Gender and Race As Prognostic Factors In Patients Treated With Rituximab For B-Cell Non-Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3053-3053
Author(s):  
Mendel Goldfinger ◽  
Santiago Aparo ◽  
Krishna Gundabolu ◽  
Stefan K Barta

Abstract Introduction The International Prognostic Index (IPI) and the age-adjusted IPI (aaIPI) are the most commonly used tools to predict outcomes in patients with Non-Hodgkin Lymphoma (NHL). The IPI does not take into account sex or race. In the pre-rituximab era, sex was found to be a strong predictor of poor prognosis in low-grade lymphomas. While there is emerging evidence that female sex is associated with better survival in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP, much less is known about the prognostic impact of race. We retrospectively assessed the impact of sex and race on overall survival in patients with indolent and aggressive NHL treated at any stage with rituximab at our institution. Methods We retrospectively identified all patients >/=18 years who were diagnosed with B-cell NHL (except SLL/CLL and Burkitt lymphoma) between 1/1/2000 and 12/31/2010 and received rituximab at any stage as part of their therapy at the Montefiore Medical Center. We collected data on histology, age (<60 vs. >/=60), date of diagnosis, date and status at last follow-up, and stage from the MECCC Cancer registry, and we obtained data on the Charlson Comorbidity Index (CCI) from Clinical Looking Glass® (CLG), an interactive software application developed at Montefiore Medical Center which integrates clinical and administrative datasets. The histological subtypes DLBCL and grade 3 follicular lymphoma (FL) were classified as “high-grade lymphoma” (HGL), while other types of lymphoma were termed “low-grade lymphoma” (LGL; these included marginal zone lymphoma, mantle cell lymphoma, grade 1 & 2 FL, and malignant lymphoma NOS). Self-reported race was classified as White, Black, Hispanic or “Other”. Only <2% of the patients were of “Other” racial background and therefore excluded from this analysis. The primary outcome was overall survival (OS) calculated as time from diagnosis to time of death. We used the Kaplan-Meier (KM) method to describe OS for race and sex and the log-rank test to test for significance (p<0.05). We used a Cox proportional hazard (CPH) model to assess the association of variables with OS. Except for age, race and sex, variables that were not significantly associated with OS (i.e. p-value>0.10 in the multivariate model) were excluded from the final model (backward elimination). Results 353 patients were included in the analysis. Median follow-up for all patients was 37.3 months (range 0.03-202.40). Baseline characteristics between male and females were similar with the exception of age at diagnosis and histology (see Table 1). On univariate analysis there was no OS difference between male and female patients (p=0.13), while race was associated with significant differences in OS (p=0.04; see Fig. 1). In the multivariate model, only stage >/=3 was associated with worse survival (Hazard Ratio [HR] 2.78, 95% CI 1.62-4.77; p<0.0001), but there was no significant association with OS for type of lymphoma (HGL vs. LGL) or the CCI (low vs. high score) and these 2 variables were therefore eliminated from the final multivariate model. In the final multivariate model, female sex was associated with a 37% reduction in the risk of death (HR 0.63; 95%CI 0.40-0.98; p=0.04), while race was no longer associated with OS (Hispanic vs. White: HR 0.76, 95%CI 0.41-1.40, p=0.38; Black vs. White: HR 0.66, 95%CI 0.40-1.10; p=0.11; Black vs. Hispanic: HR 1.15; 95% CI 0.63-2.08, p=0.65). Conclusions Female patients treated at any stage with rituximab for high-grade and low-grade B-cell NHL at our institution experienced longer OS. However, we observed no racial disparity in survival in our analysis. Disclosures: No relevant conflicts of interest to declare.

2008 ◽  
Vol 2 ◽  
pp. CMO.S336
Author(s):  
Florentina Silvia Delli ◽  
Thomas Zaraboukas ◽  
Ioanna Mandekou-Lefaki

Primary cutaneous lymphomas are the second most common site of extranodal non-Hodgkin lymphoma. A specifically type named extranodal marginal zone B-cell lymphomas are indolent low-grade neoplasma. We report a case of a 42-year-old white man with multiple subcutaneous tumors located on the trunk and neck. The histopathological exam showed a non-epidermotropic, dense lymphocytic infiltrate. Histologic, immunohistochemical and cytologenetic analysis diagnosed primary cutaneous B-cell lymphoma MALT type. Investigation for other extranodal MALT lymphoma gastrointestinal tract, lung, salivary and thyroid glands was negative. The patient refused radiotherapy, but he accepted every 6 months close follow-up. Over a seven years period, we noticed a progressively disappearance of the skin lesions. The necessity of aggressive treatment of this disease with excellent prognosis is discussed. The treatment necessity of primary cutaneous B-cell lymphoma MALT type is discussed.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 463-463 ◽  
Author(s):  
Roberta Zappasodi ◽  
Gaia C Ghedini ◽  
Italia Bongarzone ◽  
Lorenzo Castagnoli ◽  
Maida de Bortoli ◽  
...  

