scholarly journals Localized DLBCL of the Tonsil: A U.S. Population-Based Survival Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2522-2522
Author(s):  
Jorge A Florindez ◽  
Izidore S. Lossos ◽  
Juan Pablo Alderuccio
Keyword(s):  
Lymph Nodes ◽  
Family Member ◽  
Survival Data ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Treatment Modalities ◽  
Subdistribution Hazard ◽  
Common Location ◽  
Neck Lymph Nodes

Abstract INTRODUCTION: The Waldeyer ring represents a common location of diffuse large B-cell lymphoma (DLBCL) arising in the head and neck. Within the Waldeyer ring, tonsils are the most common site. Chemotherapy with or without consolidation with radiotherapy are the most common approaches. However, the benefit of radiotherapy over chemotherapy as a single approach in patients with localized DLBCL remains unclear. In this study we analyzed the survival effect of different treatment modalities along with clinical variables in two cohorts of patients with stage I DLBCL involving either the tonsils or the neck lymph nodes (LN). METHODS: This is a retrospective analysis of patients with stage I DLBCL with primary involvement of the tonsil or neck lymph nodes derived from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2015 with follow up through 2017. We concentrated our analysis on patients with Ann Arbor stage I and treated with chemotherapy and/or radiotherapy. We excluded cases without histologic confirmation, untreated, incomplete survival data or unknown cause of death. The major end-points of this study were overall survival (OS) and lymphoma-specific survival (LSS). Kaplan-Meier and log-rank test were used in the OS analysis with Cox proportional hazard regression model to assess predictors of OS. LSS was evaluated using competing risk analysis. The Fine and Gray subdistribution hazard model was used to assess the effect of demographic and treatment related variables on the risk of lymphoma-specific death. We reported subdistribution hazard ratios (SHR) with corresponding 95% confidence intervals. RESULTS: 1978 (tonsil: 311 and neck LN: 1667) patients with DLBCL met the inclusion criteria. Overall, most patients were ≥ 60 years (n=1130, 57.1%), male (n=1101, 55.7%), white (n=1631, 82.5%), non-Hispanic (n=1775, 89.7%), and treated with chemotherapy (n=935, 47.3%) followed by chemotherapy/radiotherapy (n=929, 47%). Patients <60 years (48.9% vs 41.8%; P=0.019), non-White race (21.9% vs 16.7%; P=0.029) and Hispanic origin (14.1% vs 9.5%; P=0.013) were more common in DLBCL in tonsil compared to neck LN. Patients with tonsil DLBCL exhibited longer median OS compared to neck LN (16.2 vs. 14.2 years; P=0.033) (Figure 1A). In patients with tonsil DLBCL, consolidation with radiation did not lead to longer median 5-year OS (83.9%, 95%CI 76.7-89% vs 81.8%, 95%CI 74.1-87.4%; P=0.523) or LSS (HR=0.73, 95%CI 0.37-1.42; P=0.350) compared to chemotherapy (Figure 1B and Table 1). Contrary, patients with neck LN demonstrated better OS (5-year OS 82.6%, 95% 79.7-85.1 vs 72.2% 95%CI 68.9-75.2%; P<0.001) and LSS (HR=0.55, 95%CI 1.51-3.14; P<0.001) if they received consolidation with radiotherapy compared to chemotherapy only (Figure 1C and Table 2). CONCLUSION: Based on our analysis consolidation with radiotherapy does not improve OS or LSS in patients with stage I tonsil DLBCL treated with chemotherapy. Conversely, consolidation with radiation significantly improves survival in patients with localized LN DLBCL. Figure 1 Figure 1. Disclosures Lossos: NCI: Research Funding; Seattle Genetics: Consultancy; Stanford University: Patents & Royalties; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment. Alderuccio: ADC Therapeutics: Consultancy, Research Funding; Oncinfo / OncLive: Honoraria; Puma Biotechnology: Other: Family member; Inovio Pharmaceuticals: Other: Family member; Agios Pharmaceuticals: Other: Family member; Forma Therapeutics: Other: Family member.

