No other clinical abnormality was noted, except for recent weight loss. His biological data were normal. A computed tomography (CT) scan detected lymphadenopathies (left supraclavicular, left axillary and mesenteric), splenomegaly with nodules and a left kidney tumor. The bone marrow biopsy was normal. The 18 FDG PET image and SUV are presented in figure 1 . Left axillary lymphadenectomy revealed an NLPHL. Because of weight loss and disease diffusion, a splenectomy was performed to test for high-grade lymphoma transformation. The macroscopic examination revealed a 16.5 ! 10.5 ! 6.5-cm splenomegaly with two nodules. The performed histological and immunophenotypical analyses confirmed the diagnosis of diffuse large B cell lymphoma (DLBCL). The patient was treated by eight RCHOP cycles. Complete remission was still observed 42 months later. Nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL) has been clearly individualized from classic Hodgkin’s lymphoma [1] . In the absence of a bulky tumor, the outcome is favorable [2] . However, with a median follow-up time of 6.5 years, up to 14% of patients experience a high-grade non-Hodgkin’s lymphoma (NHL) transformation [3] . This event usually imposes a new biopsy that may be guided by 18 fluorodeoxyglucose positron emission tomography ( 18 FDG PET), which has been proposed to discriminate between lowgrade and high-grade NHL [4, 5] . Schoder et al. [4] showed that the standardized uptake value (SUV, fig. 1) was lower in indolent than in aggressive NHL: 7.0 8 3.1 and 19.6 8 9.3, respectively. The suggested cut-off value for the distinction between indolent and high-grade lymphoma, with 100% specificity, was 13, using a receiver operating characteristic (ROC) technique. In a large series of NLPHL, the median SUV was 6.1 (range, 1.2–20.1) [6] . No SUV data were available concerning an aggressive transformation. So we report, for the first time, two cases of NLPHL high-grade transformation with 18 FDG PET SUV data. First case: a 51-year-old man presented in April 2008 with a 10-year history of left axillary lymphadenopathy. Received: June 12, 2012 Accepted after revision: October 14, 2012 Published online: January 11, 2013

Long-term responses have been reported after autologous stem cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL). We conducted a prospective, randomized trial of ASCT in previously untreated CLL patients. We enrolled 241 patients < 66 years of age with Binet stage B or C CLL. They received 3 courses of mini-CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone/prednisolone) and then 3 courses of fludarabine. Patients in complete response (CR) were then randomized to ASCT or observation, whereas the other patients were randomized to dexamethasone, high-dose aracytin, cisplatin (DHAP) salvage followed by either ASCT or 3 courses of fludarabine plus cyclophosphamide (FC). The primary end point was event-free survival (EFS). After up-front treatment, 105 patients entered CR and were randomized between ASCT (n = 52) and observation (n = 53); their respective 3-year EFS rates were 79.8% and 35.5%; the adjusted hazard ratio was 0.3 (95% CI: 0.1-0.7; P = .003). Ninety-four patients who did not enter CR were randomized between ASCT (n = 46) and FC (n = 48); their respective 3-year EFS rates were 48.9% and 44.4%, respectively; the adjusted hazard ratio was 1.7 (95% CI: 0.9-3.2; P = .13). No difference in overall survival was found between the 2 response subgroups. In young CLL patients in CR, ASCT consolidation markedly delayed disease progression. No difference was observed between ASCT and FC in patients requiring DHAP salvage.

