Complete remission after first-line radio-chemotherapy as predictor of survival in extranodal NK/T cell lymphoma

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>Extranodal nasal-type NK/T-cell lymphoma is a rare and severe disease. Considering the rarity of this lymphoma in Europe, we conducted a multicentric retrospective study on nasal-type NK/T cell lymphoma to determine the optimal induction strategy and identify prognostic factors.</p> <p><b>Methods</b></p> <p>Thirty-six adult patients with nasal-type NK/T-cell lymphoma were recruited and assessed. In total, 80 % of patients were classified as having upper aerodigestive tract NK/T-cell lymphoma (UNKTL) and 20 % extra-upper aerodigestive tract NK/T-cell lymphoma (EUNKTL).</p> <p><b>Results</b></p> <p>For advanced-stage disease, chemotherapy alone (CT) was the primary treatment (84 % <it>vs.</it> 10 % for combined CT + radiation therapy (RT), respectively), while for early-stage disease, 50 % of patients received the combination of CT + RT and 50 % CT alone. Five-year overall survival (OS) and progression-free survival (PFS) rates were 39 % and 33 %. Complete remission (CR) rates were significantly higher when using CT + RT (90 %) <it>versus</it> CT alone (33 %) (p < 0.0001). For early-stage disease, CR rates were 37 % for CT alone <it>versus</it> 100 % for CT + RT. Quality of response was significantly associated with survival, with 5-year OS being 80 % for CR patients <it>versus</it> 0 % for progressive disease patients (p <it><</it> 0.01).</p> <p><b>Conclusion</b></p> <p>Early RT concomitantly or sequentially with CT led to improved patient outcomes, with quality of initial response being the most important prognosticator for 5-year OS.</p

Long-term follow-up of patients with newly diagnosed follicular lymphoma in the prerituximab era: Effect of response quality on survival - A study from the groupe d'etude des lymphomes de l'adulte

Purpose: First-line treatment for patients with newly diagnosed follicular lymphoma (FL) still remains debated, even in the rituximab-based combination therapy era. Few studies have addressed the question whether complete remission (CR) translates into better survival. The aim of this study was to assess the long-term follow-up of prospectively treated patients with FL and the potential correlation between response quality to first-line treatment and overall survival (OS). Patients and Methods: Data from 536 patients with FL with low (n = 193) or high (n = 343) tumor burden enrolled from October 1986 to May 1995 in the French and Belgian GELF86 studies were analyzed. Data from these trials have been previously reported for low-tumor burden and high-tumor burden patients. Results: Median follow-up was 14.9 years, and median OS was 9.8 years. Treated patients who achieved a complete response (CR; n = 194; 45%) had a significant longer OS than those only reaching a partial response (PR; n = 168; 39%) throughout treatment (hazard ratio [HR], 0.55; 95% CI, 0.42 to 0.72; P < .001) in an univariate time-dependent Cox model. Similar findings were found when response to treatment (CR v PR) was adjusted for potentially confounding factors in a multivariate model (HR, 0.53; 95% CI, 0.38 to 0.73; P < .001). Conclusion: These data provide a long follow-up of these patients' cohorts and indicate that a better response to first-line treatment translates into an improved survival for patients with FL. Therefore, response-adapted therapy aiming to achieve a CR should be considered as first-line treatment. © 2009 by American Society of Clinical Oncology

Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial

Background The outcome of diff use large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18–59 years, the potential survival benefi t provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. Methods We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclo phosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18–59 years with untreated diff use large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of effi cacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. Findings One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75–86) in the R-ACVBP group and 67% (59–73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38–0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81–91] vs 73% [66–79]; HR 0·48 [0·30–0·76]; p=0·0015) and overall survival (92% [87–95] vs 84% [77–89]; HR 0·44 [0·28–0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3–4 haematological toxic eff ects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]). Interpretation Compared with standard R-CHOP, inten sifi ed immunochemotherapy with R-ACVBP signifi cantly improves survival of patients aged 18–59 years with diff use large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic eff ects of the intensive regimen were raised but manageable. Funding Groupe d’Etudes des Lymphomes de l’Adulte and Amgen

Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial.

A French and Belgian multicenter phase 3 trial was conducted in medically fit patients with untreated chronic lymphocytic leukemia. Of 178 patients enrolled in the study, 165 were randomly assigned to receive 6 courses of oral fludarabine and cyclophosphamide (FC) in combination with rituximab (FCR; 375 mg/m(2) in cycle one, 500 mg/m(2) in all subsequent cycles) or alemtuzumab (FCCam; 30 mg subcutaneously injected on cycle days 1-3); each cycle was 28 days. Recruitment was halted prematurely because of excess toxicity; 8 patients died in the FCCam group, 3 from lymphoma and 5 from in-fection. Overall response rates were 91% with FCR and 90% with FCCam (P = .79). Complete remission rates were 33.75% with FCR and 19.2% with FCCam (P = .04). Three-year progression-free survival was 82.6% with FCR and 72.5% with FCCam (P = .21). Three-year overall survival was similar between the 2 arms at 90.1% in the FCR arm and 86.4% in the FCCam arm (P = .27). These results indicate that the FCCam regimen for the treatment of advanced chronic lymphocytic leukemia was not more effective than the FCR regimen and was associated with an unfavorable safety profile, representing a significant limitation of its use. This study is registered with www.clinicaltrials.gov as number NCT00564512

