scholarly journals MDR1 polymorphisms Have an Impact on the Prognosis of Chinese Diffuse Large B Cell Lymphoma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5029-5029
Author(s):  
Miao Kourong ◽  
Xiao Zhengrui ◽  
Ni Ying ◽  
Yin Guangli ◽  
Jianyong Li
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Association Studies ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Genotype 2 ◽  
Allele Group ◽  
Large B Cell

Abstract MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP) dependent efflux transporter that plays a fundamental role of transport harmful compounds outside cells to maintain optimal health. The present study aimed to investigate whether the MDR1 gene single nucleotide polymorphisms (SNPs) were associated with the prognosis of diffuse large B-cell lymphoma (DLBCL). Three common SNPs, including C1236T, G2677T/A and C3435T were focused on and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing. At locus C1236T, patients carrying T allele (genotype CT and TT) had a prolonged overall survival (OS) when compared with patients with CC genotype (2-year OS 82.6% vs. 60.0%, respectively; HR=0.1, 95% CI 0.01-0.6, p =0.016). At locus C3435T, complete remission/ complete remission unconfirmed (CR/CRu) rate in C allele group was significantly higher than T allele group (66.7% vs. 51.9%, respectively; p=0.009). The progression-free survival (PFS) curves of with T (genotype CT and TT) and without T (genotype CC) were significantly different (2-year PFS 46.4% in with T group vs.73.7% in without T group, respectively; HR=1.9, 95% CI 1.0-3.6, p=0.045). At locus G2677T/A, the age for genotypes AG and AT groups were significantly younger than the other genotypes (51.1±12.6 years vs. 57.7±13.4 years, respectively; p=0.033). In the haplotype analysis of loci 1236-3435, compared with T-C group, the C-T group displayed an inferior PFS rate (2-year PFS 23.0% vs. 50.6%, respectively; HR=7.8, 95% CI 1.9-32.6, p=0.005), while C-C and T-T groups showed an intermediate PFS rate. Our findings demonstrate that genotype CT+TT at locus C1236T, allele C and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL, as well as haplotype of T-C in loci 1236-3435. Besides, genotypes at locus G2677T/A might affect age at diagnosis, which has important prognostic value for DLBCL. These results could provide evidence that the MDR1 SNPs may influence the biologic feature and prognosis of DLBCL and shade new lights in disease association studies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Nivolumab plus gemcitabine, dexamethasone, and cisplatin chemotherapy induce durable complete remission in relapsed/refractory primary mediastinal B-cell lymphoma: a case report and literature review

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094507
Author(s):  
Gang Huang ◽  
Ju Huang ◽  
Zhili Zhang ◽  
Chongchong Xue ◽  
Yuan Liu
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Cell Lymphoma ◽  
Combined Therapy ◽  
B Cell Lymphoma ◽  
Immune Checkpoint Blockade ◽  
Large B Cell Lymphoma ◽  
Clinical Trial Designs ◽  
Potential Use ◽  
Large B Cell

Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon, but aggressive, type of B-cell lymphoma. Patients with relapsed refractory PMBCL (rrPMBCL) have limited therapeutic options and usually have a relatively poor outcome. Immune checkpoint blockade has become a potential treatment for this disease. We report here a case of a female patient with rrPMBCL who was treated with nivolumab plus gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy. Complete remission was achieved after four cycles of combined therapy. With continued nivolumab maintenance monotherapy, she has remained in complete remission for longer than 28 months. This is the first report of nivolumab plus GDP chemotherapy inducing complete remission in patient with rrPMBCL. This case supplements the limited literature and provides implications for clinical trial designs regarding the potential use of nivolumab in the treatment of rrPMBCL.

scholarly journals Twenty Years of Autologous Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma: A Single Portuguese Center Experience

2016 ◽  
Vol 29 (3) ◽  
pp. 205
Author(s):  
Margarida Dantas Brito ◽  
Fernando Campilho ◽  
Rosa Branca ◽  
Carlos Vaz ◽  
Susana Roncon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
First Complete Remission

<p><strong>Introduction:</strong> Diffuse large B-cell lymphoma can be cured in 60% – 70% of patients. Autologous stem cell transplantation is the standard treatment for relapsed disease. This high-intensity treatment after first complete remission in patients with high International Prognostic Index remains controversial and was performed in our department during some years. <br /><strong>Material and Methods:</strong> Retrospective study, review of clinical records. <br /><strong>Results:</strong> This study evaluates the outcome of 113 patients transplanted between 1992 and 2012. Considering status before transplantation patients were divided in groups: a) first complete remission after 1 line of chemotherapy (n = 64); b) first complete remission after ≥ two chemotherapy lines (n = 15); c) second complete remission (n = 15); d) more advanced diseased (n = 19). Chemotherapy used in first line therapy was mainly R-CHOP (n = 71) and CHOP (n = 28). The median follow-up of patients still alive was 34 months (1 - 221). At five years, overall survival was 73% (± 5) and disease free survival was 75% (± 5).<br /><strong>Conclusion:</strong> Conventional chemotherapy followed by autologous stem cell transplant is a safe and efficient option for selected patients. In our series 70% high-risk patients were free from disease with this strategy.</p>

