scholarly journals Extended Use of Rituximab in Older Adults with Non-Hodgkin Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1279-1279
Author(s):  
Matthew J. Matasar ◽  
Coral L. Atoria ◽  
Elena B. Elkin ◽  
Chadi Nabhan
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Rural Areas ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
The United States ◽  
Non Hodgkin Lymphoma ◽  
To Receive

Abstract Background: The introduction of rituximab has improved outcomes in B-cell non-Hodgkin lymphoma (BCL) across all histologies. Extended use of rituximab, or maintenance rituximab, improves progression-free survival in follicular lymphoma (FL) patients who achieve a response to induction rituximab with or without chemotherapy, but there is no evidence of an overall survival benefit. There is currently little evidence to support extended use of rituximab in other histologic subgroups, and older patients in particular may be at risk of adverse events. Our objective was to characterize patterns and predictors of extended rituximab therapy in a population-based cohort of older BCL patients in the United States. Methods: In the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset,we identified patients 66 years and older diagnosed with BCL in 2000-2010. Histology was classified as diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), FL, mantle cell lymphoma (MCL), other indolent BCL, and BCL not otherwise specified (NOS). We identified Medicare claims for rituximab starting at any point following diagnosis. Extended rituximab therapy was defined as a duration of greater than 7 months with no gap in rituximab claims greater than 6 months. Demographic and clinical characteristics associated with extended rituximab were evaluated in multivariable logistic regression. Results: There were 24,232 BCL patients who received rituximab during the study period. The cohort was predominantly white (91%), half were men, 15% had a Charlson comorbidity score ≥2, and 12% were 85 years or older. DLBCL was the most common histology (44%), followed by FL (21%), other indolent BCL (17%), BCL-NOS (13%), MCL (6%), and BL (1%). Overall, most patients (85%) received rituximab for ≤7 months, but duration varied by histology (Table 1). More than a quarter of FL patients had extended therapy, including 7% who had rituximab for more than 24 months. Among patients with other histologies, receipt of extended therapy varied from 20% (other indolent BCL) to 8% (BL). Compared with FL patients and controlling for demographic and disease characteristics, patients with other histologies were less likely to receive extended rituximab therapy (p<0.0001). Adjusted odds ratios were 0.91 (95% CI 0.78-1.05) for MCL, 0.83 (0.75-0.91) for other indolent BCL, 0.67 (0.60-0.75) for BCL-NOS, 0.32 (0.29-0.36) for DLBCL, and 0.28 (0.15-0.53) for BL. However, 75% of patients who had extended rituximab, and 63% of those who had rituximab >24 months, were of non-FL histology. Controlling for histology and other characteristics, extended rituximab therapy was more likely among women (adjusted OR 1.09, 95% CI 1.01-1.18), and less likely among unmarried patients (0.92, 0.85-0.99) and those in rural areas (0.84, 0.75-0.94). There was significant regional variation (p<0.0001), with patients in the West (adjusted OR 0.86, 95% CI 0.79-0.95), and Midwest (0.75, 0.66-0.86) less likely to receive extended rituximab than those in the Northeast. There was no significant relationship between extended therapy and age, race, or comorbidity. Conclusions: While FL patients were more likely than others to receive extended rituximab, the majority of patients receiving extended rituximab had other diagnoses across the entire spectrum of B-cell lymphoma, for which extended rituximab is neither indicated nor supported by guidelines or prospective data. After controlling for histology, several demographic characteristics significantly influenced the duration of therapy. Extended use of rituximab – particularly in patients for whom it is not clearly indicated – may have important implications for clinical outcomes, toxicity, and costs. Table 1 Duration of rituximab use across B-cell lymphoma histologic subgroups Histology Duration of Rituximab N ≤7 mos >7-24 mos >24 mos DLBCL 10,567 91% 7% 2% FL 5,001 76% 17% 7% BL 127 92% 6% 2% MCL 1,339 79% 16% 5% Other indolent 4,095 80% 15% 5% BCL NOS 3,103 83% 13% 4% Total 24,232 80% 15% 5% Disclosures Matasar: Merck: Research Funding; GlaxoSmithKline: Research Funding; Genentech: Honoraria; Spectrum: Honoraria. Nabhan:Celgene: Honoraria, Research Funding.

