Background A positive family history of chronic diseases including cancer can be used as an index of genetic and shared environmental influences. The tumours studied have several putative risk factors in common including occupational exposure to certain pesticides and a positive family history of cancer. Methods We conducted population-based studies of Hodgkin lymphoma (HL), Multiple Myeloma (MM), non-Hodgkin's Lymphoma (NHL), and Soft Tissue Sarcoma (STS) among male incident case and control subjects in six Canadian provinces. The postal questionnaire was used to collect personal demographic data, a medical history, a lifetime occupational history, smoking pattern, and the information on family history of cancer. The family history of cancer was restricted to first degree relatives and included relationship to the index subjects and the types of tumours diagnosed among relatives. The information was collected on 1528 cases (HL (n = 316), MM (n = 342), NHL (n = 513), STS (n = 357)) and 1506 age ± 2 years and province of residence matched control subjects. Conditional logistic regression analyses adjusted for the matching variables were conducted. Results We found that most families were cancer free, and a minority included two or more affected relatives. HL [(ORadj (95% CI) 1.79 (1.33, 2.42)], MM (1.38(1.07, 1.78)), NHL (1.43 (1.15, 1.77)), and STS cases (1.30(1.00, 1.68)) had higher incidence of cancer if any first degree relative was affected with cancer compared to control families. Constructing mutually exclusive categories combining "family history of cancer" (yes, no) and "pesticide exposure ≥10 hours per year" (yes, no) indicated that a positive family history was important for HL (2.25(1.61, 3.15)), and for the combination of the two exposures increased risk for MM (1.69(1.14,2.51)). Also, a positive family history of cancer both with (1.72 (1.21, 2.45)) and without pesticide exposure (1.43(1.12, 1.83)) increased risk of NHL. Conclusion HL, MM, NHL, and
Ye, Xibiao; Mneina, Ayat; Johnston, James B; Mahmud, Salaheddin M
Evidence on the effect of statin use on non-Hodgkin lymphoma (NHL) is not clear. We conducted a systematic review and meta-analysis to examine the associations between statin use and NHL risk and survival. We searched multiple literature sources up to October 2014 and identified 10 studies on the risk of diagnosis with NHL and 9 studies on survival. Random effects model was used to calculate pooled odds ratio (PORs) for risk and pooled hazard ratio (PHR) for survival. Heterogeneity among studies was examined using the Tau-squared and the I-squared (I(2) ) tests. Statin use was associated with reduced risk for total NHL (POR = 0.82, 95% CI 0.69-0.99). Among statin users, there was a lower incidence risk for marginal zone lymphoma (POR = 0.54, 95% CI 0.31-0.94), but this was not observed for other types of NHL. However, statin use did not affect overall survival (PHR = 1.02, 95% CI 0.99-1.06) or event-free survival (PHR = 0.99, 95% CI 0.87-1.12) in diffuse large B-cell lymphoma. There is suggestive epidemiological evidence that statins decrease the risk of NHL, but they do not influence survival in NHL patients. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Osian, S. Rausch; Leal, A.D.; Allmer, C.; Maurer, M.J.; Nowakowski, G.; Inwards, D.J.; Macon, W.R.; Ehlers, S.L.; Weiner, G.J.; Habermann, T.M.; Cerhan, J.R.; Thompson, C.A.
There are few studies examining complementary and alternative medicine (CAM) use and beliefs among non-Hodgkin lymphoma (NHL) survivors. 719 NHL patients from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource who completed the 3-year post-diagnosis questionnaire were included in this study. 636 (89%) reported ever using CAM, with 78% utilizing vitamins, 54% alternative therapies and 45% herbals. Female gender was associated with increased overall CAM use (P<.0001) as well as use of vitamins (P<.0001), herbals (P=.006) and alternative therapy (P=.0002) for cancer. Older age (>60) was associated with increased vitamin use (P=.005) and decreased herbal use (P=.008). Among users, 143 (20%) believe CAM assists healing, 123 (17%) believe CAM relieves symptoms, 122 (17%) believe CAM gives a feeling of control, 110 (15%) believe CAM assists other treatments, 108 (15%) believe CAM boosts immunity, 26 (4%) believe CAM cures cancer, and 36 (5%) believe CAM prevents the spread of cancer. PMID:24745936
Sharma, Manisha; Mannan, Rahul; Madhukar, Mohit; Navani, Sanjay; Manjari, Mridu; Bhasin, Tejinder Singh; Gill, Karamjit Singh
Introduction: The distribution of the major subtypes of non-Hodgkin’s lymphoma (NHL) differs across geographic regions. This study, from the north Indian state of Punjab, has incorporated immunophenotypic findings while investigating the distribution of NHL subtypes based on World Health Organization (WHO)/ Revised European-American Classification of Lymphoid Neoplasms (REAL) system of classification. Patients and methods: Over all seventy seven cases of lymphoma over a period of one year (between April 2012 and April 2013) were diagnosed in the Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar (Punjab). Of these 30 cases (39%) were of Hodgkin’s Lymphoma (HL) and 47 cases (61%) were of Non Hodgkins lymphoma NHL. Of the total of cases of lympho-proliferative disorders, the diagnosis of NHL was done by light microscopy alone. All the cases diagnosed provisionally as NHL were taken up for immunophenotyping with Immunohistochemical (IHC) studies. There was 100 % concordance between the light microscopy and IHC studies. The individual NHL cases were classified according to the WHO/REAL classification according to the positive or relevant negative immonophenotypic expression and tabulated to ascertain the morphological spectrum of NHL in this part of the country. Results: B-cell lymphomas formed 89.3%, whereas T-cell lymphomas formed 10.7% of the NHLs. Diffuse Large B-Cell Lymphoma (DLBCL) was the most common subtype (46.8% of all NHLs). B-cell small lymphocytic lymphoma, Mantle-Cell Lymphoma (MCL), marginal zone B-cell lymphomas (including MALT lymphomas), Diffuse, mixed small cleaved cell and large-cell type and Follicular centre-cell lymphomas amounted to 17%, 12.8%, 2.1%, 2.1% and 4.3%, respectively. Among the T-cell lymphomas, T-cell lymphoblastic lymphoma, anaplastic large-cell lymphomas of T/null-cell type, and Angioimmunoblastic T-cell lymphoma (AITL) accounted for 6.4%, 2.1%, and 2.1% of all NHL cases
Coad, N A; Jones, T J; Muir, K R; Parkes, S E; Smith, K; Raafat, F; Mann, J R
We have performed DNA analysis by means of fluorescence-activated cell cytometry on paraffin-embedded tissue from the diagnostic biopsy specimens in 40 cases of non-Hodgkin's lymphoma (NHL) and 25 of Hodgkin's disease (HD) and from 50 normal tonsils as controls. For HD cases, aneuploidy was found in 7 of 25 (28%), a higher proportion than in two previous studies of mainly adult patients. Diploid tumors showed S-phase fractions (SPFs) similar to those of controls. In the NHL cases aneuploidy was found in 12 of 40 (30%) with no significant association with site, stage, histopathology, immunophenotype, or prognosis. SPFs were highest in abdominal and chest primary sites but were not related to stage. Burkitt's lymphomas had the highest SPFs relative to lymphoblastic (P < .01) and centroblastic lymphomas (P < .05). Significantly higher SPFs were found in B cell than in T cell tumors (P < .001). There was considerable heterogeneity for SPFs within each NHL subgroup. Survival was worse at 5 years for those with high SPFs compared with those with normal SPFs (P = .04). These results suggest that tumor DNA analysis may be useful in the evaluation of children with NHL. Larger studies are needed to define its role as an independent prognostic variable.
Follicular Lymphoma (FL/Indolent NHL); Aggressive NHL (a NHL); Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL); T-cell Lymphoma (PTCL and CTCL); B-cell Non Hodgkin Lymphoma (NHL)
Czarnota, Jenna; Gennings, Chris; Colt, Joanne S.; De Roos, Anneclaire J.; Cerhan, James R.; Severson, Richard K.; Hartge, Patricia; Ward, Mary H.
Background There are several suspected environmental risk factors for non-Hodgkin lymphoma (NHL). The associations between NHL and environmental chemical exposures have typically been evaluated for individual chemicals (i.e., one-by-one). Objectives We determined the association between a mixture of 27 correlated chemicals measured in house dust and NHL risk. Methods We conducted a population-based case–control study of NHL in four National Cancer Institute–Surveillance, Epidemiology, and End Results centers—Detroit, Michigan; Iowa; Los Angeles County, California; and Seattle, Washington—from 1998 to 2000. We used weighted quantile sum (WQS) regression to model the association of a mixture of chemicals and risk of NHL. The WQS index was a sum of weighted quartiles for 5 polychlorinated biphenyls (PCBs), 7 polycyclic aromatic hydrocarbons (PAHs), and 15 pesticides. We estimated chemical mixture weights and effects for study sites combined and for each site individually, and also for histologic subtypes of NHL. Results The WQS index was statistically significantly associated with NHL overall [odds ratio (OR) = 1.30; 95% CI: 1.08, 1.56; p = 0.006; for one quartile increase] and in the study sites of Detroit (OR = 1.71; 95% CI: 1.02, 2.92; p = 0.045), Los Angeles (OR = 1.44; 95% CI: 1.00, 2.08; p = 0.049), and Iowa (OR = 1.76; 95% CI: 1.23, 2.53; p = 0.002). The index was marginally statistically significant in Seattle (OR = 1.39; 95% CI: 0.97, 1.99; p = 0.071). The most highly weighted chemicals for predicting risk overall were PCB congener 180 and propoxur. Highly weighted chemicals varied by study site; PCBs were more highly weighted in Detroit, and pesticides were more highly weighted in Iowa. Conclusions An index of chemical mixtures was significantly associated with NHL. Our results show the importance of evaluating chemical mixtures when studying cancer risk. Citation Czarnota J, Gennings C, Colt JS, De Roos AJ, Cerhan JR, Severson RK, Hartge P, Ward MH
Background Exploring spatial-temporal patterns of disease incidence through cluster analysis identifies areas of significantly elevated or decreased risk, providing potential clues about disease risk factors. Little is known about the etiology of non-Hodgkin lymphoma (NHL), or the latency period that might be relevant for environmental exposures, and there are no published spatial-temporal cluster studies of NHL. Methods We conducted a population-based case-control study of NHL in four National Cancer Institute (NCI)-Surveillance, Epidemiology, and End Results (SEER) centers: Detroit, Iowa, Los Angeles, and Seattle during 1998-2000. Using 20-year residential histories, we used generalized additive models adjusted for known risk factors to model spatially the probability that an individual had NHL and to identify clusters of elevated or decreased NHL risk. We evaluated models at five different time periods to explore the presence of clusters in a time frame of etiologic relevance. Results The best model fit was for residential locations 20 years prior to diagnosis in Detroit, Iowa, and Los Angeles. We found statistically significant areas of elevated risk of NHL in three of the four study areas (Detroit, Iowa, and Los Angeles) at a lag time of 20 years. The two areas of significantly elevated risk in the Los Angeles study area were detected only at a time lag of 20 years. Clusters in Detroit and Iowa were detected at several time points. Conclusions We found significant spatial clusters of NHL after allowing for disease latency and residential mobility. Our results show the importance of evaluating residential histories when studying spatial patterns of cancer. PMID:21718483
Ten, Lik-Chin; Chin, Yoon-Ming; Tai, Mei-Chee; Chin, Edmund Fui-Min; Lim, Yat-Yuen; Suthandiram, Sujatha; Chang, Kian-Meng; Ong, Tee-Chuan; Bee, Ping-Chong; Mohamed, Zahurin; Gan, Gin-Gin; Ng, Ching-Ching
Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37-0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35-0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.
Ten, Lik-Chin; Chin, Yoon-Ming; Tai, Mei-Chee; Chin, Edmund Fui-Min; Lim, Yat-Yuen; Suthandiram, Sujatha; Chang, Kian-Meng; Ong, Tee-Chuan; Bee, Ping-Chong; Mohamed, Zahurin; Gan, Gin-Gin; Ng, Ching-Ching
Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37–0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35–0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology. PMID:28139690
Mathew, S.; Houldsworth, J.; Rao, P.H.
Gene amplification characterized by distinct cytogenetic structures, such as homogeneously stained regions (hsrs), aberrantly banded marked chromosomes (abms), and double minutes (dmins) chromosomes is commonly found in tumor cells, and is considered as an important mechanism by which tumor cells gain increased levels of expression of critical genes. Very little is known about gene amplification in NHL. So far, no commonly amplified gene(s) have been identified in NHL. DNA in-gel renaturation assay provided evidence for the presence of amplified DNA fragments in NHL. In order to identify the gene(s) amplified in NHL we performed a modified form of CGH (hybridization and normal chromosomes with biotin labeled tumor DNA) to a panel of 10 NHL, which showed cytogenetic evidence for gene amplification in the form of hsrs and dmins. A number of chromosomal regions were found to be non-randomly amplified: 1p32-36(9/10), 1q32-44(6/10), 6p(9/10), 6q26-27(5/10), 16(8/10), 19(7/10) and 22q(7/10). Amplification of DNA from specific chromosomal bands was noted at 4p16(8/10), 11q13(10/10), and 12q24(8/10). Tumor L-10 showed specific amplification of 2p13. This study details the first CGH study performed on a panel of NHLs to identify gene amplification and chromosomal origin of hsrs and dmins identified by conventional cytogenetic analysis. The modified CGH employed in this study indicated that gene amplification is a frequent genetic alteration in NHL.
Perea, G; Altés, A; Bellido, M; Aventín, A; Bordes, R; Ayats, R; Remacha, A F; Espinosa, I; Briones, J; Sierra, J; Nomdedéu, J F
To determine the efficacy of flow cytometry (FC) in the assessment of bone marrow (BM) in B-cell non-Hodgkin lymphoma (B-NHL). FC is a common practice, but is far from being validated. Morphological analysis and FC immunophenotyping were performed on 421 samples. T-cell lymphomas, Hodgkin's disease, chronic lymphocytic leukaemia and hairy cell leukaemia were not included in the study. Clonality was assessed by the standard kappa/lambda/CD19 test. Aberrant immunophenotypes present in the B-cell subpopulation were also investigated. A double-step procedure was employed in all cases to increase the sensitivity of the FC procedure. Of 380 evaluable samples, 188 corresponded to follicular lymphoma (FL), 58 to diffuse large B-cell lymphoma (DLBCL), 57 to mantle cell lymphoma (MCL), seven to Burkitt's lymphoma and the remaining 70 samples to other low-grade lymphomas. Morphological marrow infiltration was found in 148 cases, and flow immunophenotyping identified 138 cases with BM involvement. A concordance between the two methods was detected in 298 cases (79%). There was a discordance in 82 cases (21%): morphology positive/FC negative in 46 cases and morphology negative/FC positive in 36 (61% of all cases with discordance were from FL). There was no difference in outcome when patients with discordances were compared with patients without discordances. Most samples showed concordance between morphological and FC results. FC identified BM involvement in the absence of morphological infiltration. Morphology/FC discordance seems to have no influence on the outcome of FL patients. Copyright 2004 Blackwell Publishing Limited
Buchmann, Inga; Neumaier, Bernd; Schreckenberger, Mathias; Reske, Sven
The nucleoside 3'-deoxy-3'-fluorothymidine (alovudine) is an antiviral agent accumulating in proliferating cells. We prospectively evaluated the biodistribution of the PET tracer [18F]3'-deoxy-3'-fluorothymidine (FLT) and its value in detecting manifestations of non-Hodgkin's lymphoma (NHL). In this pilot study, 7 patients (6 male, 1 female) with indolent NHL (2), NHL in transformation (2) or aggressive NHL (3) were examined. Patients received initial staging or restaging with an interval of at least 10 weeks between therapy and positron emission tomography (PET). Mean doses of 324 +/- 165 MBq FLT were injected intravenously. Static PET scans were performed 50-70 minutes after application. Maximum standardized uptake values (SUV) of organs and NHL manifestations were calculated. FLT-positive lesions were verified by biopsies (3 lesions) or aspiration smears (5 lesions in 4 patients). Biodistribution: The tracer accumulated physiologically in hematopoietic marrow and in the liver. It was renally excreted. SUV of organs 1 hour after injection were: bones with hematopoietic marrow, 9.9 +/- 4.7; liver, 5.2 +/- 1.0; kidneys, 4.0 +/- 1.7; spleen, 3.0 +/- 1.2; bones without hematopoietic marrow, 1.9 +/- 1.1; lungs, 0.8 +/- 0.3. NHL manifestations: In 7 patients, diagnosis was verified as true positive by histology/cytology. Maximum lymphoma SUV of FLT positive lesions were 6 for the indolent group and 8-11 for lymphoma in transformation. In the aggressive group, SUV were 6, 14, and 17. The low SUV in this group was found in a highly proliferate large-cell anaplastic lymphoma combined with marked sclerosis of 30%. In this pilot study, FLT-PET was suitable in the imaging of NHL manifestations. In NHL with normal cellularity, FLT accumulated more intensely in aggressive NHL and NHL in transformation than in indolent NHL. Bones with hematopoietic marrow and the liver were the organs with the highest physiological uptake. Copyright Mary Ann Liebert, Inc.
Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom Macroglobulinemia
Chang, Cindy M.; Schroeder, Jane C.; Huang, Wen-Yi; Dunphy, Cherie H.; Baric, Ralph S.; Olshan, Andrew F.; Dorsey, Kathleen C.; Dent, Georgette A.; Cerhan, James R.; Lynch, Charles F.; Rothman, Nathaniel; Cantor, Kenneth P.; Blair, Aaron
We used fluorescence in situ hybridization (FISH) assays to identify t(14;18) translocations in archival paraffin-embedded tumor sections from non-Hodgkin lymphoma (NHL) cases enrolled in a population-based study. t(14;18) was identified in 54% of 152 cases, including 39% of diffuse large cell lymphomas (26 of 66 cases) and 84% of follicular lymphomas (36 of 43 cases). Eighty-seven percent of t(14;18)-positive cases and 57% of t(14;18)-negative cases expressed bcl-2. FISH assays detected twice as many t(14;18)-positive follicular lymphomas as PCR assays. Overall, study findings support the use of FISH assays to detect t(14;18) in archival tumor samples for epidemiologic studies of NHL subtypes. PMID:19505720
Rohde, Marius; Bonn, Bettina R; Zimmermann, Martin; Lange, Jonas; Möricke, Anja; Klapper, Wolfram; Oschlies, Ilske; Szczepanowski, Monika; Nagel, Inga; Schrappe, Martin; Loeffler, Markus; Siebert, Reiner; Reiter, Alfred; Burkhardt, Birgit
Mature B-cell Non-Hodgkin lymphoma is the most common subtype of Non-Hodgkin lymphoma in childhood and adolescence. B-cell Non-Hodgkin lymphoma are further classified into histological subtypes, with Burkitt lymphoma and Diffuse large B-cell lymphoma being the most common subgroups in pediatric patients. Translocations involving the MYC oncogene are known as relevant but not sufficient hit for Burkitt lymphoma pathogenesis. Recently published large-scale next-generation sequencing studies unveiled sets of additional recurrently mutated genes in samples of pediatric and adult B-cell Non-Hodgkin lymphoma patients. ID3, TCF3 and CCND3 are potential drivers of Burkitt-lymphomagenesis. In the present study frequency and clinical relevance of mutations in ID3, TCF3 and CCND3 were analyzed within a well-defined cohort of 84 uniformly diagnosed and treated pediatric B-cell Non-Hodgkin lymphoma patients of the Berlin-Frankfurt-Munster group (NHL-BFM). Mutation frequency was 78% (ID3), 13% (TCF3) and 36% (CCND3) in Burkitt lymphoma (including Burkitt leukemia). ID3 and CCND3 mutations were associated with more advanced stages of the disease in MYC rearrangement positive Burkitt lymphoma. In conclusion ID3-TCF3-CCND3 pathway genes are mutated in more than 88% of MYC-rearranged pediatric B-cell Non-Hodgkin lymphoma and the pathway may represent a highly relevant second hit of Burkitt lymphoma pathogenesis especially in children and adolescents.