Primary anaplastic large B-cell lymphoma in mandible: Long-term complete remission with R-CHOP regimen and involved field radiotherapy

Oral Oncology ◽  
2009 ◽  
Vol 45 (9) ◽  
pp. e113
Author(s):  
Pasquale Niscola ◽  
Massimiliano Palombi ◽  
Malgorzata Monika Trawinska ◽  
Laura Scaramucci ◽  
Marco Giovannini ◽  
...  
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Chop Regimen ◽  
Large B Cell Lymphoma ◽  
Involved Field ◽  
Involved Field Radiotherapy ◽  
Large B Cell

NIK Is Involved In the Activation of the Classical and Alternative NF-κB Pathways In Diffuse Large B Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3099-3099
Author(s):  
Lina Odqvist ◽  
Margarita Sánchez-Beato ◽  
Santiago Montes-Moreno ◽  
Ken H Young ◽  
Francesco Acquadro ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Alternative Pathway ◽  
B Cell Lymphoma ◽  
Classical Pathway ◽  
Strong Positive Correlation ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 3099 Deregulated NF-κB activity plays a role in the lymphoma pathogenesis, and has been proposed to constitute a cardinal feature of some subtypes of diffuse large B cell lymphoma (DLBCL). The NF-κB-Inducing Kinase (NIK) is essential for the activation of the alternative NF-κB pathway by inducing the phosphorylation of the NF-κB member p100, which leads to its processing to p52 and its subsequent nuclear translocation. A role for NIK in the classical NF-κB pathway as well has been shown, suggesting NIK as an attractive therapeutic target in lymphomas. Here, we study the frequency and extent of alternative and classical NF-κB activation in diffuse large B cell lymphoma, and the implication of NIK in both pathways. The activation of the classical and alternative NF-κB pathways was present in 28 and 34% of DLBCL cases respectively, as assessed by nuclear expression of p50 (classical pathway) and p52 (alternative pathway) by immunohistochemistry in a series of 301 samples. Activation of both NF-κB pathways was observed in germinal centre B-cell like (GC) and activated B-cell like (ABC) subtypes, with a slight predominance, although not significant, in ABC subtype. In contrast, the levels of p52 and p50 were significantly higher in ABC-DLBCL cell lines than those of GC subtype. The activation of both pathways was mostly overlapped and there was a strong positive correlation between nuclear p52 and p50 (p<0.001). Eighteen % of the cases expressed both p50 and p52 while only 8 and 16% expressed exclusively p50 or p52, respectively. Activation of the alternative NF-κB pathway was strongly associated with Epstein-Barr virus (EBV), since 93% of EBV+ cases expressed nuclear p52 (p<0.001). In our study, no TRAF3 deletions were detected in a panel of 25 DLBCL samples, although absence of TRAF3 was observed in one DLBCL cell line. Since NIK acts as a bottleneck in the activation of the alternative pathway but has also been described to play a role in the classical pathway, we wanted to analyze the effect of the knockdown of NIK on both pathways. Using small interference RNA in two lymphoma cell lines, we observed that the silencing of NIK had an effect on both pathways, decreasing the processing of p100 as well as p105. Taken together, our results show that the activation of NF-κB distinguishes a subset of DLBCL cases, comprising both ABC and GC subtypes, suggest a frequent overlap between the classical and alternative NF-κB pathway in DLBCL, and identify a possible role for NIK in the activation of both pathways. Disclosures: No relevant conflicts of interest to declare.

