Loss of Expression of the Pro-Apoptotic Bcl-2 Family Proteins Bak and Bax in Rituximab- and Chemotherapy-Resistant Non-Hodgkin’s Lymphoma Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4819-4819 ◽  
Author(s):  
Scott H. Olejniczak ◽  
Francisco J. Hernandez-Ilizaliturri ◽  
James L. Clements ◽  
Myron S. Czuczman
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Chemotherapy Resistance ◽  
B Cell Lymphoma ◽  
Resistant Cell ◽  
Hodgkin's Lymphoma ◽  
Down Regulation ◽  
Non Hodgkin's Lymphoma ◽  
Induced Apoptosis

Abstract Sustained remissions following standard chemotherapy are achieved in less than half of patients diagnosed with non-Hodgkin’s lymphoma (NHL). A major case of treatment failure is the development of resistance to current therapies. Early studies demonstrated that rituximab was a safe and effective monotherapy for patients with indolent B-cell lymphoma refractory or relapsed following prior chemotherapy. In one study, Davis et al. demonstrated a loss of responsiveness upon rituximab re-treatment in 60% of patients suggesting the development of antibody resistance. To study mechanisms by which cells become resistant to rituximab we induced rituximab resistance in several well characterized B-cell lymphoma cell lines (Raji, RL, SU-DHL-4) by exposing them to increasing concentrations of rituximab or rituximab plus human serum as a source of complement. Individual clones were than generated from rituximab-resistant cell lines (RRCL) by limiting dilution. Characterization of the cell lines and clones generated by repeated exposure to rituximab revealed that in addition to gaining a rituximab-resistant phenotype they also developed concurrent chemotherapy resistance. In rituximab-sensitive parental cell lines, chemotherapy induced apoptosis via the intrinsic pathway. However, apoptotic cell death was completely blocked in resistant cell lines and clones. Upon investigation of potential mediators of both rituximab and chemotherapy resistance, we observed a significant down-regulation of the pro-apoptotic Bcl-2 family proteins Bax and Bak. We therefore hypothesize that resistance to chemotherapy- and rituximab-induced apoptosis is due to the down-regulation of Bax and Bak observed in all rituximab-resistant cell lines and clones characterized to date. We are currently investigating the mechanism(s) underlying the down-regulation of Bax and Bak protein in RRCL. Preliminary data suggests that wild-type Bax and Bak mRNA is expressed at a comparable level in RRCL and parental cells. This strongly suggests that Bax and Bak protein expression may be differentially controlled via post-transcriptional mechanisms in resistant cells. Currently, we are evaluating expression of Bax and Bak in archived lymphoma biopsy specimens and their correlation to treatment response or resistance. If a clinical correlation is identified, therapies aimed at restoring Bak and/or Bax expression may someday prove useful in circumventing clinical resistance to currently used immuno +/− chemotherapy-based regimens.

Rituximab resistance and its association with changes in the internal domain of CD20 antigen and down-regulation of pro-apoptotic protein Bax and Bak in both rituximab-resistant cell lines (RRCL) and diffuse large B-cell lymphoma (DLBCL) patient (pt) samples

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17509-17509
Author(s):  
N. M. Reddy ◽  
F. J. Hernandez-Ilizaliturri ◽  
S. Olejniczak ◽  
J. Knight ◽  
M. S. Czuczman
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Structural Changes ◽  
Chemotherapy Resistance ◽  
B Cell Lymphoma ◽  
Resistant Cell ◽  
Down Regulation ◽  
Dlbcl Patient ◽  
Cd20 Antigen ◽  
Apoptotic Proteins