Tsurusawa, Masahito; Watanabe, Tomoyuki; Gosho, Masahiko; Mori, Tetsuya; Mitsui, Tetsuo; Sunami, Shosuke; Kobayashi, Ryoji; Fukano, Reiji; Tanaka, Fumiko; Fujita, Naoto; Inada, Hiroko; Sekimizu, Masahiro; Koh, Katsuyoshi; Kosaka, Yoshiyuki; Komada, Yoshihiro; Saito, Akiko M; Nakazawa, Atsuko; Horibe, Keizo
The objective of this study was to assess the impact of the primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) in the management of childhood B-cell non-Hodgkin lymphoma (B-NHL). Patients with advanced-stage mature B-NHL were randomized to receive prophylactic G-CSF (G-CSF+) or not receive G-CSF (G-CSF-) based on protocols of the B-NHL03 study. The G-CSF group received 5 μg/kg/d Lenograstim from day 2 after each course of six chemotherapy courses. Fifty-eight patients were assessable, 29 G-CSF + and 29 G-CSF-. G-CSF + patients showed a positive impact on the meantime to neutrophil recovery and hospital stay. On the other hand, they had no impact in the incidences of febrile neutropenia, serious infections, stomatitis and total cost. Our study showed that administration of prophylactic G-CSF through all six chemotherapy courses for childhood B-NHL showed no clinical and economic benefits for the management of childhood B-NHL treatment.
Shaughnessy, P; Uberti, J; Devine, S; Maziarz, R T; Vose, J; Micallef, I; Jacobsen, E; McCarty, J; Stiff, P; Artz, A; Ball, E D; Berryman, R; Dugan, M; Joyce, R; Hsu, F J; Johns, D; McSweeney, P
Before US regulatory approval, an expanded access program provided plerixafor to patients with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HD) or multiple myeloma (MM) who had not previously failed mobilization and were otherwise candidates for auto-SCT. Patients received granulocyte-CSF (G-CSF) 10 mcg/kg daily and plerixafor 0.24 mg/kg starting on day 4 with apheresis on day 5; all repeated daily until collection was complete. Overall, 104 patients received 1 dose of plerixafor. The addition of plerixafor to G-CSF resulted in a median threefold increase in peripheral blood CD34+ cell count between days 4 and 5. Among 43 NHL patients, 74% met the target of 5 × 10(6) CD34+ cells/kg (median, 1 day apheresis, range 1-5 days); among 7 HD patients, 57% met the target of 5 × 10(6) CD34+ cells/kg (median, 2 days apheresis, range 1-3); and among 54 MM patients, 89% met the target of 6 × 10(6) CD34+ cells/kg (median, 1 day apheresis, range 1-4). Overall, 93% of patients had 2 × 10(6) CD34+ cells/kg collected within 1-3 days. Plerixafor-related toxicities were minimal. Engraftment kinetics, graft durability and transplant outcomes demonstrated no unexpected outcomes. Efficacy and safety results were similar to results in phase II and III clinical trials.
Ghassemi, Ali; Banihashem, Abdollah; Ghaemi, Nosrate; Elmi, Saghi; Erfani Sayyar, Reza; Elmi, Sam; Esmaeili, Habibollah
Background: Acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) are the most common malignancies in children and adolescents. Therapies such as corticosteroids, cytotoxic and radiotherapy will have harmful effect on bone mineral density (BMD) which can lead to increased possibility of osteoporosis and pathological fractures. Subjects and methods: This 3-year cross-sectional study was performed in 50 children with ALL (n=25) and NHL (n=25) at Dr. Sheikh Children's Hospital in Mashhad. Half the patients received chemotherapy alone (n=25), while the other half received chemotherapy plus radiotherapy (n=25). We assessed them in the remission phase by DEXA bone mineral densitometry at the lumbar spine and femoral neck (hip). The survey results were adjusted in accordance with age, height, sex and Body Mass Index. Results : The mean age was 3.93± 8.28 years. There was no significant difference in bone biomarkers (Ca, P, ALP, PTH) among ALL, NHL and also the two treatment groups. Children with ALL had lower density at the hip and lumbar spine (p-value<0.001 and p-value=0.018, respectively). Among the total of 50 patients, 3 patients had normal results for detected hip BMD (6%), while 14 (28%) had osteopenia and 33 had osteoporosis (66%). Only one patient had normal BMD among all the patients who received chemotherapy plus radiotherapy, whereas 2 patients had normal BMD with just chemotherapy treatment. Conclusion : Given that 94% of our patients had abnormal bone density, it seems to be crucial to pay more attention to the metabolic status and BMD in children with cancer. PMID:27489591
Jayakody, Nimeshi; Harris, E Clare; Coggon, David
Background Phenoxy herbicides have been used widely in agriculture, forestry, parks and domestic gardens. Early studies linked them with soft tissue sarcoma (STS) and non-Hodgkin lymphoma (NHL), but when last reviewed by the International Agency for Research on Cancer in 1986, the evidence for human carcinogenicity was limited. Sources of data We searched Medline and Embase, looking for cohort or case-control studies that provided data on risk of STS and/or NHL in relation to phenoxy herbicides, and checked the reference lists of relevant publications for papers that had been missed. Areas of agreement, areas of controversy The extensive evidence is not entirely consistent, and a hazard of STS or NHL cannot firmly be ruled out. However, if there is a hazard, then absolute risks must be small. Growing points, areas timely for developing research Extended follow-up of previously assembled cohorts may be the most efficient way of further reducing uncertainties. PMID:25790819
NHL; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Intermediate-Grade; Lymphoma, Large-Cell; Lymphoma, Low-Grade; Lymphoma, Mixed-Cell; Lymphoma, Small-Cell; Leukemia, Lymphocytic, Chronic; Leukemia, B-Cell, Chronic; Leukemia, Prolymphocytic; Leukemia, Small Lymphocytic; Lymphoma, Small Lymphocytic; Lymphoma, Lymphoplasmacytoid, CLL; Lymphoplasmacytoid Lymphoma, CLL; CLL; SLL
Jaeger, Ulrich; Trneny, Marek; Melzer, Helen; Praxmarer, Michael; Nawarawong, Weerasak; Ben Yehuda, Dina; Goldstein, David; Mihaljevic, Bilijana; Ilhan, Osman; Ballova, Veronika; Hedenus, Michael; Hsiao, Liang-Tsai; Au, Wing-Yan; Burgstaller, Sonja; Weidinger, Gerhard; Keil, Felix; Dittrich, Christian; Skrabs, Cathrin; Klingler, Anton; Chott, Andreas; Fridrik, Michael A.; Greil, Richard
We investigated rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (n=662) or follicular lymphoma grade 3b (n=21) in first complete remission. Patients were randomized to rituximab maintenance (n=338) or observation (n=345). At a median follow-up of 45 months, the event-free survival rate (the primary endpoint) at 3 years was 80.1% for rituximab maintenance versus 76.5% for observation. This difference was not statistically significant for the intent-to-treat population (likelihood ratio P=0.0670). The hazard ratio by treatment arm was 0.79 (95% confidence interval 0.57–1.08; P=0.1433). The secondary endpoint, progression-free survival was also not met for the whole statistical model (likelihood ratio P=0.3646). Of note, rituximab maintenance was superior to observation when treatment arms only were compared (hazard ratio: 0.62; 95% confidence interval 0.43–0.90; P=0.0120). Overall survival remained unchanged (92.0 versus 90.3%). In subgroup analysis male patients benefited from rituximab maintenance with regards to both event-free survival (84.1% versus 74.4%) (hazard ratio: 0.58; 95% confidence interval 0.36–0.94; P=0.0267) and progression-free survival (89.0% versus 77.6%) (hazard ratio: 0.45; 95% confidence interval 0.25–0.79; P=0.0058). Women had more grade 3/4 adverse events (P=0.0297) and infections (P=0.0341). Men with a low International Prognostic Index treated with rituximab had the best outcome. In summary, rituximab maintenance in first remission after R-CHOP-like treatment did not prolong event-free, progression-free or overall survival of patients with aggressive B-non-Hodgkin lymphoma. The significantly better outcome of men warrants further studies prior to the routine use of rituximab maintenance in men with low International Prognostic Index. This trial is registered under EUDRACT #2005-005187-90 and www.clinicaltrials.gov as #NCT00400478. PMID:25911553
Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. The EORTC Lymphoma Group.
Carde, P; Meerwaldt, J H; van Glabbeke, M; Somers, R; Monconduit, M; Thomas, J; de Wolf-Peeters, C; de Pauw, B; Tanguy, A; Kluin-Nelemans, J C
A first-generation CHOP-like cyclic combination chemotherapy (CT) regimen using cyclophosphamide 600 mg/m2 IV d1, hydroxorubicin (doxorubicin) 50 mg/m2 IV d1, VM26 60 mg/m2 IV d1, and prednisone 40 mg/m2 PO d1-5 (CHVmP) was compared to a second-generation combination wherein vincristine 1.4 mg/m2 IV and bleomycin 6 mg/m2 IM/IV were added at mid-interval (d15) to the former drugs (CHVmP + VB) in the treatment of intermediate- and high-grade malignant NHL. From April 1980 to January 1986, 141 eligible patients with stage III-IV unfavorable histologies (except T lymphoblastic NHL) entered this EORTC randomized trial. In both arms adjuvant radiotherapy (30 Gy) was given in instances of bulky or residual disease. In all patient subsets the outcome favored the second-generation regimen. The difference was even greater in patients with Diffuse Large Cell Lymphoma (DLCL). At 5 years, overall survival was 53% with CHVmP + VB versus 29% (p = 0.002). The advantage was due to a higher complete remission (CR) rate (80% versus 50%, p = 0.01). Indeed, once CR was achieved the relapse-free survival (RFS) was not significantly influenced (59% versus 49%). No significant additional toxicity could be attributed to vincristine and bleomycin. This study demonstrates a clear benefit for intermediate- and high-risk malignant NHL and particularly DLCL from intercalating non-myelotoxic drugs at mid-cycle intervals, without adverse effects.
Carroll, Gemma; Breidahl, William; Robbins, Peter
To assess the MRI findings of musculoskeletal lymphoma primarily presenting clinically as a bone lesion or soft tissue mass. Magnetic resonance imaging of 23 cases of musculoskeletal lymphoma were retrospectively reviewed. Features assessed included tumour location, morphology, signal intensity (SI) characteristics, cortical destruction, involvement of multiple anatomic compartments, encasement of adjacent neurovascular structures/tendons and subcutaneous oedema. Osseous lesions were typically poorly defined and hypointense on T1-weighted imaging. T2-weighted SI was usually heterogeneous, with 54% of cases having a 'mosaic' pattern of marrow replacement. Ninety-two per cent of osseous tumours had cortical abnormalities, most commonly a permeative pattern. A periosseous soft tissue cuff was present in 46% of cases while 38% had a more significant extraosseous component. All cases of soft tissue lymphoma were iso-/slightly hyperintense to muscle on T1-weighted images and hyperintense on T2-weighted images. Multicompartment involvement by extraosseous tumour was present in 75% of cases, and 67% had subcutaneous oedema. Eighty-three per cent of soft tissue tumours showed encasement of adjacent structures. Multifocal lymphoma had similar morphology and SI characteristics to single-site lesions. Histopathologically, there were 21 cases of non-Hodgkin's lymphoma and two of Hodgkin's lymphoma. Magnetic resonance imaging features of primary osseous lymphoma include T2 heterogeneity, a periosseous soft tissue cuff or a more substantial mass, and cortical disruption often disproportionate to the extent of extraosseous tumour. Features characteristic of soft tissue lymphoma include relative homogeneity on T1- and T2-weighted imaging, multicompartment involvement and encasement of neurovascular structures. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.
Vitolo, Umberto; Angrili, Francesco; DeCosta, Lucy; Wetten, Sally; Federico, Massimo
Treatment of non-Hodgkin lymphoma (NHL) requires chemotherapy regimens with significant risk of febrile neutropenia (FN). For patients at ≥20% FN risk, guidelines recommend primary prophylaxis (PP) with granulocyte-colony stimulating factor (G-CSF). This study assessed whether G-CSF use in NHL was in line with recommendations in routine practice. This was a retrospective, observational study of adult NHL patients receiving first-line (R)CHOP-like chemotherapy and G-CSF support between June 2010 and 2012, in Italy. The primary outcome was whether G-CSF was provided as PP, which was defined as G-CSF initiation on days 1-3 after chemotherapy, ≥3 days' use for daily G-CSFs and continued prophylaxis from cycle 1 across all cycles. Secondary prophylaxis was defined as continued prophylaxis from cycle 2 or later, and all other use was defined as Suboptimal. The analysis included 199 patients, 61% of whom had diffuse large B cell lymphoma and 21% follicular lymphoma. (R)CHOP-21 was given to 52% of patients and (R)CHOP-14 to 32%. Overall, 29% of patients received PP, while two-thirds received Suboptimal G-CSF. Of patients receiving daily G-CSF, 3% received PP and 94% received Suboptimal use; with pegfilgrastim, 65% received PP and 26% Suboptimal use. FN occurred in 13 patients (7%) and grade 3/4 neutropenia in 43%. Chemotherapy dose delays occurred in 22% and dose reductions in 18% of patients. Delivery of G-CSF, particularly daily G-CSFs, was not in accordance with guideline or product label recommendations in a large proportion of NHL patients receiving chemotherapy in Italy.
Contreras, E; Bagán, J V; Lloria, E; Borja, A; Millán, M A; Jiménez, Y
The non-Hodgkin lymphomas (NHL) represent an heterogeneous group of malignancies of lymphoreticular histogenesis. In most cases, they initially arise within lymph nodes but so-called extranodal lymphomas are also found. The NHL has low incidence in the oral cavity. It may involve bone and/or soft tissues as a primary or secondary manifestation. We present a review of the literature and four clinical cases of intraoral NHL. The first couple of cases are primary forms, the third one is associated to HIV infection and the last one is an oral presentation as a component of more widely disseminated disease.
Lukens, John N; Nasta, Sunita D; Fram, Brianna; Glatstein, Eli; Plastaras, John P
We evaluated whether staging with positron emission tomography (PET) or treatment with rituximab after involved-field radiation therapy (IFRT) results in an improved progression-free survival (PFS) for early-stage indolent non-Hodgkin lymphoma (NHL). We identified 42 patients with stage I/II low-grade NHL treated with initial IFRT at our institution between 1992 and 2009, who had been staged with computed tomography (CT) or PET. A retrospective analysis was performed to evaluate PFS according to staging by CT or PET, and by receipt of rituximab after IFRT. Overall PFS was 68% and 61% at 5 and 10 years, respectively. There was no significant difference in PFS whether patients were staged by CT (n=17) or by PET (n=25), with 5-year PFS rates of 76% and 60%, respectively. Eleven patients received 4 weekly doses of rituximab after IFRT, with no improvement in 5-year PFS: 46% for rituximab-treated patients versus 72% for patients who were not given rituximab. However, more patients who were given rituximab were stage II. Patients with limited stage indolent NHL staged with either CT or PET and treated with IFRT have favorable PFS compared with historical controls. The administration of 4 weekly doses of rituximab after IFRT did not improve PFS in these patients. The use of rituximab in this setting should be evaluated in a randomized prospective study.
Long-term results of dose-intensive chemotherapy with G-CSF support (TCC-NHL-91) for advanced intermediate-grade non-Hodgkin's lymphoma: a review of 59 consecutive cases treated at a single institute.
Akutsu, Miyuki; Tsunoda, Saburo; Izumi, Tohru; Tanaka, Masaru; Katano, Susumu; Inoue, Koichi; Igarashi, Seiji; Hirabayashi, Kaoru; Furukawa, Yusuke; Ohmine, Ken; Sato, Kazuya; Kobayashi, Hiroyuki; Ozawa, Keiya; Kirito, Keita; Nagashima, Takahiro; Teramukai, Satoshi; Fukushima, Masanori; Kano, Yasuhiko
We evaluated the long-term outcome of very dose-intensive chemotherapy (TCC-NHL-91) for advanced intermediate-grade lymphoma, in which an eight-cycle regimen with 11 drugs was given with granulocyte colony-stimulating factor (G-CSF) support (total 18 weeks). Fifty-nine patients were treated during February 1, 1991 and March 31, 2001 (median age: 48 years). Forty-three patients (73%) were in a high-intermediate risk or high-risk group (HI/H) according to the age-adjusted International Prognostic Index (aa-IPI). Forty-six patients received 7 or 8 cycles of therapy. Ten of 15 patients over age 60 stopped before 7 cycles. Forty-three patients with an initial bulky mass or a residual mass received involved-field radiation. Overall, 56 patients (95%) achieved complete remission (CR). Grade 4 hematotoxicity was observed in all patients. With a median follow-up of 128 months, the 10-year overall survival (OS) and progression-free survival (PFS) rates were 76% and 61%, respectively. Neither aa-IPI risk factors nor the index itself was associated with response, OS, or PFS. One patient died of sepsis during the therapy and one died of secondary leukemia. This retrospective study suggests that the TCC-NHL-91 regimen achieves high CR, OS, and PFS in patients with advanced intermediate-grade lymphoma up to 60 years old and may be a valuable asset in the management of this disease. Further evaluation and prospective studies of the TCC-NHL-91 are warranted.
