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Adam M. Greenbaum,Damian J. Green,Leona A. Holmberg,Ted Gooley,Brian G. Till,Lihua E. Budde,Heather Rasmussen,Oliver W. Press,Ajay K. Gopal 대한혈액학회 2018 Blood Research Vol.53 No.3
Background Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may ad-versely affect stem cell collection. Here we describe the lymphoma subset of a pro-spective, non-randomized phase II study of bendamustine, etoposide, and dex-amethasone (BED) as a mobilization agent for lymphoid malignancies. Methods This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m2 IV d 1, 2), etoposide (200 mg/m2 IV d 1‒3), and dexamethasone (40 mg PO d 1‒4) followed by filgrastim (10 mcg/kg/d sc. through collection). Results We successfully collected stem cells from all patients, with a median of 7.9×106/kg of body weight (range, 4.4 to 17.3×106/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). Conclusion For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.
Adam M. Greenbaum,Jonathan R. Fromm,Ajay K. Gopal,A. McGarry Houghton 대한혈액학회 2022 Blood Research Vol.57 No.2
Background B-cell non-Hodgkin lymphomas (NHL) are hematologic malignancies that arise in the lymph node. Despite this, the malignant cells are not cleared by the immune cells present. The failure of anti-tumor immunity may be due to immune checkpoints such as the PD-1/PDL-1 axis, which can cause T-cell exhaustion. Unfortunately, unlike Hodgkin lymphoma, checkpoint blockade in NHL has shown limited efficacy. Methods We performed an extensive functional analysis of malignant and non-malignant lymph nodes using high dimensional flow cytometry. We compared follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and lymph nodes harboring reactive hyperplasia (RH). Results We identified an expansion of CD8+PD1+ T-cells in the lymphomas relative to RH. Moreover, we demonstrate that these cells represent a mixture of activated and exhausted T-cells in FL. In contrast, these cells are nearly universally activated and functional in DLBCL. This is despite expression of counter-regulatory molecules such as PD-1, TIM-3, and CTLA-4, and the presence of regulatory T-cells. Conclusion These data may explain the failure of single-agent immune checkpoint inhibitors in the treatment of DLBCL. Accordingly, functional differences of CD8+ T-cells between FL and DLBCL may inform future therapeutic targeting strategies.
Adam M. Greenbaum,Damian J. Green,Leona A. Holmberg,Ted Gooley,Brian G. Till,Lihua E. Budde,Heather Rasmussen,Oliver W. Press,Ajay K. Gopal 대한혈액학회 2018 Blood Research Vol.53 No.3
Background Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may ad-versely affect stem cell collection. Here we describe the lymphoma subset of a pro-spective, non-randomized phase II study of bendamustine, etoposide, and dex-amethasone (BED) as a mobilization agent for lymphoid malignancies. Methods This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m2 IV d 1, 2), etoposide (200 mg/m2 IV d 1‒3), and dexamethasone (40 mg PO d 1‒4) followed by filgrastim (10 mcg/kg/d sc. through collection). Results We successfully collected stem cells from all patients, with a median of 7.9×106/kg of body weight (range, 4.4 to 17.3×106/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). Conclusion For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.