Elderly Very Poor Performance Status Patients with Aggressive B Cell Lymphomas Can Gain Long Term Remissions with Intensive Chemotherapy with Encouraging Response Rates and Overall Survival (OS).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2794-2794
Author(s):  
Stella J Bowcock ◽  
Vincenzo Fontana ◽  
Yvonne Noble ◽  
Susan Ward ◽  
Keith Winyard ◽  
...  

Abstract Abstract 2794 Introduction Patients (pts) of older age, poor performance status (PS) and advanced stage with aggressive B cell lymphomas are regarded as poor prognosis and may receive no treatment, or palliative rather than curative chemotherapy. Studies suggest these pts may be undertreated and poor outcome may be partly related to undertreatment. Our unit has had a policy of offering treatment with curative intent to all pts presenting with aggressive B cell lymphomas, whatever their age or PS providing comorbidities allow. We reviewed the outcome of this policy. Methods All pts age≥70 years with diffuse large B cell lymphoma (DLBCL) or Burkitts lymphoma (BL) between 2000–2010 incl. were found from histology, chemotherapy and registry records. Poor PS pts were selected by including all who were inpatients during their 1st chemotherapy cycle, or if untreated, at diagnosis. If ECOG PS had not been prospectively recorded, ≥2 staff (from the 6 who were present throughout the 10 years) independently attributed status from memory and hospital notes. Only confirmed bedbound pts were designated PS4. Percentage chemotherapy doses delivered were calculated against the projected full dose and categorised into ≥85% Full, 60–85% RD, 30–60% HD. Pts receiving CHOP±R or CODOX-M/IVAC were called intensive (Int) and pts receiving low dose regimens called non-intensive (NI). Results 61 pts were found and 37 were inpatients. Of the 37 inpatients, 30 received chemotherapy, 29 for DLBCL and 1 for BL. Of the 30 treated pts (table 1) where parameters were assessable, LDH raised 92%, R-IPI ≥3 97%, PS 3/4 in 93%, stage3/4 86%, albumin <35g/l 70%. Of the 30 patients treated with chemotherapy, 18 achieved a CR with a median OS of 39 months(m) (range 8–123). There were 23 Int pts (9 were PS4, 7 of these being moribund), and 16 achieved CR median OS 48 m (range 12–99), 6 of them being PS4 and 4 were moribund. All pts achieving CR remained so except 1 late relapse (96m). Comorbidities were supported but did not influence treatment decisions except poor ejection fraction or dementia. (7 patients received no chemotherapy; declined ×3, cancer ×1, dementia ×1, not referred ×2) Discussion Our data show that very poor PS elderly pts can achieve CR (70%) with good OS with current intensive chemotherapy (CHOP±R, CODOX-M/IVAC±R). Further discussion refers to these pts (Int). CRs not only occurred in the PS2/3 pts, but also in 6/9 PS4 pts. The survivors could not be predicted and included 4 moribund pts. Toxicities were acceptable. Three of 4 moribund pts who survived received HD chemotherapy which was staggered due to emergency presentation. The 2nd cycle was given as soon as possible if improvement occurred (all responders did) with escalation of chemotherapy doses. This aggressive chemotherapeutic approach may have contributed to the good response rate. Our data show that putative toxicity is not a barrier to treatment with judicious dose reduction in the 1st cycle. Retrospective PS attribution was a weakness of the study. But objective parameters eg LDH, IPI, albumin and chemotherapy dose delivered concurred with the scores supporting their validity. PS4 criteria were objective. These data are important because they represent pts mostly excluded from trials. Recent data suggest that comorbidities may not influence survival. Our data support this. We suggest that elderly very poor PS pts can tolerate curative chemotherapy with encouraging remission rates and OS. Previous poor results may be due partly to undertreatment and most pts should be offered proper curative chemotherapy. A positive medical team attitude may be important. Disclosures: No relevant conflicts of interest to declare.

2021 ◽  
Vol 11 (9) ◽  
pp. 844
Author(s):  
Yu-Fen Tsai ◽  
Yi-Chang Liu ◽  
Ching-I Yang ◽  
Tzer-Ming Chuang ◽  
Ya-Lun Ke ◽  
...  