Coggon, David; Ntani, Georgia; Harris, E Clare; Jayakody, Nimeshi; Palmer, Keith T
To provide further information on the possible carcinogenicity of phenoxy herbicides, and in particular their relationship to soft tissue sarcoma (STS), non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). We extended follow-up to December 2012 for 8036 men employed at five factories in the UK which had manufactured phenoxy herbicides, or in a contract spraying business. Mortality was compared with that for England and Wales by the person-years method. Nested case-control analyses compared men with incident or fatal STS (n=15) or NHL/CLL (n=74) and matched controls (up to 10 per case). 4093 men had died, including 2303 since the last follow-up. Mortality from all causes and all cancers was close to expectation, but an excess of deaths from NHL was observed among men who had worked for ≥1 year in jobs with more than background exposure to phenoxy herbicides (19 deaths, SMR 1.85, 95% CI 1.12 to 2.89). Four deaths from STS occurred among men potentially exposed above background (3.3 expected). In the nested case-control analyses, there were no significantly elevated risks or consistent trends across categories of potential exposure for either STS or NHL/CLL. Among men who had worked for ≥1 year in potentially exposed jobs, the highest OR (for STS) was only 1.30 (95% CI 0.30 to 5.62). Our findings are consistent with the current balance of epidemiological evidence. If phenoxy herbicides pose a hazard of either STS or NHL, then any absolute increase in risk is likely to be small. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Coggon, David; Ntani, Georgia; Harris, E Clare; Jayakody, Nimeshi; Palmer, Keith T
Objectives To provide further information on the possible carcinogenicity of phenoxy herbicides, and in particular their relationship to soft tissue sarcoma (STS), non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). Methods We extended follow-up to December 2012 for 8,036 men employed at five factories in the UK which had manufactured phenoxy herbicides, or in a contract spraying business. Mortality was compared with that for England and Wales by the person-years method. Nested case-control analyses compared men with incident or fatal STS (n=15) or NHL/CLL (n=74) and matched controls (up to 10 per case). Results 4,093 men had died, including 2,303 since the last follow-up. Mortality from all causes and all cancers was close to expectation, but an excess of deaths from NHL was observed among men who had worked for ≥ 1 year in jobs with more than background exposure to phenoxy herbicides (19 deaths, standardised mortality ratio 1.85, 95% confidence interval (CI) 1.12-2.89). Four deaths from STS occurred among men potentially exposed above background (3.3 expected). In the nested case-control analyses, there were no significantly elevated risks or consistent trends across categories of potential exposure, for either STS or NHL/CLL. The highest odds ratio (for STS in men who had worked for ≥1 year in potentially exposed jobs) was only 1.30 (95%CI 0.30-5.62). Conclusions Our findings are consistent with the current balance of epidemiological evidence. If phenoxy herbicides pose a hazard of either STS or NHL then any absolute increase in risk is likely to be small. PMID:25694496
A colloboration with several large population-based cohorts to determine whether the prevalence or level of t14;18 is associated with risk of NHL and to investigate the clonal relationship between translocation-bearing cells and subsequent tumors
... Lymphoma What Are the Key Statistics About Non-Hodgkin Lymphoma? Non-Hodgkin lymphoma (NHL) is one of ... Hodgkin Lymphoma Research and Treatment? More In Non-Hodgkin Lymphoma About Non-Hodgkin Lymphoma Causes, Risk Factors, ...
Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951.
De Moerloose, Barbara; Suciu, Stefan; Bertrand, Yves; Mazingue, Françoise; Robert, Alain; Uyttebroeck, Anne; Yakouben, Karima; Ferster, Alice; Margueritte, Geneviève; Lutz, Patrick; Munzer, Martine; Sirvent, Nicolas; Norton, Lucilia; Boutard, Patrick; Plantaz, Dominique; Millot, Frederic; Philippet, Pierre; Baila, Liliana; Benoit, Yves; Otten, Jacques
The European Organisation for Research and Treatment of Cancer 58951 trial for children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) addressed 3 randomized questions, including the evaluation of dexamethasone (DEX) versus prednisolone (PRED) in induction and, for average-risk patients, the evaluation of vincristine and corticosteroid pulses during continuation therapy. The corticosteroid used in the pulses was that assigned at induction. Overall, 411 patients were randomly assigned: 202 initially randomly assigned to PRED (60 mg/m(2)/d), 201 to DEX (6 mg/m(2)/d), and 8 nonrandomly assigned to PRED. At a median follow-up of 6.3 years, there were 19 versus 34 events for pulses versus no pulses; 6-year disease-free survival (DFS) rate was 90.6% (standard error [SE], 2.1%) and 82.8% (SE, 2.8%), respectively (hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in the PRED (HR = 0.56) and DEX groups (HR = 0.59) but more pronounced in girls (HR = 0.24) than in boys (HR = 0.71). Grade 3 to 4 hepatic toxicity was 30% versus 40% in pulses versus no pulses group and grade 2 to 3 osteonecrosis was 4.4% versus 2%. For average-risk patients treated according to Berlin-Frankfurt-Muenster-based protocols, pulses should become a standard component of therapy.
Chung, Ellen M; Pavio, Michael
Lymphoma is the third most common pediatric neoplasm. Non-Hodgkin lymphoma (NHL) accounts for nearly half of cases and commonly involves extranodal sites. Compared with adults, this histologic spectrum of pediatric NHL is very narrow and consists of aggressive tumors. Patients typically present with widespread disease. Generally, NHL occurring in children includes Burkitt lymphoma, lymphoblastic lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma. Staging and assessment of therapeutic response are usually based on FDG-PET/CT. Due to the increased susceptibility of young patients to the effects of ionizing radiation, alternative methods of imaging are being explored. Published by Elsevier Inc.
Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951
Suciu, Stefan; Bertrand, Yves; Mazingue, Françoise; Robert, Alain; Uyttebroeck, Anne; Yakouben, Karima; Ferster, Alice; Margueritte, Geneviève; Lutz, Patrick; Munzer, Martine; Sirvent, Nicolas; Norton, Lucilia; Boutard, Patrick; Plantaz, Dominique; Millot, Frederic; Philippet, Pierre; Baila, Liliana; Benoit, Yves; Otten, Jacques
The European Organisation for Research and Treatment of Cancer 58951 trial for children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) addressed 3 randomized questions, including the evaluation of dexamethasone (DEX) versus prednisolone (PRED) in induction and, for average-risk patients, the evaluation of vincristine and corticosteroid pulses during continuation therapy. The corticosteroid used in the pulses was that assigned at induction. Overall, 411 patients were randomly assigned: 202 initially randomly assigned to PRED (60 mg/m2/d), 201 to DEX (6 mg/m2/d), and 8 nonrandomly assigned to PRED. At a median follow-up of 6.3 years, there were 19 versus 34 events for pulses versus no pulses; 6-year disease-free survival (DFS) rate was 90.6% (standard error [SE], 2.1%) and 82.8% (SE, 2.8%), respectively (hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in the PRED (HR = 0.56) and DEX groups (HR = 0.59) but more pronounced in girls (HR = 0.24) than in boys (HR = 0.71). Grade 3 to 4 hepatic toxicity was 30% versus 40% in pulses versus no pulses group and grade 2 to 3 osteonecrosis was 4.4% versus 2%. For average-risk patients treated according to Berlin-Frankfurt-Muenster–based protocols, pulses should become a standard component of therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003728. PMID:20407035
Dürr, Hans Roland; Müller, Peter Ernst; Hiller, Erhard; Maier, Markus; Baur, Andrea; Jansson, Volkmar; Refior, Hans Jürgen
Malignant lymphoma of bone is rare. In many cases, its diagnosis is delayed because of unspecific clinical signs and equivocal radiographs. Therapy in general is multimodal, including surgery and radio- and chemotherapy. Our objective was to demonstrate the clinical and radiological aspects of the lesion to optimize diagnostic approaches and to evaluate treatment and prognostic factors. Thirty-six patients with malignant lymphoma of bone who were surgically treated over a 15-year-period were retrospectively reviewed. Seventeen of them showed a singular bone non-Hodgkin's lymphoma (NHL) which was classified as primary lymphoma of the bone (PLB). In 13 cases, dissemination of the disease with multiple bone or visceral involvement was apparent (dNHL). Six patients suffered from bone involvement due to Hodgkin's disease (HD). Surgical treatment was indicated for diagnostic reasons or complications due to the disease. Radiation and chemotherapy were part of the oncological treatment. The patients' mean age was 57 years. The main symptom in malignant bone lymphoma in 33 patients was pain, with an average duration of 8 months. In the secondary cases, bone involvement appeared on average 57 months after the initial diagnosis. An osteolytic pattern was seen in 58% of the lesions. Soft-tissue involvement was seen in 71% of cases (PLB 80%, dNHL 73%, HD 40%) and was the primary diagnostic sign associated with this disease. The 5-year survival rate was 61% (PLB 88%, dNHL 38%, HD 50%). Multiple vs solitary bone involvement was the most significant factor in the prognosis. Extraskeletal involvement significantly decreased survival. No correlation was found between gender, age, location, or histological subtypes and survival. Bone involvement in NHL appears late in the extraskeletal disease. The clinical appearance is nonspecific, and the delay between the onset of symptoms and diagnosis is often long. One of the major radiologic signs is the existence of a soft-tissue tumor
Blum, Kristie A.
With the recent success of the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, and the phosphoinositide-3-kinase (PI3K) inhibitor, idelalisib, in the treatment of patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), a number of new agents targeting the B-cell receptor (BCR) pathway are in clinical development. In addition, multiple trials combining these agents with conventional cytotoxic chemotherapy, immunomodulatory agents, monoclonal antibodies, or other kinase inhibitors are underway. This review will summarize the current data with the use of single agent and combination therapy with BCR inhibitors in NHL. In addition, commonly encountered as well as serious toxicities and hypothesized resistance mechanisms will be discussed. Lastly, this review will examine the future of these agents and opportunities to maneuver them into the front-line setting in selected NHL subtypes. PMID:26637705
Woods, J.; Polissar, L.; Severson, R.; Heuser, L.
A population-based case-control study evaluated the relationship between soft tissue sarcoma and non-Hodgkin's lymphoma and past exposure to phenoxy herbicides and chlorophenols in western Washington state. A major purpose of the study was to determine if the risk of cancer was elevated in relation to chemicals potentially contaminated with 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD). A total of 160 men with soft tissue sarcoma and 581 men with non-Hodgkin's lymphoma were group-matched with 694 randomly selected controls and were interviewed in person. Among the general population, no increased risks for either cancer were seen in relation to intensity or duration of past exposure to phenoxy herbicides or chlorophenols. Preliminary risk estimates for specific occupations that involve phenoxy herbicide or chlorophenol exposure included: farmer, herbicide formulator, applicator, forest sprayer, farmland sprayer, work in sprayed area, and work with or manufacture chlorophenyls. In addition, the risks of both soft tissue sarcoma and non-Hodgkin's lymphoma were elevated among men with past exposure to various insecticides, organic solvents and metals, and among those with preexisting compromise of the immune system. Multivariate studies are in progress to ascertain the contribution of diverse factors to the risks of soft tissue sarcoma or non-Hodgkin's lymphoma in association with phenoxy herbicides, chlorophenols, and/or TCDD.
... zone lymphomas are a group of indolent (slow-growing) NHL B-cell lymphomas, which account for approximately 12 percent of all B-cell lymphomas. The median age for diagnosis is 65 years old. There are three types of marginal zone lymphoma: ...
Primary prophylaxis with granulocyte colony-stimulating factor (GCSF) reduces the incidence of febrile neutropenia in patients with non-Hodgkin lymphoma (NHL) receiving CHOP chemotherapy treatment without adversely affecting their quality of life: cost-benefit and quality of life analysis.
Lee, Sophie; Knox, Angela; Zeng, Irene S L; Coomarasamy, Christin; Blacklock, Hilary; Issa, Samar
Treatment of non-Hodgkin lymphoma (NHL) with cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP) is known to be associated with a significant risk of febrile neutropenia (FN) of up to 50% [Osby et al. 2003 Blood 101(10): 3840-3848; Lyman and Delgado 2003 Cancer 98(11): 2402-2409]. This study sought to examine the impact of primary granulocyte colony-stimulating factor (GCSF) prophylaxis on the incidence of FN, quality of life and overall cost. In this retrospective cohort study, a group of 65 consecutive patients who received CHOP chemotherapy for NHL between December 2006 and October 2009 was studied. Patients either received filgrastim (300 mcg, average of seven doses), pegylated filgrastim (6 mg, single dose), or no GCSF prophylaxis. In addition, 19 patients were asked to complete Functional Assessment of Cancer Therapy: General quality-of-life questionnaires. Overall, patients who received primary GCSF prophylaxis had significantly fewer FN compared to those who did not (5 vs. 60%, p < 0.0001; numbers needed to treat of 1.8; 95% confidence interval, 1.6-2.9). Cost-benefit analysis showed that the GCSF prophylaxis was associated with only a small increase in direct financial cost ($238 NZD [US$189] more to give primary GCSF prophylaxis per patient vs. no prophylaxis). The quality of life assessment showed that the patients' quality of life scores were similar to the published data from the validation study population (466 patients with mixed cancers) for Functional Assessment of Cancer Therapy. Our study shows that primary GCSF prophylaxis is effective in preventing FN in patients receiving CHOP chemotherapy for NHL without adversely affecting their quality of life, and is cost effective.
Vinorelbine, gemcitabine, procarbazine and prednisone (ViGePP) as salvage therapy in relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL): results of a phase II study conducted by the Gruppo Italiano per lo Studio dei Linfomi.
Di Renzo, Nicola; Brugiatelli, Maura; Montanini, Antonella; Vigliotti, Maria Luigia; Cervetti, Giulia; Liberati, Anna Marina; Luminari, Stefano; Spedini, Pierangelo; Giglio, Gianfranco; Federico, Massimo
Patients with aggressive NHL who fail initial treatment or subsequently relapse have a very poor outcome and less than 20-25% achieve a prolonged disease-free interval with salvage therapies. To improve the outcome of patients with refractory aggressive NHL not suitable for High Dose Therapy (HDT) and Autologous Stem Cell Transplant (ASCT), the efficacy of a combination of gemcitabine, vinorelbine, procarbazine and prednisone (ViGePP) were tested. Between November 1999 and September 2002, 69 patients with relapsed or refractory aggressive NHL were treated with ViGePP regimen, every 4 weeks up to six courses. At the end of planned chemotherapy patients could receive additional radiotherapy on residual masses or on sites of previously bulky disease. Sixty-six patients were available for evaluation of study end-points. Thirty patients were refractory to therapy and 36 patients had relapsed after remission obtained with previous therapy. At the end of therapy, complete remission (CR) rate was 23%, 3-year relapse free survival rate was 40% and 3-year overall survival rate was 25% for the whole series (29% and 20% for relapsed and refractory patients, respectively). Patients achieving CR with ViGePP had a significantly better survival as compared with the remaining ones (p = 0.0003). ViGePP as used in the present setting has demonstrated a promising activity, comparable to other conventional dose regimens. Although CR was achieved only in a minority of patients, this was durable in a significant proportion of them. This regimen should be tested in less heavily pre-treated patients and probably in combination with new active agents such Rituximab. Further developments of this combination are warranted.
... Non-Hodgkin Lymphoma About Non-Hodgkin Lymphoma What’s New in Non-Hodgkin Lymphoma Research and Treatment? Research ... done on NHL is focused on looking at new and better ways to treat this disease. Chemotherapy ...
Combination of rituximab and nonpegylated liposomal doxorubicin (R-NPLD) as front-line therapy for aggressive non-Hodgkin lymphoma (NHL) in patients 80 years of age or older: a single-center retrospective study.
Ricciuti, Giuseppina; Finolezzi, Erica; Luciani, Stefania; Ranucci, Elena; Federico, Massimo; Di Nicola, Marta; Zecca, Isaia Antonio Luca; Angrilli, Francesco
The incidence of non-Hodgkin lymphoma in patients 80 years of age or older is 50 times higher than in 20- to 24-year-olds. Very elderly patients are often not treated with standard immunochemotherapy because of poor performance status, comorbidities, and toxicity concerns. We retrospectively analyzed data for 29 patients diagnosed with diffuse large B-cell lymphoma or grade 3B follicular lymphoma and treated with rituximab in combination with nonpegylated liposomal doxorubicin between January 2010 and August 2015. The median age was 84 years. The overall 3-year survival, cause-specific survival, and progression-free survival rates were 46%, 55%, and 44%, respectively. Among prognostic factors, only the achievement of complete remission strongly correlated with overall survival, cause-specific survival, and progression-free survival rates. Treatment caused very mild toxicity, without treatment-related hospitalization or toxic deaths.
... don't know why a person gets non-Hodgkin lymphoma. You are at increased risk if you have ... system or have certain types of infections. Non-Hodgkin lymphoma can cause many symptoms, such as Swollen, painless ...
Daneshpouy, Marjan; Bataille, Dominique; Rivet, Jacqueline; Riviere, Olivier; Morel, Pierre; Amouroux, Jacques; Briere, Josette; Sigaux, Francois; Janin, Anne
Direct involvement of the joints is unusual in patients with non-Hodgkin's lymphoma (NHL). This may pose a diagnostic problem for pathologists, especially since synovial localization can disclose NHL. In the following case of T-cell NHL with eosinophilia, we point out the essential importance of clonality analysis on frozen tissue to distinguish between synovial NHL and specific inflammatory damage.
Iwahara, Yoshihito; Shinohara, Tsutomu; Naruse, Keishi; Komatsu, Yukihisa
Primary bone lymphoma and primary adrenal lymphoma are rare clinicopathological entities of non-Hodgkin's lymphoma (NHL). We present the first case of diffuse large B-cell lymphoma with the involvement of a single bone and both adrenal glands alone with adrenal insufficiency. As primary extranodal NHL may have other unusual extranodal lesions, which may present unexplained clinical findings, patients with primary extranodal NHL require careful systemic examination, even when lymphadenopathy is absent. 2017 BMJ Publishing Group Ltd.
Sousou, Tarek; Friedberg, Jonathan
Indolent Non Hodgkin's lymphoma (NHL) comprises a group of incurable, generally slow growing lymphomas highly responsive to initial therapy with a relapsing and progressive course. Rituximab, an anti CD-20 antibody, has had a large impact on treatment of indolent NHL. Its effectiveness as a single agent and in conjunction with known chemotherapy regimens has made it a standard of care in the treatment of NHL. Analysis of data obtained from NHL clinical trials as well as data from the National Cancer Institute indicates that the overall survival of indolent NHL has improved since the discovery of rituximab. Given its effectiveness and tolerability, it is currently being investigated as a maintenance agent with encouraging results. This review summarizes several landmark trials utilizing rituximab as a single agent and in combination with chemotherapy for treatment of NHL. In addition, a review of the studied rituximab maintenance dosing schedules and its impact on NHL will also be presented. Overall, rituximab has changed the landscape for treatment of indolent NHL however additional research is necessary to identify the optimal dosing schedule as well as patients most likely to respond to prolonged rituximab therapy. PMID:20350660
Tennese, Alysa; Skrabek, Pamela J; Nasr, Michel R; Sekiguchi, Debora R; Morales, Carmen; Brown, Theresa C; Weisenburger, Dennis D; Perry, Anamarija M
Composite lymphomas consist of 2 or more distinct lymphomas occurring in a single anatomical site or simultaneously in different sites and can be composed of any combination of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, or Hodgkin lymphoma (HL). Cases of composite lymphomas with more than 2 lymphomas are extremely rare, with only 4 reports in the literature. We report the case of a 49-year-old man with a triple composite lymphoma in a single lymph node, consisting of small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma in situ. The patient received multiple courses of chemotherapy and an autologous stem cell transplant, which resulted in complete remission. Then, 6 years after the stem cell transplant, he developed classical HL. This unique case is, to our knowledge, the first report of a patient with triple composite lymphoma consisting of 3 small mature B-cell NHLs, who subsequently developed a fourth lymphoma.
Essential facts Non-Hodgkin's lymphoma (NHL) is a cancer of the lymphatic system. According to Cancer Research UK, it is the sixth most common cancer in the UK, with 13,413 new cases diagnosed in 2013. There were 4,801 deaths from NHL in 2014. The disease has many subtypes, with two main broad categories: high-grade or aggressive and low-grade or indolent.