Comparison Between CD20-Negative and CD20-Positive Diffuse Large B Cell Lymphoma; Characteristics and Clinical Outcome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4891-4891
Author(s):  
Jungmin Jo ◽  
Changhoon Yoo ◽  
Yongchel Ahn ◽  
Seong Joon Park ◽  
Shin Kim ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Risk Group ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract Abstract 4891 Background CD20 is a non-glycosylated phosphoprotein expressed on the surface of all mature B-cells. CD20 is expressed on all stages of B cell development except the first and last. However, complete lack of CD20 expression occurred in a few cases without previous rituximab (R-) treatment. The immunohistochemostry (IHC) studies which we used were not perfect for confirmation of expression. However, we intended to investigate characteristics and clinical outcome of CD20-negative diffuse large B-cell lymphoma (DLBCL), not detected with usual method, and to compare with CD20-positive. Methods The records of Non-Hodgkin's Lymphoma patient registry were reviewed in Asan Medical Center. Between September 2003 and February 2009, a total of 407 patients were diagnosed DLBCL and 16 patients (3.9%) out of 407 confirmed CD20-negative DLBCL by IHC. The rest of patients (n=391) were CD20-positive and unconfirmed cases were excluded. Retrospective analysis of complete response (CR), disease-free survival (DFS), and overall survival (OS) was performed. Results The median age was 60.5 years old (range 31–81) in CD20-negative patients. Ten patients were males. The Ann Arbor stage was I in 3 patients, II in 3 patients, and III or IV in 10. Six patients were low risk group, 7 patients in intermediate, and 3 in high risk group according to international prognostic index (IPI). Most of patients (62.5%) received cyclophosphamide, doxorubicin, vincristin, and prednisone (CHOP) chemotherapy in CD20-negative and 295 patients (75.4%) with R-CHOP in CD20-positive DLBCL. The Baseline characteristics was not different in both groups except Hans classifier (p=0.02). With a median follow-up time of 32.3 months (range 0.5–83.4), the CR rate was 73.5%, the 3-year OS was 69.5%, and 3-year DFS 74.2% in all patients. CD20-positive and CD20 negative groups had a CR rate of 73.7%, 68.8% (p=0.146), respectively, a 3-year OS of 70.7%, 40.0% (p=0.003), a 3-year DFS of 75.4%, 44.6% (p< 0.001), respectively. The 3-year OS and DFS also had significant difference with adjusted IPI (p<0.001, respectively). Conclusions CD20-negaive DLBLC was not infrequently with usual IHC method (around 4%). The survival outcome was poor compared with CD20-positive DLBLC because of high relapse rate. It was caused without rituximab treatment in CD20-negative. Development of novel target agents like rituximab should be explored to improve outcome and maintain the CR status of CD20-negative DLBCL. Disclosures: No relevant conflicts of interest to declare.

Diffuse Large B-Cell Lymphoma in the Elderly: Outcome of Patients From a Single Center

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2693-2693
Author(s):  
Jean-Marc Schiano de Colella ◽  
Diane Coso ◽  
Benjamin Esterni ◽  
Anne-Marie Stoppa ◽  
Vadim Ivanov ◽  
...  
Keyword(s):  
B Cell ◽  
Older Patients ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
Population Characteristics ◽  
Large B Cell Lymphoma ◽  
Age Of Diagnosis ◽  
Large B Cell

Abstract Abstract 2693 Introduction: Treatment of Diffuse Large B-Cell Lymphoma (B-DLCL) is not well coded in the elderly patients. They may receive full dose immunochemotherapy, low dose chemotherapy or palliative treatment regarding co morbidities, Performans Status (PS), psychological, social or mental state. The lack of age-adapted prognosis factors including geriatric scales induce a subjective choice for the treatment. The purpose of the study is to evaluate the outcome of all the patients treated in a single institute for a B-DLCL, with comparison of age of diagnosis and treatment received. Methods: All patients with B-DLCL, age≥70 years, treated in the Paoli-Calmettes institute between 1995 and 2008 were included, excepted patients with intra-ocular and cerebral localizations or with a “Burkitt-like” histology. Were also excluded patients with incomplete data. Treatments were simplified for statistic analysis in three types: CHOP Like (CH-L): three chemotherapies with anthracyclin (or etoposide in place if cardiac impossibility) with conventional doses, mini-CHOP-Like (mCH-L): with reduce doses of anthracyclin and cyclophosphamide, or COP Like (C-L): two agents without anthracyclin. Factors studied in the different items are systematically Age (70–79 vs olders), PS (0–1 vs 2–4), LDH, Ann Arbor stage (AA:1–2 vs 3–4) and type of chemotherapy. Results: From 1995 to 2008, 212 patients with B-DLCL were admitted in the Paoli-Calmettes institute for a B-DLCL. The median age was 76 years [range 70–90], 70% of the patients had a PS=0–1 and 30% a PS=2–4, LDH was increased in 55% of patients, AA was 3–4 in 58% of cases. The repartition of chemotherapy was 56% for CH-L, 33% for mCH-L and 11% for C-L. In the 70–79 age subgroup, CH-L is predominant (67% vs 25% for the older patients, p<0.0001). Four patients died before therapy initiation. Survival curves for mCH-L and C-L are identical, with no difference of population characteristics and patients are grouped for the final analysis (mCH-CL group). Rituximab was added to the chemotherapy in 63% of cases. Overall Survival at 12 and 60 month was respectively 73% and 47% with a median [IC95] of 48.8 month. Age at diagnosis is statistically significant with a 5-year survival of 53% and 29% for respectively 70–79 years and older (p=0.0045). Patients characteristics of the age subgroups are different only for the type of chemotherapy infused (p<0.0001) and not for the others factors analyzed. Choice of chemotherapy was also important (P=0.0011) with an OS of 55% and 37% respectively for CH-L and mCH-CL protocols. In this case, patients characteristics are different in term of date of diagnosis (p<0.001), age of diagnosis (p<0.001), PS (0.04) and AA (0.011). Surprisingly, there is no difference in OS when rituximab was given (p=0.7), and despite the difference of treatment, there is no difference of incidence of relapse in the two age groups (p=0.97). Conclusion: Survival of our elderly population of patients with B-DLCL is comparable to the literature. With non-selected patients, repartition of factors from the IPI score is not different in the two age subgroups, but the more intensive chemotherapy is given in the less older patients. Moreover, OS is increased in this CH-L protocol, in contrast with the same incidence of relapse. Furthermore, the use of rituximab, a major treatment of B-DLCL in the elderly, do not influence OS in this non-selected population of patients. These data confirm the requirement of a more discriminant prognosis model than the IPI score for the daily practice, including relevant geriatric factors. Disclosures: No relevant conflicts of interest to declare.