Abstract Abstract 463 We recently reported that vaccination with autologous monocyte-derived dendritic cells pulsed with dying autologous tumor cells elicited a clinical response strongly associated with multifaceted antitumor immune-activation in relapsed indolent non-Hodgkin lymphoma (NHL) patients. We have now set out to determine whether vaccine-induced humoral response is directed against common indolent NHL-restricted antigens (ags), which could thus be exploited as novel targets for therapy. Antibodies (Abs) were purified from pre- and post-vaccine patients' serum samples, biotin-conjugated, and initially tested by immunohistochemistry (IHC) and flow cytometry (FC) on allogeneic tumors biopsies or live tumor cells, both primary tumors and cell lines. We found that post-vaccine Abs from responders (R) reacted with allogeneic NHL at significantly higher levels than their matched pre-vaccine samples or non-R Abs. Furthermore, Rs' post-vaccine sera significantly impaired the growth of DOHH-2 and RL-19 follicular lymphoma (FL) cell lines, as revealed by standard 3-(4,5- dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. To identify the therapeutically targeted NHL ags, we then used biotin-conjugated patient Abs to immunoblot one-dimensional SDS-PAGE of DOHH-2 cell protein fractions obtained by isoelectrofocusing. Protein bands differentially revealed by post-vaccine Abs from R were analyzed by Mass Spectrometry (MS). One differential band migrating at about 100 kDa was revealed among the most acidic protein fractions only when post-vaccine samples from R were used. MS analysis identified heat shock protein (HSP) 105 in the differentially reacting bands. Immunoprecipitation with a commercial anti-HSP105 Ab followed by Western blot analysis with biotin-conjugated pre- and post-vaccine Abs from R confirmed the increased ability of the post-vaccine sample to recognize HSP105. FC disclosed HSP105 both on the cell membrane and in the cytoplasm of a panel of B-cell NHL cell lines and normal B cells. The extent of HSP105 surface expression increased in function of lymphoma istotype aggressiveness. The antitumor activity of anti-HSP105 Ab, measured by MTT assays, was thus higher against Burkitt's lymphoma (BL) cell lines than germinal centre-derived diffuse large B cell lymphoma and FL cell lines, which displayed an IC50 of 4.5, 7.5, 11.7 μg/ml, respectively. To confirm these finding in primary human tumors, we performed IHC analyses of HSP105 on 68 diagnostic NHL specimens (35 low-grade and 33 high-grade NHL) and 23 non-malignant lymph nodes obtained from our Institutional Tissue Bank. Low-grade NHL's cytoplasmic immunoreactivity was mainly restricted to actively proliferating cells (i.e. Ki67 positive germinal centre cells), whereas high-grade NHL displayed a significantly higher expression of HSP105, measured both as intensity and percentage of positive cells (p=0.0002). In addition, malignant cells in high-grade NHL more often displayed a specific cell-surface staining. Interestingly, the expression pattern and intensity of HSP105 was widely superimposable on that of the proliferation marker Ki67, as detected by the specific monoclonal Ab Mib-1. Lastly, the therapeutic effects of HSP105 functional inhibition was studied in Namalwa BL xenotransplanted SCID mice using a specific commercial Ab. Treated mice showed a significant delay in tumor growth compared to untreated control animals (p=0.0014). Taken as a whole, our results indicate that HSP105 could be a new potential biotarget for the treatment of NHL and a novel candidate biomarker for an improved management of B-cell lymphoma. Its location on the normal B cell surface, and its increasing expression with NHL aggressiveness open a new area in which to assess its role in B-cell biology and lymphoma physiopathology. Disclosures: No relevant conflicts of interest to declare.