Current treatment approaches in CLL aim at achieving the best clinical response without detectable minimal residual disease (MRD) in order to prolong the duration of response and potentially overall survival. Such a goal could be achieved by combining chemotherapy and monoclonal antibodies. This phase II trial was designed to evaluate the safety and the efficacy of alemtuzumab given as consolidation therapy after 3 courses of oral fludarabine and cyclophosphamide (FC)(F 40 mg/m2 and C 250 mg/m2 D1 to D3 every 4 weeks) in patients (pts) aged 65 to 70 years with previously untreated Binet stage B or C CLL. Pts who had achieved either complete response (CR) or partial response (PR) after FC were eligible for consolidation with alemtuzumab. Alemtuzumab was administered subcutaneously (SC) at the dose of 10 mg thrice a week for 8 consecutive weeks. Cytomegalovirus (CMV) antigenemia was monitored every week and alemtuzumab should be discontinued in pts with more than 3 positive nuclei. Such stringent stopping rules for CMV reactivation, as well as the limitation of FC regimen to 3 courses and of the duration of alemtuzumab treatment to 8 weeks, were adopted in this trial targeting elderly patients in first-line treatment because of the severe infectious toxicities reported by others with similar strategies. MRD was evaluated by 6-color flow cytometry before, during and after alemtuzumab treatment and all samples were centralized in 1 center (Avicenne hospital, Bobigny). From June 2004 to January 2008, 55 patients with advanced (stage B or C) fully annotated CLL have been recruited in 14 French centers. Response to induction was evaluable in 51 of them (suicide before FC 1 pt and missing data 3 pts). CR was achieved in 18 pts (34.6%) and PR in 22 pts (42.3%) for an overall response rate (ORR) of 77% after 3 courses of FC. FC regimen was discontinued in 6 pts (progression 1 pt, renal carcinoma 1 pt, neutropenia 2 pts, pure red cell aplasia (PRCA) 1 pt, myocardial infarction 1 pt) and stable disease was observed in 5 pts. All the responding pts except 2 (breast cancer in 1 CR pt and lung carcinoma in 1 PR pt) proceeded to alemtuzumab consolidation after a planned 2-month period of rest (median 63 days, range 33 to 152). Alemtuzumab treatment was fully completed in 29/38 pts (76%), while it was stopped prematurely (mainly between the 6th and 8th weeks) in 9 pts (24%). CMV reactivation occurred in 8 pts (21%) but it was associated with systemic symptoms in only 1 case (pneumonia). Grade 3-4 neutropenia was observed in 9 pts at some point during alemtuzumab treatment. Eleven of the 21 PR pts (52%) converted from PR to CR after lemtuzumab consolidation while 2 patients went from CR to PR. Overall, 26 pts were in CR after the whole treatment strategy (FC followed by alemtuzumab), accounting for 51% of the entire cohort. Blood MRD could be assessed sequentially in two-thirds of pts. While all patients but 1(33/34 pts) were MRD positive after chemotherapy and before alemtuzumab treatment, only 5/22 pts (23%) had detectable MRD at the sensitivity level of 10-4 after the end of alemtuzumab consolidation, and 12 of the 25 assessed pts (48%) still had undetectable MRD at 6 months after the end of treatment. With a median follow up of 34 months (range 2 to 58), only 6 out of the 38 pts (16%) who received FC followed by alemtuzumab consolidation had CLL disease progression. Five patients have died (CLL 1 pt, solid tumors 3 pts, stroke 1 pt). No serious delayed infectious complication was observed and 2 patients developed auto-immune cytopenia. Because of the low number of events (disease progression) observed so far, no correlation between the duration of response and the MRD status could be made until now. In conclusion, the administration of only 3 courses of FC yielded a rather high response rate in previously untreated elderly CLL patients and a short (8 weeks) alemtuzumab consolidation course could be thereafter administered safely, leading to a high rate of PR to CR switches, a high proportion of patients without detectable blood MRD after the end of treatment, and durable responses.

