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1.
Rituximab in combination with fludarabine and cyclophosphamide in the treatment of patients with recurrent follicular lymphoma 总被引:2,自引:0,他引:2
Sacchi S Pozzi S Marcheselli R Federico M Tucci A Merli F Orsucci L Liberati M Vallisa D Brugiatelli M;Italian Lymphoma Study Group 《Cancer》2007,110(1):121-128
BACKGROUND: The current study was conducted to asses the safety profile and clinical activity of rituximab in combination with fludarabine and cyclophosphamide in patients with recurrent follicular lymphoma (FL). METHODS: This study was a noncomparative, multicenter, phase II study. Between March 2000 and December 2002, 54 patients with recurrent FL were enrolled in the FC+R trial. Patients received fludarabine at a dose of 25 mg/m(2) and cyclophosphamide at a dose of 300 mg/m(2) daily for 3 consecutive days, every 3 weeks for 4 cycles. Rituximab was administered at a dose of 375 mg/m(2) beginning 2 weeks after the first course of fludarabine and cyclophosphamide and then on Day 1 of each cycle thereafter. The planned treatment duration was 10 weeks. RESULTS: Overall, 92% of patients completed the planned therapy in 10 to 14 weeks and 74% achieved a complete response (CR). Among patients with BCL2-positive bone marrow, 86% obtained a molecular disease remission (MR). The median survival from treatment (SFT), the duration of disease remission (DR), and time to disease progression (TTP) had not been reached after a median follow-up of 45 months. Of the baseline characteristics, >2 previous treatments, BCL2-positive bone marrow, and low Follicular Lymphoma International Prognostic Index (FLIPI) score were found to be associated with better DR and/or TTP. Hematologic toxicity was transient and reversible, with the exception of 3 patients with severe and prolonged neutropenia. Three patients presented with infections, 1 of whom died of bronchopneumonia. CONCLUSIONS: The FC+R scheme, a nonanthracycline-containing regimen lasting up to 10 weeks, was found to be relatively well-tolerated and demonstrated significant antilymphoma activity with excellent clinical CR and molecular response rates. 相似文献
2.
A phase II study to evaluate the combination of fludarabine, mitoxantrone and dexamethasone (FMD) in patients with follicular lymphoma 总被引:1,自引:1,他引:0
C. R. Crawley J. M. Foran R. K. Gupta A. Z. S. Rohatiner K. Summers J. Matthews I. N. M. Micallef J. A. Radford S. A. Johnson P. W. Johnson J. W. Sweetenham T. A. Lister 《Annals of oncology》2000,11(7):861-865
Background:Molecular response is being investigated as atherapeutic goal in follicular lymphoma (FL). High response rates in FL withthe fludarabine combination FMD have been associated with molecularremission. A phase II study of FMD in FL was therefore conducted.
Patients and methods:Fifty-four patients, ten of whom were newlydiagnosed received FMD. Forty-four percent of the previously treated patientshad chemoresistant disease. Treatment comprised: fludarabine 25mg/m2 days 1–3, mitoxantrone 10 mg/m2 day 1, anddexamethasone 20 mg days 1–5. Blood/bone marrow was collected forquantitation of t(14;18) by real-time PCR.
Results:The overall response rate was 37 of 54 (69%),complete responses being seen in 11 patients (20%), with no differencebetween newly diagnosed and the previously treated patients. However, theresponse rate in chemosensitive relapse was 84%, compared to44% in patients in whom the last prior regimen had failed. Molecularresponses were seen in 17 of 25 and PCR negativity in 8 of 25, althoughmolecular and clinical responses did not always correlate. Toxicity wasmoderate, 19 patients required admission. However, in 6 of 12 patients,subsequent G-CSF mobilised stem cell harvests failed.
Conclusions:FMD was well tolerated but with a lower than expectedresponse rate. Molecular responses were seen in the majority of respondingpatients however, molecular remission was rare. 相似文献
3.