Outcomes of Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) Patients Treated with R-CHOP.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2812-2812 ◽  
Author(s):  
Michelle A. Fanale ◽  
Chao-Ming Lai ◽  
Peter McLaughlin ◽  
Jorge Romaguera ◽  
Luis Fayad ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Hodgkin's Lymphoma ◽  
Stage Iii ◽  
Field Radiation

Abstract Abstract 2812 Introduction: Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) constitutes 5% of Hodgkin's lymphoma (HL) diagnoses. Recently gene expression profiling has shown significant overlap between NLPHL, T-cell-rich B cell lymphoma (TCRBCL), and classical HL (Brune, V et al, J Exp Med, 2008). NLPHL patients also have an approximate 7% risk of transformation at 10 years to diffuse large B-cell lymphoma (DLBCL) and TCRBCL (Al-Mansour, M et al, JCO, 2010). Data from multiple groups (Nogova, L et al, Ann Onc, 2005, Chen, RC et al, JCO, 2010, Wirth, A et al, Cancer, 2005) support extended progression-free survivals (PFS) for stage IA/IIA patients treated with radiation alone. While chemotherapy is generally recommended for patients with stage IB/IIB or III/IV disease, there is lack of guidelines on whether classical HL-directed regimens, such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), or B-cell lymphoma-directed regimens, such as R-CHOP (rituximab, cychlophosphamide, doxorubicin, vincristine, prednisone) should be used. Given the similarities between NLPHL and indolent CD20+ B-cell non-Hodgkin's lymphoma (NHL), our group started using the R-CHOP regimen for patients with NLPHL requiring systemic therapy. In order to examine the potential efficacy of this approach, we conducted a retrospective analysis of treatment outcomes in patients who received R-CHOP versus other regimens treated at UT MDACC from 1995 to 2010. Results: 83 patients were referred. 6 patients were found to have NLPHL with transformation to DLBCL or TCRBCL. 3 had alternative diagnoses. 11 lacked full immunophenotyping to confirm diagnosis. 63 patients had confirmed diagnoses of NLPHL (39 stage I/II and 24 stage III/IV). 52 NLPHL patients were evaluable (10 did not complete full treatment planning or were lost to follow-up and 1 is currently completing therapy). 7 patients had extranodal disease (thyroid, breast, lung, liver, bone marrow/cortex) and 8 had spleen involvement. Overall their median age at diagnosis was 40, male:female ratio was 2.5, and median follow-up is 46 months (range 8–149 months). 6 patients had relapse of NLPHL, 2 patients had transformation at a median of 39 months (1 to DLBCL, 1 to TCRBCL), 4 patients died (1 from acute myelogenous leukemia with deletion 7, 1 from DLBCL, 2 from unrelated causes while in remission), and 2 patients underwent autologous stem cell transplant (1 for relapsed NLPHL in 3rd complete remission and 1 for transformation to TCRBCL). Therapies for stage I/II NLPHL included: surgical excision alone (2 patients with stage IA disease declined radiation treatment), subtotal nodal irradiation (STNI), mantle field radiation, involved field radiation (IFRT), rituximab (R) alone and plus IFRT, ABVD plus STNI, R-ABVD, COPP (cyclophosphamide, vincristine, procarbazine, prednisone) plus IFRT, and R-CHOP alone and plus IFRT. Therapies for stage III/IV included: mantle field radiation (1 patient who declined chemotherapy), NOVP (mitoxantrone, vincristine, vinblastine, prednisone) plus mantle field radiation, ABVD, R-ABVD, R-CHOP alone and plus IFRT. A total of 15 patients received R-CHOP alone (4 stage I/II, 11 stage III/IV) and 5 patients received R-CHOP plus IFRT (4 stage I/II, 1 stage III/IV). Response to R-CHOP as assessed by CT scan criteria was 100% overall response rate (ORR) with 90% complete remissions (CR). No R-CHOP patients have had relapses or transformation with a median follow-up of 42 months (range 8–111 months). One patient treated with R-CHOP died of unrelated causes while in remission. However, with other therapies 19% have relapsed after median remissions of 38 months (range 4 to 72 months). R-CHOP when compared to other treatments has a trend towards improved PFS (Figures 1, 2, and 3). Survival rates for NLPHL patients at 5 years with 95% confidence intervals are: R-CHOP: PFS 0.95 (0.86, 1), OS (overall survival) 0.95 (0.86, 1) and other therapies: PFS 0.71 (0.55, 0.92), OS 0.91 (0.8, 1). Conclusions: Our data demonstrates that RCHOP is an effective regimen for the treatment of patients with NLPHL. A prospective evaluation of R-CHOP as a front-line treatment of NLPHL is under consideration. Disclosures: Fanale: Seattle Genetics: Research Funding; Novartis: Honoraria, Research Funding; Millenium: Research Funding; Genentech: Research Funding. Off Label Use: Given the CD20 positivity of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) rituximab has been evaluated previously for relapsed NLPHL and was shown to be efficacious. Rituximab however is not FDA approved for NLPHL. This is a retrospective study that evaluates the use of R-CHOP and other therapies for NLPHL. Current NCCN guidelines support consideration of R-CHOP for NLPHL treatment, and given the rarity of the disease there is no one defined preferred chemotherapy regimen. This information will be disclosed to the audience. Fayad:Genentech: Research Funding. Rodriguez:Genentech: Research Funding. Shah:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Novartis: Research Funding. Younes:Genentech: Honoraria, Research Funding; SBIO: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Seattle Genetics: Honoraria, Research Funding.

