R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study

Martı́n, Alejandro; Conde, Eulogio; Arnán, Montserrat; Canales, Miguel; Debén, Guillermo; Sancho, Juan‐Manuel; Andreu, Rafael; Salar, Antonio; García-Sánchez, Pedro; Vázquez, Laura Hernández; Nistal, Sara; Requena, María J.; Donato, Eva; Gonzalez, Javier; Léon, Antonio; Ruiz, Camilo; Grande, Carlos; González‐Barca, Eva; Caballero, Marı́a Dolores

doi:10.3324/haematol.13440

Cited by 158 publications

(136 citation statements)

References 27 publications

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“…This cooperation may then improve the killing effects to lymphoma cells. In 2008, studies by Vellenga et al [22] and Martin et al [23] have shown that the addition of Rtx to DHAP (cisplatin-cytarabin-dexamethasone) chemotherapy and ESHAP (etoposide, cytarabine, cisplatin, and methylprednisolone) chemotherapy can both significantly improve the remission rates of CD20 + lymphoma patients, clinically demonstrating the positive role of Rtx to chemotherapy drugs.…”

Section: Resultsmentioning

confidence: 99%

“…The results also showed that the Rtx's enhancing effect became weakened as the concentration of chemotherapy drugs and the stimulation time increased (e.g., when the concentration was 20 μg/ml and the stimulation time was 48 h the addition of Rtx just resulted in a little decrease of cell viability). Both cisplatin and cytarabine are commonly used chemotherapy drugs in treating B-cell lymphomas [22], [23]. Cisplatin molecules can cross-link DNAs in the cancer cell, which ultimately triggers the cellular apoptosis.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy

Xiao

Liu

et al. 2016

IEEE Trans. Biomed. Eng.

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Abstract-The applications of targeted drugs in treating cancers have significantly improved the survival rates of patients. However, in the clinical practice, targeted drugs are commonly combined with chemotherapy drugs, causing that the exact contribution of targeted drugs to the clinical outcome is difficult to evaluate. Quantitatively investigating the effects of targeted drugs on chemotherapy drugs on cancer cells is useful for us to understand drug actions and design better drugs. The advent of atomic force microscopy (AFM) provides a powerful tool for probing the nanoscale physiological activities of single live cells. In this paper, the detailed changes in cell morphology and mechanical properties were quantified on single lymphoma cells during the actions of rituximab (a monoclonal antibody targeted drug) and two chemotherapy drugs (cisplatin and cytarabine) by AFM. AFM imaging revealed the distinct changes of cellular ultramicrostructures induced by the drugs. The changes of cellular mechanical properties after the drug stimulations were measured by AFM indenting. The statistical histograms of cellular surface roughness and mechanical properties quantitatively showed that rituximab could remarkably strengthen the killing effects of chemotherapy drugs. The study offers a new way to quantify the synergistic interactions between targeted drugs and chemotherapy drugs at the nanoscale, which will have potential impacts on predicting the efficacies of drug combinations before clinical treatments.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy

Xiao

Liu

et al. 2016

IEEE Trans. Biomed. Eng.

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“…However, in a number of investigations the majority of patients did not previously receive treatment with rituximab. Thus, the conclusions drawn by Martin et al (35), appear to suggest that the impact of rituximab in the salvage setting is limited. The authors concluded that prior exposure to rituximab is an adverse prognostic determinant for the efficacy of the same monoclonal antibody on overall and progression-free survival of relapsed or refractory patients.…”

Section: Discussionmentioning

confidence: 97%

“…As shown by the studies reported in Table I (12,16,17,25,26,28,29,33,35,(37)(38)(39), the addition of rituximab to salvage chemotherapy improves the response rate, without decreasing the mobilization and collection of PbSC. Moreover, the original reports provide evidence of the lack of significant toxicity due to the addition of rituximab to salvage chemotherapy.…”