Background: Hepatitis C virus (HCV) in diffuse large B-cell lymphoma (DLBCL) is associated with a higher prevalence and distinctive clinical characteristics and outcomes. Methods: A retrospective analysis of adult DLBCL patients from 2011 to 2015 was studied. Results: A total of 206 adult DLBCL were enrolled with 22 (10.7%) HCV-positive patients. Compared to HCV-negative patients, the HCV-positive group had a poor performance status (p = 0.011), lower platelet count (p = 0.029), and higher spleen and liver involvement incidences (liver involvement, p = 0.027, spleen involvement, p = 0.026), and they received fewer cycles of chemotherapy significantly due to morbidity and mortality (p = 0.048). Overall survival was shorter in HCV-positive DLBCL (25.3 months in HCV-positive vs. not reached (NR), p = 0.049). With multivariate analysis, poor performance status (p < 0.001), advanced stage (p < 0.001), less chemotherapy cycles (p < 0.001), and the presence of liver toxicity (p = 0.001) contributed to poor OS in DLBCL. Among HCV-positive DLBCL, the severity of liver fibrosis was the main risk factor related to death. Conclusion: Inferior survival of HCV-positive DLBCL was observed and associated with poor performance status, higher numbers of complications, and intolerance of treatment, leading to fewer therapy. Therefore, anti-HCV therapy, such as direct-acting antiviral agents, might benefit these patients in the future.


2007 ◽  
Vol 25 (21) ◽  
pp. 3168-3173 ◽  
Author(s):  
Maurilio Ponzoni ◽  
Andrés J.M. Ferreri ◽  
Elías Campo ◽  
Fabio Facchetti ◽  
Luca Mazzucchelli ◽  
...  

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of diffuse LBCL characterized by preferential intravascular growth of malignant lymphocytes, aggressive behavior, and an often fatal course. IVLBCL usually affects elderly patients with poor performance status, elevated lactic dehydrogenase serum levels, anemia, and B symptoms. It displays some differences in clinical presentation among diverse geographical areas, mostly between patients diagnosed in Western countries and Japan. In addition, data from the literature suggest that pathologic diagnostic criteria as well as clinical features of this disease may be broader than described in current classification scheme(s). Under the sponsorship of the International Extranodal Lymphoma Study Group, clinicians and pathologists with interest in IVLBCL, coming from Western and Eastern countries, joined to reach a consensus on defining features as well as to focus on the most urgent unresolved issues in IVLBCL. To this end, a representative group of IVLBCL patients coming from both the aforementioned geographical areas were collectively analyzed. Additional features of IVLBCL were proposed both under clinical and pathologic stand points. At the meeting, it emerged that IVLBCL may have additional histopathologic/cytologic definition criteria with respect to those currently recommended, some clinical features are not randomly distributed worldwide, recent therapeutic approaches, such as anti-CD20–containing regimens, may improve outcome, and kidney, spleen, and liver involvement may show peculiar histopathologic features. Finally, a provisional practical diagnostic approach to hemophagocytosis-associated patients and a proposal for the most useful criteria in the settings of differential diagnosis are included.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4900-4900
Author(s):  
Julia Horn ◽  
Martina Kleber ◽  
Ulrike Kohlweyer ◽  
Stefanie Hieke ◽  
Regina Herzog ◽  
...  