scholarly journals Prognostic Impact of Gastrointestinal Involvement in Newly Diagnosed Diffuse Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5400-5400
Author(s):  
David Kasouha ◽  
Nicola Lehners ◽  
Katharina Kriegsmann ◽  
Gerlinde Egerer ◽  
Anthony D Ho ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Elevated Serum ◽  
B Cell Lymphoma ◽  
Treatment Modalities ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Curative Intent ◽  
Large B Cell Lymphoma

Abstract Introduction: Involvement of >1 extranodal site is regarded as a poor prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). It is necessary to clarify the prognostic impact of specific extranodal sites. Gastrointestinal (GI) involvement is one of the most frequently involved extranodal sites. Methods: Patients with newly diagnosed DLBCL treated at the University of Heidelberg between 06/2001 and 07/2015 were identified and included in this retrospective analysis. Data on clinical characteristics and treatment modalities were obtained by review of medical charts. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The impact of variables on PFS and OS was evaluated by univariate log-rank tests and by multivariate analysis using the Cox proportional hazards model. Results: A total of 1001 patients were identified of whom 119 (11.9%) presented with GI involvement. Median age of patients with GI involvement was 63.3 years [range 19.1-86.7], 71 (59.7%) were male. 92 patients had an available international prognostic index (IPI) score, 36 (39.1%) IPI 0-1, 33 (35.9%) IPI 2-3, and 23 (25%) IPI 4-5. The most frequently involved organs of GI were stomach (51.3%), small intestine (39.5%), colon (20.2%), and esophagus (2.5%). 107 (89.9%) patients were treated in curative intent and were further analyzed regarding the prognostic impact of several factors on outcome. 80.4% of them received CHOP-like therapies, 17.8% received chemotherapy more aggressive than CHOP, typically addition of etoposide or treatment with high-dose methotrexate in case of CNS involvement, 87.9% received additional rituximab, and 22.4% additional radiotherapy In DLBCL patients with GI involvement, we identified factors associated with worse OS (P<.05) by univariate analysis: B symptoms, elevated serum LDH, and involvement of more than two extranodal sites. On the contrary, age (>60 years), sex, Ann Arbor Stage (AAS) III/IV, and Performance Status of Eastern Cooperative Oncology Group (ECOG) more than one, and elevated serum sCD25 did not have any significant impact on OS. B symptoms were as well associated with decreased PFS (P<.05) by univariate analysis. Multivariate Cox Regression analysis revealed that patients with elevated serum LDH at diagnosis had significantly worse OS (P<.05), and patients with B symptoms had significantly worse PFS (P<.05). Regarding first-line treatment modalities, escalation of chemotherapy to more aggressive regimes than CHOP was associated with a prolonged OS and PFS in univariate analysis, not in multivariate analysis. Radiotherapy did not have any significant impact on OS or PFS. Regarding all DLBCL patients treated with curative intent, GI involvement did not have any significant prognostic impact on OS or PFS. Conclusions: In this retrospective registry analysis of patients with newly diagnosed DLBCL with GI involvement, B symptoms, elevated serum LDH, and involvement of more than two extranodal sites were identified as risk factors for inferior OS. Escalation of chemotherapy to more aggressive regimes than CHOP was associated with a prolonged OS and PFS. Further analyses are required as toward which treatment modalities might be best suited to improve prognosis of GI involvement. Disclosures Kriegsmann: Celgene: Research Funding; BMS: Research Funding.

