Search

Doxorubicin-based immunochemotherapy, with interferon, has been shown to improve survival in patients with advanced follicular lymphoma. High-dose chemotherapy with stem-cell support is effective in follicular lymphoma in relapse but remains controversial as a first-line therapy. In a randomized study using a purged autologous stem-cell support, we compared these 2 approaches in patients with advanced follicular lymphoma. Newly diagnosed advanced follicular lymphoma patients (172 patients) were randomly assigned either to an immunochemotherapy regimen (cyclophosphamide, doxorubicin, teniposide, prednisone, and interferon) or to a high-dose therapy followed by purged autologous stem-cell transplantation. Compared with the patients who received chemotherapy and interferon, patients treated with high-dose therapy had a higher response rate (69% vs 81%, P = .045) and a longer median event-free survival (not reached vs 45 months). This did not translate into a better survival rate due to an excess of secondary malignancies after transplantation. The Follicular Lymphoma Prognostic Index identified a subgroup of patients with a significantly higher event-free survival rate after high-dose therapy. Autologous stem-cell transplantation cannot be considered as the standard first-line treatment of follicular lymphoma for patients younger than 60 years old with a high tumor burden.

The H97-I trial (1997-2004) for Hodgkin lymphoma at intermediate stage (HL-I) included 269 patients who were randomized to receive three or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The 197 patients who reached complete remission (CR) (73.2%, p = 0.41 between arms) received radiotherapy (RT); their 10-year progression-free survival (PFS) rate was 87.7 ± 3.0%, similar to that of the 180 patients of a historical control group (HCG) in CR after three ABVD cycles before RT. The 59 patients who reached post-ABVD partial remission (PR) received one course of intensive chemotherapy (i.v., mg/m(2), vindesine 5, adriamycin 90, BCNU 140, etoposide 600, methylprednisolone 600) before RT. In spite of this additional intensive chemotherapy, their PFS rate (78.4 ± 6.3%) remained significantly lower (p = 0.03) than that of the 197 patients who reached post-ABVD CR, and was similar to that of the 60 patients of the HCG in PR after three ABVD cycles who did not receive additional chemotherapy before RT.

Purpose: To report long-term pulmonary, thyroid, and ocular complications in patients who had conditioning regimens including total body irradiation (TBI) before bone marrow transplantation (BMT). Methods and Materials: Between June 1986 and December 1995, 478 patients received TBI in our institution. The present study includes 186 adult patients who had complete remission lasting one year or more after BMT. There were 108 males and 78 females. Median age was 36.5 years (range 15–60). Initial diagnoses were lymphomas (50%), acute lymphoid leukemias (16%), acute myeloid leukemias (16%), chronic myeloid leukemia (13%), aplastic anemia (3%), and myelodysplasia (2%). At the time of BMT, 43.5% of patients were in complete response and 56.5% in partial response. Treatment consisted of a single dose TBI at 10 Gy in 9% and fractionated TBI delivering 12 to 13.5 Gy in 6 fractions in 91%. From 1986 to October 1991, TBI was performed in lateral position with 9 MV energy (57% of patients) and thereafter in alternate prone and supine positions with 15 MV energy (43%). Chemical conditioning regimen was cyclophosphamide (60 mg/kg at D-4 and D-3) in 69% and CBV (cyclophosphamide 1500 mg/m 2 from D-6 to D-3, BCNU 300 mg/m 2 at D-6, VP-16 200 mg/m 2 from D-6 to D-4) in 25%. Fifty eight percent of patients received autologous and 42% allogeneic BMT. All patients had clinical, biologic, and functional examinations at one-year intervals. Results: Median follow-up from BMT was 49 months (range 12–136). Late pulmonary effects were observed only in functional explorations, without clinical effect, including restrictive syndrome in 8% and alteration in the diffusing capacity of carbon monoxide in 12%. No patient showed clinical thyroid symptoms, and 10% developed biologic dysfunction: hypothyroidism (6.5%), thyroiditis (3%), and Basedow disease (0.5%). Ocular complications occurred in 29.5%, including cataract (15%), dry syndrome (13%), and keratitis (1.5%). In univariate and multivariate analysis, pulmonary complications were statistically increased by chronicle graft vs. host disease (GVHD) vs. no ( p = 0.02), prone and supine vs. lateral TBI position ( p = 0.02), and with 15 MV vs. 9 MV beam energy ( p = 0.02). Cataract occurred less frequently with fractionated than with single-dose TBI ( p = 0.000002). No differences were observed regarding age, sex, initial diagnosis, status at the time of BMT, conditioning chemotherapy regimen, and total dose of TBI. Conclusion: From this retrospective study it was shown that long-term complications of TBI were not symptomatic in most patients. The role of parameters of irradiation and especially position of treatment and beam energy should be emphasized and assessed with a longer follow-up.