Stefano Luminari MD Luigi Marcheselli MS Stefano Sacchi MD Samantha Pozzi MD Alessia Bari MD Fiorella Ilariucci MD Caterina Stelitano MD Francesco Angrilli MD Antonio Lazzaro MD Luca Baldini MD 《Cancer》2009,115(9):1906-1913
BACKGROUND:
Recent experience has suggested that there has been a stepwise improvement in the survival outcomes of patients who have follicular lymphoma with the introduction of new treatment options. In the current study, the authors report the results of 2 subsequent phase 2 trials of 238 previously untreated patients.METHODS:
In a trial of bleomycin, epidoxorubicin, cyclophosphamide, vincristine, and prednisone (BACOP) plus fludarabine, mitoxantrone, and dexamethasone (FND), 144 patients received 2 BACOP treatments followed by 4 FND treatments. In a trial of BACOP plus fludarabine and rituximab (FR), 94 patients received 3 BACOP treatments followed by 4 FR treatments.RESULTS:
The complete remission (CR) rate for BACOP/FND was 62%. After a median follow‐up of 60 months, the failure‐free survival (FFS) and overall survival (OS) rates at 4 years were 53% and 77%, respectively. The CR rate for BACOP/FR was 79%. After a median follow‐up of 36 months, the FFS and OS rates at 4 years were 56% and 97%, respectively, which were significant compared with the CR and OS rates achieved with BACOP/FND. Twenty‐five of 42 bcl‐2‐positive patients attained a molecularly negative CR and had improved FFS. No significant differences were observed between the 2 trials in the percentage of infections or neutropenia.CONCLUSIONS:
The CR and OS rates achieved with BACOP/FR were better, and overall toxicity did not increase. Furthermore, patients who received rituximab had a better FFS compared with patients who received chemotherapy alone. Finally, although conclusions between nonrandomized groups may depend on differences in observed and unobserved prognostic features, the current results suggested that the addition of rituximab to anthracycline‐fludarabine–containing regimens have a favorable effect on the prognosis of patients with advanced follicular lymphoma. Cancer 2009. © 2009 American Cancer Society. 相似文献4.
Brad S. Kahl MD Nancy L. Bartlett MD John P. Leonard MD Ling Chen PhD Kristen Ganjoo MD Michael E. Williams MD Myron S. Czuczman MD K. Sue Robinson MD Robin Joyce MD Richard H. van der Jagt MD Bruce D. Cheson MD 《Cancer》2010,116(1):106-114
BACKGROUND:
Bendamustine hydrochloride is a novel alkylating agent. In this multicenter study, the authors evaluated the efficacy and toxicity of single‐agent bendamustine in patients with rituximab‐refractory, indolent B‐cell lymphoma.METHODS:
Eligible patients (N = 100, ages 31‐84 years) received bendamustine at a dose of 120 mg/m2 by intravenous infusion on Days 1 and 2 every 21 days for 6 to 8 cycles. Histologies included follicular (62%), small lymphocytic (21%), and marginal zone (16%) lymphomas. Patients had received a median of 2 previous regimens (range, 0‐6 previous regimens), and 36%were refractory to their most recent chemotherapy regimen. Primary endpoints included overall response rate (ORR) and duration of response (DOR). Secondary endpoints were safety and progression‐free survival (PFS).RESULTS:
An ORR of 75% (a 14% complete response rate, a 3% unconfirmed complete response rate, and a 58% partial response rate) was observed. The median DOR was 9.2 months, and median PFS was 9.3 months. Six deaths were considered to be possibly treatment related. Grade 3 or 4 (determined using National Cancer Institute Common Toxicity Criteria [version 3.0.19]. reversible hematologic toxicities included neutropenia (61%), thrombocytopenia (25%), and anemia (10%). The most frequent nonhematologic adverse events (any grade) included nausea (77%), infection (69%), fatigue (64%), diarrhea (42%), vomiting (40%), pyrexia (36%), constipation (31%), and anorexia (24%).CONCLUSIONS:
Single‐agent bendamustine produced a high rate of objective responses with acceptable toxicity in patients with recurrent, rituximab‐refractory indolent B‐cell lymphoma. Cancer 2010. © 2010 American Cancer Society. 相似文献5.