Can a Dose-Dense RCHOP-Like Regimen Be Effectively Used In a Community Setting? Results of a Phase II Study Employing Pegylated Liposomal Doxorubicin In Elderly (> age 60) or Cardiac Compromised (LVEF <45%) Patients with Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2797-2797
Author(s):  
Stephen J. Noga ◽  
Judith Bosley ◽  
Pamela Nickoles
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Research Funding ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Dose Dense

Abstract Abstract 2797 Chemotherapy employing the RCHOP every 21 day regimen has become the standard of care for patients with DLBCL. Although the GELA study did include older patients, NHL incidence rises more steeply with age, with a third of cases occurring in patients over 75 years of age. Community oncologists see an ever-increasing NHL age group with multiple co-morbidities. There is also debate whether DLBCL is more aggressive/chemo-resistant at the higher age range. For many, cardiac issues exclude them from an adriamycin-based regimen and possible cure. Since pegylated liposomal doxorubicin (PLD) has a reported lower cardiac toxicity profile even at higher overall doses than doxorubicin, it was substituted into a dose-dense RCHOP regimen. To this end, we developed a phase II dose-dense/dose escalation study of PLD (Doxil®,20 mg/m2: cohort I, 25 mg/m2: cohort II, 30 mg/m2: cohort III), cyclophosphamide (CY, 750 mg/m2), vincristine (1.4 mg/m2: 2 mg max), prednisone (100 mg PO days 1–5) and rituximab (375 mg/m2) on day 1 followed by pegfilgrastim (Neulasta®, 6 mg, SC) on day 2 of a 14 day cycle. Patients received a planned 6 cycles of chemotherapy or 2 cycles past best response. Patients >60 years or with left ventricular ejection fractions (LVEF) <45% were enrolled with ECOG performance status (PS) of 0 – 3. Three, 6 and 8 patients (17 total) were enrolled on cohorts I – III, respectively, Intent to treat (ITT) data included all patients. Response/survival data excluded 2 patients who deteriorated by start of cycle 1 chemotherapy. Safety and SAE's were assessed with each cohort. Quantitative LVEF was obtained with each cycle, CT's every 3 cycles and PET/CT at baseline and within 60 days of chemotherapy completion. Median age was 78 (62-87), 59% were female and baseline LVEF from 12% (with AICD but ECOG PS1) to 87% (median 60%). There was no reduction in LVEF for patients receiving >1 cycle of chemotherapy. Patients who were hospitalized (PS>2) or who's PS declined rapidly between study entry and cycle 1 initiation rapidly became too moribund to complete planned therapy. Relative dose intensity [RDI: (delivered chemotherapy/time to complete)/(planned chemotherapy/planned time to complete)] for the entire group averaged 96 (83 – 100)% for PLD, median 100%, and 97 (86 – 100)%, median 100%, for cyclophosphamide. Nearly all patients (92%) achieved a CR/nCR with a 77% CR rate. Despite an every 14 day anthracycline regimen, Grade >2 hematologic toxicities were manageable and others were low. Overall Survival in the ITT population was 65% and 37% at 12 and 24 months, respectively. Censoring for patients removed in or after cycle 1 yielded a survival rate of 73% at 12 months and 42% at 24 months. This elderly patient population had significant long term morbidities, post-chemotherapy, leading to mortality from cardiac disease, ARF and liver failure besides lymphoma related causes. Adjusting for the non-lymphoma deaths gave adjusted survivals of 85% and 71% at 12 and 24 months, respectively. We conclude that it is feasible to deliver a dose-dense anthracycline regimen to geriatric patients with acceptable toxicity. Indeed, 71% of study patients were ≥ 70 years and 47% were ≥ 80 years. Microarray analysis may pinpoint which elderly patients may require a more intensive regimen to effect cure. Grade (%) N F/N Hosp F/N Tpenia PPE Cardiac Stomatitis All 88 24 24 82 65 24 47 3 24 12 12 24 6 12 6 4 41 12 12 6 6 - - Neutropenia =N, Febrile Neutropenia =F/N, Hospitalization for F/N = Hosp F/N, Thrombocytopenia = Tpenia, Palmar- Plantar erythrodysesthesia = PPE Disclosures: Noga: Amgen: Honoraria, Research Funding, Speakers Bureau, none; Millenium Takada: Consultancy, Honoraria, Research Funding, Speakers Bureau, none; Ortho-Centicor: Research Funding, Speakers Bureau, none; Cephalon: Honoraria, Speakers Bureau, none; Pfizer: Speakers Bureau, none; Cellgene: Honoraria, Research Funding, Speakers Bureau, none. Off Label Use: Doxil (pegylated liposomal doxorubicin) in place of adriamycin in a CHOP-R regimen for DLBCL.

