American lymphoma (REAL) classification. Cases of PTCL were retrieved from the records of the Department of Pathology and classified according to the REAL classification. In addition, cases of anaplastic large cell lymphoma (ALCL) were divided into classical, small cell, and primary cutaneous subtypes, and immunostaining for the anaplastic large-cell kinase (ALK) protein was performed on all cases of ALCL. Clinical features, response to therapy and survival were abstracted. Ninety-two cases of PTCL with adequate clinical information were retrieved. There were 40 cases of ALCL (30 classical, 7 small cell variant, 3 primary cutaneous), 28 PTCL, unspecified, 13 angioimmunoblastic T-cell lymphoma and 11 with other entities. The patients had a median age of 48 years with a range of 6-84 and had an estimated overall survival (OS) of 49% and progression-free survival (PFS) of 22% at 5 years. The International Prognostic Index (IPI) was a significant prognostic factor for both progression-free and OS. Histology was a significant predictor of PFS with anaplastic large cell having the best prognosis. ALK expression was not associated with an improved progression-free or overall-survival in patients with systemic T-cell ALCL. In conclusion, the REAL classification describes distinct PTCL entities. The IPI is the most important predictor of progression-free and OS in patients with PTCL. ALK expression may not provide prognostic information for systemic ALCL.     

Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG).

BACKGROUND: We designed a dose- and time-intensified high-dose sequential chemotherapy regimen for patients with relapsed and refractory Hodgkin lymphoma (HD). PATIENTS AND METHODS: Eligibility criteria included age 18-65 years, histologically proven primary progressive (PD) or relapsed HD. Treatment consisted of two cycles DHAP (dexamethasone, high-dose cytarabine, cisplatinum); patients with chemosensitive disease received cyclophosphamide followed by peripheral blood stem cell harvest; methotrexate plus vincristine, etoposide and BEAM plus peripheral blood stem cell transplantation (PBSCT). RESULTS: A total of 102 patients (median age 34 years, range 18-64) were enrolled. The response rate was 80% (72% complete response, 8% partial response). With a median follow-up of 30 months (range 3-61 months), freedom from second failure (FF2F) and overall survival (OS) were 59% and 78% for all patients, respectively. FF2F and OS for patients with early relapse were 62% and 81%, for late relapse 65% and 81%; for PD 41% and 48%, and for multiple relapse 39% and 48%, respectively. In multivariate analysis response after DHAP (P <0.0001) and duration of first remission (PD and multiple relapse versus early and late relapse; P=0.0127) were prognostic factors for FF2F. Response after DHAP (P <0.0081), duration of first remission (P=0.0017) and anemia (P=0.019) were significant for OS. CONCLUSION: Based on the promising results of this study, a prospective randomized European intergroup study was started comparing this intensified regimen with two courses of DHAP followed by BEAM (HD-R2 protocol).     

Evaluation of clinical trial eligibility and prognostic indices in a population‐based cohort of systemic peripheral T‐cell lymphomas from the Danish Lymphoma Registry