Abstract Abstract 4900 Introduction: Clinical studies have shown that Rituximab plus Bendamustin (R-B) in indolent lymphoma results in favourable responses, progression free survival (PFS) and lower toxicity as compared to R-CHOP. The aim of this analysis was to characterize response and tolerability of R-B in patients with LBCL, who were not qualifying for R-CHOP due to age, comorbidity and/or prior pretreatment (including anthracyclines). Methods: We retrospectively identified consecutive patients with LBCL receiving at least two cycles of R-B in our department between 2003 and 2010 using our electronic tumor documentation system. Patient characteristics, response to R-B, and toxicity were assessed. Results: We identified 9 caucasian patients (5 females, 4 males) with LBCL; their median age was 71 years (range; 51–82). Two presented with stage I/II, seven with stage III/IV disease at initial diagnosis and before R-B. Six patients had a low or intermediate IPI and three were high risk. Four patients received R-B as first-line therapy, and five were treated for relapsed or refractory disease. Main determinants for the R-B-selection were contraindications for anthracyclines in five patients and advanced age and/or poor performance status in four patients. A median of four R-B-cycles were applied (range; 2–6). Response with achievement of CR and PR was observed in 6/9 (CR: 2, PR: 4), two achieved SD. Only one pt showed PD after four R-B cycles. The response of R-B in first-line vs. relapsed appeared similar. Of note, one female patient with secondary LCBL, after initial Hodgkin's lymphoma and C-MOPP chemotherapy (CTx) and mediastinal irradiation - with excellent response to R-B- failed to successfully mobilize PBSC thereafter. However, she was effectively mobilized with R-Ara-C-thiotepa (peripheral blood CD34+ cells were 5.82 vs. 54/μl, obtaining no vs. 6.72 × 106 CD34+ cells/kg KG via leukapheresis, respectively). Clinical tolerance of R-B in all patients was excellent in a total of 31 R-B-cycles, only two major CTC-events occurred: one infection (CTC grade III) and one thromboembolism (grade IV). Median PFS and overall Survival (OS) were 16 (7- not reached) and 20 (11-21) months. Conclusions: If standard R-CHOP cannot be given due to age, comorbidity or CTx-contraindications (e.g. anthracyclines), R-B may represent an effective treatment in LBCL. Larger cohorts and prospective clinical trials are needed to confirm these promising results. Currently, patients with grade III/IV follicular lymphoma are additionally evaluated for response and tolerability under R-B, also being presented at the meeting. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Marta Davidson ◽  
Alexandra Rice ◽  
Douglas A. Stewart ◽  
Carolyn Owen

Background: Clinical trials are the gold standard by which therapies in oncology are evaluated and ultimately form the bases for approval of novel therapies. Stringent eligibility criteria limit the participation of many "real-world" patients and thus undermine the generalizability of trial results. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of Non-Hodgkin lymphoma (NHL) and is curable in the majority of patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The addition of rituximab to CHOP is the only clear advancement in DLBCL therapy in the last 20 years. Though a large minority of patients are not cured by R-CHOP, several subsequent novel therapies have failed to demonstrate benefit in Phase 3 clinical trials. We hypothesized that real world patient populations differ from clinical trial populations with trial eligibility excluding the poor-outcome patients who might benefit most from novel therapy. Methods: We performed a retrospective chart review of all patients 18 years of age or older who were registered within the Alberta Cancer Registry with a new diagnosis of pathology-confirmed DLBCL, between January 1, 2010 and December 31, 2011. Clinical characteristics were reviewed to assess patient eligibility to participate in 3 landmark clinical trials for DLBCL on the basis of inclusion and exclusion criteria defined by each study. The trials included Pfreundschuh, M. et al. (2006) and Coiffier, B. et al. (2002), which were assessed together as representing the landmark studies for rituximab added to CHOP, and the GOYA trial (2017) which evaluated obinutuzumab-CHOP vs R-CHOP. Categorical variables are presented as frequencies and percentages. Univariate probabilities of overall-survival were calculated by Kaplan-Meier method. Results: We identified 480 patients with a diagnosis of DLBCL within the Alberta Cancer Registry. A total of 390 patients were eligible for our study with 20 patients excluded for CNS lymphoma, 29 for unclassifiable B-cell lymphoma, 2 patients who died at the time of diagnosis, and 25 patients with previously treated indolent lymphoma. In addition, 14 patients were excluded for insufficient clinical data. Table 1 demonstrates the clinical characteristics of the population. Out of 390 patients, only 130 (33%) patients met inclusion for the rituximab studies and 134 (34%) for the GOYA study. Table 2 demonstrates the most common criteria leading to trial exclusion, including poor performance status, limited stage disease, inappropriate IPI, transformed lymphoma, history of second primary malignancy, and viral infections. Trial ineligible patients had significantly inferior overall survival compared to trial eligible patients (Figure1). Conclusions: The majority of real-world DLBCL patients are excluded from clinical trials and have inferior outcomes compared to trial eligible patients. The selection of patients with more favourable outcomes for clinical trials may contribute to failure to demonstrate a benefit of novel therapies. Broadening inclusion criteria to include patients with transformed disease and poor performance status could aid in improving the generalisability of DLBCL clinical trials. Disclosures Stewart: Gilead: Honoraria; Roche: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Teva: Honoraria; Sandoz: Honoraria; AstraZeneca: Honoraria; Novartis: Honoraria. Owen:AbbVie, F. Hoffmann-La Roche, Janssen, Astrazeneca, Merck, Servier, Novartis, Teva: Honoraria.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5047-5047
Author(s):  
Brady E Beltran ◽  
Jose M Malaga ◽  
Julio C Chavez ◽  
Eduardo M. Sotomayor ◽  
Jorge J Castillo