scholarly journals MSKCC Early Experience Using Radiotherapy As a Bridging Strategy for Relapsed Diffuse Large B Cell Lymphoma before CD19 CAR T Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3238-3238 ◽  
Author(s):  
Brandon Imber ◽  
M. Lia Palomba ◽  
Carl DeSelm ◽  
Connie Lee Batlevi ◽  
Parastoo B. Dahi ◽  
...  
Keyword(s):  
Family Member ◽  
Board Of Directors ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Equity Ownership ◽  
Grade 3 ◽  
Bridging Strategy

Background: CD19-targeted chimeric antigen receptor T cell (CAR T) therapies have remarkable overall response rates (ORR) for relapsed diffuse large B cell lymphoma (DLBCL). There is strong rationale to use a radiotherapy (RT) bridge during the cell manufacturing process including palliation, local control and cytoreduction with limited count impact. Recent data from our institution suggests RT may augment an immune response and sensitize antigen negative cells to CAR-mediated death. This series details our early experience using RT conditioning. Methods: 13 patients (median age 64 years) with DLBCL (n=9) or transformed follicular lymphoma (n=4) were analyzed. Overall, patients had a median of 2 prior therapies (range 1-8) including 3 with autologous transplant, 3 with distant RT and 1 with CAR T infusion. Several CAR products were used, including axicabtagene ciloleucel (n=8), JCAR017 (n=3, per NCT02631044), tisagenlecleucel (n=1) and EGFRt/19-28z/4-1BBL "armored" CAR (n=1, per NCT03085173). Most patients (n=10) began RT post apheresis with median duration between RT and CAR infusion of 20d (range 13-80, Figure 2). The most common RT regimen (n=8) was 20 Gy in 5 fractions (range 20-47 Gy) but 2 received our pre-transplant regimen of 30 Gy in 20 BID fractions. None received concurrent chemotherapy with RT but one had a cycle post RT and pre CAR. All had cyclophosphamide and fludarabine lymphodepletion. PET response was evaluated by Lugano criteria. Results: Three patients had limited stage PET avid disease at RT and were treated comprehensively pre-CAR. The remaining 10 were advanced stage and were treated palliatively to limited sites. Irradiated sites included the pelvis/groin (n=4), neck (n=3), intraabdominal (n=2) and extremity (n=2). Most (n=10) had intensity modulated radiotherapy. RT fields were large (median planning treatment volume of 887 cc, range 163-1641). Post RT PET interpretation was challenging given a short interval since RT ended (median 11d) but of 11 evaluable patients, many (n=8, 73%) had partial response (PR). Though locally controlled, most (n=10, 91%) had out of field progressive disease (PD) pre-CAR. Post CAR T, no severe adverse events in the RT field were noted, 9/13 had cytokine release syndrome (n=1 grade 3, n=2 grade 2) and 4 had neurotoxicity (n=3 grade 3). At day 30, ORR was 90%; of 10 evaluable patients, 7 had complete response (CR) and 2 had partial response (PR). Of the 7 evaluable patients at day 90, 4 (57%) had continued CR and the other 3 (43%) had PD and subsequently died from DLBCL. One relapsed at 95d post armored CAR both in and out of the RT field, and the other relapsed at 64d post JCAR017 primarily out of field. Conclusions: Use of RT as a CAR T bridging strategy is feasible and associated with excellent pre-CAR local control and initial post CAR ORR in a cohort of heavily pre-treated DLBCL patients. We observed moderate serious CAR toxicity that did not appear to be augmented by RT. Future efforts should clarify the optimal RT timing/dose and assess the potential for incremental immunogenicity with combined therapy. Disclosures Palomba: Hemedicus: Other: Immediate Family Member, Speakers Bureau ; Merck & Co Inc.: Other: Immediate Family Member, Consultancy (includes expert testimony); Seres Therapeutics: Other: Immediate Family Member, Equity Ownership and Membership on an entity's Board of Directors or advisory committees; STRAXIMM: Other: Immediate Family Member, Membership on an entity's Board of Directors or advisory committees; Kite Pharmaceuticals: Other: Immediate Family Member, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Noble Insights: Consultancy; Evelo: Other: Immediate family member, Equity Ownership; MSK (IP for Juno and Seres): Other: Immediate Family Member, Patents & Royalties - describe: intellectual property rights . Batlevi:Juno Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Giralt:Celgene: Consultancy, Research Funding; Takeda: Consultancy; Sanofi: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Noy:Medscape: Honoraria; Prime Oncology: Honoraria; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding; NIH: Research Funding; Janssen: Consultancy. Park:Amgen: Consultancy; Autolus: Consultancy; AstraZeneca: Consultancy; GSK: Consultancy; Incyte: Consultancy; Kite Pharma: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Allogene: Consultancy. Sauter:Juno Therapeutics: Consultancy, Research Funding; Genmab: Consultancy; GSK: Consultancy; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Kite/Gilead: Consultancy; Precision Biosciences: Consultancy; Sanofi-Genzyme: Consultancy, Research Funding. Scordo:Angiocrine Bioscience, Inc.: Consultancy; McKinsey & Company: Consultancy. Shah:Janssen: Research Funding; Amgen: Research Funding. Sadelain:Memorial Sloan Kettering Cancer Center: Employment; Juno Therapeutics: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics: Consultancy, Patents & Royalties. Perales:Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; MolMed: Membership on an entity's Board of Directors or advisory committees; NexImmune: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Medigene: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Kyte/Gilead: Research Funding; Miltenyi: Research Funding.