Section: Discussionmentioning

confidence: 98%

Role of conventional salvage multiple-drug chemotherapy in relapsed and refractory aggressive non-Hodgkin lymphomas

et al. 2010

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Abstract. Autologous stem cell transplantation is the standard care for patients with relapsed or refractory aggressive nonHodgkin lymphomas. Of the patients who are sensitive to second-line chemotherapy, approximately 40-50% are likely to be cured using this approach. The optimal salvage regimen for pre-transplant debulking is controversial and these second-line chemotherapies are particularly important for patients who cannot undergo transplantation for various reasons including age, comorbidity and insufficient stem cell collection. Numerous reports regarding this topic are available. This study evaluated reports published in the last 5 years, focusing on conventional multiple-drug second-line chemotherapies (with or without rituximab), and disregarding single-agent investigational phase-II trials. Results are encouraging, particularly when considering that the more recent and less toxic combinations appear to be equivalent to or even more favourable than previous, more aggressive approaches. Previous results obtained using a combination of mitoxantrone, carboplatin, cytarabine and methylprednisolone, are further updated and included in this study. In conclusion, the most effective conventional chemotherapy currently available for patients with relapsed or refractory nonHodgkin lymphomas obtains complete remission rates of up to 50-70%; the achievement of a complete remission is the most important factor associated with a better outcome. Although the addition of rituximab is beneficial and safe, it is more effective in patients who have previously not been exposed to this monoclonal antibody. The addition of cycles of salvage chemotherapy to those strictly required for mobilization of peripheral blood stem cells ultimately improves the response rate.

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“…15 In general, a high risk of early progression is now more common because patients receive rituximab during first-line treatment. 16,17 Regarding toxicity and feasibility, high-dose TEC produced little non-hematological toxicity, other than reversible oral mucositis (grade 3, 50%; grade 4, 13%), possibly explained by the inclusion of etoposide in the high-dose protocol. Treosulfan as a single agent at high dose exerts little mucosal toxicity, 18 and we observed fewer cases of mucositis (43%, grades 3 and 4) in an earlier trial when treosulfan at the same dose was combined with either melphalan or thiotepa.…”

Section: Discussionmentioning

confidence: 99%

Risk-adapted, treosulfan-based therapy with auto- and allo-SCT for relapsed/refractory aggressive NHL: a prospective phase-II trial

Koenigsmann

Casper

Kahl

et al. 2013

Bone Marrow Transplant

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Since the outcome of relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) is highly variable, a risk-adapted treatment approach was evaluated. After two cycles of DHAP, patients received high-dose treosulfan/etoposide/carboplatinum (TEC) and autologous stem cell rescue. After TEC, low-risk patients with late relapse (41 year after first CR who achieved CR after DHAP received no further treatment. Patients with late relapse who achieved CR or PR only after TEC underwent a second cycle of TEC. High-risk patients with early relapse/refractory disease received treosulfan/fludarabine followed by allogeneic transplantation. Rituximab was added in patients with B-cell lymphoma (86%). At entry, 36% of all 57 patients had refractory disease, 32% early and 32% late relapse. During DHAP treatment, progression occurred in 32% of patients. Of 33 patients who received TEC, 5 received second TEC and 15 allogeneic transplantation. Main toxicity after TEC was oral mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In total, 42% patients achieved CR. Median OS was 21.4 months for all patients and 32.6 for those who underwent allogeneic transplantation. International prognostic index (IPI) at study entry was highly discriminative at predicting OS (Po0.0001). Risk-adapted, treosulfan-based therapy with auto-and allo-SCT is feasible. Long-term survival is possible with allogeneic transplantation. Keywords: relapsed non-Hogkin's lymphoma; treosulfan; autologous transplantation; allogeneic transplantation; risk-adapted therapy INTRODUCTION High-dose chemotherapy with auto-SCT has been the standard approach for relapsed aggressive non-Hodgkin's lymphoma (NHL) since the PARMA trial, 1 which reported a higher 5-year OS rate (53%) compared with that of conventional chemotherapy only (32%). Disease-free survival after a high-dose therapy is higher in cases of chemosensitive relapse than in cases of chemoresistant relapse, 2 and cytoreductive salvage therapy is more efficient after late relapse than after early relapse. 3 The application of allogeneic transplantation for these patients has evolved at a slower pace, 4-8 and a treatment-related mortality greater than 40% has led to the questioning of its role. 9 Treosulfan is an alkylating agent with a steep dose-response curve. High-dose treosulfan and fludarabine before allogeneic transplantation has shown efficacy with little toxicity in AML and myelodysplastic syndromes. 10,11 Treosulfan has also been investigated as a high-dose therapy before auto-SCT in ovarian cancer and other solid tumors. 12,13 A previous study demonstrated its activity in a high-dose combination regimen for relapsed Bone Marrow Transplantation

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R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study

Cited by 158 publications

References 27 publications

Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy

Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy

Role of conventional salvage multiple-drug chemotherapy in relapsed and refractory aggressive non-Hodgkin lymphomas

Risk-adapted, treosulfan-based therapy with auto- and allo-SCT for relapsed/refractory aggressive NHL: a prospective phase-II trial

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