Clinical trials (CTs) are needed to improve the outcome for peripheral T‐cell lymphomas (PTCL), and accrual into CTs is one of the main recommendations in international treatment guidelines. The use of risk‐adapted strategies has been suggested as a way to optimize treatment outcome in PTCL. The aim of the present study was to evaluate CT eligibility and selected prognostic indices in a population‐based PTCL cohort of 481 PTCL patients identified from the Danish Lymphoma Registry in the period 2000–2010. According to five predefined parameters (age, performance status, P‐creatinine, P‐ALAT and measurable tumour lesion), patients were subdivided into four groups: ‘younger fit’, ‘elderly fit’, ‘frail’ and ‘not CT eligible’. International prognostic index (IPI), prognostic index for T‐cell lymphoma (PIT) and anaplastic lymphoma kinase (ALK) protein expression were tested at subtype‐specific level. Overall, 41% of the patients were considered eligible for interventional CTs implicating curatively intended multiagent chemotherapy, including, if considered appropriate, consolidating stem cell transplantation (SCT), as part of the upfront management strategy. Moreover, 28% was elderly fit and eligible for interventional CT, including those with SCT as part of the trial design. Approximately 7% were defined as ‘too frail’ for aggressive treatment schedules, whereas 24% were deemed not to be eligible for any CT. Both overall and progression‐free survivals were effectively predicted by IPI and PIT (p < 0.001). ALK‐positive anaplastic large cell lymphoma patients were significantly younger (median age 40 vs. 62, p < 0.001) and had a better outcome than their ALK‐negative counterparts (p < 0.001). However, ALK expression lost its prognostic significance when adjusting for age. In a population‐based cohort of adult Caucasian PTCL patients, approximately half were eligible for multiagent chemotherapy with or without consolidating SCT. Both IPI and PIT are useful prognostic indices in all ‘primary nodal’ PTCL entities. The prognostic value of ALK protein expression in anaplastic large cell lymphoma is significantly downsized when adjusting for age. Copyright © 2014 John Wiley & Sons, Ltd.     

Primary diffuse large B-cell lymphoma of the breast: prognostic factors and outcomes of a study by the International Extranodal Lymphoma Study Group.

BACKGROUND: Primary diffuse large B-cell lymphoma (DLBCL) of breast is rare. We aimed to define clinical features, prognostic factors, patterns of failure, and treatment outcomes. PATIENTS AND METHODS: A retrospective international study of 204 eligible patients presenting to the International Extranodal Lymphoma Study Group-affiliated institutions from 1980 to 2003. RESULTS: Median age was 64 years, with 95% of patients presenting with unilateral disease. Median overall survival (OS) was 8.0 years, and median progression-free survival 5.5 years. In multifactor analysis, favourable International Prognostic Index score, anthracycline-containing chemotherapy, and radiotherapy (RT) were significantly associated with longer OS (each P < or = 0.03). There was no benefit from mastectomy, as opposed to biopsy or lumpectomy only. At a median follow-up time of 5.5 years, 37% of patients had progressed--16% in the same or contralateral breast, 5% in the central nervous system, and 14% in other extranodal sites. CONCLUSIONS: The combination of limited surgery, anthracycline-containing chemotherapy, and involved-field RT produced the best outcome in the pre-rituximab era. A prospective trial on the basis of these results should be pursued to confirm these observations and to determine whether the impact of rituximab on the patterns of relapse and outcome parallels that of DLBCL presenting at other sites.     

Clinical characteristics and outcomes of Castleman disease: a multicenter Consortium study of 428 patients with 15-year follow-up

Castleman disease (CD) has been reported as a group of poorly understood lymphoproliferative disorders, including unicentric CD (UCD) and idiopathic multicentric CD (iMCD) which are human immunodeficiency virus (HIV) negative and human herpes virus 8 (HHV-8) negative. The clinical and independent prognostic factors of CD remain poorly elucidated. We retrospectively collected the clinical information of 428 patients with HIV and HHV-8 negative CD from 12 large medical centers with 15-year follow-up. We analyzed the clinicopathologic features of 428 patients (248 with UCD and 180 with iMCD) with a median age of 41 years. The histology subtypes were hyaline-vascular (HV) histopathology for 215 patients (56.58%) and plasmacytic (PC) histopathology for 165 patients (43.42%). Most patients with UCD underwent surgical excision, whereas the treatment strategies of patients with iMCD were heterogeneous. The outcome for patients with UCD was better than that for patients with iMCD, 5-year overall survival (OS) rates were 95% and 74%, respectively. In further analysis, a multivariate analysis using a Cox regression model revealed that PC subtype, hepatomegaly and/or splenomegaly, hemoglobin ≤ 80 g/L, and albumin ≤ 30 g/L were independent prognostic factors of CD for OS. The model of iMCD revealed that age > 60 years, hepatomegaly and/or splenomegaly, and hemoglobin ≤ 80 g/L were independent risk factors. In UCD, single-factor analysis identified two significant risk factors: hemoglobin ≤ 100 g/L and albumin ≤ 30 g/L. Our study emphasizes the distinction of clinical characteristics between UCD and iMCD. The importance of poor risk factors of different clinical classifications may direct more precise and appropriate treatment strategies.     