scholarly journals Ibrutinib in Relapsed or Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma: Final Results from a Prospective Phase II Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1596-1596
Author(s):  
Solomon A. Graf ◽  
Ryan D. Cassaday ◽  
Karolyn K. Morris ◽  
Sanaz Behnia ◽  
Qian Vicky Wu ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Tumor Burden ◽  
Genetics Research ◽  
Non Hodgkin Lymphoma ◽  
Prospective Phase ◽  
Previously Treated

Background : Relapsed or refractory (R/R) transformed indolent B-cell non-Hodgkin lymphoma (iB-NHL) is an uncommon clinical entity associated with poor prognosis. Unfortunately, most trials of aggressive B-NHL tend to specifically exclude transformed disease resulting in scant prospective data to guide therapy. We performed a prospective phase II trial of single agent ibrutinib in patients with previously treated transformed iB-NHL and now report the final results (NCT02207062). Methods : Eligibility included measurable, biopsy-proven transformed iB-NHL, no prior ibrutinib, ECOG 0-2, and prior receipt of ≥ 1 line of therapy for the transformed disease. Treatment consisted of oral ibrutinib 560 mg daily until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response rate (ORR, per Lugano criteria by independent radiology review), with a predefined threshold of success ≥ 30%. Secondary endpoints included clinical benefit rate (CBR, defined as ORR and/or stable disease of ≥ 6 months), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoints included ORR according to cell-of-origin (COO) of transformed lymphoma assessed by Hans algorithm and disease burden measured by computed tomography (CT) and metabolic tumor volume (MTV). Results : From October 2014 to March 2019, 20 patients were treated (Table 1). At enrollment, patients had received a median of 4 prior therapies (range 2 to 9) and were refractory to chemotherapy in 10 (50%) cases. Histology of transformed disease was diffuse large B cell lymphoma (DLBCL) in all patients. Two patients came off study prior to response assessment and without clinical evidence of disease progression: 1 after 1.3 months for intractable mucositis and 1 who died suddenly and without known cause 1.9 months into treatment. Median time on therapy was 3.1 months range (0.6 to 48.0) with 3 (15%) patients continuing on therapy > 1 year. Eighteen patients were evaluable for response. The ORR was 39% (complete response = 17%) and CBR was 44%. Median PFS and OS were 4.1 and 22.4 months, respectively, and median duration of response was 2.3 months; estimated 12-month PFS was 18% (Figure 1). ORR was more common in cases of low tumor burden but this association did not meet statistical significance on univariate analysis (p = 0.15 for maximum tumor < 5 cm by CT and p = 0.06 for MTV < 100 cm3). ORR was superior after prior autologous hematopoietic stem cell transplantation (auto-HSCT) (p = 0.01) and was not associated with DLBCL COO (p = 0.75). Dose holds for toxicity were required on 6 occasions in 5 (25%) patients for a median duration of 17.5 days (range 8 to 21); no reductions in dose were performed. Ibrutinib was resumed after resolution of toxicity at full dose in each case with the exception of an episode of pneumonia that, despite resolution, prompted the patient to stop treatment on study. Adverse events (AEs) considered related to ibrutinib were most commonly grade 1-2 and included fatigue (55%), bruising (55%), and diarrhea (35%). Grade ≥ 3 AEs included atrial arrythmia in 2 patients and the following AEs in 1 patient each: ventricular arrythmia, neutropenia, lymphopenia, mucositis/esophagitis, nausea, pneumonia, sepsis, and death of unknown cause. Conclusions : Ibrutinib appears active in R/R transformed iB-NHL and may provide extended disease control for a subset of patients or as part of a bridging strategy prior to CAR-T or transplant. The observed toxicity profile was consistent with other trials. Efficacy may be greater in cases of lower tumor burden and in patients previously treated with auto-HSCT. Further investigation of ibrutinib and focused study of agents in transformed iB-NHL is warranted. Disclosures Graf: BeiGene: Research Funding; AstraZeneca: Research Funding; TG Therapeutics: Research Funding. Cassaday:Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Kite/Gilead: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Other: Spouse's disclosure: employment, stock and other ownership interests; Amgen: Consultancy, Research Funding. Lynch:Rhizen Pharmaceuticals S.A: Research Funding; Incyte Corporation: Research Funding; Takeda Pharmaceuticals: Research Funding; T.G. Therapeutics: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy; Juno Therapeutics: Research Funding. Krakow:Bellicum Pharmaceuticals: Research Funding; Highpass Bio: Research Funding; Magnolia Innovations: Consultancy. Smith:Denovo Biopharma: Research Funding; Acerta Pharma BV: Research Funding; Portola Pharmaceuticals: Research Funding; Incyte Corporation: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Ignyta (spouse): Research Funding; Ayala (spouse): Research Funding; Pharmacyclics: Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Seattle Genetics: Research Funding. Gopal:Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte: Honoraria; Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte.: Consultancy; Teva, Bristol-Myers Squibb, Merck, Takeda, Seattle Genetics, Pfizer, Janssen, Takeda, and Effector: Research Funding. OffLabel Disclosure: Ibrutinib is not approved for previously treated transformed indolent B-cell lymphoma.

