Concurrent Administration of High-Dose Rituximab Before and After Autologous Stem-Cell Transplantation for Relapsed Aggressive B-Cell Non-Hodgkin’s Lymphomas

Khouri, Issa F.; Saliba, Rima M.; Hosing, Chitra; Okoroji, Grace-Julia; Acholonu, Sandra; Anderlini, Paolo; Couriel, Daniel R.; Lima, Marcos de; Donato, Michèle; Fayad, Luis; Giralt, S.; Jones, Roy B.; Körbling, Martin; Maadani, Farzaneh; Manning, John T.; Pro, Barbara; Shpall, Elizabeth J.; Younes, Anas; McLaughlin, Peter; Champlin, Richard E.

doi:10.1200/jco.2005.08.012

Cited by 119 publications

(74 citation statements)

References 28 publications

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“…54,55 Thus, our study further strengthens the evidence for the benefit of adding rituximab to intensive programs with autograft for DLB-CL patients, exploiting not only its antitumor activity, but also its in vivo purging effect on PBSC harvests. [10][11][12][13]56,57 In conclusion, the efficacy of combining early hd-chemotherapy, multiple PBPC support and rituximab in high-risk DLB-CL is shown in this prospective multicenter study, confirming the recent promising observations with early dose intensity and autograft in poor prognosis aggressive lymphoma. 5,7,8 Thus, in spite of a number of novel treatment approaches that are under development and are expected to improve our lymphoma management strategies, intensified treatments with autograft should still be considered as effective therapeutic weapons, worthy of being evaluated in comparison with other intensified chemoimmunotherapy schedules not requiring autologous progenitor cell support.…”

Section: Tablesupporting

confidence: 76%

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi)

et al. 2007

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A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/ cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam þ 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged o65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months followup, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.

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Section: Tablesupporting

confidence: 76%

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi)

et al. 2007

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“…A recent follow-up of the expanded study reported that the projected 3-year OS and relapsefree survival to be 91 and 84%, respectively. Khouri et al 25 and the MD Anderson Cancer Center used premobilization rituximab followed by BEAM in combination with highdose rituximab (1000 mg/m 2 ) after transplant. Sixty-seven aggressive NHL patients treated with this approach successfully underwent stem cell harvest and transplantation.…”

Section: Original Approachmentioning

confidence: 99%

Autotransplant conditioning regimens for aggressive lymphoma: are we on the right road?

Fernandez

Escalón

Pereira

et al. 2007

Bone Marrow Transplant

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High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard approach for chemosensitive, relapsed aggressive non-Hodgkin's lymphoma (NHL). Various conditioning regimens have been used as treatment before ASCT and disease-free (DFS) and overall survival (OS) rates range from 34 to 60% and 26 to 46%, respectively. To date, few comparative randomized trials have been performed and no regimen has demonstrated superiority to another. Reduction of disease relapse remains the major hurdle for improving patient outcome and in vitro and in vivo purging of lymphoma cells has not necessarily enhanced results. Rituximab pre-mobilization and post-transplant appear to provide better response rates with OS approaching 87-91% at 2-3 years. Newer approaches with radioimmunotherapy may raise DFS to 78% and OS to 93%, albeit with short follow-up. Advances in the conditioning regimens and supportive care have reduced transplant-related mortality to less than 10%. In this review we discuss commonly utilized conditioning regimens, describe their pros and cons and address purging and present conditioning strategies. Owing to the poor outcome with conventional chemotherapy in mantle cell, Burkitt's and T-cell lymphoma, we propose the standard approach of frontline ASCT for these high-risk lymphoma patients. Finally, we will present novel strategies, which can enhance the anti-lymphoma effect, at the same time reducing toxicity, to improve the outcome of ASCT in NHL patients.

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“…In a second trial, high-dose rituximab, 1000 mg/m 2 rather than standard-dose 375 mg/m 2 , was administered during stem cell mobilization, BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy, and on days 1 and 8 after HSCT in 67 patients. 21 At a median follow-up of 20 months, estimated 2-year disease-free and overall survival (OS) were 67% and 80%, respectively (P = 0.002), significantly better than those of a historical control group receiving the same preparative regimen without rituximab 43% and 53%, respectively (P = 0.004).…”

Section: Dlbcl Treatmentmentioning

confidence: 98%

Rituximab in the treatment of B-cell non-Hodgkin lymphoma, focus on outcomes and comparative effectiveness

Badin

Hayslip

2010

CEOR

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Rituximab is an important and well established component in the treatment of many patients with B-cell non-Hodgkin lymphoma. In this paper we review recent clinical trials investigating the addition of rituximab to standard chemotherapy regimens for treatment of patients with diffuse large B cell lymphoma and follicular lymphoma. This report focuses upon treatment efficacy, quality of life, and safety of rituximab or rituximab-containing regimens. More uniquely, we review economic aspects of lymphoma treatments, including the cost of standard chemotherapy regimens with or without rituximab, cost effectiveness of rituximab in both induction and maintenance treatment, and lymphoma’s impacts on patient’s productivity and their caregivers. We conclude that adding rituximab to standard chemotherapy treatment for patients with B-cell non-Hodgkin lymphoma is safe and cost-effective in numerous settings during both induction and maintenance therapies. Despite extensive review of the literature, many important questions have yet to be answered in the rituximab era and these represent important directions for future study.

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Concurrent Administration of High-Dose Rituximab Before and After Autologous Stem-Cell Transplantation for Relapsed Aggressive B-Cell Non-Hodgkin’s Lymphomas

Abstract: The results of this study suggest that using HD-R and autologous SCT is a feasible and promising treatment for patients with B-cell aggressive NHL.

Cited by 119 publications

References 28 publications

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi)

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi)

Autotransplant conditioning regimens for aggressive lymphoma: are we on the right road?

Rituximab in the treatment of B-cell non-Hodgkin lymphoma, focus on outcomes and comparative effectiveness

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