17509 Background: Resistance to rituximab (R) has been observed in lymphoma pts. To define the molecular basis for rituximab resistance we developed various RRCL and previously demonstrated changes in CD20 structure, membrane reorganization following rituximab exposure and deregulation of pro-apoptotic proteins Bax/Bak leading to rituximab/chemotherapy resistance. In our current work we evaluated changes in the structure/expression of CD20 and/or pro-apoptotic proteins in primary tumor specimens from DLBCL pts treated with rituximab in combination with CHOP (R-CHOP). Methods: We obtained frozen lymphoid material from patients with DLBCL who achieved a remission (sensitive lymphoma) or failed (resistant lymphoma) R-CHOP therapy. Protein lysates were obtained from each sample. Structural changes in CD20 were determined by Western blotting using various antibodies recognizing epitopes located in the internal (GST77 and 1439) and external domain (rituximab) of CD20. In addition, we studied the expression of Bax and Bak. Results: Variability in the expression and structure of CD20 was found in the pt samples. Rituximab binding to its surface CD20 antigen was preserved in all patients. However, differences in C- and N-terminal expression were found across DLBCL specimens. In addition, down-regulation of Bax/Bak was observed in some pts with resistant lymphomas. Patients who responded to R-CHOP were noted to either have an intact CD20 and/or express Bax/Bak. On the other hand, resistant lymphomas had altered CD20 isoforms and a downregulation of Bax/Bak. Conclusions: Our current preliminary data suggests a positive correlation to our pre-clinical data generated from B-cell NHL cell-lines and will be evaluated in a larger number of primary NHL tumor specimens. No significant financial relationships to disclose.

scholarly journals Use of pembrolizumab with or without pomalidomide in HIV-associated non-Hodgkin’s lymphoma

2021 ◽  
Vol 9 (2) ◽  
pp. e002097
Author(s):  
Kathryn Lurain ◽  
Ramya Ramaswami ◽  
Ralph Mangusan ◽  
Anaida Widell ◽  
Irene Ekwede ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hiv And Aids ◽  
Hodgkin's Lymphoma ◽  
People Living With Hiv ◽  
Oncogenic Viruses ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

BackgroundNon-Hodgkin’s lymphoma (NHL) is currently the most common malignancy among people living with HIV (PLWH) in the USA. NHL in PLWH is more frequently associated with oncogenic viruses than NHL in immunocompetent individuals and is generally associated with increased PD-1 expression and T cell exhaustion. An effective immune-based second-line approach that is less immunosuppressive than chemotherapy may decrease infection risk, improve immune control of oncogenic viruses, and ultimately allow for better lymphoma control.MethodsWe conducted a retrospective study of patients with HIV-associated lymphomas treated with pembrolizumab±pomalidomide in the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute.ResultsWe identified 10 patients with stage IV relapsed and/or primary refractory HIV-associated NHL who were treated with pembrolizumab, an immune checkpoint inihibitor, with or without pomalidomide. Five patients had primary effusion lymphoma (PEL): one had germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL); two had non-GCB DLBCL; one had aggressive B cell lymphoma, not otherwise specified; and one had plasmablastic lymphoma. Six patients received pembrolizumab alone at 200 mg intravenously every 3 weeks, three received pembrolizumab 200 mg intravenously every 4 weeks plus pomalidomide 4 mg orally every day for days 1–21 of a 28-day cycle; and one sequentially received pembrolizumab alone and then pomalidomide alone. The response rate was 50% with particular benefit in gammaherpesvirus-associated tumors. The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three patients with PEL had leptomeningeal disease: one had a complete response and the other two had long-term disease control. There were four immune-related adverse events (irAEs), all CTCAEv5 grade 2–3; three of the four patients were able to continue receiving pembrolizumab. No irAEs occurred in patients receiving the combination of pembrolizumab and pomalidomide.ConclusionsTreatment of HIV-associated NHL with pembrolizumab with or without pomalidomide elicited responses in several subtypes of HIV-associated NHL. This approach is worth further study in PLWH and NHL.

