Long-Term Follow-Up of the Prospective Randomized AATT Study (Autologous or Allogeneic Transplantation in Patients With Peripheral T-Cell Lymphoma).

JCO Primary analysis of the phase III randomized AATT study showed that younger patients with peripheral T-cell lymphoma (PTCL) consolidated with autologous or allogeneic transplantation (alloSCT) had similar event-free survival (EFS) and overall survival (OS). Seven-year EFS of patients randomly assigned to alloSCT was 38% (95% CI, 25 to 52) compared with 34% (95% CI, 22 to 47) for patients randomly assigned to autologous transplantation of hematopoietic stem cells (autoSCT); OS was 55% (95% CI, 41 to 69) and 61% (95% CI, 47 to 74). Among patients undergoing alloSCT (n = 26) or autoSCT (n = 41) on study, the cumulative progression/relapse rate was 8% (95% CI, 0 to 19) and 55% (95% CI, 35 to 74).

Radiotherapy in younger patients with advanced aggressive B-cell lymphoma-long-term results from the phase 3 R-MegaCHOEP trial.

The role of consolidative radiotherapy (RT) for patients with aggressive B-cell lymphoma has not been fully elucidated. The R-MegaCHOEP trial investigated the use of high-dose chemotherapy and rituximab with subsequent autologous stem cell transplantations compared to conventional immunochemotherapy (R-CHOEP) for high-risk patients up to 60 years. The study protocol included RT for patients with bulky (maximum diameter ≥7.

Radiation and Dose-densification of R-CHOP in Aggressive B-cell Lymphoma With Intermediate Prognosis: The UNFOLDER Study.

UNFOLDER (Unfavorable Young Low-Risk Densification of R-Chemo Regimens) is an international phase-3 trial in patients 18-60 years with aggressive B-cell lymphoma and intermediate prognosis defined by age-adjusted International Prognostic Index (aaIPI) of 0 and bulky disease (≥7.5 cm) or aaIPI of 1. In a 2 × 2 factorial design patients were randomized to 6× R-CHOP-14 or 6× R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso[lo]ne) and to consolidation radiotherapy to extralymphatic and bulky disease or observation.

Radiation and Dose-densification of R-CHOP in Primary Mediastinal B-cell Lymphoma: Subgroup Analysis of the UNFOLDER Trial.

UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal B-cell lymphoma (PMBCL). In a 2 × 2 factorial design, patients were randomized to 6× R-CHOP-14 or R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso(lo)ne) and to consolidation radiotherapy to extralymphatic/bulky disease or observation. Response was assessed according to the standardized criteria from 1999, which did not include F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET) scans.

Rituximab plus high-dose chemotherapy (MegaCHOEP) or conventional chemotherapy (CHOEP-14) in young, high-risk patients with aggressive B-cell lymphoma: 10-year follow-up of a randomised, open-label, phase 3 trial.

Background: R-MegaCHOEP was the first phase 3 study comparing high-dose chemotherapy plus rituximab followed by autologous haematopoietic stem-cell transplantation (HSCT) with conventional chemotherapy plus rituximab in first-line therapy for patients aged 60 years or younger with high-risk aggressive B-cell lymphoma. Little is known about the long-term outcomes of these patients. We aimed to evaluate the long-term efficacy and safety of conventional chemotherapy versus high-dose chemotherapy after 10 years of follow-up in the R-MegaCHOEP trial.

A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL.

First-line therapy for younger patients with peripheral T-cell non-Hodgkin lymphoma (T-NHL) consists of 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide (CHOEP), consolidated by high-dose therapy and autologous stem cell transplantation (auto-SCT). We hypothesized that allogeneic stem cell transplantation (allo-SCT) could improve outcomes. 104 patients with peripheral T-cell non-Hodgkin lymphoma, except ALK+ anaplastic large cell lymphoma, 18 to 60 years, all stages, and all age adjusted International Prognostic Index scores, except 0 and stage I, were randomized to 4 cycles of CHOEP and 1 cycle of dexamethasone, cytosine-arabinoside, and platinum (DHAP) followed by high-dose therapy and auto-SCT or myeloablative conditioning and allo-SCT.

Alemtuzumab plus CHOP versus CHOP in elderly patients with peripheral T-cell lymphoma: the DSHNHL2006-1B/ACT-2 trial.

PTCL patients exhibit poor survival with existing treatments. We investigated the efficacy of CHOP combined with alemtuzumab in 116 PTCL patients age 61-80 in an open-label, randomized phase 3 trial. Alemtuzumab was given on day 1, to a total of 360 mg in 21 patients, or 120 mg in 37.

Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial.

Background: Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis.

Methods: This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany.