Abstract Abstract 3900 Current treatment approaches in CLL aim at achieving the best clinical response without detectable minimal residual disease (MRD) in order to prolong the duration of response and potentially overall survival. Such a goal could be achieved by combining chemotherapy and monoclonal antibodies. This phase II trial was designed to evaluate the safety and the efficacy of alemtuzumab given as consolidation therapy after 3 courses of oral FC (F 40 mg/m2 and C 250 mg/m2 D1 to D3 every 4 weeks) in patients (pts) aged 65 to 70 years with previously untreated Binet stage B or C CLL. Pts who had achieved either complete response (CR) or partial response (PR) after FC were eligible for consolidation with alemtuzumab. Alemtuzumab was administered subcutaneously (SC) at the dose of 10 mg thrice a week for 8 consecutive weeks. CMV antigenemia was monitored every week and alemtuzumab should be discontinued in pts with more than 3 positive nuclei. Such stringent stopping rules for CMV reactivation, as well as the limitation of FC regimen to 3 courses and of the duration of alemtuzumab treatment to 8 weeks, were adopted in this trial targeting elderly patients in their first line treatment because of the severe infectious toxicities reported by others with similar strategies. MRD was evaluated by 6 color flow cytometry before, during and after alemtuzumab treatment and all samples were centralized in one center (RL & FC). From June 2004 to January 2008, 55 patients with advanced (stage B or C) fully annotated CLL have been recruited in 14 french centers. Response to induction is evaluable in 51 of them (suicide before FC 1 pt and missing data 3 pts). A CR was achieved in 18 pts (34.6%) and a PR in 22 pts (42.3%) for an overall response rate (ORR) of 77% after 3 courses of FC. FC regimen was discontinued in 6 pts (progression 1 pt, renal carcinoma 1 pt, neutropenia 2 pts, PRCA 1 pt, myocardial infarction 1 pt) and a stable disease was observed in 5 pts. All the responding pts except two of them (onset of breast cancer in one CR pt and of lung carcinoma in one PR pt) proceeded to alemtuzumab consolidation after a planned 2 month period of rest (median 63 days, range 33 to 152). Alemtuzumab treatment was fully completed in 29/38 pts (76%) while it has been stopped prematurely (mainly between the 6th and 8th weeks) in 9 pts (24%). CMV reactivation occurred in 8 pts (21%) but it was associated with systemic symptoms in only one case (febrile pneumonia). A grade 3–4 neutropenia was observed in 9 pts at some point during alemtuzumab treatment. Eleven of the 21 PR pts (52%) converted from PR to CR after alemtuzumab consolidation while 2 patients went down from CR to PR. Overall, 26 pts were in CR after the whole treatment strategy (FC followed by alemtuzumab) accounting for 51% of the entire cohort. Blood MRD could be assessed sequentially in roughly two thirds of pts. While all patients but one (33/34 pts) were MRD positive after chemotherapy and before alemtuzumab treatment, only 8/22 pts (36%) had detectable MRD at the sensitivity level of 10-4 after the end of alemtuzumab consolidation, and 12 out of the 25 assessed pts (48%) still had undetectable MRD at 6 months after the end of treatment. With a median follow up of 34 months (range 2 to 58), only 6 out of the 38 pts (16%) who received FC followed by alemtuzumab consolidation, had CLL disease progression. Five patients have died but only one from CLL (solid tumors 3 pts, stroke 1 pt). No serious delayed infectious complication was observed and two patients developed auto-immune cytopenia (AIHA 1 pt and ITP 1 pt). Because of the few number of events (disease progression) observed so far, no correlation between the duration of response and the MRD data could be done by now. In conclusion, three courses of FC only yielded a rather high response rate in previously untreated elderly CLL patients and a short (8 weeks) alemtuzumab consolidation course could thereafter be administered safely, leading to a high rate of PR to CR switches, a high proportion of patients with undetectable blood MRD after the end of treatment and durable responses. Disclosures: Cazin: LFB Biotechnologies: Honoraria. Cymbalista:Roche (d) Mundipharma (e) Genzyme (e): Honoraria, Research Funding.

Nodular, lymphocyte‐predominant Hodgkin lymphoma (NLPHL) represents a rare entity.

Introduction Hodgkin's lymphoma is defined by a malignant proliferation of Reed-Sternberg or Hodgkin cells that are clonally related B-cell-derived malignant cells. This disease is characterized by a good outcome (cure rate more than 80%). Initial thoracic involvement is usual and the more frequent localization is the mediastinum, following by the lung parenchyma and the pleura. In the last two cases, histological diagnosis is warranted since this involvement modified the staging and the prognosis of the disease. State of the art Early one, infectious diseases were the most frequent complications. Functional deficiency following mediastinal radiotherapy and chemotherapy (including bleomycin) is often detected, whathever this is associated with symptom or CT scan abnormalities. Granulomatous disease can be associated at any time during the disease and differential diagnosis from relapse is often difficult. Finally, these patients have an increased risk of developing solid cancers and particularly lung cancers. Perspectives and conclusions Hodgkin lymphoma patients are more likely to die from acute and late treatment-related toxicities and the major task is to reduce treatment associated toxicity while maintening cure rate.