scholarly journals Incidence and Characteristics of CD20 Monoclonal Antibody-Induced Interstitial Pneumonitis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4567-4567
Author(s):  
Jacob Newton Stein ◽  
Natalie S Grover ◽  
Janhvi Rabadey ◽  
Christopher Dittus
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Interstitial Pneumonitis ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Antibody Therapy ◽  
B Cell Lymphoma ◽  
Monoclonal Antibody Therapy ◽  
Non Hodgkin Lymphoma

Abstract Background: CD20 monoclonal antibody therapy is the backbone of treatment for B-cell non-Hodgkin lymphoma. Several studies have described an association between the use of rituximab and non-infectious interstitial pneumonitis, with estimates ranging from 3.9% to 8.4%. 1-3 However, several novel CD20 monoclonal antibodies have been introduced in the past decade, with obinutuzumab gaining FDA approval in 2013, ofatumumab first approved in 2014, and rituximab/hyaluronidase human approved as a subcutaneous route of rituximab in 2017. While the use of these agents has rapidly increased in clinical practice, the incidence of pneumonitis with these agents is not well known. Thus, we have performed a retrospective review of patients with B cell lymphoma treated with CD20 monoclonal antibody therapy to determine the incidence and characteristics of pneumonitis with these novel agents. Methods: We evaluated all patients at the University of North Carolina at Chapel Hill with B-cell lymphoma who were treated with CD20 monoclonal antibody therapy from 2014 to 2020. We performed individual chart review to verify the presence of interstitial pneumonitis, as defined by presence of respiratory symptoms (cough, dyspnea, fever, chest pain) in addition to imaging findings (pulmonary opacity on chest X-ray and/or ground glass opacities on chest computed tomography (CT)) without alternative cause (CHF with pulmonary edema, COPD flare, infectious cause including bacterial, fungal or viral pneumonia/bronchitis). We extracted demographic data, comorbid conditions, tobacco use history, and timing of pneumonitis related to CD20 monoclonal antibody exposure. We determined rates of pneumonitis based on agent and chemotherapy backbone. Results: We identified 18 cases of chart-confirmed interstitial pneumonitis over a six-year period, out of 2,207 patients treated with CD20-monoclonal antibody therapy. Seven (39%) were current or former smokers, with a median of 30 pack-years smoked. Five (29%) had a history of hypersensitivity reaction to rituximab infusion. Pneumonitis developed after a median of 4 cycles, and 16 days from the most recent CD20 monoclonal antibody infusion. Ten (56%) had diffuse large B-cell lymphoma, 4 (22%) had mantle cell lymphoma, and 1 (6%) each had follicular lymphoma, chronic lymphocytic leukemia, hairy cell leukemia, and Waldenstrom's macroglobulinemia. Eight cases (44%) occurred among patients being treated with R-CHOP, 2 (11%) were treated with BR, 2 (11%) were receiving single agent rituximab, although several other regimens were represented. Most cases occurred in patients being treated with infusional rituximab, but the rate remained quite low (14/1654, 0.8%). Four occurred in patients receiving subcutaneous rituximab hycela out of 167 treated patients (2.4%), less than prior estimates of pneumonitis with monoclonal antibody therapy. Most cases of pneumonitis were treated with steroids (n=15, 83%), although none required infliximab or anti-TNF agents, and no cases of pneumonitis were fatal. Most notably, we did not identify any cases of pneumonitis among patients treated with ofatumumab (n=51) or obinutuzumab (n=58). Conclusion: This retrospective review reinforced the safety of novel anti-CD20 agents, with low rates of interstitial pneumonitis among patients treated with infusional or subcutaneous rituximab. Cases that did occur were effectively treated with steroids, and there were no fatalities associated with pneumonitis. Ofatumumab and obinutuzumab were not associated with any cases of interstitial pneumonitis. Bibliography 1. Katsuya H, Suzumiya J, Sasaki H, et al. Addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy has a high risk of developing interstitial pneumonia in patients with non-Hodgkin lymphoma. Leuk Lymphoma. 2009;50(11):1818-1823. doi:10.3109/10428190903258780 2. Salmasi G, Li M, Sivabalasundaram V, et al. Incidence of pneumonitis in patients with non-Hodgkin lymphoma receiving chemoimmunotherapy with rituximab. Leuk Lymphoma. 2015;56(6):1659-1664. doi:10.3109/10428194.2014.963075 3. Liu X, Hong X-N, Gu Y-J, Wang B-Y, Luo Z-G, Cao J. Interstitial pneumonitis during rituximab-containing chemotherapy for non-Hodgkin lymphoma. Leuk Lymphoma. 2008;49(9):1778-1783. doi:10.1080/10428190802270886 Figure 1 Figure 1. Disclosures Grover: Novartis: Consultancy; Genentech: Research Funding; ADC: Other: Advisory Board; Kite: Other: Advisory Board; Tessa: Consultancy. Dittus: BeiGene: Other: Advisory Board; Seattle Genetics: Research Funding; AstraZeneca: Research Funding; Genentech: Research Funding.