Morton, Lindsay M.; Sampson, Joshua N.; Cerhan, James R.; Turner, Jennifer J.; Vajdic, Claire M.; Wang, Sophia S.; Smedby, Karin E.; de Sanjosé, Silvia; Monnereau, Alain; Benavente, Yolanda; Bracci, Paige M.; Chiu, Brian C. H.; Skibola, Christine F.; Zhang, Yawei; Mbulaiteye, Sam M.; Spriggs, Michael; Robinson, Dennis; Norman, Aaron D.; Kane, Eleanor V.; Spinelli, John J.; Kelly, Jennifer L.; Vecchia, Carlo La; Dal Maso, Luigino; Maynadié, Marc; Kadin, Marshall E.; Cocco, Pierluigi; Costantini, Adele Seniori; Clarke, Christina A.; Roman, Eve; Miligi, Lucia; Colt, Joanne S.; Berndt, Sonja I.; Mannetje, Andrea; de Roos, Anneclaire J.; Kricker, Anne; Nieters, Alexandra; Franceschi, Silvia; Melbye, Mads; Boffetta, Paolo; Clavel, Jacqueline; Linet, Martha S.; Weisenburger, Dennis D.; Slager, Susan L.
Background Non-Hodgkin lymphoma (NHL), the most common hematologic malignancy, consists of numerous subtypes. The etiology of NHL is incompletely understood, and increasing evidence suggests that risk factors may vary by NHL subtype. However, small numbers of cases have made investigation of subtype-specific risks challenging. The International Lymphoma Epidemiology Consortium therefore undertook the NHL Subtypes Project, an international collaborative effort to investigate the etiologies of NHL subtypes. This article describes in detail the project rationale and design. Methods We pooled individual-level data from 20 case-control studies (17471 NHL cases, 23096 controls) from North America, Europe, and Australia. Centralized data harmonization and analysis ensured standardized definitions and approaches, with rigorous quality control. Results The pooled study population included 11 specified NHL subtypes with more than 100 cases: diffuse large B-cell lymphoma (N = 4667), follicular lymphoma (N = 3530), chronic lymphocytic leukemia/small lymphocytic lymphoma (N = 2440), marginal zone lymphoma (N = 1052), peripheral T-cell lymphoma (N = 584), mantle cell lymphoma (N = 557), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (N = 374), mycosis fungoides/Sézary syndrome (N = 324), Burkitt/Burkitt-like lymphoma/leukemia (N = 295), hairy cell leukemia (N = 154), and acute lymphoblastic leukemia/lymphoma (N = 152). Associations with medical history, family history, lifestyle factors, and occupation for each of these 11 subtypes are presented in separate articles in this issue, with a final article quantitatively comparing risk factor patterns among subtypes. Conclusions The International Lymphoma Epidemiology Consortium NHL Subtypes Project provides the largest and most comprehensive investigation of potential risk factors for a broad range of common and rare NHL subtypes to date. The analyses contribute to our understanding of the multifactorial nature of NHL
Adult Diffuse Large B-Cell Lymphoma; Mantle Cell Lymphoma Recurrent; Lymphoma, Follicular; Marginal Zone B-Cell Lymphoma; Malignant Lymphoma - Lymphoplasmacytic; Waldenstrom Macroglobulinemia; Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia (CLL); T-Cell Lymphoma
Wu, Yaxun; Xu, Xiaohong; Miao, Xiaobing; Zhu, Xinghua; Yin, Haibing; He, Yunhua; Li, Chunsun; Liu, Yushan; Chen, Yali; Lu, Xiaoyun; Wang, Yuchan; He, Song
Sam68 (Src-associated in mitosis 68 kDa), a substrate for tyrosine kinase c-Src during mitosis, is up-regulated in a variety of human cancers and acts oncogenically promoting tumour progression. This study has explored biological function and clinical significance of Sam68 in non-Hodgkin's lymphoma (NHL). To examine Sam68 expression in NHL, clinically, eight diffuse large B-cell lymphomas and four reactive lymphoid hyperplasia fresh-frozen tissues were obtained for western blot and quantitative real-time PCR analyses. Using immunohistochemical staining, paraffin wax embedded sections from 164 cases of NHL patients were used to evaluate prognostic value of Sam68. Cell Counting Kit-8 (CCK-8) and soft agar colony assays were conducted to investigate the role of Sam68 in cell viability and cell proliferation respectively. Furthermore, effects of Sam68 on cell adhesion-mediated drug resistance (CAM-DR) was determined by CCK-8 assay and flow cytometric analysis. Expression status of Sam68 inversely correlated with clinical outcomes of patients with NHL, and it was also an independent prognostic factor for the outcomes. In addition, Sam68 was associated with proliferation of NHL cells. Knock-down of its gene inhibited cell proliferation and colony formation by delaying cell cycle progression. Furthermore, OCI-Ly8 and Jeko-1 cells adhering to FN and HS-5 expressed higher Sam68 protein, compared to their suspension counterparts. Sam68 promoted cell adhesion-mediated drug resistance (CAM-DR) via the AKT pathway. Increased Sam68 expression in NHL resulted in poor prognosis, and it promoted CAM-DR in NHL via AKT. © 2015 John Wiley & Sons Ltd.
Desai, Dinkar; Pandit, Siddharth; Jasphin, Shiny; Shetty, Akhil S.
Non-Hodgkin's lymphoma (NHL) is the third common malignant lesion of the oral region. Plasmablastic lymphomas are rare, aggressive neoplasms occurring mostly in human immunodeficiency virus (HIV) infected individual which accounts for approximately 2.6% of all NHL. It usually presents as a diffuse growth and with diffuse pattern of histological presentation. It is very difficult to differentiate this lymphoma from other NHL. Immunohistochemical evaluation of various markers is an important criteria of the diagnostic protocol. Here, we describe a case of plasmablastic lymphoma in a 50-year-old female HIV-infected patient. The diagnosis was based on histopathological examination and immunophenotyping. PMID:27795651
Skibola, Christine F.; Curry, John D.; Nieters, Alexandra
BACKGROUND Genetic susceptibility studies of lymphoma may serve to identify at risk populations and to elucidate important disease mechanisms. METHODS This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. RESULTS Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G>A and IL10 -3575T>A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol assessments are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro- and endocrine-immune cross-talk with lymphomagenesis, but will need replication in larger populations. CONCLUSIONS Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations. PMID:17606447
In a large international collaborative analysis of risk factors for non-Hodgkin lymphoma (NHL), scientists were able to quantify risk associated with medical history, lifestyle factors, family history of blood or lymph-borne cancers, and occupation for 11
Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL an...
Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL an...
Chihara, Dai; Nastoupil, Loretta J.; Williams, Jessica N.; Lee, Paul; Koff, Jean L.; Flowers, Christopher R.
Non-Hodgkin lymphoma (NHL) comprises numerous biologically and clinically heterogeneous subtypes, with limited data examining risk factors for these distinct disease entities. Many limitations exist when studying lymphoma epidemiology, therefore until recently little was known regarding the etiology of NHL subtypes. This review highlights the results of recent pooled analyses examining risk factors for NHL subtypes. We outline heterogeneity and commonality among risk factors for NHL subtypes, with proposed subtype-specific as well as shared etiologic mechanisms. In addition, we describe how the study of lymphoma epidemiology may translate into prevention or therapeutic targeting as we continue to explore the complexities of lifestyle and genetic factors that impact lymphomagenesis. PMID:25864967
Perry, Anamarija M; Perner, Yvonne; Diebold, Jacques; Nathwani, Bharat N; MacLennan, Kenneth A; Müller-Hermelink, Hans K; Bast, Martin; Boilesen, Eugene; Armitage, James O; Weisenburger, Dennis D
Comparative data on the distribution of non-Hodgkin lymphoma (NHL) subtypes in Southern Africa (SAF) is scarce. In this study, five expert haematopathologists classified 487 consecutive cases of NHL from SAF using the World Health Organization classification, and compared the results to North America (NA) and Western Europe (WEU). Southern Africa had a significantly lower proportion of low-grade (LG) B-NHL (34·3%) and a higher proportion of high-grade (HG) B-NHL (51·5%) compared to WEU (54·5% and 36·4%) and NA (56·1% and 34·3%). High-grade Burkitt-like lymphoma was significantly more common in SAF (8·2%) than in WEU (2·4%) and NA (2·5%), most likely due to human immunodeficiency virus infection. When SAF patients were divided by race, whites had a significantly higher frequency of LG B-NHL (60·4%) and a lower frequency of HG B-NHL (32·7%) compared to blacks (22·5% and 62·6%), whereas the other races were intermediate. Whites and other races had a significantly higher frequency of follicular lymphoma and a lower frequency of Burkitt-like lymphoma compared to blacks. The median ages of whites with LG B-NHL, HG B-NHL and T-NHL (64, 56 and 67 years) were significantly higher than those of blacks (55, 41 and 34 years). Epidemiological studies are needed to better understand these differences.
Xavier, Ana C; Armeson, Kent E; Hill, Elizabeth G; Costa, Luciano J
Survivors of classical Hodgkin lymphoma (cHL) are at an increased risk of developing secondary non-Hodgkin lymphomas (sNHLs). To the authors' knowledge, the outcome of patients with sNHL compared with their de novo counterparts (dnNHL) is unknown. Data from 26,826 cases of HL from the Surveillance, Epidemiology, and End Results (SEER) program that were diagnosed between 1992 and 2009 were used to obtain the risk of further development of different subtypes of sNHL. The survival of patients with sNHL was compared with that of matched patients with dnNHL. The estimated cumulative incidence of sNHL was 2.50% (95% confidence interval [95% CI], 2.10-2.89) at 15 years from the diagnosis of cHL. The standardized incidence ratio was 10.5 (95% CI, 8.9-12.4) for aggressive B-cell NHL, 4.0 (95% CI, 3.1-5.1) for indolent B-cell NHL, and 14.6 (95% CI, 10.3-20.1) for T-cell NHL. Patients with indolent B-cell sNHL had a worse overall survival compared with their dnNHL counterparts (hazards ratio [HR] of death, 2.7; 95% CI, 1.3-5.7). Survival was not significantly different between patients with sNHL and those with dnNHL with regard to aggressive B-cell NHL (HR, 1.3; 95% CI, 0.6-2.7) or T-cell NHL (HR, 0.8; 95% CI, 0.3-1.8). The risk of developing sNHL after cHL is substantial. Although patients with indolent B-cell sNHL have inferior survival, patients with aggressive B-cell sNHL and T-cell sNHL have survival comparable to that of their de novo counterparts. © 2013 American Cancer Society.
CD22-binding peptides that initiate signal transduction and apoptosis in non -Hodgkin’s lymphoma (NHL), 2) optimize CD22-mediated signal transduction...positive non -Hodgkin’s lymphoma (NHL), much as rituximab (Rituxan) is an option to patients with CD20-positive NHL. By sequencing the heavy and...Int J Pept Res Ther (2008) 14:237–246 8. O’Donnell RT, Pearson D, McKnight HC, Ma YP, Tuscano JM. Treatment of non -Hodgkin’s lymphoma xenografts with
Howlader, Nadia; Shiels, Meredith S; Mariotto, Angela B; Engels, Eric A
The human immunodeficiency virus (HIV) epidemic has strongly influenced non-Hodgkin lymphoma (NHL) incidence in the U.S. general population, but its effects on NHL mortality trends are unknown. Using SEER cancer registry data, we assessed NHL mortality rates in the United States (2005-2012) and mapped NHL deaths to prior incident cases. Data included HIV status at NHL diagnosis. We describe the proportion of NHL deaths linked to an HIV-infected case, for 3 AIDS-defining subtypes [diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and central nervous system (CNS) lymphoma] and within demographic categories. We also present incidence-based mortality (IBM) rates showing the impact of HIV on mortality trends and describe survival after NHL diagnosis by calendar year. Of 11,071 NHL deaths, 517 (4.6%) were in HIV-infected persons. This proportion was higher in deaths mapped to DLBCL (7.3% with HIV), Burkitt lymphoma (33.3%), and CNS lymphoma (17.6%), and among deaths from these subtypes, for people aged 20-49 years (46.6%), males (15.2%), and blacks (39.3%). IBM rates declined steeply during 2005-2012 for HIV-infected NHL cases (-7.6% per year, P = 0.001). This trend reflects a steep decline in incident NHL among HIV-infected people after 1996, when highly active antiretroviral therapy was introduced. Five-year cancer-specific survival improved more markedly among HIV-infected cases (9%-54%) than HIV-uninfected cases (62%-76%) during 1990-2008. The HIV epidemic has strongly contributed to NHL deaths, especially for AIDS-defining NHL subtypes and groups with high HIV prevalence. Declining NHL mortality rates for HIV-infected cases reflect both declining incidence and improving survival. Cancer Epidemiol Biomarkers Prev; 25(9); 1289-96. ©2016 AACR. ©2016 American Association for Cancer Research.
Madan, Ravi A; Chang, Victor T; Dever, Lisa L
Although highly active antiretroviral therapy has improved the clinical course of patients with HIV, this population remains at a significantly increased risk for non-Hodgkin's lymphoma (NHL). Spinal cord compression is a rare presentation of NHL, regardless of the patient population. We encountered a patient with HIV-related NHL who presented with a thoracic spinal cord compression and had a complicated clinical course as a result of the atypical presentation.
Murphey, Mark D; Kransdorf, Mark J
Primary lymphoma of bone and soft tissue is rare and almost invariably of B-cell origin. Osseous lymphoma usually reveals aggressive bone destruction and associated soft tissue extension. Soft tissue involvement is optimally depicted by MR imaging. Cortical destruction allowing communication between the intraosseous and soft tissue components may be subtle with small striations of extension. Lymphoma of the deep soft tissues usually reveals long cones of intramuscular or intermuscular tumor again best depicted by MR imaging. Cutaneous or subcutaneous lymphoma demonstrates multiple nodules and plaquelike thickening. Copyright © 2016 Elsevier Inc. All rights reserved.
Barrena, Susana; Almeida, Julia; Del Carmen García-Macias, María; López, Antonio; Rasillo, Ana; Sayagués, Jose María; Rivas, Rosa Ana; Gutiérrez, María Laura; Ciudad, Juana; Flores, Teresa; Balanzategui, Ana; Caballero, María Dolores; Orfao, Alberto
To establish the utility of flow cytometry (FCM) for screening and diagnosis of B cell non-Hodgkin lymphoma (B-NHL) from lymphoid tissue samples obtained by fine-needle aspiration (FNA). We compared prospectively FCM versus cytology/histology analysis of FNA samples for the diagnostic screening and further World Health Organization (WHO) subclassification of B-NHL. FCM and cytology showed a high degree of agreement (93%); however, diagnosis of reactive processes (RP), B-NHL and T-NHL by FCM showed higher sensitivity than cytology (92-100% versus 64-94%, respectively), without false positive NHL cases. The antibody combination used did not allow a positive diagnosis of Hodgkin lymphoma as distinct from a RP. A high concordance rate was found between FCM and histopathology (74%) in subtyping B-NHL. In this regard, mantle-cell lymphoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma showed the highest degree of agreement (100% concordant rates). In turn, FCM showed higher sensitivity/specificity in classifying follicular lymphoma (FL) and large B cell lymphomas, while the opposite occurred for marginal-zone and lymphoplasmacytic lymphomas. FCM enhances the diagnostic ability of FNA cytology, playing a crucial role in a rapid and accurate differential diagnosis between RP, B-NHL and T-NHL. In addition, immunophenotyping of FNA samples contributes to a more precise subclassification of B-NHL when combined with histopathology and genetic/molecular data. © 2011 Blackwell Publishing Limited.
Rajagopal, Meyyappa Devan; Kar, Rakhee; Basu, Debdatta; Cyriac, Sunu Lazar
Composite lymphoma is a rare tumor composed of two or more distinct lymphomas in the same topographic site or tissue. Several combinations of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, and Hodgkin lymphoma can occur with different prognoses and treatments. The coexistence of a B-cell NHL and a T-cell NHL is unusual. The exact etiology of composite lymphoma is unknown; however, few mechanisms have been proposed to explain its pathogenesis. The chemotherapeutic protocols are heterogeneous but are essentially targeted against the high-grade component. Most of the cases show worse outcome with a median survival of 12 months. In this article, we report a case of composite lymphoma which was initially diagnosed as diffuse large B-cell lymphoma, and the presence of CD3-positive atypical cells in the bone marrow urged us to re-evaluate the lymph node biopsy following which a focus of Alk-1-positive anaplastic large cell lymphoma was identified.
Miles, Rodney R; Shah, Rikin K; Frazer, J Kimble
Molecular genetic abnormalities are ubiquitous in non-Hodgkin lymphoma (NHL), but genetic changes are not yet used to define specific lymphoma subtypes. Certain recurrent molecular genetic abnormalities in NHL underlie molecular pathogenesis and/or are associated with prognosis or represent potential therapeutic targets. Most molecular genetic studies of B- and T-NHL have been performed on adult patient samples, and the relevance of many of these findings for childhood, adolescent and young adult NHL remains to be demonstrated. In this review, we focus on NHL subtypes that are most common in young patients and emphasize features actually studied in younger NHL patients. This approach highlights what is known about NHL genetics in young patients but also points to gaps that remain, which will require cooperative efforts to collect and share biological specimens for genomic and genetic analyses in order to help predict outcomes and guide therapy in the future. © 2016 John Wiley & Sons Ltd.
Miles, Rodney R.; Shah, Rikin K.; Frazer, J. Kimble
Summary Molecular genetic abnormalities are ubiquitous in non-Hodgkin lymphoma (NHL), but genetic changes are not yet used to define specific lymphoma subtypes. Certain recurrent molecular genetic abnormalities in NHL underlie molecular pathogenesis and/or are associated with prognosis or represent potential therapeutic targets. Most molecular genetic studies of B- and T-NHL have been performed on adult patient samples, and the relevance of many of these findings for childhood, adolescent and young adult NHL remains to be demonstrated. In this review, we focus on NHL subtypes that are most common in young patients and emphasize features actually studied in younger NHL patients. This approach highlights what is known about NHL genetics in young patients but also points to gaps that remain, which will require cooperative efforts to collect and share biological specimens for genomic and genetic analyses in order to help predict outcomes and guide therapy in the future. PMID:26969846
Vendrell, J R; Alcaraz, A; Gutíerrez, R; Rodríguez, A; Barranco, M A; Carretero, P
Contribution of one case of non-Hodgkin lymphoma (NHL) with vesical involvement, that presented clinically with urological symptomatology. Vesical involvement is typical of NHL, and is becoming more frequent in association with the increased number of AIDS patients under immunosuppressive therapy. It should be expected that this currently unusual entity will become more common in the future.
Askling, J; Ekbom, A
To study the association between chronic infections and non-Hodgkin's lymphoma (NHL), we assessed the risk of NHL in a Swedish cohort of 5050 individuals with tuberculosis 1939–1960. The overall relative risk was moderately increased, largely accounted for by high risks following severe tuberculosis diagnosed a long time ago. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11139323
Vajdic, Claire M.; Falster, Michael; Engels, Eric A.; Martínez-Maza, Otoniel; Turner, Jennifer; Hjalgrim, Henrik; Vineis, Paolo; Seniori Costantini, Adele; Bracci, Paige M.; Holly, Elizabeth A.; Willett, Eleanor; Spinelli, John J.; La Vecchia, Carlo; Zheng, Tongzhang; Becker, Nikolaus; De Sanjosé, Silvia; Chiu, Brian C.-H.; Dal Maso, Luigino; Cocco, Pierluigi; Maynadié, Marc; Foretova, Lenka; Staines, Anthony; Brennan, Paul; Davis, Scott; Severson, Richard; Cerhan, James R.; Breen, Elizabeth C.; Birmann, Brenda; Grulich, Andrew E.; Cozen, Wendy
Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis. PMID:18263783
Mamorska-Dyga, Aleksandra; Ronny, Faisal M. H.; Puccio, Carmelo; Islam, Humayun
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, with about 30% of new cases presenting with extranodal disease. Lesions originating from soft tissues of the upper extremities are extremely rare and may mimic other malignancies like sarcoma. We present a case of an elderly patient with right upper extremity (RUE) mass which was proven to be DLBCL instead of sarcoma. We emphasize the increasing need for investigating new therapeutic options for patients of extreme age and/or with underlying heart disease. PMID:27486587
Farming and exposure to pesticides have been linked to non-Hodgkin lymphoma (NHL), and multiple myeloma (MM) in previous studies. We evaluated use of insecticides, fungicides and fumigants and risk of NHL, including MM and other NHL sub-types in the Agricultural Health Study, a ...