BACKGROUND: Nodular, lymphocyte-predominant Hodgkin lymphoma (NLPHL) represents a rare entity. METHODS: A clinical registry was launched from 1973 to 2003 in France. To determine the histologic transformation (HT) rate to diffuse large B-cell lymphoma (DLBCL) and long-term outcomes, 164 patients were selected after histologic review. RESULTS: The median follow-up was 9.5 years. The high biopsy rate (85%) at each recurrence enabled the analysis of HT. The median patient age was 30 years (range, 6-69 years), 80% of patients were men, 83% had Ann Arbor stage I/II disease, 65% had supradiaphragmatic-disease; 27% received radiotherapy, 9% received chemotherapy, 29% received combined-modality therapy, and 35% were followed with a watch-and-wait strategy. All 106 treated patients achieved complete remission and 66 patients developed disease recurrence at a median of 3.3 years (range, 0.4-18.3 years after diagnosis). The majority of recurrences were NLPHL, but 19 patients progressed to DLBCL at a median of 4.7 years (range, 0.4-18 years after diagnosis). The 10-year cumulative HT rate was 12% and was found to be associated significantly with a poor prognosis. The 10-year overall survival rate was 91%. Fourteen patients died (7 died of progressive disease, 3 died of secondary cancers, and 4 died from other causes). HT was diagnosed at a median of 4.7 years (range, 0.4-18 years after diagnosis). The 19 patients who had HT were treated with curative intent: Nine patients received high-dose therapy with subsequent autologous stem cell transplantation (ASCT), and 10 patients received different chemotherapy regimens. The overall survival rate after HT did not differ between patients who underwent ASCT and the others. CONCLUSIONS: This long-term follow-up study confirmed that NLPHL is a separate entity that has a favorable clinical presentation and outcome despite frequent recurrences. The current findings also emphasize the importance of biopsies at the time patients develop recurrent disease to evaluate HT. Cancer 2010;116:631-9. (C) 2009 American Cancer Society.