6.
Fludarabine–Mitoxantrone–Rituximab regimen in untreated indolent non‐follicular non‐Hodgkin's lymphoma: experience on 143 patients
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Pier Luigi Zinzani Cinzia Pellegrini Alessandro Broccoli Letizia Gandolfi Vittorio Stefoni Beatrice Casadei Roberto Maglie Lisa Argnani Stefano Pileri 《Hematological oncology》2015,33(3):141-146
Indolent non‐follicular lymphomas (inFLs) are generally regarded as incurable, apart from extranodal mucosa‐associated lymphatic tissue lymphomas, which can be partially cured by surgery, local radiotherapy, or antibiotic treatment. The aim of the present study was to test the degree of effectiveness and the safety of the regimen containing fludarabine, mitoxantrone, and rituximab (FMR) in inFL patients considering all the different entities belonging to this group. An observational retrospective study was conducted on 143 inFL patients providing that their first chemoimmunotherapy performed was FMR regimen and diagnosis from September 2000 to March 2011. There were 32 small lymphocytic lymphomas and 111 marginal zone lymphomas. At the end of treatment, overall response rate was 96.5% with 88% of complete responses (CR) and 8.5% of partial responses. With a median follow‐up of 48 months, 10 out of 125 (8%) CR patients had disease relapse, yielding an estimated 9‐year disease‐free survival (DFS) of 74.9% and an estimated 10‐year overall survival of 92.8%. The estimated 9‐year progression free survival was 70.5%. The 10 relapsed patients showed lymphoma recurrence within 52 months: after this time, the DFS curve presented a plateau configuration. Only two (1.4%) patients developed a secondary hematological neoplasia. This study showed promising findings for the use of a fludarabine‐based regimen in combination with rituximab in the front‐line treatment of symptomatic inFL with a noteworthy high percentage of CR associated to an interesting long‐term DFS and favorable acute and long‐term safety profile. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
7.
Andrew M. Evens DO MSc Ann Vanderplas MS Ann S. LaCasce MD Allison L. Crosby MS Auayporn P. Nademanee MD Mark S. Kaminski MD Gregory A. Abel MD MPH Michael Millenson MD Myron S. Czuczman MD Maria A. Rodriguez MD Joyce Niland PhD Andrew D. Zelenetz MD PhD Leo I. Gordon MD Jonathan W. Friedberg MD MSc 《Cancer》2013,119(20):3662-3671
8.
BCL2 mutation spectrum in B‐cell non‐Hodgkin lymphomas and patterns associated with evolution of follicular lymphoma
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Regula Burkhard Govind Bhagat Sergio B. Cogliatti Davide Rossi Gianluca Gaidano Laura Pasqualucci Urban Novak 《Hematological oncology》2015,33(1):23-30
BCL2 is a target of somatic hypermutation in t(14;18) positive and also in a small fraction of t(14;18) negative diffuse large B‐cell lymphoma (DLBCL), suggesting an aberrant role of somatic hypermutation (ASHM). To elucidate the prevalence of BCL2 mutations in lymphomas other than DLBCL, we Sanger‐sequenced the hypermutable region of the BCL2 gene in a panel of 69 mature B‐cell lymphomas, including Richter's syndrome DLBCL, marginal‐zone lymphomas, post‐transplant lymphoproliferative disorders, HIV‐associated and common‐variable immunodeficiency‐associated DLBCL, all known to harbour ASHM‐dependent mutations in other genes, as well as 16 t(14,18) negative and 21 t(14;18) positive follicular lymphomas (FLs). We also investigated the pattern of BCL2 mutations in longitudinal samples from 10 FL patients relapsing to FL or transforming to DLBCL (tFL). By direct sequencing, we found clonally represented BCL2 mutations in 2/16 (13%) of t(14;18) negative FLs, 2/16 (13%) HIV‐DLBCLs, 1/9 (11%) of Richter's syndrome DLBCL, 1/17 (6%) of post‐transplant lymphoproliferative disorders and 1/2 (50%) common‐variable immunodeficiency‐associated DLBCL. The proportion of mutated cases was significantly lower than in FLs carrying the t(14;18) translocation (15/21, 71%). However, the absence of t(14;18) by FISH or PCR and the molecular features of the mutations strongly suggest that BCL2 represents an additional target of ASHM in these entities. Analysis of the BCL2 mutation pattern in clonally related FL/FL and FL/tFL samples revealed two distinct scenarios of genomic evolution: (i) direct evolution from the antecedent FL clone, with few novel clonal mutations acquired by the tFL major clone, and (ii) evolution from a common mutated long‐lived progenitor cell, which subsequently acquired distinct mutations in the FL and in the relapsed or transformed counterpart. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
9.