scholarly journals Molecular Sub-typing of Diffuse Large B-cell Lymphoma

2021 ◽  
Author(s):  
Thomas Drago
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Rapid Development ◽  
B Cell Lymphoma ◽  
The United States ◽  
Cellular Level ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is the most common form of Non-Hodgkin Lymphoma (NHL) in adults. Affecting nearly 7 out of every 100,000 people in the United States annually, this hematogenous neoplasm is known for its aggressiveness and rapid development. Being the most common NHL, it has been divided into several subgroups based on pathogenesis and treatment methods. In particular, subtypes such as germinal center, activated B-cell-like, and primary mediastinal diffuse large B-cell lymphomas  have been divided by their uniqueness of pathology at the cellular level. Knowing the numerous cytokines, inflammatory markers, and other microcellular processes that these lymphomas disrupt can help target an effective therapeutic at the disease.

scholarly journals Clinical significance of metabolism-related biomarkers in non-Hodgkin lymphoma – MCT1 as potential target in diffuse large B cell lymphoma

2019 ◽  
Vol 42 (3) ◽  
pp. 303-318 ◽  
Author(s):  
Julieta Afonso ◽  
Tatiana Pinto ◽  
Susana Simões-Sousa ◽  
Fernando Schmitt ◽  
Adhemar Longatto-Filho ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Clinical Significance ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Potential Target ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Mediastinal Gray Zone Lymphoma with Features Intermediate between Classical Hodgkin Lymphoma and Primary Mediastinal B-Cell Lymphoma

2016 ◽  
Vol 136 (3) ◽  
pp. 186-190 ◽  
Author(s):  
Haa-Na Song ◽  
Seok Jin Kim ◽  
Young Hyeh Ko ◽  
Won Seog Kim
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Systemic Chemotherapy ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Gray Zone ◽  
Bulky Disease ◽  
Gray Zone Lymphoma ◽  
Frontline Therapy

Background: Mediastinal gray zone lymphoma (MGZL) shares clinical characteristics with primary mediastinal B-cell lymphoma (PMBCL) and nodular sclerosing Hodgkin lymphoma (NSHL). However, MGZL is extremely rare, and an appropriate treatment for it has not yet been established. Methods: We retrospectively analyzed 8 patients who were treated with systemic chemotherapy for MGZL between 2007 and 2014. Results: The patients with MGZL were predominantly young and male (median age 26 years), and 62.5% of patients had bulky disease. The overall response rate (ORR) and complete remission (CR) rate were both 75% (6/8) for all treated patients The median overall survival (OS) and progression-free survival (PFS) was 40.7 and 3.9 months, respectively. Most responders (4/6, 66.7%) were treated with R-CHOP (rituximab + cyclophosphamide, hydroxydaunorubicin, Oncovin and prednisolone) as the frontline therapy. The CR rate of patients who received R-CHOP and those who did not was 100% (4/4) and 50% (2/4), respectively. Particularly striking was the finding that the median PFS of patients who received R-CHOP frontline chemotherapy was 11.4 months, which was superior to the median PFS of patients who did not receive R-CHOP. Conclusions: Of the 8 patients with MGZL who were treated with systemic chemotherapy, superior treatment responses were observed in patients who received R-CHOP as the frontline therapy.