Purpose: To evaluate the efficacy of total abdominopelvic (TAI) and total body irradiation (TBI) in heavily pretreated follicular non-Hodgkin’s lymphoma (NHL). Patients and Methods: From 1983 to 1998, 34 patients received TAI ( n = 22) or TBI ( n = 12). All had Stage III or IV, Class B, C, D NHL in the working formulation and failed after receiving 1–5 regimens of chemotherapy. TAI was given at 20 Gy over a 3-week period. TBI was delivered in two successive half-body irradiations of 15 Gy over a 2-week period with a 4-week interval between each. Results: Mean follow-up from TAI or TBI was 120 months (range, 6–180). Seventy-six percent of patients achieved complete response and 24% partial response. Median survival was 62 months, 5-year and 10-year overall survival was 59% and 41%, and disease-free survival was 56% and 30%, respectively. Grade III or IV toxicity was gastrointestinal in 38% of patients and hematologic in 30%. No toxic death or delayed complications were observed. Conclusion: Extended-field irradiation is feasible and efficient after failure of chemotherapy in follicular NHL.

To evaluate the therapeutic efficacy of moderate-dose total abdominopelvic irradiation (TAI) in a retrospective series of pretreated non-Hodgkin's lymphomas (NHL).From 1977 to 1994, 45 patients received TAI after failure of chemotherapy (CT). According to the Working Formulation, 10 patients were diagnosed with class A (group I), 19 with class B, C, or D (follicular) (group II), and 16 with class E or more severe (group III) NHL. Irradiation consisted of two daily fractions of 0.80 Gy each for a total dose of 20 Gy.Mean follow-up after TAI was 102 months (range 8-156). For the entire group, the complete response (CR) rate was 66%, the partial response (PR) rate 29%, 10-year overall survival (OS) 35%, 10-year disease-free survival (DFS) 29%, and median survival 32 months. When results between subgroups were compared, CR was 70% in group I, 84% in group II, and 44% in group III; and survival was statistically higher in group II than in groups I and III: 10-year OS 52% vs. 10% (p0.01) and 31% (p0.05), respectively, 10-year DFS 37% vs. 10% (p0.03) and 19% (p0.05), respectively. Grade III or IV complications were gastrointestinal in 27% of patients and hematologic in 25%.Large-field irradiation in moderate doses could provide an alternative to bone marrow transplantation in refractory NHL, especially in cases showing a follicular growth pattern.