Low-grade lymphoma is the commonest form of lymphoma in the USA and Europe with a long natural history with multiple responses and relapses. The tendency has been to use simple oral medication until patients have more advanced aggressive disease but new agents such as the purine analogues, mitoxantrone and monoclonal antibodies has led to re-evaluation of this approach. As purine analogues inhibit DNA repair in lymphoid cells, a new combination of fludarabine, mitoxantrone, and dexamethasone (FND) has been developed that is well tolerated and very effective. In a phase II study, in 51 patients 47% complete remissions and 47% partial remissions were noted. FND is now being used in a randomization comparative trial with alternating triple therapy as frontline treatment for low-grade lymphoma at the M. D. Anderson Cancer Center with monitoring by polymerase chain reaction for rearrangement of the bcl-2 gene in blood and bone marrow cells. The high activity and low morbidity of FND makes it as attractive as initial therapy for patients. 相似文献
10.
Katsuhiro Miura Hideki Tsujimura Yasufumi Masaki Masaki Iino Jun Takizawa Yoshinobu Maeda Kazuhiko Yamamoto Shinobu Tamura Akiyo Yoshida Hideo Yagi Isao Yoshida Koichi Kitazume Taro Masunari Ilseung Choi Yasutaka Kakinoki Ritsuro Suzuki Tadashi Yoshino Shigeo Nakamura Yoshihiro Hatta Takashi Yoshida Masatoshi Kanno 《Hematological oncology》2021,39(1):51-59
Bendamustine and rituximab (BR) are widely used in patients with follicular lymphoma (FL) previously treated with conventional immunochemotherapy, but the role of consolidation radioimmunotherapy in these patients is unknown. This study evaluated the efficacy and safety of consolidation with 90Yttrium‐ibritumomab tiuxetan (90Y‐IT) after re‐induction therapy with BR in patients with previously treated FL. This study included adult patients with relapsed FL who had undergone one or two prior therapies. Re‐induction therapy with BR was administered every 4 weeks up to 4–6 cycles. If patients achieved at least partial response, 90Y‐IT was administered as consolidation therapy. The primary endpoint was 2‐year progression‐free survival (PFS) after consolidation. A total of 24 FL patients (median age 60 years) who had undergone one (n = 17) or two (n = 7) prior treatments received BR. After BR therapy, 22 patients proceeded to consolidation with 90Y‐IT, resulting in an overall 88% response rate to the protocol treatment. Within a median observation period of 46.8 months, the estimated 2‐year PFS rate after the consolidation among the 22 patients receiving 90Y‐IT was 59% (95% confidence interval [CI], 38%–77%). Patients whose remission after previous treatment had lasted ≥2 years had a significantly higher 2‐year PFS rate than patients whose remission after previous treatment had been <2 years (68% vs. 33%, Wilcoxon p = 0.0211). Major adverse events during the protocol treatment and within 2 years after the consolidation were hematological toxicities, but they were generally acceptable. Consequently, the estimated 2‐year overall survival after the consolidation was 95% (95% CI, 74%–99%). In conclusion, in a subset of patients with previously treated FL, 90Y‐IT consolidation after BR re‐induction conferred a durable remission, indicating that consolidation therapy using 90Y‐IT may be a novel therapeutic option for patients with relapsed FL (UMIN000008793). 相似文献
11.
