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Item does not contain fulltext, PURPOSE: For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors (NCT00005584). PATIENTS AND METHODS: Patients aged 15-70 years with untreated supradiaphragmatic HL with at least one risk factor (age >/= 50, involvement of 4-5 nodal areas, mediastinum/thoracic ratio >/= 0.35, erythrocyte sedimentation rate (ESR) >/= 50 without B-symptoms or ESR >/= 30 and B-symptoms) were eligible for the randomised, open label, multicentre, non-inferiority H9-U trial. The limit of non-inferiority was set at 10% for the difference between 5-year event-free survival (EFS) estimates. From October 1998 to September 2002, 808 patients were randomised to receive either the control arm 6-ABVD-IFRT (n = 276), or one of the two experimental arms: 4-ABVD-IFRT (n = 277) or 4-BEACOPPbaseline-IFRT (n = 255). RESULTS: Results in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPPbaseline-IFRT (5-year EFS, 88.8%) were not inferior to 6-ABVD-IFRT (5-year EFS, 89.9%): difference of 4.0% (90%CI, -0.7%-8.8%) and of 1.1% (90%CI,-3.5%-5.6%) respectively. The 5-year overall survival estimates were 94%, 93%, and 93%, respectively. Patients treated with combined modality treatment chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vincristine (Oncovin), cyclophosphamide, procarbazine, etoposide and prednisone (BEACOPP)baseline more often developed serious adverse events requiring supportive measures and hospitalisation compared with patients receiving the chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD). CONCLUSIONS: The trial demonstrates that 4-ABVD followed by IFRT yields high disease control in patients with early-stage HL and risk factors responding to chemotherapy. Although non-inferior in term

Background: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate. Patients and methods: We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute. Results: One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0-1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP [hazards ratio (HR) = 0.6, P = 0.07]. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P=0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06). Conclusion: Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

A widely accepted definition of resistance or intolerance to hydroxyurea (HU) in patients with essential thrombocythemia (ET) is lacking. An international working group (WG) was convened to develop a consensus formulation of clinically significant criteria for defining resistance/intolerance to HU in ET. To this aim, an analytic hierarchy process (AHP), a multiple-attribute decision-making technique, was used. The steps consisted of selecting the candidate criteria for defining resistance/intolerance; identifying the motivations that could influence the preference of the WG for any individual criterion; comparing the candidate criteria in a pair-wise manner; and grading them according their ability to fulfill the motivations. Every step in the model was derived by questionnaires or group discussion. The WG proposed that the definition of resistance/intolerance should require the fulfillment of at least one of the following criteria: platelet count greater than 600,000/micro l after 3 months of at least 2 g/day of HU (2.5 g/day in patients with a body weight over 80 kg); platelet count greater than 400,000/micro l and WBC less than 2500/micro l or Hb less than 10 g/dl at any dose of HU; presence of leg ulcers or other unacceptable muco-cutaneous manifestations at any dose of HU; HU-related fever.

Intermediate or unfavourable stage Hodgkin's lymphoma (HL) definition relies upon at least three different scoring systems defined by cooperative groups (EORTC, GHSG and Canadian-ECOG). We aimed to investigate their efficacy and their correlation with International Prognostic Score (IPS) for advanced HL. We studied a population of 1156 patients with localized stage HL treated prospectively within GELA centres in H8 (518 patients) and H9 (638 patients) protocols. Median age: 30 yr, 18%, Female 50%; stage I: 25%; stage II: 75%. According to scoring systems 70% had 0-1 EORTC factors; 60% 0-1 GHSG factors and 82% 0-1 Canadian factors. The IPS for advanced stages was available only in H9 study with 64% 0-1 factor. Survival curves according to each of the different scoring systems could significantly discriminate the subgroup populations. When a multivariate Cox analysis was performed for overall survival (OS) including all the scoring system variables: age > 45 yr, sex male, Haemoglobin < 10.5 g/dL, lymphocytes < 600/microL, B symptoms with elevated ESR, extra nodal sites did retain an independent significant value. Probability of OS was 99%, 98%, 92%, 82% and 73% for patients with 1-5 factors, respectively P < 0.0001. These factors are similar for most of them with those described in the IPS when stages III and IV are replaced by extra nodal localization. This new score should be validated in other prospective trials, as it will simplify the Hodgkin prognostic scoring systems for localized and advanced stages.