Clinical characteristics and pathological classification of non-Hodgkin's lymphoma in Kuwait. Results of a collaborative study with the International Lymphoma Study Group (ILSG)

Kuwait was chosen by the International Lymphoma Study Group (ILSG) as one of the sites attending in the project on "Clinical characteristics and pathological classification of non Hodgkin's lymphoma (NHL) in the developing countries". The Kuwait study involved 206 cases of NHL, diagnosed, staged and treated in the Kuwait Cancer Control Center (KCCC). All cases were reviewed and reclassified independently by the pathologists of KCCC and the International Lymphoma Study Group (ISLG) using the latest World Health Organization (WHO) classification of neoplastic disease of the hematopoietic and lymphoid tissues. Immunophenotyping as to B- or T-cell was documented in all cases. Three main pathological entities (diffuse large B-cell lymphoma, follicular lymphoma, peripheral T-cell lymphoma) were identified and studied thoroughly. The intense cooperation between experts of the ISLG and pathologists of the KCCC proved that the WHO classification was fully reproducible in Kuwait. The high incidence of extranodal lymphomas (53%) observed in the KCCC may not be due to special ethnic or environmental conditions in Kuwait but rather be due to a selection of patients coming to our center.     

Treatment of alpha chain disease. Results of a prospective study in 21 Tunisian patients by the Tunisian-French intestinal Lymphoma Study Group

Between 1981 and 1985, the authors studied 21 Tunisian patients with alpha chain disease. Twenty of 21 underwent laparotomy. According to Galian et al. six patients were classified Stage A, two Stage B, and 13 Stage C. The therapeutic regimen included the following: (1) Antibiotics: In the case of intestinal bacterial overgrowth (IBO), antibiotics selected by their antibiograms were delivered; in absence of IBO, metronidazole plus ampicillin were first given. The antibiotic treatment was changed in case of therapeutic failure. (2) Chemotherapy: From 1981 to 1983 a cyclophosphamide, Adriamycin (doxorubicin), teniposide (VM-26), prednisone (CHVP) protocol (Adriamycin 35 mg/m2, teniposide 50 mg/m2 day 2, cyclophosphamide 300 mg/m2 days 2 through 4, prednisone 40 mg/m2 days 1 through 10) was used. After 1983 bleomycin 15 mg, Adriamycin 30 mg, vinblastine 10 mg were given on day 15. Serum immunoelectrophoresis and immunohistochemical study of duodenojejunal specimens were made on a 3-month and 6-month basis, respectively. Survival curve analysis was made according to Kaplan and Meier. Results were as follows: (1) Stage A: Six patients were first treated by antibiotics alone; two complete responses (CR) persisting 42 and 55 months later were observed, respectively. The four antibiotic failures were submitted to further chemotherapy with four subsequent failures and two deaths. (2) Stage B-C: Chemotherapy led to nine CR with one precocious relapse, a salvage chemotherapy allowing to one more CR. (3) All stages mixed, percentage of survival reached 90 +/- 12% at 2 years and 67 +/- 25% at 3 years, all patients alive beyond 3.5 years being disease-free.     