Phase 2 study of gemcitabine in combination with rituximab in patients with recurrent or refractory Hodgkin lymphoma 总被引:4,自引:0,他引:4
Oki Y Pro B Fayad LE Romaguera J Samaniego F Hagemeister F Neelapu S McLaughlin P Goy A Younes A 《Cancer》2008,112(4):831-836
BACKGROUND: The management of recurrent or refractory Hodgkin lymphoma (HL) remains challenging. The objective of this phase 2 trial was to investigate the activity of gemcitabine in combination with rituximab in patients with recurring or refractory HL. METHODS: Patients were considered eligible if they had recurring or refractory HL, had received >or=2 prior chemotherapy regimens, had an Eastern Cooperative Oncology Group (ECOG) performance status 相似文献
12.
Prognostic significance of metabolic tumor burden by positron emission tomography/computed tomography in patients with relapsed/refractory diffuse large B‐cell lymphoma
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Ukihide Tateishi Mitsuaki Tatsumi Takashi Terauchi Kiyoshi Ando Nozomi Niitsu Won Seog Kim Cheolwon Suh Michinori Ogura Kensei Tobinai 《Cancer science》2015,106(2):186-193
The aim of the present study was to investigate the feasibility of measuring metabolic tumor burden using [F‐18] fluorodeoxyglucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) in patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) treated with bendamustine–rituximab. Because the standardized uptake value is a critical parameter of tumor characterization, we carried out a phantom study of 18F‐FDG PET/CT to ensure quality control for 28 machines in the 24 institutions (Japan, 17 institutions; Korea, 7 institutions) participating in our clinical study. Fifty‐five patients with relapsed or refractory DLBCL were enrolled. The 18F‐FDG PET/CT was acquired before treatment, after two cycles, and after the last treatment cycle. Treatment response was assessed after two cycles and after the last cycle using the Lugano classification. Using this classification, remission was complete in 15 patients (27%) and incomplete in 40 patients (73%) after two cycles of therapy, and remission was complete in 32 patients (58%) and incomplete in 23 patients (42%) after the last treatment cycle. The percentage change in all PET/CT parameters except for the area under the curve of the cumulative standardized uptake value–volume histogram was significantly greater in complete response patients than in non‐complete response patients after two cycles and the last cycle. The Cox proportional hazard model and best subset selection method revealed that the percentage change of the sum of total lesion glycolysis after the last cycle (relative risk, 5.24; P = 0.003) was an independent predictor of progression‐free survival. The percent change of sum of total lesion glycolysis, calculated from PET/CT, can be used to quantify the response to treatment and can predict progression‐free survival after the last treatment cycle in patients with relapsed or refractory DLBCL treated with bendamustine–rituximab. 相似文献
13.
14.
Combined lenalidomide,low‐dose dexamethasone,and rituximab achieves durable responses in rituximab‐resistant indolent and mantle cell lymphomas
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Amanda Gordon BSN CRNP Nicole A. Aqui MD Sunita D. Nasta MD Jakub Svoboda MD Anthony R. Mato MD MSCE Stephen J. Schuster MD 《Cancer》2014,120(2):222-228
15.