scholarly journals Non-Hodgkin’s Lymphoma: A Case Report

2021 ◽  
pp. 264-267
Author(s):  
Aditya Patel ◽  
Samrudhi Gujar ◽  
Savita Pohekar ◽  
Ruchira Ankar ◽  
Arati Raut ◽  
...  
Keyword(s):  
United States ◽  
B Cell ◽  
Lymphoid Tissue ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The United States ◽  
Incidence Rates ◽  
Hodgkin's Lymphoma ◽  
Paediatric Ward ◽  
Non Hodgkin's Lymphoma

Introduction: Hodgkin's and non-lymphomas Hodgkin's are malignant tumours of lymphoid tissue. Non-lymphomas Hodgkin's are a type of lymphoid tissue cancers that arise from T or B cells or their progenitors, and can be indolent or aggressive. B-cell lymphomas account for around 80% of all cases in the United States. Chronic lymphocytic leukaemia or small lymphocytic lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, and primary cutaneous B-cell lymphoma are all examples of Non-Hodgkin's Lymphoma. Non-Lymphoma Hodgkin's is the sixth most prevalent malignancy in the United States, with incidence rates nearly doubling in the last 35 years. With each decade of life, the incidence rises; the median age upon diagnosis is 66. In India, the incidence rates in urban regions are many times higher than in rural areas, with the incidence being higher in metropolitan cities and among Indian immigrants, implying that urban lifestyles and economic advancement may boost cancer incidence. In 2010, NHL was projected to have caused roughly 0.36 million new cases and 0.19 million deaths. Case Presentation: A male patient of Two and half years from Shiwangaon MO, was admitted to Paediatric Ward, AVBRH on 31st May, 2021 with a known case of Non-Hodgkin Lymphoma which was diagnosed itself at AVBRH on 31st May,2021. My patient was brought with a chief complain of swelling in the testicular region for 6 days. As narrated by the patient’s father, my patient was apparently alright 6 months back and then patient develop swelling in temporal region suddenly, associated with pain on touch, as the swelling develops more and uncomfortable, patient was brought immediately to AVBRH and was admitted in Paediatric Ward for further investigation.

Acquirement of Rituximab Resistance Is Associated with the Development of Chemotherapy Resistance in B-Cell Lymphoma Cells: Evidence of Shared Pathways of Resistance between Chemotherapeutic Agents and Biological Therapies.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2297-2297
Author(s):  
Scott H. Olejniczak ◽  
Francisco J. Hernandez ◽  
Myron S. Czuczman
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
Chemotherapy Resistance ◽  
B Cell Lymphoma ◽  
Parental Cell ◽  
Chemotherapeutic Agents ◽  
Lymphoma Cells ◽  
Apoptotic Effects

Abstract Pre-clinical studies have demonstrated that rituximab triggers apoptotic signals in B-cell lymphoma cells upon biding to CD20 antigen. Downstream signaling events observed in lymphoma cells following in vitro exposure of rituximab or chemotherapy include: 1) activation of the intrinsic apoptotic pathway and 2) increased mitogen activated protein kinase (MAPK) activity. In addition, pre-clinical and clinical studies strongly suggest that rituximab may sensitize lymphoma cells to apoptotic effects of various drugs used to treat NHL. Despite its anti-tumor activity, many patients relapse after initial response to rituximab-based therapy and demonstrate variable degrees of rituximab resistance. To further study the impact of rituximab resistance in cellular responses to chemotherapy we developed several rituximab resistant cell lines (RRCL) derived from Raji, SU-DHL-4 and RL cells by exposing cells to escalating doses of rituximab with (4RH cells) or without (2R cells) human serum. The rituximab resistance of each RRCL was confirmed by immunological assays. Subsequently, lymphoma cells (parental and RRCL) were exposed to various chemotherapeutic agents (cisplatin, doxorubicin, paclitaxel, or vincristine) for up to 48 hours. Detection of cell death was determined by trypan blue and/or propidium iodine staining. Caspase-3 activity was measured by PhiPhi Lux G1D2 enzymatic cleavage. Bcl-2 expression was determined by Western blotting. Chemotherapy resistance to all agents tested was observed in RRCL when compared to parental Raji, SU-DHL-4 and RL cell lines. In addition, caspase-3 activity was lower in RRCL following chemotherapy exposure than in parental cell lines. A significantly lower percent of RRCL cells within sub-G0/G1 peaks in cell cycle histograms confirmed that RRCL were less sensitive to chemotherapy-induced apoptosis. Additionally, an increase in Bcl-2 expression was observed in RRCL when compared parental cell lines. Our data strongly suggest that chemotherapy resistance emerges concomitantly with the acquirement of rituximab resistance in lymphoma cells. Chronic exposure to rituximab appears to cause overexpression of Bcl-2, which likely renders RRCL less susceptible to the apoptotic effects of chemotherapy agents. Ongoing studies are aimed at identifying and overcoming rituximab/chemotherapy shared cellular pathways of resistance.