2019 ◽  
Vol 50 (3) ◽  
pp. 109-115
Author(s):  
Beata Grygalewicz

StreszczenieB-komórkowe agresywne chłoniaki nieziarnicze (B-cell non-Hodgkin lymphoma – B-NHL) to heterogenna grupa nowotworów układu chłonnego, wywodząca się z obwodowych limfocytów B. Aberracje cytogenetyczne towarzyszące B-NHL to najczęściej translokacje onkogenów takich jak MYC, BCL2, BCL6 w okolice genowych loci dla łańcuchów ciężkich lub lekkich immunoglobulin. W niektórych przypadkach dochodzi do wystąpienia kilku wymienionych aberracji jednocześnie, tak jak w przypadkach przebiegających z równoczesną translokacją genów MYC i BCL2 (double hit), niekiedy także z obecnością rearanżacji BCL6 (triple hit). Takie chłoniaki cechuje szczególnie agresywny przebieg kliniczny. Obecnie molekularna diagnostyka cytogenetyczna przy użyciu techniki fluorescencyjnej hybrydyzacji in situ (FISH) oraz, w niektórych przypadkach, aCGH jest niezbędnym narzędziem rozpoznawania, klasyfikowania i oceny stopnia zaawansowania agresywnych, nieziarniczych chłoniaków B-komórkowych. Technika mikromacierzy CGH (aCGH) była kluczowym elementem wyróżnienia prowizorycznej grupy chłoniaków Burkitt-like z aberracją chromosomu 11q (Burkitt-like lymphoma with 11q aberration – BLL, 11q) w najnowszej klasyfikacji nowotworów układu chłonnego Światowej Organizacji Zdrowia (World Health Organization – WHO) z 2016 r. Omówione zostaną sposoby różnicowania na poziomie cytogenetycznym takich chłoniaków jak: chłoniak Burkitta (Burkitt lymphoma – BL), chłoniak rozlany z dużych komórek B (diffuse large B-cell lymphoma – DLBCL) oraz 2 nowych jednostek klasyfikacji WHO 2016, czyli chłoniaka z komórek B wysokiego stopnia złośliwości z obecnością translokacji MYC i BCL2 i/lub BCL6 (high-grade B-cell lymphoma HGBL, with MYC and BCL2 and/or BCL6 translocations) oraz chłoniaka BLL, 11q.


2021 ◽  
Vol 148 (12) ◽  
pp. 102-107
Author(s):  
Trinh Le Huy ◽  
Tran Dinh Anh

Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare non-Hodgkin’s lymphoma with limited data. We here report a case of primary breast diffuse large B-cell lymphoma mimicking breast cancer. A 52-year-old woman had a painless mass in her right breast. Fine needle aspiration cytology and core biopsy were performed which suggested malignant features but could not confirm the specific subtype. Excisional biopsy then was conducted revealing non-Hodgkin lymphoma, which was subsequently confirmed with histopathology and diagnosed as diffuse large B-cell lymphoma (DLBCL). A chest computed tomography scan revealed a 3.5 cm sized breast mass with skin thickening and modest lymphadenopathy in the ipsilateral axilla. The patient received six courses of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab) chemotherapy, then whole breast radiation (30Gy in 15 fractions). At 12 months of follow-up, the patient survives with no evidence of disease. No morbidities occurred in this patient during the follow-up period. We briefly review the current practice pattern in patients with primary breast diffuse large B-cell lymphoma.


2020 ◽  
pp. 4241-4244
Author(s):  
S. J. Bourke

Lymphocytic infiltrations of the lung arise from the proliferation of bronchus-associated lymphoid tissue, resulting in a spectrum of rare conditions ranging from benign polyclonal lymphoid interstitial pneumonia to monoclonal primary malignant lymphomas of the lung. Lymphoid interstitial pneumonia is most commonly seen in Sjögren’s syndrome or other connective tissue diseases, and in association with HIV infection, and is characterized by reticulonodular shadowing on CT imaging and (usually) a good response to corticosteroids. Primary pulmonary lymphomas fall into three categories: lymphomatoid granulomatosis, low-grade B-cell lymphoma, and high-grade B-cell lymphoma. The latter require treatment with cytotoxic drugs and have a poor prognosis.


2019 ◽  
Vol 67 (2) ◽  
pp. 224-240
Author(s):  
Urszula Jankowska ◽  
Dariusz Jagielski ◽  
Michał Czopowicz ◽  
Rafał Sapierzyński

The aim of this study was to evaluate the epidemiology, clinical and laboratory characteristics of canine lymphomas as well as some aspects of treatment outcomes. The study was conducted on Boxer dogs with lymphoma diagnosed by cytology and immunocytochemistry (CD3 and CD79 alpha). During the study period, lymphoma was diagnosed in 63 Boxers; 86.8% were T-cell (based on the Kiel classification: small clear cell lymphoma, pleomorphic small cell lymphoma, pleomorphic mixed T-cell lymphoma, pleomorphic large T-cell lymphoma, lymphoblastic lymphoma/acute lymphoblastic leukaemia) and 13.2% were B-cell lymphomas (according to the Kiel classification: B-cell chronic lymphocytic leukaemia, centroblastic/centroblastic polymorphic lymphoma). Overall survival (OS) was significantly longer in dogs with low-grade than with high-grade lymphoma (median OS of 6.8 and 4.7 months, respectively; P = 0.024). OS was not influenced by WHO clinical stage, WHO clinical substage, presence of splenomegaly, early administration of glucocorticoids or the time from the first presentation to the beginning of chemotherapy. There are no significant differences in clinical and laboratory parameters between low-grade and high-grade lymphomas. Boxer dogs are predisposed to T-cell lymphoma, with a predominance of high-grade tumour, especially pleomorphic, mixed small and large T-cell subtype. It is possible that Boxer dogs may respond less favourably to chemotherapy than patients of other breeds.