Abstract Introduction: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare hematologic malignancy with a poor prognosis when treated with current therapies. Clinical factors have been developed to prognosticate survival in EBV-positive DLBCL patients; however, more refined, easy to use and reliable prognostic tools are needed. The neutrophil to lymphocyte ratio (NLR) has been reported prognostic in patients with DLBCL (Troppan et al. BJC 2014). We have investigated the prognostic value of the NLR in the overall survival (OS) of patients with untreated EBV-positive DLBCL. Methods: We included patients with a pathological diagnosis of EBV-positive DLBCL who were diagnosed and treated at our institution between 2001-2014. We excluded cases with primary cutaneous CNS involvement, and patients with >50% incomplete data. IRB approval was obtained prior to research. Pathological samples were reviewed by hematopathologists to confirm the diagnosis. Pertinent clinicopathological data such as age, sex, performance status, LDH levels, stage, extranodal sites of disease, absolute neutrophil and lymphocyte counts were collected through chart review, and are presented using descriptive statistics. The NLR was calculated by dividing the absolute neutrophil by the lymphocyte count, and dichotomized in NLR>=5 and NLR<5. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate Cox models were fitted to evaluate hazard ratios (HR) for OS. Results: A total of 46 patients were included in our analysis. The median age was 73 years (range 25-95 years) with male predominance (70%). Poor performance status (ECOG >1) was seen in 25 (58%), elevated LDH levels in 19 (46%), 1+ extranodal site in 24 (57%), and advanced stage (stage 3 and 4) in 23 (53%) of patients. Based on the NLR, 13 patients (39%) had NLR>=5. Patients with NLR >=5 were more likely to present with poor performance (ECOG >1; 85% vs. 15%; p=0.04), elevated LDH levels (69% vs. 31%; p=0.04), advanced stage (III and IV, 69% vs. 31%, p=0.05), and IPI score 3-5 (77% vs.23%; p=0.02). There were no differences in age, sex and number of extranodal sites. NLR>=5 was associated with a worse OS (HR 2.67, 95% CI 1.01-7.01; p=0.047). Conclusion: The NLR appears as a novel and easy to use prognostic factor for OS in patients with untreated EBV-positive DLBCL. Our findings support the need for validation of the NLR in larger retrospective or prospective studies in patients with EBV-positive DLBCL. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1888-1888
Author(s):  
Esa Jantunen ◽  
Carmen Canals ◽  
Didier Blaise ◽  
Alessandro Rambaldi ◽  
Herve Tilly ◽  
...  