Abstract Abstract 878 Introduction: We investigated, in a prospective randomized study, the place of ASCT in the frontline treatment of CLL. Patients and methods: From March 2001 to December 2007, 241 patients were included in the trial. Eligibility criteria were previously untreated stage B and C CLL patients under 66 years, characterized by Matutes score 4-5, absence of cyclin D1 expression, baseline flow assessment of ZAP 70 and CD38 expression, karyotype and FISH analysis, IgHv mutational status (centralized). Preceding randomization, initial chemotherapy consisted of 3 monthly courses of mini CHOP regimen as previously described, followed by 3 monthly courses of fludarabine, IV or oral. Patients achieving CR (NCI 1996 criteria plus normal CT scan) were randomized between observation and ASCT. Non CR patients were offered cisplatin/cytosine-arabinoside/dexamethasone (DHAP) rescue and randomized whatever the response between ASCT or 3 subsequent monthly IV courses of Fludarabine-Cyclophosphamide (FC). Conditioning regimen for ASCT consisted of cyclophosphamide IV (60 mg/sqm d-5-4) and fractionated total body irradiation (10 Gy). The primary end-point of the study was event-free survival at 3 years. Responses after initial treatment (i.e.before randomization) and after completion of therapy, overall survival, side effects, prognostic significance of clinical and biological characteristics at baseline were other endpoints. Results: Baseline characteristics were: gender (M/F: 3), age (median 56.4 years, range 33.3-66), stage B (185 patients) or C (56 patients). All enrolled cases but five (236 patients) started the treatment. Among them, 206 completed the six planned courses of initial chemotherapy. For the 236 patients, CR rate was 43.6%, and overall response was 89.8%. Forty two patients were not randomized because of treatment failure (19) or patient/physician decisions (23). After an observed median follow-up of 40.2 months (Q1-Q3, 17.9-47.9) at the reference date (1/1/2009), the overall survival for the 241 patients was 87.8% (95% CI, 83.3-92.6) at 3 years and 75.4% (95% CI, 66.2-88.6) at 5 years. For the 199 randomized patients, the overall survival was 90.9% (95% CI, 86.7-95.3) at 3 years. Among them 105 patients were in CR after initial treament and were allocated to ASCT (53 patients) or observation (52 patients) with a 3 years EFS of respectively 78.7% (95% CI, 67.7-91.4) and 31.3% (95% CI, 20.1-48.8) (p<0.00001). The median EFS from the start of the studied treatment was 26.2 months in the observation arm (not reached in the ASCT arm). Randomization (p=0.0001), mutational status (p<0.00001) and 11q deletion (p=0.001) remained independent prognostic factors for EFS in a multivariate analysis. There was no difference between ASCT and observation arms in terms of overall survival with 98% (95% CI, 94.3-100) and 97.5% (95% CI, 92.2-100)respectively. For the 94 patients not achieving CR and rescued with DHAP, the EFS at 3 years was 46.5% (95% CI, 33.6-66.3) in the ASCT arm (46 patients) and 43.2% (95% CI, 29.8-62.5) in the FC arm (48 patients). There was not statistical difference between these 2 arms but for the 34 patients actually autografted the EFS was 57.8% (95% CI, 41.7-80.2). The overall survival was not different for ASCT and FC arms: 81,2% (95% CI, 70.3-93.9) and 85,4% (95% CI, 75.1-97) respectively. In multivariate analysis, the only prognostic factor influencing the EFS (p=0.0001) and the overall survival (p=0.04) was the 17p deletion. The mutational status (non mutated) and the 17p deletion remained adverse prognostic factors in patients actually autografted. For the whole study, 28 patients allocated to ASCT did not receive this treatment mainly because of mobilisation failures (14 pts). Four MDS were recorded within the follow-up frame. Conclusions: ASCT is a safe procedure which significantly improves response duration in patients attaining CR after a first line treatment. For patients not in CR, ASCT or consolidation with 3 FC courses provide similar results on response duration but ASCT could be considered in patients without 17p deletion or with mutated IGHV gene. Disclosures: Van Den Neste: Roche: Research Funding.

PURPOSE:A prospective multicenter trial evaluated a risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation (ASCT) for 245 Hodgkin's lymphoma (HL) patients who experience treatment failure with first-line therapy.PATIENTS AND METHODS:Poor-risk patients (150 with primary refractory disease or > or = two of the following risk factors at first relapse: time to relapse < 12 months, stage III or IV at relapse, and relapse within previously irradiated sites) or intermediate-risk patients (95 with one risk factor at relapse) were eligible for tandem or single ASCT, respectively.RESULTS:Among poor-risk patients, 105 (70%), including 30 of 55 with cytoreductive chemotherapy-resistant disease, received tandem ASCT, whereas 92 intermediate-risk patients (97%) received single ASCT. According to intent-to-treat analysis, the 5-year freedom from second failure and overall survival (OS) estimates were 73% and 85%, respectively, for the intermediate-risk group and 46% and 57%, respectively, for the poor-risk group. Outcomes were similar for primary refractory and poor-risk/relapsed HL. For patients with chemotherapy-resistant disease, the 46% 5-year OS rate achieved with tandem ASCT compares favorably with the previously reported 30%. Outcomes for partial and complete responders to cytoreduction receiving tandem ASCT did not differ significantly and were better than those previously reported for partial responders receiving single ASCT, but not superior to those reported for complete responders receiving single ASCT. Six poor-risk patients (4%) died from toxicity.CONCLUSION:Single ASCT is appropriate for intermediate-risk patients. For poor-risk patients, our results suggest a benefit of tandem ASCT for half of the patients with chemotherapy-resistant disease and partial responders, but not for complete responders to cytoreductive chemotherapy.