Farming and exposure to pesticides have been linked to non-Hodgkin lymphoma (NHL), and multiple myeloma (MM) in previous studies. We evaluated use of insecticides, fungicides and fumigants and risk of NHL, including MM and other NHL sub-types in the Agricultural Health Study, a ...
Lunning, Matthew; Vose, Julie M.
Summary Indolent lymphoma comprises a unique and challenging subset of non-Hodgkin lymphoma (NHL). While definitions of indolence will vary, the most common indolent NHL subtypes include follicular lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma. Patients with indolent NHL (iNHL) excluding those with rare localized presentations are often met with an incurable but highly treatable NHL. In the rituximab era, response rates are approaching 90% with rituximab plus chemotherapy and time to next treatment are beginning to be measured in years. As a result of a prolonged natural history, we are encountering a gridlock of novel regimens and agents that appropriately fill peer-reviewed journals. In this review, we tackle a spectrum of topics in the management of indolent lymphoma including the initial approach to the newly diagnosed patient, approaches to first cytotoxic chemotherapy, maintenance and consolidation techniques, as well as highlight promising treatments on the horizon in iNHL. Clinicians continue to face tough choices in the management of iNHL. Through well-thought out clinical trials and peer-reviewed vetting of data we will continue to determine how to best manage the clinical continuum that is iNHL. PMID:23063143
Mandell, L.R.; Wollner, N.; Fuks, Z.
The records of 95 consecutive children less than or equal to 21 years of age with previously untreated diffuse histology NHL registered in our protocols from 1978 to 1983 were reviewed. Seventy-nine patients were considered eligible for analysis. The histologic subtypes represented included lymphoblastic (LB) 37%; histiocytic (DHL) 29%; undifferentiated (DU) 19%; poorly differentiated (DPDL) 9%; and unclassified (UNHL) 6%. Distribution of the patients according to stage showed Stage I, 0%; Stage II, 11%; Stage III, 53%; Stage IV, 36%. Four different Memorial Hospital protocols for systemic chemotherapy were used (LSA2L2 73%; L10 9%; L17 10%; L17M 8%); however, the IT (intrathecal) chemotherapy was uniform (Methotrexate: 6.0-6.25 mg/M2 per treatment course) and was included in the induction, consolidation, and maintenance phases of all treatment protocols. Cranial radiation was included in the induction, consolidation, and maintenance phases of all treatment protocols. Cranial radiation was not included in the CNS prophylaxis program. The overall median time of follow-up was 43 months. The overall CNS relapse rate was 6.3%; however, the incidence of CNS lymphoma presenting as the first isolated site of relapse in patients in otherwise complete remission (minimum follow-up of 19 months with 97% of patients off treatment) was only 1/58 (1.7%). Our data suggest that IT chemotherapy when given in combination with modern aggressive systemic combination chemotherapy, and without cranial radiation appears to be a highly effective modality for CNS prophylaxis regardless of stage, histology, or bone marrow or mediastinal involvement. (Abstract Truncated)
De Re, Valli; Caggiari, Laura; Garziera, Marica; De Zorzi, Mariangela; Repetto, Ombretta
Hepatitis C virus (HCV) is a positive, single-stranded RNA virus, which has been associated to different subtypes of B-cell non-Hodgkin lymphoma (B-NHL). Cumulative evidence suggests an HCV-related antigen driven process in the B-NHL development. The underlying molecular signature associated to HCV-related B-NHL has to date remained obscure. In this review, we discuss the recent developments in this field with a special mention to different sets of genes whose expression is associated with BCR coupled to Blys signaling which in turn was found to be linked to B-cell maturation stages and NF-κb transcription factor. Even if recent progress on HCV-B-NHL signature has been made, the precise relationship between HCV and lymphoma development and phenotype signature remain to be clarified.
Suarez, F; Lecuit, M
Non-Hodgkin lymphomas (NHLs) are malignant proliferations of lymphoid cells. Lymphoid cells proliferate in a physiological manner in response to antigen-dependent and antigen-independent signals. Some lymphotropic viruses, such as Epstein-Barr virus and human T-lymphotropic virus 1, as well as pathogens leading to chronic antigenic stimulation (such as Helicobacter pylori and hepatitis C virus), are associated with NHL. We review here some of the pathophysiological features of infection-associated NHL.
Wiodarska, I.; Styl, M.; Mecucci, C.
Reciprocal translocations involving the chromosomal region 3q27 and one of the immunoglobulin loci at 14q32, 2p12 or 22q11 have been identified as the third most common type of chromosomal abnormality in Non Hodgkin`s lymphomas (NHLs), in addition to t(14;18) and t(8;14). These abnormalities appeared to be strongly associated with a diffuse, large cell subtype of B-cell NHL. Recently, a t(3;14) and t(3;22) have been cloned and a new transcriptional unit at 3q27, designated BCL-5, BCL-6 or LAZ3, has been identified. The gene appears to encode a new zinc finger protein with the putative function of a transcription factor. Rearrangements of the BCL-6 gene have been detected not only in cases with a typical t(3;14), t(2;3) and t(3;22), but also in a few NHL cases carrying 3q27 translocations not involving Ig genes. We report on nine B-NHL cases with a 3q27/BCL-6 rearrangement demonstrated by cytogenetic, FISH, and Southern analysis. Cytogenetic analysis complemented by FISH studies showed the presence of a classical t(3;14) or a t(3;22) in three cases and a variety of chromosomal aberrations involving the 3q27 locus in the remaining cases. Some of these translocations were not previously identified by conventional banding analysis. In three patients chromosome painting demonstrated involvement of both chromosome at the 3q24 band. We conclude: 3q27/BCL-6 rearrangements seem not to be restricted to diffuse large cell lymphoma. We here documented 3q27/BCL-6 abnormalities in Richter syndrome and follicular lymphomas. The variety of 3q27 aberrations at cytogenetic level suggests that, in addition to immunoglobulin genes, a number of other genes spreading over the human genome may deregulate BCL-6 in lymphomas. Chromosome painting is a powerful tool to demonstrate 3q27 abnormalities, not identified by conventional banding analysis.
Davis, Gregory M; Low, Wai Y; Anderson, Joshua W T; Boag, Peter R
TRIM-NHL proteins are highly conserved regulators of developmental pathways in vertebrates and invertebrates. The TRIM-NHL family member NHL-2 in Caenorhabditis elegans functions as a miRNA cofactor to regulate developmental timing. Similar regulatory roles have been reported in other model systems, with the mammalian ortholog in mice, TRIM32, contributing to muscle and neuronal cell proliferation via miRNA activity. Given the interest associated with TRIM-NHL family proteins, we aimed to further investigate the role of NHL-2 in C. elegans development by using a synthetic RNAi screening approach. Using the ORFeome library, we knocked down 11,942 genes in wild-type animals and nhl-2 null mutants. In total, we identified 42 genes that produced strong reproductive synthetic phenotypes when knocked down in nhl-2 null mutants, with little or no change when knocked down in wild-type animals. These included genes associated with transcriptional processes, chromosomal integrity, and key cofactors of the germline small 22G RNA pathway. Copyright © 2017 Davis et al.
Stuplich, Moritz; Mayer, Karin; Kim, Young; Thanendrarajan, Sharmilan; Simon, Matthias; Schäfer, Niklas; Glas, Martin; Schmidt-Wolf, Ingo G H; Herrlinger, Ulrich
Richter syndrome (RS) describes the development of high-grade non-Hodgkin's lymphoma (NHL) from low-grade NHL. RS isolated to the brain is very rare and has a poor prognosis. We describe the cases of high-grade large B-cell diffuse NHL in a 56-year-old male with chronic lymphocytic leukemia and in a 71-year-old female with previously unknown low-grade NHL, both with initial appearance of neurological symptoms. This report extends the literature of central nervous system RS and particularly highlights the importance of a thorough diagnostic evaluation of patients with low-grade NHL presenting with neurological symptoms. Copyright © 2011 S. Karger AG, Basel.
Kunami, Naoko; Takamatsu, Yasushi; Fujita, Mana; Katsuya, Hiroo; Sasaki, Hidenori; Wakamatsu, Shinichi; Ishitsuka, Kenji; Nabeshima, Kazuki; Tamura, Kazuo
A 72-year-old man with extranodal natural killer cell lymphoma (ENKL) presented with a painless swelling of the left forearm. He was initially diagnosed as having a bacterial cellulitis and received antimicrobial therapy. However, his left arm became increasingly swollen in association with fever and redness of the lesion. Therefore, he underwent focal dissection. Because of persistent swelling, the left arm was rebiopsied 9 months later, and a diagnosis of ENKL developing in the subcutis was established. He was treated with focal radiation therapy in combination with dexamethasone, etoposide, ifosfamide, methotrexate and L-asparaginase. The lesion was significantly reduced in size but did not disappear completely. Two months later the lesion became necrotic, although swelling of the forearm lesion, left axillary and cervical lymph nodes were kept under control. We then performed amputation of the left forearm since it could not be saved medically. The patient currently remains alive and well without progression 2 years after amputation. When evaluating panniculitis, which is difficult to cure, ENKL should be considered in the differential diagnosis and treated appropriately.
Shahid, Ruqaiya; Gulzar, Rubina; Avesi, Lubna; Hassan, Saba; Danish, Farheen; Mirza, Talat
To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. Cross-sectional analytical study. Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. Out of the 318 cases, 79 (25%) were Hodgkin Lymphomas (HL) and 239 (75%) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95%) were B cell lymphomas and 24 (10.05%) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95% of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HLwas significantly higher in the younger age group and that of NHLwas higher in the older age group (p < 0.001). Primary lymph node involvement was reported in 175 (55%) and cervical lymph node was the most frequent site. Extra nodal involvement was seen in 93 (29%) of all cases and was reported in 87 (36.4%) of NHLand 6 (7.5%) of HL. The most common extra nodal site was the gastrointestinal tract. Hodgkin lymphoma comprises 25% and non-Hodgkin lymphoma comprises 75% of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHLis three times more common than T-cell lymphoma. DLBCLis the most frequent lymphoma. ALCLis the most common T-cell, and mixed cellularity is the most common Hodgkin lymphoma.
van Wijngaarden, E; Savitz, D A
This case-control study examined occupational sunlight exposure and death from non-Hodgkin lymphoma (NHL) and NHL subtypes among 188 cases and 1880 controls selected from a cohort of 138,905 male electric utility workers. Exposure was classified according to work history linked to indices of cumulative sunlight exposure. Odds ratios and 95% confidence intervals were derived from conditional logistic regression models and were conditioned on the matching factors birth year and ethnicity. Mortality from NHL and intermediate/high-grade lymphomas was not related to cumulative sunlight exposure, with odds ratios around the null. For low-grade lymphomas, a dose-response gradient was observed for exposure in the past 12 to 21 years, but this result seemed to be sensitive to cut points for categorization of cumulative exposure. These data do not provide evidence for an association between occupational sunlight exposure and mortality from NHL or NHL subtypes.
Peveling-Oberhag, J; Arcaini, L; Bankov, K; Zeuzem, S; Herrmann, E
Many epidemiological studies provide solid evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin's lymphoma (B-NHL). However, the most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). We conducted a literature search to identify studies that included patients with HCV-associated B-NHL (HCV-NHL) who received AVT, with the intention to treat lymphoma and viral disease at the same time. The primary end point was the correlation of sustained virological response (SVR) under AVT with lymphoma response. Secondary end points were overall lymphoma response rates and HCV-NHL response in correlation with lymphoma subtypes. We included 20 studies that evaluated the efficacy of AVT in HCV-NHL (n = 254 patients). Overall lymphoma response rate through AVT was 73% [95%>confidence interval, (CI) 67-78%]. Throughout studies there was a strong association between SVR and lymphoma response (83% response rate, 95%>CI, 76-88%) compared to a failure in achieving SVR (53% response rate, 95%>CI, 39-67%, P = 0.0002). There was a trend towards favourable response for AVT in HCV-associated marginal zone lymphomas (response rate 81%, 95%>CI, 74-87%) compared to nonmarginal zone origin (response rate 71%, 95%>CI, 61-79%, P = 0.07). In conclusion, in the current meta-analysis, the overall response rate of HCV-NHL under AVT justifies the recommendation for AVT as first-line treatment in patients who do not need immediate conventional treatment. The strong correlation of SVR and lymphoma regression supports the hypothesis of a causal relationship of HCV and lymphomagenesis.
Lu, Y; Sullivan-Halley, J; Cozen, W; Chang, E T; Henderson, K; Ma, H; Deapen, D; Clarke, C; Reynolds, P; Neuhausen, S L; Anton-Culver, H; Ursin, G; West, D; Bernstein, L
Family history of haematopoietic malignancies appears to be a risk factor for non-Hodgkin's lymphoma (NHL), but whether risk varies by family member's gender is unclear. Among 121 216 women participating in the prospective California Teachers Study, NHL risk varied by type of haematopoietic malignancy and gender of the relative.
Lu, Y; Sullivan-Halley, J; Cozen, W; Chang, E T; Henderson, K; Ma, H; Deapen, D; Clarke, C; Reynolds, P; Neuhausen, S L; Anton-Culver, H; Ursin, G; West, D; Bernstein, L
Family history of haematopoietic malignancies appears to be a risk factor for non-Hodgkin's lymphoma (NHL), but whether risk varies by family member's gender is unclear. Among 121 216 women participating in the prospective California Teachers Study, NHL risk varied by type of haematopoietic malignancy and gender of the relative. PMID:19156148
Li, Shi-Jun; Chen, Hui-Ping; Chen, Ying-Hua; Zhang, Li-hua; Tu, Yuan-Mao; Liu, Zhi-hong
To determine the spectrum of renal lesions in patients with kidney involvement in non-Hodgkin's lymphoma (NHL) by renal biopsy. The clinical features and histological findings at the time of the renal biopsy were assessed for each patient. We identified 20 patients with NHL and renal involvement, and the diagnosis of NHL was established following the kidney biopsy in 18 (90%) patients. The types of NHL include the following: chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 8), diffuse large B-cell lymphoma (n = 4), T/NK cell lymphoma (n = 3), lymphoplasmacytic lymphoma (n = 2), cutaneous T-cell lymphoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1) and mantle cell lymphoma (n = 1). All presented with proteinuria, and 15 patients had impaired renal function. The pathological findings included (1) membranoproliferative glomerulonephritis-like pattern in seven patients; (2) crescent glomerulonephritis in four; (3) minimal-change disease in three, and glomeruli without specific pathological abnormalities in three; (4) intraglomerular large B-cell lymphoma in one; (5) intracapillary monoclonal IgM deposits in one; (6) primary diffuse large B-cell lymphoma of the kidneys in one; and (7) lymphoma infiltration of the kidney in eight patients. A wide spectrum of renal lesions can be observed in patients with NHL, and NHL may be first proven by renal biopsies for evaluation of kidney injury or proteinuria. Renal biopsy is necessary to establish the underlying cause of renal involvement in NHL.
Harrison, Lara CV; Luukkaala, Tiina; Pertovaara, Hannu; Saarinen, Tuomas O; Heinonen, Tomi T; Järvenpää, Ritva; Soimakallio, Seppo; Kellokumpu-Lehtinen, Pirkko-Liisa I; Eskola, Hannu J; Dastidar, Prasun
Background To show magnetic resonance imaging (MRI) texture appearance change in non-Hodgkin lymphoma (NHL) during treatment with response controlled by quantitative volume analysis. Methods A total of 19 patients having NHL with an evaluable lymphoma lesion were scanned at three imaging timepoints with 1.5T device during clinical treatment evaluation. Texture characteristics of images were analyzed and classified with MaZda application and statistical tests. Results NHL tissue MRI texture imaged before treatment and under chemotherapy was classified within several subgroups, showing best discrimination with 96% correct classification in non-linear discriminant analysis of T2-weighted images. Texture parameters of MRI data were successfully tested with statistical tests to assess the impact of the separability of the parameters in evaluating chemotherapy response in lymphoma tissue. Conclusion Texture characteristics of MRI data were classified successfully; this proved texture analysis to be potential quantitative means of representing lymphoma tissue changes during chemotherapy response monitoring. PMID:19545438
Distribution of lymphomas in Poland according to World Health Organization classification: analysis of 11718 cases from National Histopathological Lymphoma Register project - the Polish Lymphoma Research Group study.
Szumera-Ciećkiewicz, Anan; Gałązka, K; Szpor, J; Rymkiewicz, G; Jesionek-Kupnicka, D; Gruchała, A; Ziarkiewicz-Wróblewska, B; Poniatowska-Broniek, G; Demczuk, S; Prochorec-Sobieszek, M
Most national lymphoma registers rely on broad classifications which include Hodgkin and non-Hodgkin lymphomas (NHL), multiple myeloma and leukaemia. In Poland the National Histopathological Lymphoma Register project (NHLR) was implemented by hematopathologists in accordance with the 2008 WHO classification into haematopoietic and lymphoid tissues. We present the NHLR data and compare lymphoma distribution in Poland, Europe, as well as in North Central and South America. Records of 11718 patients diagnosed in 24 pathology departments from all over the country were retrieved and reclassified into indolent and aggressive lymphomas according to the 2008 revised WHO classification system. DLBCL (32.9%; 2587), CLL/SLL (31.84%; 2504) and MCL (9.04%; 711) were the three most frequent NHL. The ratio of indolent to aggressive NHL was 1.72; 63.25% (4809) to 36.25% (2794) of cases respectively. Multiple myeloma was less frequent as compared to the data from population-based national cancer register (13.32% vs. 28.94%). Major differences between NHLR and European and American data on NHL subtypes concered: higher incidence of aggressive B-cell lymphomas including DLBCL, lower FL and MALT incidence rate. The percentage of unclassified lymphomas in the study was minimal due to participation of hematopathologists.
Tocchini, Cristina; Ciosk, Rafal
TRIM-NHL proteins are key regulators of developmental transitions, for example promoting differentiation, while inhibiting cell growth and proliferation, in stem and progenitor cells. Abnormalities in these proteins have been also associated with human diseases, particularly affecting muscular and neuronal functions, making them potential targets for therapeutic intervention. The purpose of this review is to provide a systematic and comprehensive summary on the most studied TRIM-NHL proteins, highlighting examples where connections were established between structural features, molecular functions and biological outcomes.
Casulo, Carla; Friedberg, Jonathan
Marginal zone lymphomas (MZL) are a diverse group of indolent lymphoproliferative disorders that comprise three subtypes: nodal, splenic and mucosal associated marginal zone lymphomas (MALT). Histologic transformation (HT) to an aggressive lymphoma is a rare event that can occur in any subtype, and at lower frequency compared to other indolent non Hodgkin lymphomas (NHL) like follicular lymphoma. There are few data directly associated with risk and prognosis of transformation in MZL. However, recent advances in the understanding of molecular and genetic features of MALT have contributed to an evolving appreciation of HT in this disease. Optimal treatment of HT of MZL remains unknown. Much of the approach to managing transformed MZL is extrapolated from other indolent NHLs. Copyright © 2016 Elsevier Ltd. All rights reserved.