Identification of a Diagnostic Gene Signature for SGN-40, Anti-CD40 Monoclonal Antibody, in Pre-Clinical NHL Models and the Role of FAS in SGN-40 Mediated Apoptosis.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1593-1593
Author(s):  
Xiaoyan Shi ◽  
Bart Burington ◽  
Tom Januario ◽  
Jeffrey T Lau ◽  
Shang-Fan Yu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Cell Lines ◽  
Germinal Center ◽  
Gene Signature ◽  
Resistant Cell ◽  
Lymphoma Cell ◽  
Hodgkin's Lymphoma ◽  
Sensitive Cell ◽  
Non Hodgkin's Lymphoma

Abstract SGN-40, an anti-CD40 monoclonal antibody, is a humanized IgG1 antibody that binds to CD40, mediates effector cell functions (ADCC/ADCP) and activates downstream signaling pathways. SGN-40 has shown activity in a phase I single agent multi-dose trial in non Hodgkin’s lymphoma, with greatest activity in diffuse large B-cell lymphoma (Advani et al. 2008, ICML). Previous in vitro studies implicated down-regulation of the germinal center expressed protein Bcl-6, upregulation of p53 family member TAp63a, and FAS death receptor induction as potential mechanisms leading to lymphoma cell death (Lewis et al. 2007, AACR, ASH). In order to further define the apoptosis signaling mechanism, we assessed the ability of SGN-40 to inhibit proliferation and promote apoptosis across a large panel of non-Hodgkin’s lymphoma cell lines. SGN-40 reduced cell viability in 58% (18/31) of cell lines tested. To identify the genes that may be promoting apoptosis and/or inhibiting proliferation, we compared gene expression levels before and after SGN-40 exposure in both sensitive and resistant cell lines, as well as in normal B-cells. SGN-40 strikingly and specifically upregulated FAS on the cell surface of sensitive cell lines. Furthermore, the addition of soluble FAS-Fc dampened SGN-40-induced apoptosis in a subset of sensitive cell lines, suggesting a dependence on a FAS-FASL interaction. These data imply that FAS-dependent apoptosis may directly contribute to the anti-tumor effect of SGN-40. Our data also demonstrate that SGN-40 sensitivity is dependent on the point in B-cell development at which the NHL cell lines were transformed. Sensitive cell lines had a gene signature characteristic of minimal activation of CD40 signaling prior to SGN-40 exposure, whereas resistant cell lines had a signature consistent with prior constitutive signaling downstream of CD40. Thus, SGN-40 appears to elicit its apoptotic properties through activation of CD40 signaling in NHL cell lines not previously exposed to CD40L signaling in the germinal center environment at the time of lymphocyte transformation (GCB lymphomas). In order to develop a clinically feasible assay from FFPE tissue, we developed a 14-gene signature by Stepwise Linear Modeling, utilizing genes from the CD40 pathway activation and GCB gene sets; the classifier gave >96% accuracy (30/31) on the ‘training’ set of cell lines and 75% (3/4) accuracy on a ‘test’ set of xenografts. Overall, our data provides unique insights into SGN-40 mechanisms of action, provides a testable hypothesis of the clinical mechanism of action, and a potential diagnostic test to identify patients more likely to benefit from SGN-40. Efforts are currently underway to test the clinical relevance of these findings.