Robert A. Baiocchi MD Lapo Alinari MD Mark E. Lustberg MD Thomas S. Lin MD Pierluigi Porcu MD Xiaobai Li Jeffrey S. Johnston John C. Byrd MD Kristie A. Blum MD 《Cancer》2011,117(11):2442-2451
BACKGROUND:
In vitro studies in mantle cell lymphoma (MCL) cell lines and patient‐derived cells have demonstrated synergistic apoptosis with combined rituximab and bortezomib (R‐bortezomib) compared with single‐agent bortezomib. Therefore, the authors of this report evaluated R‐bortezomib in a preclinical model and in a phase 2 clinical trial.METHODS:
A Hu‐MCL‐severe combined immunodeficiency (SCID) model engrafted with the Jeko cell line was treated with R‐bortezomib, bortezomib, or rituximab. Twenty‐five patients with relapsed follicular lymphoma (n = 11) and MCL (n = 14) received 375 mg/m2 rituximab on Days 1 and 8 and 1.3 to 1.5 mg/m2 bortezomib on Days 1, 4, 8, and 11 every 21 days for a median of 3 cycles (range, 1‐5 cycles).RESULTS:
R‐bortezomib resulted in a statistically significant improvement in overall survival in Hu‐MCL‐SCID mice. In the clinical trial, the overall response rate was 40% in all 25 patients, 55% in patients with follicular lymphoma, and 29% in patients with MCL. The estimated 2‐year progression‐free survival (PFS) rate was 24% (95% confidence interval [CI], 10%‐53%) in all patients and 60% (95% CI, 20%‐85%) in responding patients. Thirteen patients (52%) developed grade 3 neurotoxicity, which consisted of constipation/ileus, sensory or motor neuropathy, or orthostatic hypotension. Patients who were heterozygous for the CD32a (Fcγ receptor IIa) 131 histidine (H) to arginine (R) polymorphism had a significantly decreased PFS (P = .009) after R‐bortezomib compared with HH and RR homozygotes.CONCLUSIONS:
R‐bortezomib had significant activity in patients with relapsed or refractory follicular lymphoma and MCL, although an unexpectedly high incidence of grade 3 neurologic toxicity was a potential limiting factor with this combination. Cancer 2011. © 2010 American Cancer Society. 相似文献16.
Pier Luigi Zinzani Cinzia Pellegrini Letizia Gandolfi Beatrice Casadei Enrico Derenzini Alessandro Broccoli Federica Quirini Lisa Argnani Stefano Pileri Monica Celli Stefano Fanti Venerino Poletti Vittorio Stefoni Michele Baccarani 《Hematological oncology》2013,31(4):183-188
Bronchial‐associated lymphoid tissue (BALT) lymphoma is an extranodal primary pulmonary lymphoma. The optimal therapy for this rare disease is still debated, and few heterogeneous data are available in literature. The aim of our study was to critically review data of patients with BALT lymphoma treated in first‐line therapy with fludarabine and mitoxantrone‐containing regimens (with or without rituximab) to investigate the effectiveness and the safety of this approach and patients' survival. An observational retrospective study was performed on homogenous clinical data from 17 patients with biopsy‐proven diagnosis of BALT. All the patients were treated with fludarabine and mitoxantrone‐containing regimen therapy. Radiological findings were also reviewed to assess the role of 18fluoro‐deoxyglucose positron emission tomography in the initial assessment and in the monitoring of this extranodal lymphoma. A high percentage of response was observed: 82.3% of patients achieved a complete response, 11.8% a partial response. Furthermore, a very remarkable progression‐free survival (71%) and overall survival (100%) were estimated at 14 years. No relevant toxicities were registered. Our results support the use of fludarabine and mitoxantrone‐containing regimens as first‐line therapy in the treatment of BALT lymphoma even if further data are necessary to consolidate our findings. Positron emission tomography scanning may provide additional valuable information in the assessment of BALT lymphoma. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
17.