Long-term follow up of the CLL2007FMP trial evaluating fludarabine and cyclophosphamide in combination with either rituximab or alemtuzumab in previously untreated patients with chronic lymphocytic leukemia

International audienc

Autologous hematopoietic stem cell transplantation in chronic lymphocytic leukemia: results of European intergroup randomized trial comparing autografting versus observation

Contains fulltext : 95663.pdf (publisher's version ) (Closed access)We present results of a phase 3 randomized trial of autografting in chronic lymphocytic leukemia versus observation for responding patients after first- or second-line treatment. The primary objective was to demonstrate that autografting improves the 5-year event-free survival (EFS) from 30% to 50%. There were 223 enrolled patients, 72% men and 28% women, 83% after first and 17% after second-line treatment. Binet stages were progressive A 13%, B 67%, C 20%; at randomization, 59% were in complete remission, and 41% in less than complete remission. Patients were randomized between autografting (n = 112) and observation (n = 111). Median EFS was 24.4 months (range, 16.7-32 months) in the observation group and 51.2 months (39.8-62.5 months) in the autografting group; the 5-year EFS was 24% and 42%, respectively (P < .001). Accordingly, the 5-year relapse incidence was 76% versus 54% (P < .001). Median time to relapse requiring therapy or death was 40 months (25-56 months) in the observation arm and 65 months (59-71 months) after autografting (P = .002). Cox modeling confirmed that autografting significantly improved EFS (hazard ratio 0.44, 95% confidence interval 0.30-0.65; P < .001). At 5 years, the probability of OS was 85.5% and 84.3% for autografting and observation, respectively (P = .77). In chronic lymphocytic leukemia, consolidating autografting reduces the risk of progression by more than 50% but has no effect on overall survival

The prognosis of CALM-AF10 positive adult T-cell acute lymphoblastic leukemias depends on the stage of maturation arrest.

International audience: CALM-AF10 (also known as PICALM-MLLT10) is the commonest fusion protein in T-cell acute lymphoblastic leukemia, but its prognostic impact remains unclear. Molecular screening at diagnosis identified CALM-AF10 in 30/431 (7%) T-cell acute lymphoblastic leukemia patients aged 16 years and over and 15/234 (6%) in those aged up to 15 years. CALM-AF10 positive patients were predominantly (72%) surface (s)CD3/T-cell receptor negative in adults, but predominantly (67%) T-cell receptor positive in children. Amongst 22 adult CALM-AF10+ patients treated according to the LALA94/GRAALL03-05 protocols, the poor prognosis for event-free survival (p=0.0017) and overall survival (p=0.0014) was restricted to the 15 T-cell receptor negative cases. Amongst CALM-AF10+ T-cell receptor negative patients, 82% demonstrated an early T-cell precursor phenotype, reported to be of poor prognosis in pediatric T-cell acute lymphoblastic leukemia. Early T-cell precursor acute lymphoblastic leukemia corresponded to 22% of adult LALA94/GRAALL03-05 T-cell acute lymphoblastic leukemias, but had no prognostic impact per se. CALM-AF10 fusion within early T-cell precursor acute lymphoblastic leukemia (21%) did, however, identify a poor prognostic group for event-free survival (p=0.04). CALM-AF10 therefore identifies a poor prognostic group within sCD3/T-cell receptor negative adult T-cell acute lymphoblastic leukemias and is over-represented within early T-cell precursor acute lymphoblastic leukemias, where it identifies those likely to fail treatment. Its prognosis and overlap with early T-cell precursor acute lymphoblastic leukemia in pediatric T-cell acute lymphoblastic leukemia merits analysis. The clinical trial GRAALL was registered at Clinical Trials.gov number NCT00327678

Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group

International audienceBackground There is currently no international consensus for first-line treatment (prior to autologous stem cell transplantation) in mantle cell lymphoma patients. Here, we investigated the efficacy and tolerance of VAD associated with chlorambucil (VAD+C) and rituximab or not before autologous stem cell transplantation. DESIGN AND METHODS: Between 1996 and 2005, 113 previously untreated mantle cell lymphoma patients were enrolled in two consecutive prospective phase II studies. Responses and response factors to the (R)VAD+C regimen were evaluated. The survival prognostic value of the MIPI score and Ki67 were also analyzed. RESULTS: The induction phase of 4 courses of (R)VAD+C showed very low hematologic and extra-hematologic toxicity (grade 3-4 thrombopenia and neutropenia, 9% and 2.7%, respectively and grade 3-4 extra-hematologic toxicities, 1.6%). Overall and complete response rates were 73% and 46%, respectively, and rose to 83% and 51% for the 70% of patients with less than two independent response factors (LDH, B symptoms and lymphocytosis). At the end of treatment, 65% of patients were in complete remission. Progression free and overall survival were significantly better in the transplanted population. The MIPI score was confirmed as a predictor of survival. Ki67, serum LDH, Performance Status (PS) and B symptoms were identified as independent prognostic factors of survival. A prognostic scoring system could stratify patients into three risk groups with markedly different median overall survival of 112, 44 and 11 months, respectively. Conclusions The (R)VAD+C is an effective regimen with very low toxicity. In addition to the MIPI score, Ki67 expression provides additional independent prognostic information for the prediction of overall survival (ClinicalTrials.gov Identifier: NCT00285389)