In diffuse large B-cell lymphoma (DLBCL), the combination of rituximab and CHOP (cyclophosphamide, doxorubicine, vincristine, prednisone; R-CHOP) has been shown to be more effective than CHOP for the treatment of elderly patients. Bcl-2 protein expression has been associated with poor prognosis in patients with DLBCL. To establish whether or not rituximab reduces bcl-2-assoclated treatment failure, we studied bcl-2 protein expression and clinical outcome in patients included in the Groupe d'Etude des Lymphomes de l'Adulte LNH-98-5 trial. Patients between 60 and 80 years of age were randomized to receive 8 cycles of either CHOP or R-CHOP every 3 weeks. Of the 399 patients included, 292 with histologically proven DLBCL had material available for bcI-2 study. Tumors were considered positive when at least 50% of tumor cells expressed bcl-2 protein. There were 193 (66%) bcl-2(+) patients and 99 (34%) bcl-2 patients. The response rates for R-CHOP and CHOP were, respectively, 78% and 60% (P = .01) in bcl-2(+) patients and 76% and 73% (P = .7) in bcl-2- patients. At a median of 2 years of follow-up, R-CHOP was significantly associated with a better overall survival than CHOP in bcl-2(+) patients (67% +/- 9% versus 48% +/- 11%, P = .004). In bcl-2- patients there was no statistically significant difference ( 72% +/- 12% versus 67% +/- 14%, P = .6). In addition, R-CHOP was associated with significantly better event-free survival than CHOP in bcl-2(+) patients (58% +/- 10% versus 32% +/- 10%, P < .001) but not in bcl-2- patients (60% +/- 13% versus 40% +/- 15%, P = .13). Multivariate analysis confirmed the significant benefit for survival and event-free survival of R-CHOP in bcl-2(+) patients. These results suggest that rituximab is able to prevent chemotherapy failure in patients with bcl-2 protein overexpression. (C) 2003 by The American Society of Hematology.

Between 1987 and 1993, 77 of 2855 lymphomas included in the LNH87 protocol of the GELA as non-Hodgkin lymphoma (NHL) and reviewed by a panel of pathologists had a diagnosis changed to Hodgkin lymphoma (HL). Some of these lymphomas had been initially interpreted as anaplastic large-cell lymphoma Hodgkin-like (ALCL-HL subtype). The purpose of this study was to analyze the histologic pitfalls initially encountered, to define more clearly the diagnostic criteria of lymphomas placed in the gray zone around HL, and to follow the survival of these 77 patients affected with HL and initially treated with NHL regimens. The 77 cases of HL were reviewed by three hematopathologists and immunostained with a large panel of antibodies, including CD30, CD15, CD3, CD20, CD45, CD43, LMP-1, EMA, BNH-9, TiA1, and ALK1. Each case was classified according to the Lukes-Rye system and the British National Lymphoma Investigation (BNLI) grading. The initial clinical presentation of patients was analyzed, and the overall and event-free survival rates of the 77 patients were estimated. Among the 77 HLs, 46 were misinterpreted as NHL by primary individual pathologists (12 as ALCL, 8 as ALC-LHL, 12 as peripheral T-cell lymphoma (PTCL), 6 as B-cell lymphoma, and 8 as unclassifiable NHL). The other 31 cases had been first considered by the panel as consistent with ALCL-HL (n = 18) or with PTCL(n = 13) and were changed later in view of an immunophenotype concordant with HL. Fifty-five percent of the patients completed the full NHL treatment. The 5-year event-free and overall survival rates were 54% and 77%, respectively. The current results indicate that lymphomas initially called ALCL-HL should not be regarded as a variant of ALCL, but as HL. The clinical consequences of misdiagnoses seem to be a lower event-free survival rate compared with that of classical HL, probably because of more relapses of initially inappropriately treated HL.

Purpose: To present the final analysis, with a median follow-up of 8 years, of the LNH87-2 randomized study, which compares consolidative sequential chemotherapy (ifosfamide plus etoposide, asparaginase, and cytarabine) with high-dose therapy (HDT) using cyclophosphamide, carmustine, and etoposide (CBV regimen) followed by stem-cell transplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission after induction, focusing on high/intermediate- and high-risk patients identified by the age-adjusted international prognostic index. Patients and Methods: Among the 916 eligible patients, 451 presented with two (n = 318) or three (n = 133) risk factors. After reaching complete remission to induction therapy, 236 of these higher risk patients were assessable for the consolidation phase, with 125 patients in the HDT arm and 111 in the sequential chemotherapy arm. Results: Among these 451 higher risk patients, 277 (61%) achieved complete remission after induction treatment. In the population of 236 randomized patients, HDT wets superior to sequential chemotherapy, with I-year disease-free survival rates of 55% (95% confidence interval [CI], 46% to 64%) and 39% (95% CI, 30% to 48%), respectively (P = .02; relative risk, 1.56). The 8-year survival rate was significantly superior in the HDT arm (64%; 95% CI, 55% to 73%) compared with the sequential chemotherapy arm (49%; 95% CI, 39% to 59%) (P = .04: relative risk, 1.51). Conclusion.. On the basis of the final analysis of this prospectively treated series of patients, retrospectively analyzed on the basis of the International Prognostic Index, we hypothesize that HDT benefits patients at higher risk who achieve complete remission after induction treatment. (C) 2000 by American Society of Clinical Oncology.