Abstract Limited data is available on feasibility and efficacy of ASCT in elderly patients with NHL. Patients: In 2000–2005 15869 NHL patients with ASCT were reported to EBMT database, 3133 (20%) were ≥ 60 years. Only patients with MED-B dataset and those with either diffuse large B-cell lymphoma (DLBCL), mantle cell (MCL) or follicular lymphoma (FL) were subjected to more detailed analysis. This group included 906 elderly NHL patients (median age 63 years, range 60–75) (DLBCL, n = 463; MCL, n = 208; FL, n = 235) who were compared with 3661 patients &lt; 60 years (DLBCL, n = 2149; MCL, n = 435; FL, n = 1077) regarding outcome. Bulky disease was more common in younger patients (26% vs. 15%, p &lt; 0.001) as well as B-symptoms at diagnosis (42% vs. 36%, p = 0.02). Elderly patients had received more often at least two treatment lines before ASCT (70% vs. 59%, p&lt;0.001). The median follow-up for the surviving patients was 14 months. Results: Non-relapse mortality (NRM) was higher in patients ≥ 60 years of age: 3.8% vs.2.3% at 100 days, 6.9% vs. 3.9% at 1 year and 9.4% vs. 5.8% at 3 years (p&lt;0.001). No differences in NRM were observed between patients aged 60–64 years (n = 633) and those aged 65–69 (n = 240). A higher NRM was observed in DLBCL and MCL patients compared to FL patients (p=0.001and p=0.002, respectively). Other variables associated with a higher NRM were an elevated LDH at diagnosis (p=0.04), ≥ 2 treatment lines before ASCT (p&lt;0.001); a poor performance status at ASCT (p&lt;0.001); not being in CR1 at ASCT (chemosensitive disease vs. CR1, p=0.02; chemorefractory disease vs. CR1, p&lt;0.001) and BM as stem cell source (p=0.02). In multivariate analysis, elderly patients showed a higher NRM [RR = 1.6 (CI 1.2–2.1), p=0.001]. In patients with DLBCL, age ≥ 60 years at ASCT was associated with a trend to a higher risk of relapse or progression (p =0.07) and a worse PFS (p=0.008). PFS at 2 years was 69% vs. 79% for patients in CR1 and 52% vs. 60% for patients with sensitive disease at ASCT, respectively. In MCL, elderly patients had worse PFS (p=0.008). PFS at 2 years was 78 vs. 81% for MCL patients in CR1 and 52% vs. 67%, respectively for those patients autografted with sensitive disease. Older age was not a significant prognostic factor either for relapse rate or for PFS in patients with FL. PFS at 2 years was 69% and 81% for FL patients in CR1, and 69% and 69% for FL patients with sensitive disease, respectively. Conclusions: ASCT is feasible in selected NHL patients aged 60–69 years. The outcome is promising taking into account the generally poorer prognosis of lymphomas in elderly population.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1555-1555
Author(s):  
Naoe Goto ◽  
Hisashi Tsurumi ◽  
Yuhei Shibata ◽  
Ryoko Mabuchi ◽  
Nobuhiko Nakamura ◽  
...  

Abstract Abstract 1555 Background: Tumor-infiltrating immune cells perform important functions in host immune reaction against tumor cells including diffuse large B cell lymphoma (DLBCL). Recently, variable tumor-infiltrating cells were reported to give a influence for prognosis, for example, regulatory T cell (T reg), cytotoxic T cell, macrophage and mast cell etc. Among these microenvironmental cells, we focused on Treg cell, and we assessed the distribution and prognostic significance of these cells in DLBCL. The forkhead/winged helix transcription factor 3 (FOXP3) is a transcriptional factorshown to be the key control gene in the development and function of Tregs both in mice and humans. Patients and Methods: We examined samples from 94 patients (54 men and 40 women; median age, 70 years) at diagnosis who were prospectively enrolled between 2002 and 2008. All patients treated with R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). The pattern of FOXP3 protein expression was evaluated using immunehistochemistry in paraffin-embeded tissue samples. In addition, these samples were stained with antibodies for CD10, bcl-6 and MUM-1 via tissue microarray to classify into subgroups. Results: The median percentage of FOXP3+ cells was 91/mm2 (range 4–2100 /mm2). Patients with poor performance status (PS), and high serum lactate dehydrogenase (LDH) showed lower numbers of FOXP3+ cells. (PS; p= 0.014, LDH; p=0.0048) Patients with high counts of FOXP3+ cells (>90/mm2) have better prognosis than those of low counts (5 year (5-y) overall survival (OS); 72.1%, 49.7% p=0.024, respectively). Although no prognostic difference was observed between GCB type and non-GCB type (5-y OS: GCB 71.2%, non GCB 53.1%, p=0.12), low counts of FOXP3+ cell and non-GCB type patient was poorer prognosis than high counts and non GCB type. (low 5-y OS 31.2%, high 5-y OS 69.8% p=0.02). Conclusion: Increased count of FOXP3+ tumor-infiltrating cell might predict better prognosis of DLBCL. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4833-4833
Author(s):  
Panagiotis Theodorou Diamantopoulos ◽  
Vasiliki Papadopoulou ◽  
Aikaterini Polonyfi ◽  
Athanasios G. Galanopoulos ◽  
Fani Kalala ◽  
...  