Lowenthal, R.M.; Harlow, R.W.H.; Mead, A.E.; Tuck, D.; Challis, D.R.
A rapidly fatal T-cell lymphoma developed in a 25-year-old man who, over a period of seven years, had been treated with radiotherapy and combination chemotherapy for Hodgkin's disease (HD). Non-Hodgkin's lymphoma (NHL) is increasingly being recognized as a late sequel of therapy for HD, but this is the first case in which NHL of T-cell type has been identified in such circumstances.
Anderson, L A; Gridley, G; Engels, E A; Morton, L M; Cerhan, J R; Cozen, W; Severson, R K; Davis, S; Hartge, P; Linet, M S
Antibiotic use in 759 non-Hodgkin's lymphoma (NHL) patients and 589 controls was compared. Neither total antibiotic use (odds ratio=0.7, 95% confidence interval=0.5–1.2), nor antibiotic use by site, was associated with total NHL, or NHL subtypes. There were no trends with frequency or age at first use (P trend=0.23 and 0.26, respectively). PMID:18059393
Datta, Sibnarayan; Chatterjee, Soumya; Policegoudra, Rudragoud S; Gogoi, Hemant K; Singh, Lokendra
Non-Hodgkin’s lymphoma (NHL) is among the haematological malignancies with high prevalence worldwide, causing estimated 355 900 new cases and 191 400 deaths in 2008. High prevalence of NHL is documented in economically more developed areas while low prevalence is observed in less developed areas of the globe. A wide array of environmental factors have been reported to be either directly involved or in modifying the risk of NHL development. In addition to these factors, a number of infectious agents, chiefly viruses have also been implicated in the development of NHL. This article reviews the available literature to discuss the role of hepatitis viruses in NHL development, possible mechanisms of lymphomagenesis and also identify the areas in which further research is required to better understand this disease. A brief discussion on the clinical aspects such as classification, staging, treatment approaches have also been included in this article. PMID:24175222
Schroeder, Jane C
Epidemiologic studies have failed to establish clearly whether agricultural pesticides contribute to the genesis of non-Hodgkin's lymphoma (NHL). Discordant results may be related to variation in susceptibility factors, including metabolism gene polymorphisms that might influence lymphocyte exposures to active pesticide metabolites. Associations between NHL and polymorphisms that may be relevant to pesticide metabolism have been assessed, including CYP1A1 and glutathione S-transferase variants, but the results are not highly informative because estimates were based on small numbers and convenience samples of cases and controls. Butyrylcholinesterase and paraoxonase (PON1) enzyme variants associated with altered activity and acute organophosphate toxicity are strong candidate susceptibility factors for pesticides and NHL, but others may be identified as knowledge of pesticide metabolism and relevant polymorphisms improves. Studies of metabolic susceptibility must be large and include information on specific exposures and subtypes of NHL for results to further the understanding of the relation between agricultural pesticides and NHL.
An examination of the organizational culture of the Vancouver Canucks of the NHL provides exemplars for all learning institutions. A culture connected directly to a servant-leader philosophy was identified through a cumulative qualitative case study of key personnel within the organization. Data included transcribed interviews, archival research,…
Fallah, M; Kharazmi, E; Pukkala, E; Tretli, S; Olsen, J H; Tryggvadottir, L; Sundquist, K; Hemminki, K
We aimed to estimate stratified absolute (cumulative) and relative (standardized incidence ratios; SIRs) risks of non-Hodgkin lymphoma (NHL) in relatives of NHL patients. A cohort of 169 830 first-degree relatives of 45 406 NHL patients who were diagnosed between 1955 and 2010 in five European countries was followed for cancer incidence. The lifetime (0-79 year) cumulative risk of NHL in siblings of a patient with NHL was 1.6%, which represents a 1.6-fold increased risk (SIR=1.6, 95% confidence interval (CI)=1.2-1.9) over the general population risk. NHL risk among parent-offspring pairs was increased up to 1.4-fold (95% CI=1.3-1.5; lifetime risk 1.4%). The lifetime risk was higher when NHL was diagnosed in a sister (2.5% in her brothers and 1.9% in her sisters) or a father (1.7% in his son). When there were ⩾2 NHL patients diagnosed in a family, the lifetime NHL risk for relatives was 2.1%. Depending on sex and age at diagnosis, twins had a 3.1-12.9% lifetime risk of NHL. Family history of most of the histological subtypes of NHL increased the risk of concordant and some discordant subtypes. Familial risk did not significantly change by age at diagnosis of NHL in relatives. Familial risk of NHL was not limited to early onset cases.
Perry, Anamarija M; Diebold, Jacques; Nathwani, Bharat N; MacLennan, Kenneth A; Müller-Hermelink, Hans K; Bast, Martin; Boilesen, Eugene; Armitage, James O; Weisenburger, Dennis D
Large and systematic studies of non-Hodgkin lymphoma (NHL) in the Far East (FE) with good comparative data are scarce in the literature. In this study, five expert hematopathologists classified 730 consecutive cases of newly-diagnosed NHL from four sites in the FE (excluding Japan) using the World Health Organization classification. The results were compared to 399 cases from North America (NA). We found a significantly higher male to female ratio in the FE compared to NA (1.7 versus 1.1; p < 0.05). The median ages of patients with low-grade (LG) and high-grade (HG) B-NHL in the FE (58 and 51 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). The FE had a significantly lower relative frequency of B-NHL and a higher frequency of T-NHL (82 vs. 18 %) compared to NA (90.5 vs. 9.5 %). Among mature B cell lymphomas, the FE had a significantly higher relative frequency of HG B-NHL (54.8 %) and a lower frequency of LG B-NHL (27.2 %) than NA (34.3 and 56.1 %, respectively). Diffuse large B cell lymphoma was more common in the FE (49.4 %) compared to NA (29.3 %), whereas the relative frequency of follicular lymphoma was lower in the FE (9.4 %) compared to NA (33.6 %). Among T-NHL, nasal NK/T cell NHL was more frequent in the FE (5.2 %) compared to NA (0 %). Peripheral T cell lymphoma was also more common in the FE (9.1 %) than in NA (5.3 %). Further epidemiologic studies are needed to better understand the pathobiology of these differences.
Ollberding, Nicholas J; Aschebrook-Kilfoy, Briseis; Caces, Donne Bennett D; Wright, Margaret E; Weisenburger, Dennis D; Smith, Sonali M; Chiu, Brian C-H
Greater consumption of red meat, processed meat and dairy products has been associated with an increased risk of non-Hodgkin lymphoma (NHL) in several previous reports. Phytanic acid, a saturated fatty acid obtained primarily through the consumption of ruminant meat and dairy products, may offer a potential underlying mechanism for these associations. In a population-based case-control study of 336 cases and 460 controls conducted in Nebraska during 1999-2002, we examined whether phytanic acid-containing foods or total phytanic acid intake, estimated from a food frequency questionnaire and the published phytanic acid values of 151 food items, were associated with increased NHL risk. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals for overall NHL and the common NHL histologic subtypes. In multivariable models, higher intakes of density-adjusted beef [OR(T3 vs. T1) = 1.5 (1.1-2.2); P(trend) = 0.02], total dairy products [OR = 1.5 (1.1-2.2); P(trend) = 0.02) and milk [OR = 1.6 (1.1-2.3); P(trend) = 0.01] were associated with an increased risk of NHL. Intake of total phytanic acid was positively associated with NHL risk [OR = 1.5 (1.0-2.1); P(trend) = 0.04]. In analyses stratified by NHL subtype, greater consumption of beef was associated with an increased risk of diffuse large B-cell lymphoma, and greater consumption of milk was associated with an increased risk of follicular lymphoma (FL). Total phytanic acid intake was associated with an increased risk of FL and small lymphocytic lymphoma/chronic lymphocytic leukemia. Our results provide support that total phytanic acid and phytanic acid-containing foods may increase NHL risk.
Laubert, A; Mausolf, A; Bernhards, J; Le Blanc, S; Werner, M
Of all the neoplastic conditions of the lymphatic system, Non-Hodgkin's lymphoma (NHL) represents a heterogenous group. As well as lymph nodes NHL can involve extranodal sites, including regions in head and neck. The mouth and oropharynx are typical extranodal sites, and the ENT surgeon should be aware of this possibility of the swift diagnosis of NHL is to be made. We report two patients with rare invasion of the middle ear, facial nerve paresis, and asymptomatic cerebral involvement by Non-Hodgkin's lymphoma.
Lam, Gary; Xian, Rena R; Li, Yingying; Burns, Kathleen H; Beemon, Karen L
Non-Hodgkin lymphomas (NHL) are a heterogeneous group of immune cell neoplasms that comprise molecularly distinct lymphoma subtypes. Recent work has identified high frequency promoter point mutations in the telomerase reverse transcriptase (TERT) gene of different cancer types, including melanoma, glioma, liver and bladder cancer. TERT promoter mutations appear to correlate with increased TERT expression and telomerase activity in these cancers. In contrast, breast, pancreatic, and prostate cancer rarely demonstrate mutations in this region of the gene. TERT promoter mutation prevalence in NHL has not been thoroughly tested thus far. We screened 105 B-cell lymphoid malignancies encompassing nine NHL subtypes and acute lymphoblastic leukemia, for TERT promoter mutations. Our results suggest that TERT promoter mutations are rare or absent in most NHL. Thus, the classical TERT promoter mutations may not play a major oncogenic role in TERT expression and telomerase activation in NHL.
Lam, Gary; Xian, Rena R.; Li, Yingying; Burns, Kathleen H.; Beemon, Karen L.
Non-Hodgkin lymphomas (NHL) are a heterogeneous group of immune cell neoplasms that comprise molecularly distinct lymphoma subtypes. Recent work has identified high frequency promoter point mutations in the telomerase reverse transcriptase (TERT) gene of different cancer types, including melanoma, glioma, liver and bladder cancer. TERT promoter mutations appear to correlate with increased TERT expression and telomerase activity in these cancers. In contrast, breast, pancreatic, and prostate cancer rarely demonstrate mutations in this region of the gene. TERT promoter mutation prevalence in NHL has not been thoroughly tested thus far. We screened 105 B-cell lymphoid malignancies encompassing nine NHL subtypes and acute lymphoblastic leukemia, for TERT promoter mutations. Our results suggest that TERT promoter mutations are rare or absent in most NHL. Thus, the classical TERT promoter mutations may not play a major oncogenic role in TERT expression and telomerase activation in NHL. PMID:27792139
Wong, E T; Portlock, C S; O'Brien, J P; DeAngelis, L M
Epidural spinal cord disease (ESCD), an infrequent complication of systemic non-Hodgkins lymphoma (NHL), can occur at diagnosis or at relapse, and is usually treated with radiotherapy, or infrequently surgical decompression. We retrospectively analyzed 140 patients with intermediate-grade NHL (IG-NHL) who were treated on a dose-intense protocol using doxorubicin, vincristine, and high-dose cyclophosphamide (NHL-15). There were seven episodes of ESCD in six (4.3%) patients. Five episodes were asymptomatic at presentation; one patient had back pain, leg numbness, and tingling; and one had radicular pain and mild leg weakness. None had malignant cells in the CSF. One patient received high-dose dexamethasone after laminectomy for diagnostic biopsy; otherwise, dexamethasone was used only as an anti-emetic prior to chemotherapy. Patients who developed ESCD at diagnosis received the planned course of NHL-15 chemotherapy as treatment for ESCD, and those treated with NHL-15 who developed ESCD at relapse were given a regimen containing ifosfamide, carboplatin, and etoposide (ICE). After chemotherapy alone, five of seven episodes showed radiographic resolution of ESCD and improvement of neurologic deficits. One patient received consolidation radiotherapy (2,700 cGy) to the spine after ICE for relapsed ESCD and had a complete response. One patient had progression of systemic lymphoma and ESCD despite chemotherapy. These data suggest that chemotherapy may be effective as initial treatment of ESCD in IG-NHL and may reduce the potential complications of spinal surgery and radiotherapy.
Gao, Da-Lin; Fu, Qian-Qian; Zhang, Tian-Tian; Sun, Lin; Pan, Yi; Zhai, Qiong-Li
Lymphoma rarely occurs during pregnancy, making this condition difficult to define. Lymphomas that occur in reproductive organs during pregnancy exhibit unique clinical characteristics. Among the limited cases, non-Hodgkin's lymphoma (NHL) shows a considerably higher incidence rate than Hodgkin's lymphoma (HL); NHL also displays clinical characteristics, such as high aggressiveness, advanced stage, and poor outcome. This study reports on four cases of lymphomas in non-gonadal organs (HL, n=2; NHL, n=2) during pregnancy. The tumors rapidly progressed in all patients during pregnancy but remitted at the end of pregnancy and/or therapy. The two HL cases were nodular sclerosis classical HL and treated with chemotherapy after terminating the pregnancy. One of the NHL cases was primary cutaneous follicular center lymphoma, a B cell-derived indolent lymphoma. The patient was followed up without any therapy after terminating her pregnancy. The other case was a follicular lymphoma grade 3B, which was treated with chemotherapy after delivery. We also conducted a literature review of 165 lymphoma cases occurring during pregnancy reported from 1976 to 2013 to reveal the correlation between pregnancy and lymphoma progression. Immunohistochemistry studies were performed to determine the expression of estrogen/progesterone receptors (ER/PR), and ER was weakly positive and sporadic. We concluded that lymphomas occurring during pregnancy should be managed with a prompt and reasonable treatment. High estrogen level in maternal body may affect lymphoma progression. PMID:27807508
Chiu, Yu-Hsiang; Chung, Chi-Hsiang; Lin, Kuen-Tze; Lin, Chin-Sheng; Chen, Jia-Hong; Chen, Hsiang-Cheng; Huang, Ren-Yeong; Wu, Chi-Tsung; Liu, Feng-Cheng; Chien, Wu-Chien
Sjögren syndrome (SS) is commonly known to be correlated with lymphoma. This study included 16,396 individuals in the SS cohort and 65,584 individuals in the non-SS cohort, all of whom were enrolled in the Taiwan National Health Insurance database between 2000 and 2010. We evaluated the risk factors of non-Hodgkin's lymphoma (NHL) in the primary SS cohort by applying a Cox multivariable proportional-hazards model. We increased the correlation of patients with SS and NHL, with an adjusted HR of 4.314 (95% CI 2.784 - 6.685). Of the 16,396 SS patients, 66 individuals had salivary gland slices without NHL development, while the other 16,330 individuals that did not have salivary gland slices revealed 30 individuals that developed NHL. Of the 16,396 SS patients, 128 individuals underwent immunomodulator agent therapy (including hydroxychloroquine, azathioprine, cyclosporine, methotrexate, and rituximab) without NHL development. None of the 30 individuals that developed NHL from SS received immunomodulator agents. We found that patients with SS were at an increased risk of developing NHL, with the most common NHL subgroup being diffused large B-cell lymphoma. SS patients who were candidates for salivary gland slices or immunomodulator agents were associated with a lower risk of developing lymphoma over time. We recommend that patients at a higher risk upon diagnosis of SS receive close follow-up and aggressive treatment.
Wang, Xiuli; Popplewell, Leslie L; Wagner, Jamie R; Naranjo, Araceli; Blanchard, M Suzette; Mott, Michelle R; Norris, Adam P; Wong, ChingLam W; Urak, Ryan Z; Chang, Wen-Chung; Khaled, Samer K; Siddiqi, Tanya; Budde, Lihua E; Xu, Jingying; Chang, Brenda; Gidwaney, Nikita; Thomas, Sandra H; Cooper, Laurence J N; Riddell, Stanley R; Brown, Christine E; Jensen, Michael C; Forman, Stephen J
Myeloablative autologous hematopoietic stem cell transplantation (HSCT) is a mainstay of therapy for relapsed intermediate-grade B-cell non-Hodgkin lymphoma (NHL); however, relapse rates are high. In phase 1 studies designed to improve long-term remission rates, we administered adoptive T-cell immunotherapy after HSCT, using ex vivo-expanded autologous central memory-enriched T cells (TCM) transduced with lentivirus expressing CD19-specific chimeric antigen receptors (CARs). We present results from 2 safety/feasibility studies, NHL1 and NHL2, investigating different T-cell populations and CAR constructs. Engineered TCM-derived CD19 CAR T cells were infused 2 days after HSCT at doses of 25 to 200 × 10(6) in a single infusion. In NHL1, 8 patients safely received T-cell products engineered from enriched CD8(+) TCM subsets, expressing a first-generation CD19 CAR containing only the CD3ζ endodomain (CD19R:ζ). Four of 8 patients (50%; 95% confidence interval [CI]: 16-84%) were progression free at both 1 and 2 years. In NHL2, 8 patients safely received T-cell products engineered from enriched CD4(+) and CD8(+) TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains (CD19R:28ζ). Six of 8 patients (75%; 95% CI: 35-97%) were progression free at 1 year. The CD4(+)/CD8(+) TCM-derived CD19 CAR T cells (NHL2) exhibited improvement in expansion; however, persistence was ≤28 days, similar to that seen by others using CD28 CARs. Neither cytokine release syndrome nor delayed hematopoietic engraftment was observed in either trial. These data demonstrate the safety and feasibility of CD19 CAR TCM therapy after HSCT. Trials were registered at www.clinicaltrials.gov as #NCT01318317 and #NCT01815749. © 2016 by The American Society of Hematology.
Wang, Xiuli; Popplewell, Leslie L.; Wagner, Jamie R.; Naranjo, Araceli; Blanchard, M. Suzette; Mott, Michelle R.; Norris, Adam P.; Wong, ChingLam W.; Urak, Ryan Z.; Chang, Wen-Chung; Khaled, Samer K.; Siddiqi, Tanya; Budde, Lihua E.; Xu, Jingying; Chang, Brenda; Gidwaney, Nikita; Thomas, Sandra H.; Cooper, Laurence J. N.; Riddell, Stanley R.; Brown, Christine E.; Jensen, Michael C.
Myeloablative autologous hematopoietic stem cell transplantation (HSCT) is a mainstay of therapy for relapsed intermediate-grade B-cell non-Hodgkin lymphoma (NHL); however, relapse rates are high. In phase 1 studies designed to improve long-term remission rates, we administered adoptive T-cell immunotherapy after HSCT, using ex vivo–expanded autologous central memory–enriched T cells (TCM) transduced with lentivirus expressing CD19-specific chimeric antigen receptors (CARs). We present results from 2 safety/feasibility studies, NHL1 and NHL2, investigating different T-cell populations and CAR constructs. Engineered TCM-derived CD19 CAR T cells were infused 2 days after HSCT at doses of 25 to 200 × 106 in a single infusion. In NHL1, 8 patients safely received T-cell products engineered from enriched CD8+ TCM subsets, expressing a first-generation CD19 CAR containing only the CD3ζ endodomain (CD19R:ζ). Four of 8 patients (50%; 95% confidence interval [CI]: 16-84%) were progression free at both 1 and 2 years. In NHL2, 8 patients safely received T-cell products engineered from enriched CD4+ and CD8+ TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains (CD19R:28ζ). Six of 8 patients (75%; 95% CI: 35-97%) were progression free at 1 year. The CD4+/CD8+ TCM-derived CD19 CAR T cells (NHL2) exhibited improvement in expansion; however, persistence was ≤28 days, similar to that seen by others using CD28 CARs. Neither cytokine release syndrome nor delayed hematopoietic engraftment was observed in either trial. These data demonstrate the safety and feasibility of CD19 CAR TCM therapy after HSCT. Trials were registered at www.clinicaltrials.gov as #NCT01318317 and #NCT01815749. PMID:27118452
Saylors, Gene B.; Spurgeon, Stephen E.; Cheson, Bruce D.; Greenwald, Daniel R.; O’Brien, Susan M.; Liem, Andre K. D.; Mclntyre, Rosemary E.; Joshi, Adarsh; Abella-Dominicis, Esteban; Hawkins, Michael J.; Reddy, Anita; Di Paolo, Julie; Lee, Hank; He, Joyce; Hu, Jing; Dreiling, Lyndah K.; Friedberg, Jonathan W.