Doubling rituximab in high-risk patients with aggressive B-cell lymphoma -results of the DENSE-R-MegaCHOEP trial.

To further improve outcome in young high-risk patients with diffuse large B-cell lymphoma (DLBCL) the number of rituximab (R) infusions was doubled in combination with standard CHOEP (cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone) chemotherapy. Seventy-seven patients (aged 18-60 years) with an age-adjusted International Prognostic Index of 2-3 received 12 × R (375 mg/m ) on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 99 together with eight cycles of CHOEP-14. Results were retrospectively compared to those of patients receiving 6 × R and 8 × CHOEP-14 in the standard arm of the randomized R-MegaCHOEP trial.

Allogeneic stem cell transplantation for patients with relapsed or refractory T-cell lymphoma: efficacy of lymphoma-directed conditioning against advanced disease.

Salvage chemotherapy induces disease remissions in patients with relapsed or refractory (r/r) T-cell lymphomas, but fails to provide lasting tumor control. We analyzed the outcome after peripheral blood stem and bone marrow transplantation (PBSCT, n = 80; BMT, n = 4) from matched related (MRD, n = 22) or matched and unmatched unrelated donors (MUD and MMD, n = 53 and n = 9, respectively) following conditioning with fludarabine, busulfan, and cyclophosphamide (FBC) for 84 consecutive patients with r/r T-cell malignancies. At start of conditioning LDH was elevated in 50% of cases, and residual tumor (PD, SD, PR) was detectable in 84% of patients.

Central Nervous System Prophylaxis for Aggressive B-cell Lymphoma: Who, What, and When?

Central nervous system (CNS) relapse of aggressive B-cell lymphoma is a rare but serious complication with poor survival. Different approaches have been used to define risks factors for CNS relapse and establish prophylactic measures. Although patients with low or intermediate risk of CNS relapse should not undergo special diagnostic or therapeutic measures, CNS MRI as well as cytology and flow cytometry of the cerebrospinal fluid are suggested for high-risk patients (and patients with testicular involvement) at diagnosis, and prophylactic high-dose methotrexate in patients without proven CNS involvement.

CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP.

Purpose: To develop and validate a risk score for relapse in the CNS in patients with diffuse large B-cell lymphoma (DLBCL).

Patients And Methods: A total of 2,164 patients (18 to 80 years old) with aggressive B-cell lymphomas (80% DLBCL) treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy, who were enrolled in studies from the German High-Grade Non-Hodgkin Lymphoma Study Group and the MabThera International Trial, were analyzed for occurrence of relapse/progression in the CNS. The resulting risk model was validated in an independent data set of 1,597 patients with DLBCL identified in the British Columbia Cancer Agency Lymphoid Cancer database.

Allogeneic stem cell transplantation with BEAM and alemtuzumab conditioning immediately after remission induction has curative potential in advanced T-cell non-Hodgkin's lymphoma.

Patients with relapsed or refractory advanced T cell non-Hodgkin lymphoma have a dismal prognosis and may not even reach allogeneic hematopoietic stem cell transplantation (HSCT) in adequate condition. We present the outcome of 24 consecutive patients (age range 11 to 65 years) treated at a single institution in Kiel within a recent 5.5-year time frame with allogeneic HSCT in a rather uniform approach.

Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1).

Background: High-dose therapy (HDT) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma. We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation (ASCT) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities.

Methods: We did an open-label, randomised trial comparing conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) and rituximab (R-CHOEP-14) with dose-escalated sequential HDT and rituximab (R-MegaCHOEP) followed by repetitive ASCT in high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) patients aged 18-60 years with aggressive B-cell lymphoma.

Patterns and outcome of relapse after autologous stem cell transplantation for mantle cell lymphoma.

Background: Autologous stem cell transplantation (autoSCT) has improved the outcome of patients with mantle cell lymphoma (MCL) considerably. However, little is known about the patterns and outcome of MCL recurrence after autoSCT.

Methods: The authors conducted a retrospective study of 118 patients with MCL who underwent autoSCT from August 1992 to August 2008 at 3 different referral centers in Germany.

Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group.

To evaluate outcome and prognosis of patients with T-cell lymphoma we analyzed 343 patients treated within trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Two hundred eighty-nine patients belonged to 1 of the 4 major T-cell lymphoma subtypes: anaplastic large cell lymphoma (ALCL), anaplastic large cell lymphoma kinase (ALK)-positive (n = 78); ALCL, ALK-negative (n = 113); peripheral T-cell lymphoma, unspecified (PTCLU; n = 70); and angioimmunoblastic T-cell lymphoma (AITL; n = 28). Treatment consisted of 6-8 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone) or etoposide plus (CHOEP).