Clinical Features and Prognostic Relevance of Ovarian Involvement in Non-Hodgkin's Lymphoma: a Consortium for Improving Survival of Lymphoma (CISL) Report.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4999-4999
Author(s):  
Jina Yoon ◽  
Seok Jin Kim ◽  
Jong Ho Won ◽  
Chul Won Choi ◽  
Hyeon-Seok Eom ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Disseminated Disease ◽  
Ovarian Involvement

Abstract Abstract 4999 Introduction Ovary can be involved as a primary ovarian lymphoma or secondarily involved by disseminated disease of non-Hodgkin's lymphoma. However, ovarian involvement is an extremely rare event in non-Hodgkin's lymphoma. Thus, it clinical features and prognostic relevance has rarely been addressed, and most publications refer to a single or a few cases. Thus, we retrospectively analyzed patients with ovarian involvement Patients and methods 32 patients with ovarian involvement were assembled from 8 hospitals affiliated with the CISL (Consortium for Improving Survival of Lymphoma), a Korean lymphoma study group. Primary ovarian involvement was defined as a lymphoma confined to ovary with or without involvement of adjacent lymph nodes and contiguous organs. Secondary ovarian lymphoma was defined as a secondary involvement of ovary in disseminated disease of lymphoma at initial diagnosis. Results Twelve patients had primary ovarian lymphoma (37.5%) while twenty patients (62.5%) had secondary ovarian involvement by systemic disease. The clinical manifestations of ovarian involvement were similar to that of other ovarian tumors, namely an abdominal pain (31%), abdominal distension (19%) or lower abdominal palpable mass (16%). Pathological review according to the WHO classification showed that the most common histological subtype was diffuse large B-cell lymphoma (DLBCL, 75.0%, 24/32), and the frequency of other subtypes was as follows: Burkitt lymphoma (BL, 12.5%, 4/32), lymphoblastic lymphoma (6.3%, 2/32), marginal zone B-cell lymphoma (MZL, 3.1%, 1/32), peripheral T-cell lymphoma, unspecified (PTCL-U, 3.1%, 1/32). The median age (43 years, range 18-80) was younger than that of previously reported other organs such as uterus or prostate. The presence of B symptoms was only observed in 31.3%, and the performance status was good (84.4% of patients had less than grade II of ECOG performance status). The cases involving two or more than two extranodal sites were 68.8% while cases with elevated level of serum LDH were 59.4%. Thus, 59.4% of patients had the low or low-intermediate score of IPI score. Bilateral ovarian involvement was found in 12/32 (38%) while unilateral involvement was 20/32 (63%, 9 right and 11 left side. Three patients showed the involvement of central nervous system (CNS) at diagnosis (3/32, 9.4%). These three patients had DLBCL histology and unfavorable parameters including stage IV, high IPI score and bone marrow BM involvement. Thus, the initial CNS involvement might be associated with advanced stage of lymphoma not with ovarian involvement itself. Surgical removal of involved ovary was performed in 20 patients (62%), and then they were treated with systemic chemotherapy. Twelve patients (38%) were treated with chemotherapy alone. The comparison of outcomes according to the treatment modalities showed the outcomes of chemotherapy-based treatment versus surgery-based treatment were not significantly different (2 year overall survival; 66% vs. 68%). With a median follow-up of 25 months (range 3-185), 13 patients (40.6%) relapsed. Two patients were relapsed in single lesion and 11 were relapsed in multiple lesions. The majority relapsed at various extranodal sites (11/13, 84.6%) and only 2 cases relapsed at nodal sites. Most common relapse site was CNS (4 cases among 13 cases of relapse, 31%). All CNS relapsed patients had DLBCL histology. Ovarian relapse observed in one case that had been involved both ovary at the time of diagnosis. The 2 year overall survivals (OS) were 67% (95% CI: 50 to 83%) and the 2 year progression free survivals (PFS) were 61% (95% CI: 44 to 78%). In univariate analysis, high IPI score, 2 or more extranodal sites involvement and elevated LDH level were statistically significant parameters for lower PFS; moreover, 2 or more extranodal sites involvement and elevated LDH level associated with poor OS. Conclusion Ovarian involvement of non-Hodgkin's lymphoma showed a dismal prognosis despite active treatment. Therefore, more optimal treatment strategy should be warranted. Disclosures No relevant conflicts of interest to declare.