Although agents targeting B-cell receptor signaling have provided practice-changing results in relapsed chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), they require prolonged administration and provide incomplete responses. Given synergistic preclinical activity with phosphatidylinositol 3-kinase δ and spleen tyrosine kinase inhibition, this phase 2 study evaluated the safety and efficacy of the combination of idelalisib and entospletinib. Eligible patients with relapsed or refractory CLL or NHL underwent intrapatient dose escalation with each agent. With a median treatment exposure of 10 weeks, 60% and 36% of patients with CLL or follicular lymphoma, respectively, achieved objective responses. However, the study was terminated early because of treatment-emergent pneumonitis in 18% of patients (severe in 11 of 12 cases). Although most patients recovered with supportive measures and systemic steroids, 2 fatalities occurred and were attributed to treatment-emergent pneumonitis. Increases of interferon-γ and interleukins 6, 7, and 8 occurred over time in patients who developed pneumonitis. Future studies of novel combinations should employ conservative designs that incorporate pharmacodynamics/biomarker monitoring. These investigations should also prospectively evaluate plasma cytokine/chemokine levels in an attempt to validate biomarkers predictive of response and toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01796470. PMID:26968534
Barr, Paul M; Saylors, Gene B; Spurgeon, Stephen E; Cheson, Bruce D; Greenwald, Daniel R; O'Brien, Susan M; Liem, Andre K D; Mclntyre, Rosemary E; Joshi, Adarsh; Abella-Dominicis, Esteban; Hawkins, Michael J; Reddy, Anita; Di Paolo, Julie; Lee, Hank; He, Joyce; Hu, Jing; Dreiling, Lyndah K; Friedberg, Jonathan W
Although agents targeting B-cell receptor signaling have provided practice-changing results in relapsed chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), they require prolonged administration and provide incomplete responses. Given synergistic preclinical activity with phosphatidylinositol 3-kinase δ and spleen tyrosine kinase inhibition, this phase 2 study evaluated the safety and efficacy of the combination of idelalisib and entospletinib. Eligible patients with relapsed or refractory CLL or NHL underwent intrapatient dose escalation with each agent. With a median treatment exposure of 10 weeks, 60% and 36% of patients with CLL or follicular lymphoma, respectively, achieved objective responses. However, the study was terminated early because of treatment-emergent pneumonitis in 18% of patients (severe in 11 of 12 cases). Although most patients recovered with supportive measures and systemic steroids, 2 fatalities occurred and were attributed to treatment-emergent pneumonitis. Increases of interferon-γ and interleukins 6, 7, and 8 occurred over time in patients who developed pneumonitis. Future studies of novel combinations should employ conservative designs that incorporate pharmacodynamics/biomarker monitoring. These investigations should also prospectively evaluate plasma cytokine/chemokine levels in an attempt to validate biomarkers predictive of response and toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01796470.
Zappasodi, Roberta; de Braud, Filippo; Di Nicola, Massimo
The rationale to treat lymphomas with immunotherapy comes from long-standing evidence on their distinctive immune responsiveness. Indolent B-cell non-Hodgkin lymphomas, in particular, establish key interactions with the immune microenvironment to ensure prosurvival signals and prevent antitumor immune activation. However, reports of spontaneous regressions indicate that, under certain circumstances, patients develop therapeutic antitumor immunity. Several immunotherapeutic approaches have been thus developed to boost these effects in all patients. To date, targeting CD20 on malignant B cells with the antibody rituximab has been the most clinically effective strategy. However, relapse and resistance prevent to cure approximately half of B-NHL patients, underscoring the need of more effective therapies. The recognition of B-cell receptor variable regions as B-NHL unique antigens promoted the development of specific vaccines to immunize patients against their own tumor. Despite initial promising results, this strategy has not yet demonstrated a sufficient clinical benefit to reach the regulatory approval. Several novel agents are now available to stimulate immune effector functions or counteract immunosuppressive mechanisms, such as engineered antitumor T cells, co-stimulatory receptor agonist, and immune checkpoint-blocking antibodies. Thus, multiple elements can now be exploited in more effective combinations to break the barriers for the induction of anti-lymphoma immunity.
Zappasodi, Roberta; de Braud, Filippo; Di Nicola, Massimo
The rationale to treat lymphomas with immunotherapy comes from long-standing evidence on their distinctive immune responsiveness. Indolent B-cell non-Hodgkin lymphomas, in particular, establish key interactions with the immune microenvironment to ensure prosurvival signals and prevent antitumor immune activation. However, reports of spontaneous regressions indicate that, under certain circumstances, patients develop therapeutic antitumor immunity. Several immunotherapeutic approaches have been thus developed to boost these effects in all patients. To date, targeting CD20 on malignant B cells with the antibody rituximab has been the most clinically effective strategy. However, relapse and resistance prevent to cure approximately half of B-NHL patients, underscoring the need of more effective therapies. The recognition of B-cell receptor variable regions as B-NHL unique antigens promoted the development of specific vaccines to immunize patients against their own tumor. Despite initial promising results, this strategy has not yet demonstrated a sufficient clinical benefit to reach the regulatory approval. Several novel agents are now available to stimulate immune effector functions or counteract immunosuppressive mechanisms, such as engineered antitumor T cells, co-stimulatory receptor agonist, and immune checkpoint-blocking antibodies. Thus, multiple elements can now be exploited in more effective combinations to break the barriers for the induction of anti-lymphoma immunity. PMID:26388871
Gopal, Ajay; Graf, Solomon
Introduction B-cell Non-Hodgkin lymphomas (B-NHLs) include a number of disease subtypes, each defined by the tempo of disease progression and the identity of the cancerous cell. Idelalisib is a potent, selective inhibitor of the delta isoform of phosphatidylinositol-3-kinase (PI3K), a lipid kinase whose over-activity in B-NHL drives disease progression. Idelalisib has demonstrated activity in indolent B-NHL (iB-NHL) and is approved for use as monotherapy in patients with follicular lymphoma and small lymphocytic lymphoma and in combination with rituximab in patients with chronic lymphocytic leukemia. Areas Covered Herein we review the development and pharmacology of idelalisib, its safety and efficacy in clinical studies of iB-NHL, and its potential for inclusion in future applications in iB-NHL and in combination with other therapies. Expert Opinion Idelalisib adds to the growing arsenal of iB-NHL pharmacotherapeutics and to the progression of the field toward precision agents with good efficacy and reduced toxicities. Nevertheless, idelalisib carries important risks that require careful patient counseling and monitoring. The appropriate sequencing of idelalisib with other proven treatment options in addition to its potential for combination with established or novel drugs will be borne out in ongoing and planned investigations. PMID:26818003
... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...
Teras, Lauren R; Rollison, Dana E; Pawlita, Michael; Michel, Angelika; Brozy, Johannes; de Sanjose, Silvia; Blase, Jennifer L; Gapstur, Susan M
Epstein-Barr virus (EBV) causes rare, malignant lymphomas. The role of EBV in other non-Hodgkin lymphomas (NHLs) remains unclear, but mildly reduced immune function could lead to reactivation of EBV and subsequent NHL. We examined the association between prospectively-collected plasma EBV antibodies and NHL risk in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort and conducted a meta-analysis of our and published results. The CPS-II study included 225 NHL cases and 2:1 matched controls. No associations were observed between EBV serostatus or antibody levels and risk of NHL overall. However, when including only the three most common types of NHL (diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma), high compared to low early antigen (EA-D) diffuse and BZLF1-encoded replication activator antibodies were associated with approximately 60% higher risk of NHL. Odds ratios (ORs) for EBV nuclear antigen-1 and viral capsid antigen (VCA)-p18 were elevated but not statistically significant. In the meta-analysis, both EA (summary OR = 1.52, 95% confidence interval (CI): 1.16-2.00) and VCA (summary OR = 1.20, 95% CI: 1.00-1.44) were positively associated with NHL risk. These results suggest EBV may be associated with a wider spectrum of NHL subtypes, but further study is needed to confirm and fully understand these associations.
Ice hockey has been identified as a sport with a high risk for concussions. Given the health sequelae associated with the injury, a great deal of attention has been placed on its diagnosis, management and return-to-play protocols. The highest level of ice hockey in North America is played in the National Hockey League (NHL), and concussions pose a serious threat to the health of the players and the game itself. Unfortunately, the scientific literature on concussions in ice hockey is derived mostly from research conducted on youth and amateur levels of play, leaving a gap in our knowledge at the professional level. This narrative review attempts to summarize what is known about concussion incidence, mechanisms of injury and risk factors in the NHL.
Ice hockey has been identified as a sport with a high risk for concussions. Given the health sequelae associated with the injury, a great deal of attention has been placed on its diagnosis, management and return-to-play protocols. The highest level of ice hockey in North America is played in the National Hockey League (NHL), and concussions pose a serious threat to the health of the players and the game itself. Unfortunately, the scientific literature on concussions in ice hockey is derived mostly from research conducted on youth and amateur levels of play, leaving a gap in our knowledge at the professional level. This narrative review attempts to summarize what is known about concussion incidence, mechanisms of injury and risk factors in the NHL. PMID:25550658
Adouani, Ali; Bouguila, Jed; Jeblaoui, Yassine; Ben Aicha, Mehdi; Abdelali, Mouhamed Ali; Hellali, Mouna; Zitouni, Karima; Amani, Landolsi; Issam, Zairi
Summary Introduction The mandible is an infrequent localisation of primary osseous non-Hodgkin’s lymphomas. Few cases of mandibular non-Hodgkin’s lymphomas (NHL) have been reported. Case report A rare condition of primary malignant non-Hodgkin’s lymphoma of the mandible in 53-year-old man, was reported at the Department of Maxillofacial and Plastic Surgery in Charles Nicolle Hospital (Tunis, Tunisia). Histologic and Immunohistochemical (IHC) examination Confirmed a B-Cell lymphoma. Discussion The purpose of this report is to describe this rare case of NHL of the mandible, explore the diagnosis and workup, and discuss treatment strategies. In this localisation, neither the clinical features nor the radiologic appearances are often pathognomonic. Conclusion Particular care must be taken to consider lymphoma in the differential diagnosis because this uncommon lesion can pose significant diagnostic problems and is frequently misdiagnosed. PMID:21892315
Hauptrock, Beate; Hess, Georg
Besides traditional cytostatic drugs the introduction of monoclonal antibodies has substantially influenced current treatment concepts of non-Hodgkin’s lymphoma (NHL). Rituximab, a monoclonal anti-CD20 chimeric antibody, now has been widely evaluated in the various B-cell lymphatic neoplasms. Large phase III studies helped to prove the value of this drug in follicular lymphoma as part of induction or relapse treatment as well as maintenance treatment. The addition of rituximab to the well established CHOP regimens has increased achievable cure rates in diffuse large cell lymphoma, and this combination is now accepted worldwide as standard of care. Although conflicting results are available, rituximab is widely used for the treatment of mantle cell lymphoma. For the less frequent lymphoma entities phase 2 studies show a considerable efficiency for most of these B-NHL variants. Current research focuses on combined chemoimmunotherapy approaches, optimization of dosing regimens, and combination with novel agents. PMID:19707443
De Nardo, Gerald L.
The most potent method for augmenting the cytocidal power of monoclonal antibody (MAb) treatment is to conjugate radionuclides to the MAb to deliver systemic radiotherapy (radioimmunotherapy; RIT). The antigen, MAb, and its epitope can make a difference in the performance of the drug. Additionally, the radionuclide, radiochemistry, chelator for radiometals and the linker between the MAb and chelator can have a major influence on the performance of drugs (radiopharmaceuticals) for RIT. Smaller radionuclide carriers, such as antibody fragments and mimics, and those used for pretargeting strategies, have been described and evaluated. All of these changes in the drugs and strategies for RIT have documented potential for improved performance and patient outcomes. RIT is a promising new therapy that should be incorporated into the management of patients with B-cell non-Hodgkin's lymphoma (NHL) soon after these patients have proven incurable. Predictable improvements using better drugs, strategies, and combinations with other drugs seem certain to make RIT integral to the management of patients with NHL, and likely lead to cure of currently incurable NHL.
Le, Yuan; Chen, Shaofan; Hu, Lisi; Zhang, Linli; Ullah, Shakeeb; Liu, Tengfei; Yang, Ping; Liu, Yi; Chen, Qiusheng
The aim of the present study was to investigate the expression and localization of B-cell lymphoma-2 (Bcl-2) in the oviduct of the Chinese soft-shelled turtle, Pelodiscus sinensis, during the reproductive cycle to analyze the relationship between Bcl-2 and sperm storage. Bcl-2 expression was confirmed in the P. sinensis oviduct by western blot analysis. Hematoxylin-eosin staining showed that female P. sinensis stored sperm from November to April of the following year. The oviduct showed positive immunostaining for Bcl-2 of epithelial ciliated cells, gland ducts, and gland cells. Bcl-2 expression in the oviduct was associated with sperm storage occurrence. This indicates that the survival factor Bcl-2 may play a role in P. sinensis sperm storage. © 2015 Wiley Periodicals, Inc.
Shiramizu, Bruce; Mussolin, Lara; Woessmann, Wilhelm; Klapper, Wolfram
Exciting advances have been achieved for infants, children and adolescents diagnosed with, and treated for, non-Hodgkin lymphoma (NHL). In spite of these successes, new frontiers are being paved to improve the prognosis for those who relapse or have resistant disease. This review summarizes some of the novel approaches and ideas in NHL monitoring, diagnosis and treatment as discussed at the 5th International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma on October 22nd-24th 2015 in Varese, Italy. © 2016 John Wiley & Sons Ltd.
Shiramizu, Bruce; Mussolin, Lara; Woessmann, Wilhelm; Klapper, Wolfram
Summary Exciting advances have been achieved for infants, children and adolescents diagnosed with, and treated for, non-Hodgkin lymphoma (NHL). In spite of these successes, new frontiers are being paved to improve the prognosis for those who relapse or have resistant disease. This review summarizes some of the novel approaches and ideas in NHL monitoring, diagnosis and treatment as discussed at the 5th International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma on October 22nd to 24th 2015 in Varese, Italy. PMID:27009921
Engels, Eric A.; Parsons, Ruth; Besson, Caroline; Morton, Lindsay M.; Enewold, Lindsey; Ricker, Winnie; Yanik, Elizabeth L.; Arem, Hannah; Austin, April A.; Pfeiffer, Ruth M.
Background Certain medical conditions affect risk of non-Hodgkin lymphoma (NHL), but the full range of associations is unknown. We implemented a novel method (“medical condition-wide association study,” MedWAS) to comprehensively evaluate medical risk factors for NHL documented in administrative health claims. Methods Using SEER-Medicare data, we conducted a case-control study comparing NHL cases (N=52,691, age 66+ years, with five subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL], diffuse large B-cell lymphoma [DLBCL], follicular lymphoma, marginal zone lymphoma [MZL], T-cell lymphoma [TCL]) to controls (N=200,000).We systematically screened for associations with 5926 medical conditions documented in Medicare claims more than one year before selection. Results Fifty-five conditions were variously associated with NHL. Examples include well-established associations of human immunodeficiency virus, solid organ transplantation, and hepatitis C virus with increased DLBCL risk (odds ratios [ORs] 3.83, 4.27, and 1.74, respectively), and autoimmune conditions with DLBCL and MZL (e.g., ORs of 2.10 and 4.74, respectively, for Sjögren syndrome). Risks for all NHL subtypes were increased after diagnoses of non-melanoma skin cancer (ORs 1.19–1.55), actinic keratosis (1.12–1.25), or hemolytic anemia (1.64–4.07). Nine additional skin conditions increased only TCL risk (ORs 2.20–4.12). Diabetes mellitus was associated with increased DLBCL risk (OR 1.09). Associations varied significantly across NHL subtypes for 49 conditions (89%). Conclusion Using an exploratory method, we found numerous medical conditions associated with NHL risk, and many associations varied across NHL subtypes. Impact These results point to etiologic heterogeneity among NHL subtypes. MedWAS is a new method for assessing the etiology of cancer and other diseases. PMID:27197296
Engels, Eric A; Parsons, Ruth; Besson, Caroline; Morton, Lindsay M; Enewold, Lindsey; Ricker, Winnie; Yanik, Elizabeth L; Arem, Hannah; Austin, April A; Pfeiffer, Ruth M
Certain medical conditions affect risk of non-Hodgkin lymphoma (NHL), but the full range of associations is unknown. We implemented a novel method ("medical condition-wide association study," MedWAS) to comprehensively evaluate medical risk factors for NHL documented in administrative health claims. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we conducted a case-control study comparing NHL cases [N = 52,691, age 66+ years, with five subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma (MZL), T-cell lymphoma (TCL)] to controls (N = 200,000). We systematically screened for associations with 5,926 medical conditions documented in Medicare claims more than 1 year before selection. Fifty-five conditions were variously associated with NHL. Examples include well-established associations of human immunodeficiency virus, solid organ transplantation, and hepatitis C virus with increased DLBCL risk (ORs 3.83, 4.27, and 1.74, respectively), and autoimmune conditions with DLBCL and MZL (e.g., ORs of 2.10 and 4.74, respectively, for Sjögren syndrome). Risks for all NHL subtypes were increased after diagnoses of nonmelanoma skin cancer (ORs 1.19-1.55), actinic keratosis (1.12-1.25), or hemolytic anemia (1.64-4.07). Nine additional skin conditions increased only TCL risk (ORs 2.20-4.12). Diabetes mellitus was associated with increased DLBCL risk (OR 1.09). Associations varied significantly across NHL subtypes for 49 conditions (89%). Using an exploratory method, we found numerous medical conditions associated with NHL risk, and many associations varied across NHL subtypes. These results point to etiologic heterogeneity among NHL subtypes. MedWAS is a new method for assessing the etiology of cancer and other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1105-13. ©2016 AACR. ©2016 American Association for Cancer Research.