The aim of this study was to assess the efficacy of a gemcitabine-based regimen in pretreated Hodgkin's lymphoma (HL) patients. Relapsed or refractory HL patients treated with gemcitabine, used alone or in combination with other cytotoxic agents, were retrospectively reviewed. Fifty-five patients were included in the study. Initial characteristics before gemcitabine administration were: Ann Arbor stage III–IV: 84%; International Prognostic Score less than 3 in 20/43 cases (47%); thirty-one primary refractory patients at the end of first-line therapy (56%); median number of previous chemotherapy regimens of 3. Twenty-nine patients received gemcitabine alone with a median starting dose of 750 mg/m2 per injection (range: 180–1250 mg/m2); Gemcitabine was administered at a starting dose of 1000 mg/m2 per injection (range: 500–1250) in combination with vinorelbine in 10 patients, oxaliplatin in 13 patients, and other drugs in 3 patients, with a median of 6 injections (range: 1–18). Overall response rate was 20% with 11% of complete remission. On univariate analysis, two adverse factors at progression were significant for response to gemcitabine-based regimen: stage III–IV disease and hemoglobin level less than 10.5 g/dl. In conclusion, the two identified prognostic factors for response to gemcitabine are part of the International Prognostic Score of HL, suggesting that response to gemcitabine is mainly influenced by the specific prognostic factors of HL. Moreover, with an ORR of 29%, our results of the gemcitabine administered alone regimen are not different from those reported in the literature. In contrast, the results of the various series of HL patients treated by gemcitabine-combined regimens, mainly with cisplatin or derivatives, vinorelbine, ifosfamide, doxorubicin, and prednisone, are very different due to different patient characteristics. In heavily pretreated cases, as in our study, the ORR was 26%; inversely, in patients who had received only one or two lines of chemotherapy, the ORR varied between 64% and 82% with 9% to 54% of complete remissions. This discordance can probably be explained by the prognostic impact of previous treatment lines in the response to gemcitabine. This observation emphasizes the possible interest of using gemcitabine earlier in the treatment of Hodgkin's lymphoma, namely at the time of first relapse or after first-line treatment in primary refractory HL patients.

A multicentre single-arm study testing the efficacy and toxicity of the oral combination of fludarabine and cyclophosphamide (FC) over 5 d in 75 patients with untreated B cell-chronic lymphocytic leukaemia. Oral FC demonstrated high efficacy with overall (OR) and complete response (CR) rates of 80% and 53%, respectively. Out of the 30 CR patients studied for Minimal Residual Disease (MRD) using 4-colour flow-cytometry and the 22 using Clonospecific polymerase chain reaction, 22 (66%) and 16 (68%), respectively, were MRD negative. Median survival and median treatment-free interval had not been reached at 7 years of follow-up. Median progression-free survival (PFS) was 5 years. Toxicity was acceptable, with 52% and 16% of National Cancer Institute grade 3/4 neutropenia and infections, respectively. Gastrointestinal toxicity was mild. Oral FC demonstrated a high efficacy and an acceptable safety profile and may be considered as the standard first line treatment in chronic lymphocytic leukaemia.