Fluid consumption and the risk of bladder cancer: results of a multicenter case-control study

A number of studies suggest a relation between fluid consumption and the risk of bladder cancer but results are contradictory. Different theories involving the quantity or the type of fluid consumed have been put forward to explain these relations but mechanisms remain unclear. We conducted a multicenter case-control study in several hospitals in France including 765 cases and 765 matched controls. Information collected by face-to-face interview included quantity and type of beverages consumed from the age of 18 until age at diagnosis, as well as smoking habits. Among men, we observed a slight non-significant increased risk of bladder cancer associated with total fluid intake, irrespectively of tobacco use. This was essentially due to intake of non-alcoholic drinks, coffee and bottled juice or water. Relative risks greater than 1 were observed in relation with coffee consumption. On the other hand, alcohol consumption, especially wine, was associated with relative risks less than unity. No relation could be identified between bladder cancer risk and fluid consumption among women. Our results do not support an association between total fluid consumption and bladder cancer risk. The role of the different types of fluid consumed, confounding factors and bias in the present analysis are discussed.     

Primary follicular and marginal-zone lymphoma of the breast: clinical features,prognostic factors and outcome: a study by the International Extranodal Lymphoma Study Group

BackgroundPrimary breast lymphoma (PBL) of low-grade histology is a rare disease. This multicentric retrospective study was carried out to determine clinical features, prognosis and relapse.Patients and methodsPatients with histologically proven, previously untreated follicular or marginal-zone PBL (MZL PBL) diagnosed from 1980 to 2003 were included in the study. Major end points were progression-free survival (PFS), overall survival (OS) and potential prognostic factors.ResultsWe collected data on 60 cases of PBL [36 follicular and 24 marginal-zone lymphoma (MZL)]. Stage was I_E or II_E in 57 patients and IVE in three patients due to bilateral breast involvement. Surgery, chemotherapy and radiotherapy (RT), alone or in combination, were used as first-line treatments in 67%, 42% and 52% of patients, respectively. Overall response rate was 98%, with a 93% complete response rate. Five-year PFS were 56% for MZL and 49% for follicular PBL (P = 0.62). Relapses were mostly in distant sites (18 of 23 cases); no patients relapsed within RT fields.ConclusionsOur data showed an indolent behaviour of MZL PBL, comparable to other primary extranodal MZL. Conversely, patients with follicular PBL had inferior PFS and OS when compared with limited-stage nodal follicular non-Hodgkin's lymphomas, suggesting an adverse prognostic role of primary breast localisation in this histological subgroup.     

182例局部晚期宫颈癌根治性子宫切除术加术前新辅助治疗预后分析

目的 观察局部晚期宫颈癌根治性子宫切除术加术前同期放化疗(CRCT)、单纯放疗(RT)的疗效,并分析影响预后的因素。方法 回顾分析2006—2011年收治的 182例Ⅰ_B2~Ⅲ_B期宫颈癌患者资料,其中 59例RT,123例术前每周顺铂40 mg/m²同期RT,放疗剂量 40~50 Gy分 20~25次。新辅助治疗后 2~3周行全子宫、双附件及盆腔淋巴结切除术。采用Cox法行多因素预后分析。结果 随访时间满 3年者为 69例。肿瘤直径≥4.5 cm时术前CRCT与RT的 3年无进展生存(PFS)、总生存(OS)率均相似(χ²=1.84、1.56,P=0.176、0.221),<4.5 cm时术前CRCT比RT的PFS、OS率高(χ²=5.22、4.81,P=0.022、0.018)。全组 3年PFS、OS率分别为92.0%、93.8%。Cox分析显示肿瘤直径(<6 cm与≥6 cm)是PFS、OS的影响因素(χ²=2.56、4.06,P=0.011、0.007),年龄(<48岁与≥48岁)是OS的影响因素(χ²=4.86,P=0.046),术后淋巴结状况(是否转移)是PFS的影响因素(χ²=1.04,P=0.010)。     

High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG)