Antonio Salar MD Eva Domingo‐Domenech MD Cristina Estany MD Miguel A. Canales MD Fernando Gallardo MD Octavio Servitje MD Guadalupe Fraile MD Carlos Montalbán MD 《Cancer》2009,115(22):5210-5217
BACKGROUND:
Currently, there are no consensus guidelines regarding the best therapeutic option for patients with extranodal marginal zone lymphomas of the mucosa‐associated lymphoid tissue (MALT) type.METHODS:
Patients with systemically untreated or de novo extranodal MALT lymphoma received rituximab 375 mg/m2 intravenously on Day 1 and fludarabine 25 mg/m2 intravenously on Days 1 through 5 (Days 1‐3 in patients aged >70 years) every 4 weeks, for 4 to 6 cycles. After the first cycle, oral fludarabine could be given orally at 40 mg/m2 on the same schedule. After 3 cycles, a workup was done. Patients who achieved a complete remission (CR) received an additional cycle, and patients who achieved a partial remission (PR) received a total of 6 cycles.RESULTS:
Twenty‐two patients were studied, including 12 patients with gastric lymphoma and 10 patients with extragastric MALT lymphoma. Six patients (27%) had stage IV disease. In total, 101 cycles were administered (median, 4 cycles per patients). After the third cycle, 13 patients (62%) achieved a CR, and 8 patients (38%) achieved a PR. Primary extragastric disease was an adverse factor to achieve CR after 3 cycles of chemotherapy (hazard ratio, 23.3; 95% confidence interval, 2.0‐273.3). At the end of treatment, the overall response rate was 100%, and 90% of patients achieved a CR. The progression‐free survival rate at 2 years in patients with gastric and extragastric MALT lymphoma was 100% and 89%, respectively. Toxicities were mild and mainly were hematologic.CONCLUSIONS:
Combination therapy with rituximab and fludarabine is a very active treatment with favorable safety profile as first‐line systemic treatment for patients with extranodal MALT lymphoma. Cancer 2009. © 2009 American Cancer Society. 相似文献18.
19.
Katsuyoshi Takata Ken Saito Satoshi Maruyama Tomoko Miyata‐Takata Hidekazu Iioka Shujiro Okuda Yiwei Ling Kennosuke Karube Yukari Miki Yoshinobu Maeda Tadashi Yoshino Christian Steidl Eisaku Kondo 《Cancer science》2019,110(1):443-457
Despite receiving rituximab‐combined chemotherapy, follicular lymphoma (FL) patients often suffer tumor recurrence and understand that the cause of relapse in FL would thus significantly ameliorate the tumor therapeutics. In the present study, we show that TRA‐1‐60‐expressing cells are a unique population in FL, converge to the conventional stem cell marker Oct3/4 and ALDH1‐positive population, and resist current B‐lymphoma agents. TRA‐1‐60 expression was observed in scattered lymphoma cells in FL tissues only as well as in resting B‐lymphocytes inside germinal centers. Retrospective comparison between recurrent and cognate primary tissues showed that the number of TRA‐1‐60‐positive cells from rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R‐CHOP)‐treated FL had increased relative to primary tissue, a finding corroborated by assays on different rituximab‐treated FL cell lines, FL‐18 and DOHH2, wherein TRA‐positive cell numbers increased over 10‐fold compared to the untreated sample. Concordantly, scanty TRA‐1‐60‐positive FL‐18 cells implanted s.c. into mice evinced potent tumor‐initiating capacity in vivo, where tumors were 12‐fold larger in volume (P = 0.0021 < 0.005) and 13‐fold heavier in weight (P = 0.0015 < 0.005) compared to those xenografted from TRA‐negative cells. To explain these results, gene expression profiling and qPCR analysis indicated that TRA‐1‐60‐positive cells defined a distinct population from that of TRA‐negative cells, with upregulation of multiple drug transporters and therapeutic resistance genes. Hence, TRA‐1‐60‐expressing cells in FL are considered to be vigorously intractable against conventional therapeutic agents, which may explain its refractory recurrence. 相似文献
20.
The addition of rituximab to cyclophosphamide, vincristine and prednisolone (CVP) for advanced follicular lymphoma increases median time to progression by 17 months. A US societal cost-effectiveness of R-CVP versus CVP is estimated for a representative 50-year-old patient. Progression-free survival (PFS) and overall survival are based on a randomized Phase III trial. Costs are estimated using Medicare reimbursement rates and published drug price data, and include drug and administration costs, adverse events, treatment of relapses, and end-of-life care. Utility estimates are derived from the literature and a 3% discount rate is employed. Mean overall survival is projected to be 1.51 years longer for patients assigned to R-CVP versus CVP. The cost per quality-adjusted year of life gained is $28,565. The utility associated with stable or progressive disease and the unit drug cost of rituximab most influence the findings. The cost-effectiveness ratio of R-CVP compared with CVP is projected to be cost-effective in the United States under a range of sensitivity analyses. 相似文献