No abstract

All transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA→CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients ≤75 years of age and with newly diagnosed APL were included. Induction treatment was stratified on white blood cell (WBC) count and age: patients ≤65 years of age and with an initial WBC count of ≤5,000/μL (n = 208) were randomized between ATRA→CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/μL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA →CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P = .0002) and close to significance in the elderly group (P = .086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA→CT group (P = .04, relative risk [RR] = .41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA→CT group (P = .1, RR = .62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P = .0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P= .02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P = .01), and there was a trend for better survival in patients who received maintenance ATRA (P = .22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT.

Chlorambucil does not prolong survival in patients with stage A CLL. Since deferring therapy until the disease progresses to stage B or C does not compromise survival, treatment of indolent CLL is unnecessary.

International audiencePeripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear as highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite non satisfactory results with the CHOP regimen, it remains the reference front line therapy in these diseases, but has not been challenged in phase III trials. The GOELAMS group devised an alternative therapeutic schedule including Etoposide, Ifosfamide, Cisplatin alternating with Doxorubicin, Bleomycin, Vinblastin, Dacarbazine (VIP-reinforced-ABVD) and compared it to CHOP/21 as front-line treatment in non cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-years event-free survival (EFS) rate. Secondary objectives were to compare the response rates, overall survival, and toxicities as well as identify prognostic factors. 88 patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-years EFS. ALCL type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. The VIP-rABVD regimen was not superior to CHOP/21 in term of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference arm in these lymphomas

Autologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. The multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide. The 9-year overall survival (OS) was similar in the HDT and conventional chemotherapy groups (76% and 80%, respectively). The 9-year progression-free survival (PFS) was higher in the ASCT than the chemotherapy group (64% vs 39%; P ‫؍‬ .004). A PFS plateau was observed in the HDT group after 7 years. On multivariate analysis, OS and PFS were independently affected by the performance status score, the number of nodal areas involved, and the treatment group. Secondary malignancies were more frequent in the HDT than in the chemotherapy group (6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs IntroductionFollicular lymphomas (FLs) are a subgroup of B-cell nonHodgkin lymphomas (NHLs) accounting for 15% to 30% of newly diagnosed lymphomas. [1][2][3] The natural history of this disease is characterized by a long survival that contrasts with systematic relapses. Many chemotherapy regimens have been used for treatment but have not improved long-term outcome, which depends on initial prognostic factors such as the Follicular Lymphoma International Prognostic Index (FLIPI), 4 response to first-line therapy, and minimal residual disease indicated by positivity of the bcl2 rearrangement on analysis of the polymerase chain reaction (PCR). Although new therapeutic approaches, including purine analogs and anti-CD20 monoclonal antibodies, have shown impressive response rates and prolonged progression-free survival (PFS), their effects on overall survival (OS) have yet to be confirmed. The major improvement in the management of FLs has been achieved by the use of the anti-CD20 monoclonal antibody rituximab, which improved OS in combination with chemotherapy in all 4 prospective, randomized studies published to date. [5][6][7][8][9] Before the era of monoclonal antibodies, autologous stem cell transplantation (ASCT) was evaluated as an alternative approach to standard chemotherapy. Numerous studies have shown encouraging results for patients with relapsed follicular NHL, [10][11][12][13] 10,15,16 The fourth study, from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO), compared chemotherapy to ASCT with rituximab in both arms. 17 In 2005 we published the results of the Groupe Ouest-Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS) 064 trial, showing a higher overall response rate and longer median event-free survival (EFS) in the high-dose therapy (HDT) group then the conventional chemotherapy group after a median follow-up of 5 years, with no difference in OS but a higher rate of secondary malignancies in the HDT group. 18 We report here the final results of this trial, after an extended follow-up period of 108 months (9 years...