Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma (original) (raw)

Effect of rituximab on the long-term outcome after high-dose therapy for relapsed B-cell non-Hodgkin’s lymphoma

Annals of Hematology, 2006

To better define the role of rituximab in salvage and high-dose therapy (HDT) for relapsed or refractory non-Hodgkin's lymphoma (NHL), patients treated before the implementation of rituximab in salvage and HDT (n=57, control group) were compared with patients with rituximab included in this procedure (n=36, study group). All patients had been antibody-naive at this point, and analyses were performed separately for 22 and 31 patients with aggressive, and 14 and 26 patients with indolent NHL, respectively. All patients received two courses of salvage therapy, predominantly dexamethasone, BCNU, etoposide, cytosine arabinoside, melphalan. Conditioning regimens included BCNU, etoposide, cytosine arabinoside, melphalan; BCNU, etoposide, cytosine arabinoside, cyclophosphamide or total body irradiation and cyclophosphamide, with rituximab added for patients in the study group. Despite the absence of differences in stem cell collection, haematopoietic recovery was delayed in patients with aggressive NHL treated in the study group: median days to absolute neutrophil count more than 0.5×10 9 /l, 11 vs 10 (p=0.01), and platelets more than 20×10 9 /l, 14 vs 11 (p=0.0005), with an increased requirement for platelet transfusions. No similar observations were made in indolent lymphoma patients. Remission rates were superior for patients with aggressive NHL in the study group. With a median followup of 7.25 and 4.5 years, this resulted in an improvement in OS at 4.5 years: 67 vs 45% (95% confidence interval, 47-87% vs 28-64%; p=0.0468). For patients with indolent lymphoma, no comparable benefit was detectable. Our data support the use of rituximab in HDT for patients with aggressive NHL. For patients with indolent NHL, only longer follow-up and/or randomized trials may help to fully determine the impact of rituximab on the outcome after HDT.

Preliminary outcome of rituximab-containing salvage regimens on relapsed or refractory B-cell non-Hodgkin’s lymphoma: single institution experience

The Chinese-German Journal of Clinical Oncology, 2006

Relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) is known to have a poor prognosis. The overall response rates of second line salvage regimens such as EPOCH (CTX, VCR, ADM, prednisone and VP16), DICE (dexamethasone, DDP and VP16), DHAP (dexamethasone, Ara-c and DDP) and ESHAP (VP16, dexamethasone, Ara-c and DDP) range from 30% to 70% with complete remission rates (CR) from 19.2% to 35.0% [1-5]. Although high dose chemotherapy supported by autologous haemopoietic stem cell transplantation (autoHSCT) can improve the long-term survival, it is unsuitable for elderly patients especially those who are simultaneously suffering from other diseases. Therefore, it is necessary to explore novel therapies in order to improve the clinical outcome of these patients. Rituximab alone or combined with conventional chemotherapy is the standard therapy for relapsed indolent lymphoma and untreated diffuse large B cell lymphoma [6]. In recent years, there were several publications about the relapsed aggressive B cell lymphoma treated by salvage regimen plus rituximab. It seemed that rituximab may improve the effectiveness of EPOCH, ICE, TT (paclitaxel and topotecan) and other salvage regimens [7-9]. In our study, the short term efficacy and toxicities of rituximab containing salvage regimens in treating 54 cases with relapsed or refractory B cell NHLs were reported. The main purpose of our study was to evaluate the feasibility and safety of rituximab in treating relapsed and refractory B cell lymphoma.

Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era

Journal of Clinical Oncology, 2010

Purpose Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown. Patients and Methods Patients with CD20+ DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT. Results The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respe...

High-dose therapy followed by autologous stem-cell transplantation with and without rituximab for primary treatment of high-risk diffuse large B-cell lymphoma

Annals of Oncology, 2010

Background: We aimed to determine safety and efficacy of rituximab (R) in combination with repetitive high-dose therapy (HDT) as primary treatment for diffuse large B-cell lymphoma (DLBCL). Patients and methods: Patients aged 18-60 years and elevated lactate dehydrogenase were treated with four cycles of MegaCHOEP and transplantation of autologous stem cells after cycles 2, 3 and 4. Rituximab (375 mg/m 2) was given before each cycle and 12 and 33 days after start of the last cycle of chemotherapy. Sixty-four patients given R-MegaCHOEP were compared with 29 patients who had received identical treatment without rituximab. Results: Overall survival (OS) and event-free survival (EFS) after 3 years were significantly improved in patients treated with R-MegaCHOEP (OS: 78.7% versus 55.0%, P = 0.045; EFS: 72.7% versus 47.2%, P = 0.013). In a Cox regression model adjusted for performance status and stage, relative risk of treatment failure was lower (relative risk 0.5, P = 0.041) and OS was better (relative risk 0.4, P = 0.054) for patients given R-MegaCHOEP. Grade 3/4 infections were more frequent in the R-MegaCHOEP group (18.5% versus 6.0%, P = 0.003). Conclusions: The addition of rituximab to MegaCHOEP significantly improved outcome in young patients with high-risk DLBCL. The higher incidence of grade 3/4 infections needs consideration when rituximab and HDT regimens are combined.