18518 Background: The aim of this study was to assess the efficacy and safety of gemcitabine-based regimen in heavily pretreated HL pts. Methods: Relapsed or refractory HL pts treated with gemcitabine were retrospectively reviewed. Gemcitabine was used as a single agent or administered in combination with vinorelbine, oxaliplatine, doxorubicine, vinblastine, rituximab, and/or corticosteroids. Results: Fifty-five pts treated in 9 departments of clinical hematology between January 1999 and August 2006 were included in the study. Initial characteristics before gemcitabine administration were: nodular sclerosis in 84%; sex ratio M/F 1.1; median age 29 years (range: 15–85 years); advanced stage 84%; extranodal sites were lung, bone, liver, soft tissues, and bone marrow in 68%, 31%, 13%, 21%, and 4%, respectively; Hasenclever index lower than 3 in 20/43 cases (47%). At the end of the first front-line therapy (chemotherapy ± radiotherapy), 19 pts (35%) were in complete response (CR) in whom 13 relapsed within one year, 5 were in partial response (PR), and 31 pts were primary refractory (56%). Median number of previous chemotherapeutic regimen was 3 (range 1–8), 39 pts (71%) have received radiotherapy (RT), and 34 pts (62%) one or two autologous/allogenic stem cell transplantations (A/ASCT). Twenty-nine pts received gemcitabine alone with a median initial dose per injection of 750 mg/m2 (range: 180–1250 mg/m2); Gemcitabine was administered at an initial dose per injection of 1000 mg/m2 (range: 500–1250) in combination with vinorelbine in 10 pts, oxaliplatine in 13 pts in whom 4 with rituximab, and with others drugs in 3 pts. In both cases, the median number of combined gemcitabine regimen injections was 6 (range: 1–27). Toxicity was mainly hematological (75% of pts developed bi- or pancytopenia) or infectious (13%). Among all included pts, 6 were in CR (11%) and 5 in PR with an overall response rate of 20%. Among the 6 CR, 5 pts received thereafter A/ASCT and 2 pts RT, with 2 persistent CR at 16 and 44 months. In univariate analysis, none prognostic factor for response to gemcitabine was identified. Conclusions: This study, which constitutes one of the most important series, showed a mild efficacy of gemcitabine-based regimen in heavily pretreated HL patients. No significant financial relationships to disclose.

BACKGROUND Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. METHODS From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. RESULTS The median follow-up was 92 months. In the H8-F trial, the estimated 5-year event-free survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P=0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. CONCLUSIONS Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041 [ClinicalTrials.gov].).

Purpose Approximately 15% of patients with localized and 30% with disseminated classical Hodgkin's lymphoma fail to respond or relapse after first-line treatment. Usual prognosis scoring systems are actually unable to identify this small subset of patients with good confidence, pointing out the need for additional prognostic biomarkers. Patients and Methods We prospectively analyzed the prognosis value of plasma levels of tumor necrosis factor (TNF), its soluble receptors TNF-R1 and TNF-R2, IL-10, IL1-RA, IL-6, and soluble CD30 (sCD30) when taken before any treatment in 519 consecutive patients with a first diagnosis of classical Hodgkin's lymphoma. Results Levels of TNFα higher than 46 pg/mL, TNF-R1 higher than 3 ng/mL, TNF-R2 higher than 5 ng/mL, IL-10 higher than 30 pg/mL, IL1-RA higher than 668 pg/mL, IL-6 higher than 30 pg/mL, and sCD30 higher than 80 U/mL were associated with poor event-free and overall survival. In multivariate analysis, high levels of IL1-RA, IL-6, and sCD30 were independent poor prognosis factors, and the cytokine signature based on their combination allowed the stratification of patients in four prognosis classes, reaching a 5-year event-free survival probability of 92%, 85%, 76%, and 15%, respectively. This index was more potent than other scoring systems to predict patient event-free survival, and remained independent from the international prognostic score (P < .001), adding significant prognostic information to its predictive power. Conclusion Plasma cytokine signature is sufficient to predict disease-related outcome in classical Hodgkin's lymphoma, and allows the identification of patients with very high risk of treatment failure.

Introduction Hodgkin's lymphoma is defined by a malignant proliferation of Reed-Sternberg or Hodgkin cells that are clonally related B-cell-derived malignant cells. This disease is characterized by a good outcome (cure rate more than 80%). Initial thoracic involvement is usual and the more frequent localization is the mediastinum, following by the lung parenchyma and the pleura. In the last two cases, histological diagnosis is warranted since this involvement modified the staging and the prognosis of the disease.State of the art Early one, infectious diseases were the most frequent complications. Functional deficiency following mediastinal radiotherapy and chemotherapy (including bleomycin) is often detected, whathever this is associated with symptom or CT scan abnormalities. Granulomatous disease can be associated at any time during the disease and differential diagnosis from relapse is often difficult. Finally, these patients have an increased risk of developing solid cancers and particularly lung cancers.Perspectives and conclusions Hodgkin lymphoma patients are more likely to die from acute and late treatment-related toxicities and the major task is to reduce treatment associated toxicity while maintening cure rate.