Familial risk for non-Hodgkin lymphoma and other lymphoproliferative malignancies by histopathologic subtype: the Swedish Family-Cancer Database

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 668-672 ◽  
Author(s):  
Andrea Altieri ◽  
Justo Lorenzo Bermejo ◽  
Kari Hemminki
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Familial Risk ◽  
B Cell Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Swedish Family ◽  
History Of ◽  
Large B Cell

Abstract Non-Hodgkin lymphoma (NHL) consists of a heterogeneous group of tumors. Population-based data on the familial risk for specific histopathologic subtypes have not been established. Such data are useful for clinical counseling and for searching tumor subtypes sharing common genetic pathways. We used the Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for histopathology-specific subtypes of NHL in 4455 offspring with NHL whose parents or siblings were affected with different types of lymphoproliferative malignancies. A familial history of NHL significantly increased the risk for NHL (SIRparent = 1.8; SIRsibling = 1.9) and for diffuse large B-cell lymphoma (SIRparent = 2.3), follicular lymphoma (SIRsibling = 2.3), and B-cell lymphoma not otherwise specified (NOS) (SIRsibling = 3.4). For a parental history of histopathology-specific concordant cancer, the risks were significantly increased for diffuse large B-cell lymphoma (SIR = 11.8), follicular NHL (SIR = 6.1), plasma cell myeloma (SIR = 2.5), and chronic lymphocytic leukemia (SIR = 5.9). Familial clusters for NHL seemed stronger in females and in siblings. Our study provides the first quantification of the familial risks for NHL by histopathology. The present findings give evidence for a strong familial association of NHL, with little differences in the magnitude of risks for various histopathologic subtypes. The patterns of risks in parents and siblings support the hypothesis of an autosomal-dominant component for diffuse large B-cell NHL and a recessive one for follicular NHL. (Blood. 2005;106:668-672)

Role of FDG PET/CT to Detect Bone Marrow Involvement in the Initial Staging of Aggressive Non-Hodgkin Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2892-2892 ◽  
Author(s):  
Dominic Kaddu-Mulindwa ◽  
Bettina Altmann ◽  
Gerhard Held ◽  
Marita Ziepert ◽  
Karin Menhart ◽  
...  
Keyword(s):  
B Cell ◽  
Gold Standard ◽  
Fdg Pet ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Initial Staging