Abstract 2796 Background: Diffuse large B-cell lymphoma (DLBCL) relapse prognosis is poor, and the optimal salvage treatment is not known. In a previous pilot study, vinorelbine, ifosfamide, mitoxantrone, and prednisone (NIMP) without rituximab has shown a promising efficacy in the setting of relapsed DLBCL. Aims: To evaluate the efficacy and tolerability of the combination of rituximab and NIMP in the treatment of DLBCL in first relapse. Methods: This multicentric, single-arm phase II study included patients 18 to 75 years old, with CD20-positive DLBCL in first relapse (defined as having obtained at least a PR of more than 50% to an anthracycline-based front-line regimen) occurring more than 30 days after the last chemotherapy cycle or more than one year after an autologous stem cell transplantation (ASCT) in first line. Other inclusion criteria were a performance status ≤ 2, absence of CNS involvement, and having signed an informed consent form. Patients with evidence of transformation from indolent lymphoma, primary refractory disease, or positive HIV tests were excluded. Initial and relapse biopsies were centrally reviewed. Patients received intravenous (IV) rituximab 375 mg/m2 D1, ifosfamide 1000 mg/m2 as a continuous infusion from D1 to D5, IV vinorelbine 25 mg/m2 D1 and D15, IV mitoxantrone 10 mg/m2 D1, and oral prednisone 1 mg/kg D1 to D5, repeated every 28 days for three cycles. Pegfilgrastim support (6 mg at D7) was recommended. The primary endpoint was CR/CRu after 3 cycles, and was assessed by computed tomography according to the IWG criteria. Mobilization, consolidation or subsequent salvage therapy was decided at the discretion of the investigator. All the monitoring and data management were performed by the GOELAMS clinical research assistants, with a database lock on July 27, 2010. Results: Fifty patients (21[42%] women and 29[58%] men) were included in 18 centers between December 2004 and accrual closure in April 2010. All patients received at least 1 cycle of R-NIMP. Forty-five patients were available for central pathology review, toxicity and response. The central review of all patient samples confirmed DLBCL histology. Median age at study entry was 62.9 years (range: 34.8–75.6). Median time between first diagnosis of DLBCL and relapse was 18.0 months (range: 2.4–208). The following tumor responses were observed: 67.9 % overall response rate with 20 CR/CRu (43.5%), 11 PR (24.4%), 2 SD (4.4%), and 12 (26.7%) progressed under therapy. Toxicity information was available for 109/120 (91 %) of the first 3 cycles of R-NIMP administered. The following toxicities were observed (all grades, ≥ grade 3 for all cycles): anemia (87%, 8%), neutropenia (66%; 46%), thrombopenia (65%, 14%), elevated liver tests (39%, 0%), constipation (25%, 0%), kidney failure (7%, 0%), nausea (14%, 0%), vomiting (6%, 0%), allergic reactions (5%, 0%), and mucositis (5%, 0%). Twenty-nine infectious events (27%) were observed needing hospitalization in 9 cases. Twenty-nine patients received consolidation therapy at the discretion of the investigator. Of the 11 patients who received 3 additional cycles of R-NIMP, 3 remained in CR/CRu, 1 remained in PR, 4 converted from PR to CR/CRu, and 3 progressed. Among the 11 patients who underwent ASCT, 9 were in CR at the end of the procedure, one patient died of toxicity and 1 progressed. For the 12 patients mobilized after a R-NIMP cycle, a median of 1 apheresis (range 1–4) was necessary to harvest a median of 3.85 × 106 CD34+ cells/kg. The median time to second progression or relapse (TTP2) was 11.4 months, and the median survival of 55.5 months. On multivariate analysis, the variable associated with a longer TTP2 was the achievement of CR/Cru (RR: 0,12; CI95%: 0.03–0,39; p=0.0006). Within the subgroup of patients having received a consolidation treatment, having received an ASCT was associated with a longer TTP2 (RR: 0.20; CI95%: 0.04–0.98; p=0.047). Time to first relapse or previous rituximab exposure did not affect TTP2 nor OS, whereas relapse-IPI (as a continuous variable, by 1 additional risk factor) was associated with a poor survival (RR: 2.59; CI95%: 1.25–4.45; p=0.008). Conclusions: R-NIMP is a well-tolerated regimen, yields a high complete response rate, and allows for successful mobilization of CD34+ cells. This regimen is a suitable salvage treatment for relapsed DLBCL prior to appropriate consolidation. Further investigation is warranted. ClinicalTrials.gov number: NCT00842595 Disclosures: Off Label Use: Vinorelbine in Non-Hodgkin's Lymphoma (Off-label in France).