Rituximab reduces relapse risk after allogeneic and autologous stem cell transplantation in patients with high-risk aggressive non-Hodgkin's lymphoma

British Journal of Haematology, 2003

High-dose chemotherapy and autologous stem cell transplantation (SCT) have limited success in patients with refractory aggressive lymphoma. Allogeneic SCT may offer some advantage in this setting by providing graftversus-lymphoma effect, but the relapse risk remains substantial. In this study, we evaluated the safety and efficacy of rituximab administration after SCT in patients at highrisk for post-transplant relapse, in order to reduce relapse risk. Twenty-eight patients were included with the intent to treat them with rituximab after autologous (n ¼ 16) or allogeneic (n ¼ 12) SCT. Twenty-four were given rituximab starting a median of 47 d post SCT. Three died of SCT complications prior to therapy. Nine patients not achieving a complete remission (CR) post SCT converted to CR with rituximab and with the onset of graft-versus-host disease (GVHD) in three. With a median follow-up of 12 months (range, 3-33 months) the estimated 2-year overall survival and disease-free survival was 85 ± 7% and 55 ± 13% respectively. When only those patients who were actually treated are analysed, these rates were 95 ± 7% and 64 ± 13% respectively. The relapse risk was 35 ± 14%. Seven patients had recurrent neutropenia episodes associated with severe hypogammaglobulinaemia, which were further prevented with intravenous immunoglobulin. None of the 10 allogeneic SCT recipients treated with rituximab had severe GVHD. Rituximab may be an effective adjuvant therapy after SCT to reduce the relapse rate and improve the outcome in high-risk aggressive lymphoma. Larger scale comparative trials are necessary to better define its role in SCT.

Early failure of frontline rituximab-containing chemo-immunotherapy in diffuse large B cell lymphoma does not predict futility of autologous hematopoietic cell transplantation

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2014

The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing…

Re-Treatment of Relapsed Indolent B-Cell Lymphoma With Rituximab

International Journal of Hematology, 2001

Recently, a new chimeric mouse human monoclonal antibody, rituximab (IDEC-C2B8), has been incorporated into the therapy of B-cell non-Hodgkin's lymphoma (B-NHL) that expresses CD20 . Use of rituximab has given rise to a good response rate and a relatively long progression-free survival (PFS) in patients with recurrent indolent B-NHL ; however, the toxicity and the efficacy of re-treatment with rituximab are unknown. Also, it remains to be determined if either an extended (more than 4 weeks) or a repeated dosing regimen of rituximab is effective in decreasing relapse or in prolonging PFS. Recently, we conducted multicenter phase I and phase II studies of rituximab for the treatment of recurrent indolent B-NHL . In the phase II study, more than half of the relapsed patients with indolent B-NHL responded to rituximab with an acceptable level of toxicity profiles . Here we report the results of re-treatment with rituximab in 13 patients whose B-NHL relapsed after they showed an initial response to rituximab.

The Role of Transplantation in Diffuse Large B-Cell Lymphoma: The Impact of Rituximab Plus Chemotherapy in First-line and Relapsed Settings

Current Hematologic Malignancy Reports, 2010

Rituximab has improved the prognosis of patients with diffuse large B-cell lymphoma, but a high proportion of patients with advanced disease will relapse or will fail to achieve a remission with front-line treatment. Salvage chemotherapy, followed by high-dose chemotherapy or radiation therapy and autologous stem cell transplantation, remains the best treatment option for such patients, especially those who retain chemosensitivity. Allogeneic transplantation is under investigation in this setting, often as a treatment for relapse after autologous transplantation. Treatment-related mortality due to graftversus-host disease, preparative regimen toxicity, and poor immune recovery often limits its benefits. This article reviews the role of hematopoietic stem cell transplantation in the treatment of diffuse large B-cell lymphoma, the incorporation of rituximab, and avenues of clinical investigation in this rapidly evolving field.