BACKGROUND: According to the Lugano classification (Cheson et al., JCO 2014, 32: 3059-3067) fludeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for evaluation and staging of aggressive non-Hodgkin Lymphoma (NHL). It is a matter of debate whether FDG PET/CT is sufficient to determine bone marrow (BM) involvement. We performed a pooled analysis of data from the PETAL (EudraCT 2006-001641-33) and OPTIMAL>60 trials (EudraCT 2010-019587-36) as prospective, open-label, randomized, multicenter Phase-III trials to determine whether initial staging with FDG PET/CT would allow non-invasive diagnosis of BM involvement and thus could avoid established but potentially painful and unpleasant BM biopsy (BMB). PATIENTS AND METHODS: Patients treated within the trials were included if both FDG PET/CT and BMB were performed during initial staging. Only patients with a biopsy-proven, centrally confirmed diagnosis of diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma or follicular lymphoma grade 3b were included. FDG PET/CT images and BM findings were blinded for central review by board certified PET/CT readers. Discordant findings were documented and resolved after unblinding by interdisciplinary discussion using findings of complementary imaging and/or subsequent PET examinations. Based on literature (Berthet et al., J Nucl Med 2013), a newly defined gold standard was used to confirm BM involvement. It includes a positive BMB or a positive FDG PET confirmed by targeted biopsy, complementary CT imaging or targeted MRI, or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy. RESULTS: Out of 1,976 patients a total of 930 patients met the inclusion criteria. BMB confirmed BM involvement in 85 of 930 patients (9%). According to FDG PET/CT, BM was involved in 185 out of 930 patients (20%) with 36 discordances (4%) between negative initial FDG PET/CT and positive BMB ("false negatives" with respect to previous reference standard, PRS). Discordances between positive initial FDG PET/CT and negative BMB ("false positives" by PRS) occurred in 136 patients (15%). If only BMB is used as in the PRS, the negative predictive value (NPV) of FDG PET/CT was 709/745=95% (95% confidence interval [95%CI]: 93%-97%) with a sensitivity (Sens) of 58% (95%CI: 46%-68%) and a specificity (Spec) of 84% (95%CI: 81%-86%). After discussion of these cases, 185 out of 221 cases with BM involvement were identified as true positive, resulting in a Sens of 84% for FDG PET/CT (95%CI: 78%-88%). By means of FDG PET/CT 745 cases were negative of which 709 were confirmed as true negatives, resulting in an NPV of 95% (95%CI: 93%-97%). All 185 cases with positive FDG PET/CT were evaluated as true positive for BM involvement in the unblinded synopsis of all findings, resulting in a positive predictive value (PPV) of 100% (95%CI: 98%-100%). All 709 negative FDG PET/CT findings were finally confirmed as such, so Spec was 100% (95%CI: 99%-100%). Thus, the prevalence in our total cohort analyzed was 24%, since 221 out of 930 cases had confirmed BM involvement. Diagnostic performance parameters for BMB as compared to the newly defined gold standard were Sens 85/221=38% (95%CI: 32%-45%), Spec 709/709=100% (95%CI: 99%-100%), PPV 85/85=100% (95%CI: 96%-100%) and NPV 709/845=84% (95%CI: 81%-86%), respectively. Differences between the PRS in the diagnosis of BM involvement by only BMB and the newly defined gold standard result mainly from false negative BMB due to sampling errors, which are detected by FDG PET/CT. DISCUSSION: In the majority of patients with aggressive B-cell lymphoma, routine BMB does not give any additional relevant diagnostic or prognostic information over FDG PET/CT alone and could therefore be omitted. BMB should only be performed if results would have direct therapeutic impact e.g. in patients with limited stage disease and lack of further risk factors according to the international prognostic index (IPI). Disclosures Held: MSD: Consultancy; Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Roche: Consultancy, Other: Travel support, Research Funding; Amgen: Research Funding; Acrotech: Research Funding. Stilgenbauer:Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Hoffmann La-Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Duehrsen:Amgen: Consultancy; University Hospital Essen, Germany: Employment; Takeda: Consultancy; Novartis: Consultancy; Gilead: Honoraria; Janssen: Honoraria; Gilead: Consultancy; AbbVie: Consultancy; Celgene: Research Funding; CPT: Consultancy; Takeda: Honoraria; Novartis: Honoraria; Amgen: Research Funding; Roche: Research Funding; AbbVie: Honoraria; Amgen: Honoraria; CPT: Honoraria. Hüttmann:University Hospital Essen: Employment; Takeda: Honoraria; Gilead: Honoraria. Poeschel:Amgen: Other: Travel, accommodations, expenses; Abbvie: Other: Travel, accomodations, expenses; Roche: Other: Travel, accomodations, expenses; Hexal: Speakers Bureau.

A Phase II Clinical Study of Rituximab and High-Dose Biweekly THP-COP (Pirarubicin, Cyclophosphamide, Vincristine and Predonisolone) with G-CSF for Non-Hodgkin Lymphoma: Results of a Multicentric Study of NMLSG (Niigata Malignant Lymphoma Study Group).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4734-4734
Author(s):  
Jun Takizawa ◽  
Sadao Aoki ◽  
Kazue Takai ◽  
Tohri Kurasaki ◽  
Keiichiro Honma ◽  
...  
Keyword(s):  
Clinical Study ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Histological Subtypes ◽  
Non Hodgkin Lymphoma