Malignant salivary gland tumors: A large single-institutional series evaluating long-term outcome

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16523-16523
Author(s):  
S. Limaye ◽  
R. Dulala ◽  
R. Roy ◽  
A. Thomas ◽  
D. Janson ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Survival Data ◽  
Salivary Gland Tumors ◽  
Stage I ◽  
Treatment Modalities ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Malignant Salivary Gland Tumors

16523 Background: Malignant salivary gland tumors comprise 3 to 6% of Head and Neck cancers. Long term survival data for salivary gland tumors are lacking. We undertook an analysis of all such patients treated at our institution over a 15 yr period. Methods: IRB approval was obtained for this retrospective analysis. Tumor registry data were reviewed for all adult patients diagnosed with salivary gland malignancies for the years 1990 - 2005. Age, Gender, Stage, histology, treatment modalities and survival data were recorded. Results: 200 patients were identified. Median age was 64 yrs (59–69). M:F ratio was 1:1.1 (M: 96; F: 104). Histology and stages: ( Table 1 )Mucoepidermoid Carcinoma (n=50), Adenoid Cystic Carcinoma (n=21), Acinar Cell Carcinoma (n=19), Adenocarcinoma (n=22; Stages: I= 7, II= 4, III= 3, IV= 8), Squamous (n= 12; Stages: I= 1, II= 3, III= 3, IV=5), Poorly Differentiated Carcinoma(n=10), Epithelial Myoepithelial Carcinoma (n=7), Malignant Mixed Carcinoma (n=4), Malignant Myoepithelioma (n=2), Carcinoma in Pleomorphic Adenoma (n=2) and Others (n=15). Hodgkin's and NHL (n=36).Treatment modalities: Surgery (S): n=88 (44%), Radiotherapy (RT): n=6 (3%); Chemotherapy (CT): n=6 (3%); S+RT: n =76(38%); S+CT: n=8 (4%); RT+CT: n =2(1%); S+RT+CT: n =4 (2%). Observation only : n=10(5%). Survival data (Med. survival and 5 yr OS respectively) for all histologies excluding lymphomas are: Stage I - 84 mos,93%; II - 93 mos,85%; III - 39 mos,60 %; IV - 24 mos, 40%. Survival data (Med survival and 5 yr OS) for lymphomas: Stage I - 55 mos,85%; II - 20 mos, 0%; III - 100 mos, 100%; IV- 48 mos, 25%. Median survival of all histology types excluding lymphoma by treatment: S=55 mos, S+RT= 60 mos, S+ CT= 56 mos, RT= 53 mos, RT+CT=15 mos, CT= 24 mos. Conclusions: This large series provides long term outcome data for a relatively rare group of HNCs. Long term survival is noted in several histological sub-types even in the setting of advanced disease. These data should help further define the natural history and biological behaviors of these tumors. [Table: see text] No significant financial relationships to disclose.

scholarly journals Diffuse large B-cell lymphoma in a patient with chronic myelogenous leukemia on accelerated phase with bilateral pleural effusion: a case report