On the basis of a preceding phase I study, the current trial explored bendamustine in combination with mitoxantrone and rituximab (BMR) in patients with stage III/IV relapsed or refractory indolent lymphomas and mantle cell lymphoma (MCL) with or without prior rituximab containing chemo-immunotherapy (R-chemo) treatment. Therapy consisted of bendamustine 90 mg/m² days 1 + 2, mitoxantrone 10 mg/m² day 1, rituximab 375 mg/m² day 8. Treatment was repeated on day 29 for a total of four cycles. Between 3 April and 04 July, 57 patients were recruited from 24 participating institutions, 39% of whom had received prior R-chemo therapy. Median age was 66 years (40 - 83). Lymphoma subtypes were 29 follicular (FL), 18 MCL, and 10 other indolent lymphomas. The overall response rate (ORR) was 89% with 35% CR and 54% PR. ORR in R-chemo pretreated patients was 76% (38% CR, 38% PR). After a median observation time of 27 months (1 - 43), the estimated median progression free survival is 19 months. The 2 year overall survival is 60% for patients with FL and MCL. Treatment related toxicities of grade 3/4 comprised a reversible myelosuppression (10% anemia, 78% leukocytopenia, 46% granulocytopenia, 16% thrombocytopenia). However, unexpected hospitalisations were necessary after 4% of BMR-application only. BMR is a very effective new outpatient immuno-chemotherapy with low toxicity for patients with relapsed/refractory FL, MCL and other indolent lymphomas.     

Clinical features,neurologic recovery,and risk factors of postoperative posterior fossa syndrome and delayed recovery: a prospective study

BackgroundPosterior fossa syndrome (PFS) is a known consequence of medulloblastoma resection. Our aim was to clinically define PFS, its evolution over time, and ascertain risk factors for its development and poor recovery.MethodsChildren with medulloblastoma treated at St Jude Children’s Research Hospital from 6/2013 to 7/2019 received standardized neurological examinations, before and periodically after radiation therapy. Most (98.3%) were enrolled on the ongoing multi-institutional protocol (SJMB12; {"type":"clinical-trial","attrs":{"text":"NCT 01878617","term_id":"NCT01878617"}}NCT 01878617).ResultsSixty (34%) of 178 evaluated children had PFS. Forty (23%) had complete mutism (PFS1) and 20 (11%) had diminished speech (PFS2). All children with PFS had severe ataxia and 42.5% of PFS1 had movement disorders. By multivariable analysis, younger age (P = .0005) and surgery in a low-volume surgery center (P = .0146) increased PFS risk, while Sonic Hedgehog tumors had reduced risk (P = .0025). Speech and gait returned in PFS1/PFS2 children at a median of 2.3/0.7 and 2.1/1.5 months, respectively, however, 12 (44.4%) of 27 PFS1 children with 12 months of follow-up were nonambulatory at 1 year. Movement disorder (P = .037) and high ataxia score (P < .0001) were associated with delayed speech recovery. Older age (P = .0147) and high ataxia score (P < .0001) were associated with delayed gait return. Symptoms improved in all children but no child with PFS had normal neurologic examination at a median of 23 months after surgery.ConclusionsCategorizing PFS into types 1 and 2 has prognostic relevance. Almost half of the children with PFS1 with 12-month follow-up were nonambulatory. Surgical experience was a major modifiable contributor to the development of PFS.     

Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the International Extranodal Lymphoma Study Group.

PURPOSE: To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell lymphomas (DLCL). PATIENTS AND METHODS: A retrospective international survey of 373 patients with primary testicular DLCL. RESULTS: Most patients presented with localized disease (stage I to II), and the median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal chemotherapy was given to 68 patients (18%); 133 patients (36%) received prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and median progression-free survival was 4 years. The survival curves showed no clear evidence of a substantial proportion of cured patients. A favorable international prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and prophylactic scrotal radiotherapy were significantly associated with longer survival at multivariate analysis. However, even for patients with stage I disease and good-risk IPI, the outcome seems worse than what was reported for DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were detected in 56 patients (15%) up to 10 years after presentation. A continuous risk of recurrence in the contralateral testis was seen in patients not receiving scrotal radiotherapy. CONCLUSION: Testicular DLCL is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and contralateral testicular irradiation seem to improve the outcome. Their efficacy is under evaluation in a prospective clinical trial.