Abstract Introduction CHOP chemotherapy has been accepted as the standard treatment for patients with non-Hodgkin lymphoma (NHL), but in some histological or clinical subtypes the results are not satisfactory. We have shown the efficacy and safety of high-dose biweekly THP-COP with G-CSF support (HDBW-TCOP(G)) for NHL. In this regimen, we choose pirarubicin in stead of doxorubicin because it was proven high efficacy against NHL and the lower toxicity than doxorubicin. Recently, the combination of rituximab and standard CHOP has been shown to have a synergistic effect for NHL. We performed a phase II multicentric clinical study to assessed the feasibility and toxicity of the combination chemotherapy of rituximab and HDBW-TCOP(G) (HDBW-R-TCOP(G)) compared with those of HDBW-TCOP(G). Patients and methods Between August 1998 and December 2004, Forty-one Japanese patients with previously untreated NHL from whom informed consent was obtained were included in this study. Median age was 45 (range 19–63) years. There were 19 males and 22 females. According to WHO-classification diagnoses, histological subtypes included follicular lymphoma (FL) 15(37%); nodal marginal zone B-cell lymphoma (NMZBCL) 2(5%); mantle cell lymphoma (MCL) 3(7%); anaplastic large cell lymphoma (ALCL) 1(2%), diffuse large B-cell lymphoma (DLBCL) 18(44%); peripheral T-cell lymphoma (PTCL) 1(2%), angioimmunoblastic T-cell lymphoma (AILT) 1(2%). Of 41 patients, one patient was stage 1, stage 2, 11 stage 3 and 16 stage 4. International prognostic index (IPI) included L 6; LI 22; HI 7; H 6. HDBW-TCOP(G) consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 orally from day 1 to 5; lenograstim 2.0 μg/kg/day from day 3. Fifteen patients who enrolled after rituximab was approved in Japan received therapy combined HDBW-TCOP(G) with rituximab 375mg/ m2 on day -2 (HDBW-R-TCOP(G)). Six cycles were administered at intervals of two weeks. Results Of the 41 patients treated, 32 (78.0%) achieved a complete remission (CR) and nine (22.0%) achieved a partial remission (PR), for an overall response rate of 100%. After median follow-up of 36 months (range 2.9– 81.8), progression free survival (PFS) and overall survival (OS) were 68.2% and 97.5%, respectively. PFS was 90.9% for HDBW-R-TCOP(G), and 69.5% for HDBW-TCOP(G), but no significant differences was found among two regimen. There was no significant difference in the PFS and OS between aggressive and indolent histological subtypes. 76% of patients developed Grade4 leukopenia (according to NCI criteria) but no patients experienced febrile neutropenia. 15% of patients developed G4 anemia and 17% of patients G4 thrombocytopenia. Other adverse effects were minimal. Conclusion Both HDBW-TCOP(G) and HDBW-R-TCOP(G) are feasible for NHL with acceptable toxicity. The excellent result suggests they are effective for aggressive NHL patients with poor prognostic factors and advanced stage indolent NHL.

Clinical Outcome of 119 Children with Non-Hodgkin Lymphoma Treated in a Single Center in China

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5299-5299
Author(s):  
Yonghong Zhang ◽  
Ling Jin ◽  
Jing Yang ◽  
Yanlong Duan ◽  
Chunjv Zhou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoblastic Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Pathologic Classification

