Corrado Tarella

BACKGROUND: We compared a regimen of six chemotherapeutic agents administered sequentially at high doses, followed by myeloablative treatment and bone marrow transplantation, with a regimen of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as initial or salvage treatment for adults with diffuse large-cell lymphoma. METHODS: Ninety-eight eligible patients with diffuse large-cell lymphoma of the B-cell type were randomly assigned to receive either MACOP-B (50 patients) or high-dose sequential therapy (48 patients). The study design allowed for patients in whom the assigned treatment failed to cross over to the other treatment group. RESULTS: After a median follow-up of 55 months, the patients given high-dose sequential therapy, as compared with those treated with MACOP-B, had significantly higher rates of complete response (96 percent vs. 70 percent, P=0.001), freedom from disease progression (84 percent vs. 49 percent, P<0.001), freedom from relapse (88 percent vs. 70 percent, P=0.055), and event-free survival (76 percent vs. 49 percent, P=0.004). The difference in overall survival at seven years, which also favored the group assigned to high-dose sequential therapy, was marginally significant (81 percent vs. 55 percent, P=0.09). CONCLUSIONS: High-dose sequential therapy is superior to standard-dose MACOP-B for patients with diffuse large-cell lymphoma of the B-cell type.

To evaluate in a prospective multicenter trial the feasibility and clinical efficacy of the combination of alemtuzumab (Campath-1H) with the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen (CHOP-C) as the primary treatment for patients with peripheral T-cell lymphoma (PTCL), between January 2003 and December 2005, 24 consecutive patients with PTCL entered the study and received 8 CHOP courses. Alemtuzumab was added at 30 mg subcutaneously at day -1 initially to the first 4 courses (4 patients), and then to all 8 courses (20 patients). Complete remission (CR) was achieved in 17 (71%) patients, 1 had partial remission, and 6 had stable/progressive disease. At a median follow-up of 16 months (range, 5-42 months), 14 patients were alive, 9 had died from progressive disease, and 1 had died from pneumonia at day +198 while in CR. So far, 13 are disease-free, with an overall median duration of response of 11 months. The most frequent side effects were grade 4 neutropenia and cytomegalovirus (CMV) reactivation. Major infections were Jacob-Creutzfeldt (J-C) virus reactivation, pulmonary invasive aspergillosis, Staphylococcus sepsis, and pneumonia. This study shows that CHOP-C: (1) is a feasible chemoimmunotherapy regimen; (2) is effective in PTCL with a high rate of CR achievement; and (3) is associated with mostly manageable infectious complications. This clinical trial was registered with the Osservatorio Nazionale sulla Sperimentazione cinica as ID no. 141202.

PURPOSE: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of malignancies characterized by a poor prognosis. We performed a pilot study to investigate the role of reduced-intensity conditioning (RIC) followed by allogeneic stem-cell transplantation in relapsed or refractory PTCLs. PATIENTS AND METHODS: We have conducted a phase II trial on 17 patients receiving salvage chemotherapy followed by RIC and allogeneic transplantation of hematopoietic cells. The RIC regimen consisted of thiotepa, fludarabine, and cyclophosphamide. The acute graft-versus-host disease prophylaxis consisted of cyslosporine and short course methotrexate. RESULTS: Patients had a median age of 41 years (range, 23 to 60 years). Two patients were primary chemorefractory, and 15 had relapsed disease; eight patients (47%) had a disease relapse after an autologous transplantation. After a median follow-up of 28 months from the day of study entry (range, 3 to 57 months), 14 of 17 patients were alive (12 in complete remission, one in partial remission, and one with stable disease), two died as a result of progressive disease, and one died as a result of sepsis concomitant to acute graft-versus-host disease. The estimated 3-year overall and progression-free survival rates were 81% (95% CI, 62% to 100%) and 64% (95% CI, 39% to 89%), respectively. The estimated probability of nonrelapse mortality at 2 years was 6% (95% CI, 1% to 17%). Donor lymphocyte infusions induced a response in two patients progressing after allografting. CONCLUSION: RIC followed by allogeneic stem-cell transplantation is feasible, has a low treatment-related mortality, and seems to be a promising salvage treatment for relapsed PTCL. These findings suggest that the existence of a graft-versus-T-cell lymphoma effect.

Abstract In this randomized multicenter study of 136 patients, 6 courses of CHOP (cyclo-phosphamide/doxorubicin/vincristine/prednisone) followed by rituximab (CHOP-R) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting (R-HDS) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma (FL) after the introduction of monoclonal antibodies. The analysis was intention to treat with event-free survival (EFS) as the primary endpoint. Complete remission (CR) was 62% with CHOP-R and 85% with R-HDS (P &lt; .001). At a median follow-up (MFU) of 51 months, the 4-year EFS was 28% and 61%, respectively (P &lt; .001), with no difference in overall survival (OS). Molecular remission (MR) was achieved in 44% of CHOP-R and 80% of R-HDS patients (P &lt; .001), and was the strongest independent outcome predictor. Patients relapsing after CHOP-R underwent salvage R-HDS in 71% of cases. Salvage R-HDS had an 85% CR rate and a 68% 3-year EFS (MFU, 30 months). We conclude that (1) achieving MR is critical for effective disease control, regardless of which treatment is used; (2) R-HDS ensures superior disease control and molecular outcome than CHOP-R, but no OS improvement; and (3) CHOP-R failures have a good outcome after salvage R-HDS, suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS–like treatments. This trial was registered at www.clinicaltrials.gov as no. NCT00435955.