R-CHOP21 Vs R-CHOP14 in 950 Diffuse Large B-Cell Lymphoma Patients: Results of a Multicentre Retrospective Study Form Italian Lymphoma Foundation (FIL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1615-1615
Author(s):  
Luigi Rigacci ◽  
Benedetta Puccini ◽  
Maria Giuseppina Cabras ◽  
Luca Nassi ◽  
Alberto Fabbri ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
Bulky Disease ◽  
Symptomatic Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 1615 Background: Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin's lymphoma. R-CHOP21 (C21) is considered the standard therapy but a large number of studies have tested R-CHOP14 (C14). Aims: The aim of our study was to evaluate retrospectively a cohort of patients (pts) treated with C21 or C14 and to compare the efficacy of the therapy. Methods: All pts with diagnosis of DLBCL or follicular grade IIIb lymphoma, treated with curative intent in 9 Italian Hematological Centers, were accrued. All patients treated with C14 used G-CSF as primary prophilaxis, and only elderly (over 70 years) patients treated with C21 used G-CSF as primary prophilaxis. Results: From january 2002 to june 2011, 950 pts were accrued, 643 pts were treated with C21 and 307 were treated with C14. The median age was 63 (range 19–89). The two cohorts of pts were balanced for all clinical characteristics a part for age (<60 or >60 years) with more aged pts in C21 arm (p 0.001), bone marrow positivity and more than 3 lymph node stations involved that were higher in C14 arm (p: 0.05 and p: 0.001). After induction therapy 751 pts (79%) obtained a complete remission: 501/643 (78%) after C21 and 250/307 (81%) after C14. The remaining pts obtained partial response in 110 and 48 or no response in 32 and 9 respectively for C21 and C14. After a median period of observation of 38 months 104 pts relapsed (14%), 68 (65%) in the C21 arm and 36 (35%) in the C14 arm. After a median observation period of 3 years, considering the two therapies, C21 vs C14, no differences were reported in OS (Figure 1), PFS (Figure 2) and DFS: 80% vs 84%, 69% vs 71% and 54% vs 56% respectively. In univariate analysis OS was lower in older pts (azard ratio (ar): 2.57), IPI 2 (ar: 2.09), IPI 3 (ar: 4.36), IPI 4–5 (ar: 6.36), bulky disease (ar: 1.70), symptomatic disease (ar: 2.23). In multivariate analysis factors which mantained significantly worst prognosis were older age (ar: 1.35), IPI 2 (ar: 1.95), IPI 3 (ar: 3.76), IPI 4–5 (ar: 5.01) and bulky disease (ar: 1.43). As expected hematological grade III/IV toxicity was more frequent in pts treated with C14. No differences in extra-hematological toxicity were observed. Secondary malignancies were reported: 7 in C21 and 3 in C14. After 3 years of median observation 188 pts are dead: 137 (73%) in C21 and 51 (27%) in C14 (not statistically significant, p:0.08). The large majority of pts are dead for disease progression or relapse. Conclusions: In conclusion our results confirm that C14 do not improve the results of the standard C21 in the whole lymphoma population. Dose dense therapy did not affect OS or PFS also analysing sub group of pts. As expected a higher frequency of neutropenia was observed in C21 arm but did not translate in increasing infection rate. Further prospective randomized studies are needed to verify this preliminary observations. Disclosures: No relevant conflicts of interest to declare.

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