2020 ◽  
Vol 8 (2) ◽  
pp. 743
Author(s):  
M. Huki Zukhrufan ◽  
Eifel Faheri
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Myelogenous Leukemia ◽  
X Ray ◽  
Large B Cell Lymphoma ◽  
Chest X Ray ◽  
Large B Cell ◽  
Neck Lymph Nodes

Chronic Myelogenous Leukemia (CML) is a myeloproliferative disorder of pluripotent stem cells. The pathogenesis of CML is known to be related to mutations in the form of Philadelphia chromosomes. The incidence of CML constitutes 20% of all cases of leukemia in adults. The current gold standard for CML therapy is using tyrosine kinase inhibitors (TKI), Imatinib. Non-Hodgkin Lymphoma (NHL) is a malignancy that develops from lymph nodes. In NHL the formation of malignant cells is in the form of lymphocytes that are at one of the differentiation levels of either T lymphocytes or B lymphocytes. Diffuse large B cell lymphoma is the most common NHL, representing about 40% of all lymphoma cases. NHL management is targeted chemotherapy using rituximab combined with cyclophosphamide, doxorubicine, vincristine and prednisone. A Thirty-four year-old female patient has been reported with the main complaint of fatigue and pale weakness accompanied by an enlarged abdomen. Complaints are also accompanied by a lump in the right neck, fever, productive cough and shortness of breath. The patient has been known to suffer from CML with BCR-ABL (+) since five years ago and received Imatinib therapy, but then the patient stopped treatment himself. On physical examination found anemic, multiple enlargement of the neck lymph nodes, wet crackles soft and loud in the basal of both lungs and splenomegaly. On investigations found severe anemia, thrombocytopenia and blast 13%, increased d-dimer, bronchopneumonia-compliant infiltrate and bilateral pleural effusion on chest x-ray, results of exudate pleural fluid analysis with the cytology of a malignant smear metastasis of lymphoma to the pleura, histopathology of the neck lymph nodes with chest x-ray, analysis of exudate pleural fluid with the cytology of a malignant smear metastasis of lymphoma into the pleura, histopathology of the neck lymph nodes with the results of diffuse large B-Cell lymphoma, as well as enlargement of paraaortic lymph nodes, hepatosplenomegaly and chronic pancreatitis on abdominal ultrasound. Patients was given antibiotics, transfusion of packed red cells and platelets, pleural tap and chemotherapy. The patient was planned to undergo chemotherapy for 6 cycles of 21 days, and a CD20 examination was performed. The incidence of NHL in patients with good CML in imatinib therapy is not yet certain whether there is a direct relationship.

scholarly journals Frequency, Histologic, and Prognostic Significance of CD30 Expression in AIDS-associated Diffuse Large B-Cell Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1447-1447
Author(s):  
Amina Chaudhry ◽  
Muhammad Junaid Tariq ◽  
Eshana Shah ◽  
Camille E. DeMarco ◽  
Erin G. Reid ◽  
...  
Keyword(s):  
Germinal Center ◽  
Survival Data ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cd4 T Cell ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Principle Investigator ◽  
Cd4 T Cell Count