Pathology ◽  
2019 ◽  
Vol 51 ◽  
pp. S163-S164
Author(s):  
E. Eykman ◽  
A. Field ◽  
A. Lochhead ◽  
K. Ma ◽  
M. Qiu

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 3-9 ◽  
Author(s):  
Petr Starostik ◽  
Jochen Patzner ◽  
Axel Greiner ◽  
Stephan Schwarz ◽  
Jörg Kalla ◽  
...  

Low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type can transform into high-grade diffuse large B-cell lymphoma (DLBCL). Up to 60% of the MALT lymphomas contain the recently described t(11;18). However, this translocation has not been detected in any DLBCL so far. To elucidate the pathogenesis of these tumors, microsatellite screening of 24 gastric MALT lymphomas was performed and the results were compared with aberrations detected in a previous study on gastric DLBCL. The most frequent aberration, found in 21% of the MALT lymphomas that were exclusively t(11;18)-negative cases, was amplification of the 3q26.2-27 region (harboring the locus of the BCL6 gene). Allelic imbalances in regions 3q26.2-27, 6q23.3-25, 7q31, 11q23-24, and 18q21 were shared by both MALT lymphoma and DLBCL. Loss of heterozygosity in regions 5q21 (APC gene locus), 9p21 (INK4A/ARF), 13q14 (RB), and 17p13(p53) and allelic imbalances in 2p16, 6p23, and 12p12-13 occurred exclusively in DLBCL. Only one of 10 t(11;18)-positive MALT lymphomas showed an additional clonal abnormality. These tumors thus display features of a clonal proliferation characterized by the presence of the t(11;18). However, they only rarely display secondary aberrations and do not seem to transform into DLBCL. In contrast, t(11;18)-negative MALT lymphomas show numerous allelic imbalances—some of them identical with aberrations seen in DLBCL—suggesting that this group is the source of tumors eventually transforming into high-grade DLBCL.


2016 ◽  
Vol 40 (1) ◽  
pp. e1-e16 ◽  
Author(s):  
Rose Lou Marie C. Agbay ◽  
Sanam Loghavi ◽  
L. Jeffrey Medeiros ◽  
Joseph D. Khoury

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1620
Author(s):  
Cheng-Chih Tsai ◽  
Yung-Cheng Su ◽  
Oluwaseun Adebayo Bamodu ◽  
Bo-Jung Chen ◽  
Wen-Chiuan Tsai ◽  
...  

This study investigated the epidemiological and clinical peculiarities of BCL2 and BCL6 rearrangement in patients with high grade B-cell lymphoma (HGBL) from Taiwan, compared with data from Western countries. Two hundred and eighty-two DLBCL cases from Taipei Medical University-affiliated hospitals (n = 179) and Tri-Service General Hospital (n = 103) were enrolled for this study. From the 282, 47 (16.7%) had MYC translocation; 24 of these harbored concurrent BCL2 and/or BCL6 translocation (double-hit, DH or triple-hit, TH). Twelve DH-HGBL cases had simultaneous MYC and BCL6 translocations, 8 harbored MYC and BCL2 rearrangement, while the remaining 4 patients exhibited TH. Together, 66.7% of DH/TH-HGBL patients were BCL6 rearrangement positive. Among these BCL6-rearranged DH/TH-HGBL patients, only 6 (37.5%) overexpressed MYC and BCL6 proteins simultaneously, indicating that MYC-BCL6 co-overexpression may not be plausible surrogate biomarker for screening BCL6-rearranged DH-HGBL. By the end of year 5, all patients with TH-HGBL, BCL2 DH-HGBL and all but one BCL6 DH-HGBL cases had expired or were lost to follow-up. Progression-free survival (PFS) was longer for the non-DH/TH-HGBL group compared with the DH/TH-HGBL group. While the patients with BCL2 DH-HGBL were lost to follow-up by day 800, their remaining TH-HGBL and BCL6 DH-HGBL peers exhibited very poor PFS, regardless of age strata. More so, patients with BCL6 rearrangement were 5.5-fold more likely associated with extranodal involvement compared with their BCL2-rearranged peers. Moreover,~60.0% of the BCL6-rearranged DH-HGBL cases were non-GCB, suggesting that including screening for BCL6 rearrangement in patients with the non-GCB phenotype may aid medical decision-making and therapeutic strategy. Contrary to contemporary data from western countries, 2 in every 3 patients with DH/TH-HGBL in Taiwan harbor BCL6 rearrangement. Consistent with present findings, we recommend mandatory screening for BCL6 rearrangement in patients with aggressive HGBL in Taiwan.


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