SYK and STAT3 Are Active in Diffuse Large B-Cell Lymphoma: Activity of Cerdulatinib, a Dual SYK/JAK Inhibitor

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 926-926
Author(s):  
Y. Lynn Wang ◽  
Jiao Ma ◽  
Wei Xing ◽  
Pin Lu ◽  
Karen Dresser ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Staining Pattern ◽  
B Cell Lymphoma ◽  
Down Regulation ◽  
Dual Inhibitor ◽  
Large B Cell Lymphoma ◽  
Bcr Signaling ◽  
Large B Cell

Abstract Non-Hodgkin Lymphoma (NHL) represents about 5 percent of all cancers diagnosed in the United States. While incidence of NHL has increased slightly over the past decade, death rates have been declining steadily. These declines in mortality can be attributed to improvements in treatment that are based on an increased understanding of the biology of the disease. Diffuse large B-cell lymphoma (DLBCL) accounts for ~30% of NHLs and greater than 80% of aggressive NHLs. Recent studies including large-scale genetic analyses have demonstrated the critical roles of the B-cell receptor’s (BCR) and JAK/STAT pathways in DLBCL. Herein, we investigated the anti-lymphoma activity of cerdulatinib (aka PRT062070), a novel compound that dually targets both SYK and JAK/STAT signaling pathways. To determine whether targeting both SYK and JAK/STAT is relevant in DLBCL, we examined the expression of p-SYK (pY525/526) and p-STAT3 (pY705) on a tissue microarray of 62 DLBCL primary tumors, including 41 GCB and 21 non-GCB cases. p-SYK expression was detected in 29 (47%) cases with a characteristic peri-membrane staining pattern. Of those 29 p-SYK positive cases, 17 were GCB type (17/41, 41%) and 12 were non-GCB type (12/21, 57%). p-STAT3 exhibits a characteristic nuclear staining pattern in DLBCL cases. A total of 26 (42%) stained positive for p-STAT3; 16 were GCB type (16/41, 39%) and 10 were non-GCB type (10/21, 48%). Interestingly, there are 19 cases (31%) with reactivity for both p-SYK and p-STAT3, among which, 11 were GCB type (27%) and 8 were non-GCB type (38%). SYK and STAT3 are also phosphorylated in a panel of nine DLBCL cell lines. Immunoblotting analyses showed that ABC and GCB subtypes of DLBCL cells appear to exhibit different JAK/STAT and BCR signaling profiles. For instance, p-AKT was highly expressed in GCB cells, whereas p-STAT3 was more strongly expressed in ABC cells. Overall, the DLBCL cells are more sensitive to the dual inhibitor than to the SYK-specific inhibitor alone. In both GCB and ABC cell lines, cerdulatinib induced apoptosis via down-regulation of MCL1 protein and PARP cleavage. The compound also blocked G1/S transition and caused cell cycle arrest through inhibition of RB phosphorylation and down-regulation of cyclin E. Further analyses of the cell signaling activities showed that STAT3 phosphorylation was sensitive to inhibition by cerdulatinib in ABC cell lines while phosphorylation of SYK, PLCg2, AKT and ERK was sensitive to inhibition by cerdulatinib in GCB cell lines. Importantly, JAK/STAT and BCR signaling can be blocked by cerdulatinib in GCB and non-GCB primary human DLBCL cells, which led to cell death of these cells. Our work provided mechanistic insights into the actions of SYK/JAK dual inhibitor cerdulatinib, suggesting that the drug may be a potent treatment of DLBCL with a broader anti-tumor activity in both ABC and GCB subtypes of the lymphoma. Disclosures Pandey: Portola Pharmaceuticals: Employment. Conley:Portola Pharmaceuticals: Employment. Coffey:Portola Pharmaceuticals: Employment.