Abstract Abstract 4833 Introduction. The Epstein-Barr virus has been implicated in the pathogenesis of certain human B-cell neoplasms, such as Burkitt's lymphoma, Hodgkin's disease and post-transplant lympho-proliferative disorders. Persistent latent EBV infection is, however, frequent and therefore its role is of interest in all types of B cell malignancies. In low-grade B cell lymphomas there are few reports for its potential role in higher grade transformation and its association with stereotypic BCRs in CLL. The mechanisms of EBV-associated B cell transformation are probably associated with its proteins expressed during latency; one of the most studied is the LMP1 oncoprotein, which is considered as an anti-apoptotic factor (activator of NF-êB). Recent studies, however, show evidence of coexisting apoptotic properties of LMP1. The level of oxidative stress reflects activation of caspase-mediated apoptotic pathways. Aims and methods. We measured the levels of oxidative stress in low-grade B cell lymphoma patient samples and correlated them with the expression of the LMP1 oncoprotein in order to study apoptotic functions of LMP1. Whole blood samples from 48 patients aged 51–87 (median age 74 years, 25 males, 23 females) without treatment in the previous six months were examined (chronic lymphocytic leukemia: 27, marginal zone lymphoma: 12, mantle cell lymphoma: 4, hairy cell leukemia: 2, follicular lymphoma: 2, lymphoplasmacytic lymphoma: 1). Latent EBV infection was detected with RT-PCR for the viral BXLF1 gene. LMP1 expression was quantitated with Real-Time PCR in EBV-positive patients. The levels of oxidative stress were quantitated in the sera of all patients with the use of a peroxide measuring kit (PerOx TOS/TOC kit by Immundiagnostik) and compared between the LMP1-positive (13) and LMP1-negative (35) group of patients with the use of 2-tailed Mann-Whitney test. Results. Of the fourty-eight (48) patients tested, nineteen (19) were EBV-positive. Thirteen (13) of the nineteen (19) EBV-positive ones expressed LMP1. Oxidative stress was found to be significantly higher in LMP1-negative vs LMP1-positive patients (372.3 vs 261.4 micromol/L, p=0.014). Discussion. The role of LMP1 expression is under investigation in the non EBV-related low grade B cell lymphomas. In the present study we examined a potential effect of LMP1 expression on oxidative stress and found that levels of oxidative stress were lower in LMP1-positive vs LMP1-negative patients with low-grade B cell lymphomas, reflecting an anti-apoptotic function of LMP1. In accordance with this result, LMP1 has been shown to upregulate BCL-2 using the NF-êB pathway. BCL-2 is a major inhibitor of the initiation of caspase-related apoptotic pathways and BCL-2 upregulation inhibits apoptosis resulting in lower levels of oxidative stress. However, in a study of sixty-four patients with low grade B cell lymphomas, we recently showed that LMP1 expression increases the levels of the apoptotic marker survivin, confirming that LMP1 may also possess an apoptotic function, as has been shown by another recent study on cell lines. Conclusion. The lower oxidative stress in the LMP1-expressing low grade B cell lymphoma samples shows evidence of an apoptotic function of the oncoprotein in this group of diseases. Disclosures: No relevant conflicts of interest to declare.


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