Abstract One hundred and nineteen children with non-Hodgkin lymphoma were treated between February 2003 and December 2006 in Beijing Children’s Hospital on BCH-2003-NHL protocol. The diagnosis was made by histopathology of the biopsied tissue and/or bone marrow, and disease was classified according to WHO-2001 pathologic classification. We applied modified LMB89 protocol to cases with B-cell lymphoma; modified BFM90-ALL protocol for lymphoblastic lymphoma and cutaneous T-cell/NK cell lymphoma; and modified BFM90-ALCL protocol for anaplastic large-cell lymphoma (ALCL). There were 50 cases (42%) of B cell lymphoma including 32 cases of Burkitt¡’s lymphoma, 10 cases of Burkitt-like lymphoma and 8 cases of diffuse large B cell lymphoma; 44 cases (37%) of lymphoblastic lymphoma; 19 cases (16%) of ALCL; and 6 cases (5%) of cutaneous T-cell/NK cell lymphoma. The 85 boys and 34 girls (ratio, 2.5:1) ranged in age from 2 to 15 years (median, 7.8 years) at diagnosis. B cell lymphoma typically presented as abdomen mass and acute abdomen; nasopharynx and tonsil were also common sites of involvement. Lymphoblastic lymphoma generally presented with mediastinal mass and bone marrow involvement. There was no typical presentation for ALCL. According to the St. Jude staging system, 19 cases had stage I–II, and 94 cases stage III–VI diseases (exclude 6 cases of cutaneous T-cell/NK cell lymphoma). Seven cases had CNS involvement and 25 cases involved bone marrow. The treatment duration was 2 to 8 months for B-cell lymphoma, 2.5 to 3 years for lymphoblastic lymphoma and 1 to 1.5 years for ALCL. The follow-up rate was 100% and median observation period was 23 months. The overall survival (OS) at 3 years was 90.7% and the 3-year event-free survival (EFS) estimate was 82.3%. For B-cell lymphoma, 3-year OS was 88.68% and 3-year EFS was 81.8%. For lymphoblastoma lymphoma, the rates were 89.3% and 69.4%, respectively. All cases of ALCL are alive with on undergoing treatment for relapse. Patients with ALCL achieved the best 3-year OS (100%) and had 3-year EFS of 94.2%. Grade 3 or 4 bone marrow suppression occurred in 97.5% of patients with B-cell lymphoma, 100% of those with lymphoblastic lymphoma and 89.5% of cases with ALCL. As of to date, 11 patients have died, the causes of death include infection (n=4), abandonment of therapy (n=6) and relapse (n=1). Univarate analysis showed that stage IV disease, failure to achieve complete remission after 3 months of treatment, and bulky mass are were associated with poor prognosis £all P values &lt;0.05£©. In summary, we have achieved excellent treatment results using modified international protocols. Infection and financial problem remained the main reasons of treatment failure.

Aberrant Expression of Golgin-84 in Non-Hodgkin Lymphomas and Plasma Cell Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4633-4633
Author(s):  
Ling Chen ◽  
Yaling Yang ◽  
C. Cameron Yin ◽  
Gary Lu ◽  
Su Chen ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Plasma Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoid Cells ◽  
Plasma Cell Myeloma ◽  
Expression Levels ◽  
Non Hodgkin Lymphoma

Abstract Abstract 4633 Background: Golgins are proteins of the Golgi complex. Several Golgins have been implicated in apoptosis. Expression of Golgin-84, a Golgin protein, is altered in apoptotic WEHI-231, a B-cell lymphoma line, suggesting that Golgin-84 may play a role in lymphoid tumorigenesis. Here, we aimed to determine the expression levels of Golgin-84 in human primary non-Hodgkin lymphomas and plasma cell myeloma. Design: Golgin-84 expression was investigated in non-Hodgkin lymphoma cell lines by using Western blot analysis and polyclonal antibodies. Using immunohistochemical stains, Western blotting analysis and Q-PCR, Golgin-84 expression was assessed in 5 reactive lymph nodes, 149 cases of primary non-Hodgkin lymphoma and 28 cases of primary plasma cell myeloma. Results: Immunohistochemical stains, Western blotting analysis and Q-PCR on 5 reactive lymph nodes demonstrated that Golgin-84 was expressed at low levels in lymphoid cells of germinal centers, mantle cells, marginal zones, and interfollicular areas. Golgin-84 was variably expressed in non-Hodgkin lymphoma cell lines tested, with the highest levels in cells from high-grade tumors (e.g. anaplastic large cell lymphoma; ALCL, Diffuse large B-cell lymphoma (DLBCL), ALCL and peripheral T-cell lymphoma unspecified (PTCL)) and the lowest levels in mantle cell lymphoma (MCL) cells. DLBCL, ALCL and PTCL frequently showed high expression of Golgin-84. Most lymphoplasmacytic lymphomas (LPL) and plasma cell myeloma (PCM) expressed high levels of Golgin-84. Expression levels of Golgin-84 were lower in MCL and low-grade B-cell non-Hodgkin lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). Conclusions: Golgin-84 expression levels are low in lymphoid cells of normal lymph nodes. Most (>90%) cases of LPL and PCM, and at least half of cases of DLBCL, ALCL and PTCL express high levels of Golgin-84. These findings suggest that Golgin-84 may be involved in tumorigenesis or lymphoma progression, particularly in neoplasms with plasmacytic differentiation. Disclosures: No relevant conflicts of interest to declare.

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