Safety, Pharmacokinetics, and Preliminary Clinical Activity of Inotuzumab Ozogamicin, a Novel Immunoconjugate for the Treatment of B-Cell Non-Hodgkin's Lymphoma: Results of a Phase I Study

2010 ◽  
Vol 28 (12) ◽  
pp. 2085-2093 ◽  
Author(s):  
Anjali Advani ◽  
Bertrand Coiffier ◽  
Myron S. Czuczman ◽  
Martin Dreyling ◽  
James Foran ◽  
...  
Keyword(s):  
Phase I ◽  
B Cell ◽  
Phase I Study ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Inotuzumab Ozogamicin ◽  
Large B Cell Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Large B Cell

Purpose Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. This was a phase I study to determine the maximum-tolerated dose (MTD), safety, and preliminary efficacy of inotuzumab ozogamicin in an expanded MTD cohort of patients with relapsed or refractory CD22+ B-cell non-Hodgkin's lymphoma (NHL). Patients and Methods Inotuzumab ozogamicin was administered intravenously as a single agent once every 3 or 4 weeks at doses ranging from 0.4 to 2.4 mg/m2. Outcomes included MTD, safety, pharmacokinetics, response, progression-free survival (PFS), and overall survival. Results Seventy-nine patients were enrolled. The MTD was determined to be 1.8 mg/m2. Common adverse events at the MTD were thrombocytopenia (90%), asthenia (67%), and nausea and neutropenia (51% each). The objective response rate at the end of treatment was 39% for the 79 enrolled patients, 68% for all patients with follicular NHL treated at the MTD, and 15% for all patients with diffuse large B-cell lymphoma treated at the MTD. Median PFS was 317 days (approximately 10.4 months) and 49 days for patients with follicular NHL and diffuse large B-cell lymphoma, respectively. Conclusion Inotuzumab ozogamicin has demonstrated efficacy against CD22+ B-cell NHL, with reversible thrombocytopenia as the main toxicity.

scholarly journals Diffuse large B-cell Lymphoma mimicking as cholangiocarcinoma in a young male presenting with obstructive jaundice

2021 ◽  
Vol 5 (1) ◽  
pp. 039-040
Author(s):  
Danish Muhammad ◽  
Khan Shoaib Ahmed ◽  
Samoon Dilnawaz ◽  
Majid Zain ◽  
Hanif Farina ◽  
...  
Keyword(s):  
Bile Duct ◽  
Obstructive Jaundice ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Large B Cell Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Large B Cell

The involvement of bile duct in lymphoma is considered to be very rare and is usually a sequela of a disseminated disease [1]. In contrast to secondary involvement, primary non-Hodgkin’s lymphoma arising from the bile duct is extremely rare and presents with obstructive jaundice [2,3]. Non-Hodgkin’s lymphoma (NHL) accounts for 1% - 2% of all cases of malignant biliary obstruction [4]. Hepatobiliary involvement by malignant lymphoma is usually a secondary manifestation of systemic lymphoma. The first case of Non-Hodgkin lymphoma arising from bile duct was described by Nguyen in 1982 [5]. Most common extra nodal involvement of NHL is abdomen. Although, involvement of the stomach, pancreas or common bile duct is not common [6]. We present to you a case of 31year old male who presented to us with obstructive jaundice and was later diagnosed as Diffuse Large B-Cell lymphoma.

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