Abstract Introduction: AIDS-related Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, with a variable response to chemotherapy depending on, and not limited to, cell of origin, double/triple hit, or MYC/BCL-2 co-expression status. Similar to DLBCL, AIDS-related DLBCL (ARL) with non-germinal center histology or MYC expression reports poorer response to treatment. In the immunocompetent population CD30+ DLBCL defines a histology with improved survival, however, the characteristics and outcomes of ARL expressing CD30 are not well studied. Methods: We assessed 3 cohorts of ARL. The first cohort, consisted of of an immunohistochemistry tissue microarray (TMA) of 30 ARL patients, followed by two validation cohorts. The first validation was a TMA of 80 ARL, from the AIDS Cancer Specimen Resource. Both TMAs were stained for CD10, BCL6, MUM1, CD20, Ki67, EBER, MYC (by IHC) cut off at 40%, BCL2 (by IHC) cut off 50%, and CD30 (considered positive if any CD30 was expressed on the malignant cells). The third validation cohort was from the County Hospital AIDS Malignancy Project (CHAMP), a prospective database of patients with hematological malignancies and HIV. Of the 100 cases with ARL, only 25 cases were found to have CD30 staining performed, thus only those cases were included. In total, 135 patients diagnosed with ARL were assessed. Cell of origin and germinal (GCB) vs. non-germinal center (NGC) was determined by the Hans algorithm. Statistical differences between groups were analyzed by the fisher exact test. Survival data, when available, was estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Of the 135 ARL, 30% (n=41) were CD30+. Ninety-one% of the cohort was male. EBER was 23% positive in the entire cohort (n=29/126). EBER was positive in the CD30+ vs. CD30- population, 59% (N=17) vs 26% (p&lt;0.01). Despite 59% of the CD30+ population being EBER positive, 92% of the population had a NGC phenotype, 2% was germinal, and 5% had a null phenotype (p&lt;0.01). Of the 86 patients that were CD30-, 88% were GC vs. 12% NGC (P&lt;0.01). The CD4+ T-cell count at presentation was higher in the CD30- cohort with a mean CD4+ T-cell count of 234 vs.164 cells/ul (p&lt;0.05), similar to historical studies demonstrating a similar effect in germinal vs. non-germinal center ARL. Ki67 &gt; 80% was also higher in the CD30- vs the CD30+ cohort 75 vs.60%, (p=0.052). Myc, BCL2, and double expressor lymphomas were identified 59 vs. 57%, 59 vs. 57%, and 31 vs. 28%, respectively, in the CD30+ ARL vs. the CD30- population, none were statistically significant. Survival data was only obtained for 56 of the patients. In the patients treated in the combined anti-retroviral era (ART), there was no difference in survival in the CD30+ vs. CD30- population, 74% (n=18) vs. 84% (n=12) at 5 years (p=0.8). In the 15 patients treated in the early ART era, the OS at 5 years was 48% for the CD30+ vs. 52% (p=0.4), the rest were treated in the pre-ART era. Conclusion: CD30+ ARL in this cohort represents 30% of all ARL evaluated, and presents almost exclusively as a non-germinal center phenotype and has a strong correlation with EBV. While no differences in survival were identified in this study, possible due to the small numbers of patients assessed with survival data, historically, NGC ARL have been shown to have poorer outcomes, by 20-30% in studies with da-EPOCH. As such, the need for better therapies, potentially to overcome these poor prognostic factors, should be studied further. Figure 1 Figure 1. Disclosures Reid: ADC Therapeutics: Other: Serves as Principle Investigator, Research Funding; Aptose Biosciences: Other: Serves as Principle Investigator, Research Funding; Millennium Pharmaceuticals: Other: Serves as Principle Investigator, Research Funding; Xencor: Other: Serves as Principle Investigator.

scholarly journals MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Byunghee Yoo ◽  
Alana Ross ◽  
Pamela Pantazopoulos ◽  
Zdravka Medarova
Keyword(s):  
Breast Cancer ◽  
Rna Interference ◽  
Lymph Nodes ◽  
Therapeutic Effect ◽  
Metastatic Breast ◽  
Treatment Modalities ◽  
Transcriptional Level ◽  
Metastatic Progression ◽  
Therapeutic Modalities ◽  
Metastatic Colonization

AbstractRNA interference represents one of the most appealing therapeutic modalities for cancer because of its potency, versatility, and modularity. Because the mechanism is catalytic and affects the expression of disease-causing antigens at the post-transcriptional level, only small amounts of therapeutic need to be delivered to the target in order to exert a robust therapeutic effect. RNA interference is also advantageous over other treatment modalities, such as monoclonal antibodies or small molecules, because it has a much broader array of druggable targets. Finally, the complementarity of the genetic code gives us the opportunity to design RNAi therapeutics using computational, rational approaches. Previously, we developed and tested an RNAi-targeted therapeutic, termed MN-anti-miR10b, which was designed to inhibit the critical driver of metastasis and metastatic colonization, miRNA-10b. We showed in animal models of metastatic breast cancer that MN-anti-miR10b accumulated into tumors and metastases in the lymph nodes, lungs, and bone, following simple intravenous injection. We also found that treatment incorporating MN-anti-miR10b was effective at inhibiting the emergence of metastases and could regress already established metastases in the lymph nodes, lungs, and bone. In the present study, we extend the application of MN-anti-miR10b to a model of breast cancer metastatic to the brain. We demonstrate delivery to the metastatic lesions and obtain evidence of a therapeutic effect manifested as inhibition of metastatic progression. This investigation represents an additional step towards translating similar RNAi-targeted therapeutics for the systemic treatment of metastatic disease.

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