Abbott, C R; Blewitt, R W; Bird, C C
A preliminary attempt has been made to characterise a small series of non-Hodgkin's lymphomas (NHL) by morphometric means using the Quantimet 720 Kontron MOP/AMO3 image analysis systems. In most cases it was found that the distribution of nuclear area and correlation between mean nuclear area and frequency per unit field, corresponded closely with tumour classification determined by light microscopy. These results suggest that it may be possible to devise an objective and reproducible grading system for NHL using quantitative morphometric techniques. PMID:7040479
Kramárová, E; Kogevinas, M; Anh, C T; Cau, H D; Dai, L C; Stellman, S D; Parkin, D M
Agent Orange was the most common herbicide used in the Second Indochina War in the course of military operations in the former South Vietnam. Agent Orange is contaminated by the carcinogen 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in mean concentrations of 2 mg/kg. After much dispute of a causal association between exposure to herbicides containing TCDD and occurrence of soft-tissue sarcoma and non-Hodgkin lymphoma, two simultaneous case-control studies were set up in Vietnam to examine possible relationships. Subject recruitment is ongoing, with target numbers of 150 cases of soft-tissue sarcoma and 150 cases of non-Hodgkin lymphoma and diagnoses at the Cancer Center at Ho Chi Minh City, Vietnam. Two hospital controls are matched to each case. As in other studies of cancer in persons occupationally or otherwise exposed to herbicides and their contaminants, evaluation of past exposure of the recruited subjects is among the most complicated issues. Because accurate records are usually unavailable, surrogate measures of likely exposure are often calculated. As a first approach in our studies we used the Stellman and Stellman exposure index. The index is based on matching subjects' history of residence and the information on times and locations of Agent Orange spraying recorded on HERBS tape by the U.S. Army and taking into account the distance from the spraying as well as environmental and biologic half-life of TCDD. The exposure index is calculated in two centers, New York and Hanoi, with slightly different assumptions. In addition, samples of body tissues from the subjects (20 ml blood, 2 g adipose tissue, and tumor sections in paraffin blocks) are taken and stored. Their future analysis will provide additional source of exposure assessment. Strengths and weaknesses of both exposure measures are discussed in this paper. PMID:9599715
Alavanja, Michael C. R.; Hofmann, Jonathan N.; Lynch, Charles F.; Hines, Cynthia J.; Barry, Kathryn H.; Barker, Joseph; Buckman, Dennis W.; Thomas, Kent; Sandler, Dale P.; Hoppin, Jane A.; Koutros, Stella; Andreotti, Gabriella; Lubin, Jay H.; Blair, Aaron; Beane Freeman, Laura E.
Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993–97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999–2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were
Dotlic, Snjezana; Perry, Anamarija M; Petrusevska, Gordana; Fetica, Bogdan; Diebold, Jacques; MacLennan, Kenneth A; Müller-Hermelink, Hans K; Nathwani, Bharat N; Boilesen, Eugene; Bast, Martin; Armitage, James O; Weisenburger, Dennis D
The distribution of non-Hodgkin lymphoma (NHL) subtypes varies around the world, but a systematic study of South-eastern Europe (SEEU) has never been done. Therefore, we evaluated the relative frequencies of NHL subtypes in three SEEU countries--Croatia, Romania and Macedonia. Five expert haematopathologists reviewed 632 consecutive cases of newly diagnosed NHL from the three SEEU countries using the World Health Organization classification. The results were compared to 399 cases from North America (NA) and 580 cases from Western Europe (WEU). The proportions of B- and T-cell NHL and the sex distribution in SEEU were similar to WEU and NA. However, the median ages of patients with low- and high-grade B-NHL in SEEU (60 and 59 years, respectively) were significantly lower than in NA (64 and 68 years, respectively; P < 0·05). SEEU had a significantly lower proportion of low-grade B-NHL (46·6%) and higher proportion of high-grade B-NHL (44·5%) compared to both WEU (54·5% and 36·4%, respectively) and NA (56·1% and 34·3%, respectively). There were no significant differences in the relative frequencies of T-NHL subtypes. This study provides new insights into differences in the relative frequencies of NHL subtypes in different geographic regions. Epidemiological studies are needed to better characterize and explain these differences.
Ward, M H; Zahm, S H; Weisenburger, D D; Gridley, G; Cantor, K P; Saal, R C; Blair, A
Little is known about dietary factors and non-Hodgkin's lymphoma (NHL) risk, although high intakes of animal protein and milk have been associated with NHL in two previous studies. As part of a population-based case-control study of agricultural and other risk factors for NHL in eastern Nebraska (USA), we examined the self- and proxy-reported frequency of consumption of 30 food items by 385 White men and women with NHL and 1,432 controls. Animal protein intake was not associated significantly with the risk of NHL, however, there was a nonsignificantly elevated risk of NHL among men with high milk consumption. Vitamin C, carotene, citrus fruit, and dark green vegetable intakes were inversely significantly related to the risk of NHL for men, but not for women. Among men, the odds ratios for the highest quartiles of both vitamin C and carotene intake were 0.6 (95% confidence intervals = 0.3-1.0). There were no meaningful differences in the associations of nutrient intakes and NHL risk between B- and T-cell lymphomas and histologic types. Risks for low intakes of vitamin C and carotene were greater among men and women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first-degree relatives.
Han, Tian-Jie; Li, Jun-Shan; Luan, Xiao-Tian; Wang, Ling; Xu, Hong-Zhi
Many studies suggest that high-fat diets are linked to the etiology of non-Hodgkin's lymphoma (NHL). However, the findings are inconsistent and therefore the association between fat and non-Hodgkin's lymphoma remains unclear. In this study, we aim to quantitatively assess the association between fat consumption and the risk for NHL. We reviewed 221 published cohort and case-control studies that reported relative risk (RRs) and corresponding 95% confidence intervals (CIs) of NHL and fat intake using PubMed, Cochrane, EMBASE, and Google Scholar databases. A random-effects model computed summary risk estimates. Based on our literature search, 10 of 221 studies (two cohort and eight case-control studies) were relevant to this meta-analysis. There was a significant association between total fat consumption and increased risk of NHL (RR = 1.26; 95% CI: 1.12-1.42); in addition, subgroup analysis showed a significant correlation with diffuse large B-cell lymphoma (RR = 1.41; 95% CI: 1.08-1.84) but not with follicular lymphoma (RR = 1.21; 95% CI: 0.97-1.52), small lymphocytic lymphoma/chronic lymphocytic leukemia (RR = 0.91; 95% CI: 0.68-1.23), nor with T cell lymphoma (RR = 1.12; 95% CI: 0.60-2.09). The funnel plot revealed no evidence for publication bias. Total fat consumption, particularly animal fat, increases the risk for NHL.
Graus, Francesc; Ariño, Helena; Dalmau, Josep
Paraneoplastic neurological syndromes (PNSs) rarely associate with Hodgkin lymphoma (HL) and non-HLs (NHLs). Except for paraneoplastic cerebellar degeneration (PCD) in HL and dermato/ polymyositis in both HL and NHL, other PNSs are uncommon and have only been reported as isolated case reports or short series. There are several important differences in PNSs when occurring in association with HL and NHL compared with those associated with solid tumors. First, some PNSs such as sensory neuronopathy or Lambert-Eaton myasthenic syndrome rarely occur in lymphomas, whereas others, such as granulomatous angiitis, are only described in HL. Second, onconeural antibodies are absent in most PNSs associated with lymphomas with the exceptions of Tr (δ/notch-like epidermal growth factor-related receptor) in PCD and mGluR5 in limbic encephalitis (LE). The antigens recognized by these antibodies are not expressed in lymphoma cells, suggesting the tumor itself does not trigger the PNS. Third, unlike patients with solid tumors in patients with lymphoma, the PNSs often develops at advanced stages of the disease. Furthermore, the type and frequency of PNSs are different between HL and NHL; whereas LE and PCD occur almost exclusively in patients with HL, sensorimotor neuropathies and dermatomyositis are more frequent in NHL.
Eghbali, Houchingue; Soubeyran, Pierre; Soubeyran, Isabelle; Monnerau, Alain; Cazorla, Sophie
Important progress have been recently achieved in the management of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Prognostic factors are now better defined in HD thanks to new biologic and radiologic information which complete old and relevant clinical factors. These parameters are expected to improve decision making in patient's management. However, treatment strategy is under new discussion and controversies about the role of radiotherapy and its doses. There are now enough arguments to consider radiotherapy unnecessary in advanced stages when a complete remission is achieved by chemotherapy. There is also important concern about late effects of treatment and not only secondary cancers. Non-Hodgkin's lymphomas are heterogeneous and different entities are now better defined and described, thanks to a common and similar language for immunological clinical data and treatment outcome. New strategies are under investigation using monoclonal antibodies with or without radioisotopes, in association with chemotherapy or radiotherapy. Undoubtedly, these new approaches are going to improve the overall prognosis of NHL.
Jipp, Jacob; Kay, Paul; Schwartz, Bradley
Abstract Background: Although renal involvement is often present in non-Hodgkin's lymphoma (NHL), primary renal NHL is a rare diagnosis. Case Presentation: We present a case report of a 72-year-old asymptomatic male who underwent a robot-assisted laparoscopic radical nephroureterectomy on an atrophic left kidney with evidence of an infiltrating mass. Pathology report demonstrated a grade 1 follicular lymphoma. Conclusion: Lymphoma is a differential that should be considered when evaluating a renal mass. Chemotherapy and radiation are the mainstays of treatment. PMID:27579430
Netto, D; Spielberger, R; Awasthi, S; Balaban, E P; Nowak, J A; Demian, S D
In a 69-year-old man with hepatomegaly, a diagnosis of primary non-Hodgkin's lymphoma (NHL) of the liver was made by fine needle aspiration (FNA). At the time of presentation there was no evidence of involvement of the lymph nodes, bone marrow or any other organ. Although hepatic involvement is common in advanced stages of Hodgkin's disease and NHL, primary lymphoma of the liver is rare. The purpose of this paper is to report a rare occurrence of primary lymphoma of the liver and to demonstrate the possibility of making this diagnosis by FNA.
Siddiahgari, Sirisha Rani; Yerukula, Pallavi; Lingappa, Lokesh; Moodahadu, Latha S
Extra nodal presentation of Non Hodgkins Lymphoma (NHL) is a rare entity, and data available about the NHL that primarily involves of middle ear and mastoid is limited. We report a case of diffuse large B cell lymphoma (DLBCL), in a 2 year 8 month old boy, who developed otalgia and facial palsy. Computed tomography revealed a mass in the left mastoid. Mastoid exploration and histopathological examination revealed DLBCL. This case highlights the importance of considering malignant lymphoma as one of the differential diagnosis in persistent otitis media and/facial palsy.
Beider, Katia; Ribakovsky, Elena; Abraham, Michal; Wald, Hanna; Weiss, Lola; Rosenberg, Evgenia; Galun, Eithan; Avigdor, Abraham; Eizenberg, Orly; Peled, Amnon; Nagler, Arnon
Chemokine axis CXCR4/CXCL12 is critically involved in the survival and trafficking of normal and malignant B lymphocytes. Here, we investigated the effect of high-affinity CXCR4 antagonist BKT140 on lymphoma cell growth and rituximab-induced cytotoxicity in vitro and in vivo. In vitro efficacy of BKT140 alone or in combination with rituximab was determined in non-Hodgkin lymphoma (NHL) cell lines and primary samples from bone marrow aspirates of patients with NHL. In vivo efficacy was evaluated in xenograft models of localized and disseminated NHL with bone marrow involvement. Antagonizing CXCR4 with BKT140 resulted in significant inhibition of CD20+ lymphoma cell growth and in the induction of cell death, respectively. Combination of BKT140 with rituximab significantly enhanced the apoptosis against the lymphoma cells in a dose-dependent manner. Moreover, rituximab induced CXCR4 expression in lymphoma cell lines and primary lymphoma cells, suggesting the possible interaction between CD20 and CXCR4 pathways in NHL. Primary bone marrow stromal cells (BMSC) further increased CXCR4 expression and protected NHL cells from rituximab-induced apoptosis, whereas BKT140 abrogated this protective effect. Furthermore, BKT140 showed efficient antilymphoma activity in vivo in the xenograft model of disseminated NHL with bone marrow involvement. BKT140 treatment inhibited the local tumor progression and significantly reduced the number of NHL cells in the bone marrow. Combined treatment of BKT140 with rituximab further decreased the number of viable lymphoma cells in the bone marrow, achieving 93% reduction. These findings suggest the possible role of CXCR4 in NHL progression and response to rituximab and provide the scientific basis for the development of novel CXCR4-targeted therapies for refractory NHL. ©2013 AACR.
Tosolini, Marie; Algans, Christelle; Pont, Frédéric; Ycart, Bernard; Fournié, Jean-Jacques
ABSTRACT Non-Hodgkin B-cell lymphoma (B-NHL) are aggressive lymphoid malignancies that develop in patients due to oncogenic activation, chemo-resistance, and immune evasion. Tumor biopsies show that B-NHL frequently uses several immune escape strategies, which has hindered the development of checkpoint blockade immunotherapies in these diseases. To gain a better understanding of B-NHL immune editing, we hypothesized that the transcriptional hallmarks of immune escape associated with these diseases could be identified from the meta-analysis of large series of microarrays from B-NHL biopsies. Thus, 1446 transcriptome microarrays from seven types of B-NHL were downloaded and assembled from 33 public Gene Expression Omnibus (GEO) datasets, and a method for scoring the transcriptional hallmarks in single samples was developed. This approach was validated by matching scores to phenotypic hallmarks of B-NHL such as proliferation, signaling, metabolic activity, and leucocyte infiltration. Through this method, we observed a significant enrichment of 33 immune escape genes in most diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) samples, with fewer in mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL) samples. Comparing these gene expression patterns with overall survival data evidenced four stages of cancer immune editing in B-NHL: non-immunogenic tumors (stage 1), immunogenic tumors without immune escape (stage 2), immunogenic tumors with immune escape (stage 3), and fully immuno-edited tumors (stage 4). This model complements the standard international prognostic indices for B-NHL and proposes that immune escape stages 3 and 4 (76% of the FL and DLBCL samples in this data set) identify patients relevant for checkpoint blockade immunotherapies. PMID:27622044
Abdou, Amr M.; Morton, Lindsay M.; Thomas, Rasmi; Cerhan, James R.; Gao, Xiaojiang; Cozen, Wendy; Rothman, Nathaniel; Davis, Scott; Severson, Richard K.; Bernstein, Leslie; Hartge, Patricia; Carrington, Mary
Genome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes. PMID:20385791
Slager, Susan L.
Our understanding of familial predisposition to lymphoma (collectively defined as non-Hodgkin lymphoma [NHL], Hodgkin lymphoma [HL], and chronic lymphocytic leukemia [CLL]) outside of rare hereditary syndromes has progressed rapidly during the last decade. First-degree relatives of NHL, HL, and CLL patients have an ∼1.7-fold, 3.1-fold, and 8.5-fold elevated risk of developing NHL, HL, and CLL, respectively. These familial risks are elevated for multiple lymphoma subtypes and do not appear to be confounded by nongenetic risk factors, suggesting at least some shared genetic etiology across the lymphoma subtypes. However, a family history of a specific subtype is most strongly associated with risk for that subtype, supporting subtype-specific genetic factors. Although candidate gene studies have had limited success in identifying susceptibility loci, genome-wide association studies (GWAS) have successfully identified 67 single nucleotide polymorphisms from 41 loci, predominately associated with specific subtypes. In general, these GWAS-discovered loci are common (minor allele frequency >5%), have small effect sizes (odds ratios, 0.60-2.0), and are of largely unknown function. The relatively low incidence of lymphoma, modest familial risk, and the lack of a screening test and associated intervention, all argue against active clinical surveillance for lymphoma in affected families at this time. PMID:26405224
Avivi, Irit; Farbstein, Dan; Brenner, Benjamin; Horowitz, Netanel A
Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) often present with systemic symptoms such as fatigue, shortness of breath and night sweats, mimicking pregnancy-related features which may result in delayed disease diagnosis. Furthermore, the wish to avoid investigational imaging, aiming to protect the fetus from radiation exposure, may lead to a further delay, which does not often result in significant changes in HL clinical nature and patient outcome. In contrast, a more aggressive behavior (i.e., advanced disease stage and reproductive organ involvement) of most NHL types diagnosed in pregnancy may require urgent therapeutic intervention to prevent disease progression. Current management of pregnancy-associated NHL depends on histological subtype of the disease, gestational stage at diagnosis and the urgency of treatment for a specific patient. Patients diagnosed with indolent lymphoma may often be just followed, whereas those presenting with aggressive or highly aggressive disease need to be urgently treated with chemoimmunotherapy, either after undergoing an elective pregnancy termination if diagnosed at an early gestational stage, or with pregnancy preservation, if diagnosed later. Supportive care of NHL is also important; however, granulocyte colony stimulating factor (G-CSF) which is commonly used outside of pregnancy, should be cautiously employed, considering its established teratogenicity in animals, though this is less proven in humans. In conclusion, given the paucity of studies prospectively evaluating the outcome of pregnant women with NHL, international efforts are warranted to elucidate critical issues and develop guidelines for the management of such patients.
Couceiro, Rita; Proença, Helena; Pinto, Filomena; Fonseca, Ana; Monteiro-Grillo, Manuel
Objective: To report an unusual case of systemic non-Hodgkin lymphoma (NHL) with repeated relapse in the lacrimal glands, in spite of complete remission for several years after treatment. Methods: A 78-year-old male with small lymphocytic B cell NHL, stage IV disease (lung invasion), was submitted to surgery and chemotherapy in 2001, with complete remission of the disease. In 2003 he developed a nodular lesion in the right lacrimal fossa. Pathology results revealed a local relapse of NHL. Radiation and chemotherapy were initiated and complete remission was again achieved. In 2012 the patient developed a new nodular lesion located in the left lacrimal fossa, resulting in diplopia, ptosis and proptosis of the left eye. Orbital computerized tomography (CT), ocular ultrasound and incisional biopsy were performed. Results: Orbital CT revealed a lesion infiltrating the left lacrimal gland and encircling the globe. Biopsy results confirmed a local relapse of B cell NHL. The patient was submitted to local radiation therapy with progressive resolution of ptosis, proptosis and diplopia. Response to treatment was monitored with ocular ultrasound. Conclusions: Patients with NHL diagnosis should be immediately investigated if ophthalmic or orbital symptoms develop. NHL extension to the orbit and adnexa is infrequent (5% of NHL cases) but may occur at any stage of the disease, including as a relapse site. In such cases, radiation and chemotherapy achieve good results, inducing long periods of remission. PMID:27625948
SHEN, ZHENG-LEI; YIN, LIE-FEN; MAO, WEN-WEN; LIANG, JIN; YANG, LING
The current study reports the case of a patient with Philadelphia chromosome-negative (Ph−) non-Hodgkin's lymphoma (NHL) and chronic phase (CP) Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that also possessed characteristic enlarged lymph nodes. A lymph node biopsy resulted in the diagnosis of CP-CML, in addition to T-lymphoblastic cell NHL with negative break point cluster/Abelson tyrosine kinase fusion genes in the lymph node of the patient, which was diagnosed as Ph− NHL. A review of the literature was performed in the present study to investigate the genetic differences between Ph− NHL and Ph+ NHL in patients with CML. The median age of patients with NHL and CML was 41 years. The follow-up time of patients with Ph+ NHL was significantly shorter (mean, <6 months) compared to the follow-up time of patients with Ph− NHL (mean, >15 months). Therefore the present study concludes that Ph+ NHL may be more aggressive compared with Ph+ NHL. The present study suggests that additional studies are required to assess the clinical and genetic characteristics of NHL patients with CML. PMID:27073575
Ramos-Casals, Manuel; Trejo, Olga; García-Carrasco, Mario; Cervera, Ricard; De La Red, Gloria; Gil, Victor; López-Guillermo, Armando; Ingelmo, Miguel; Font, Josep
To analyze the clinical characteristics of patients from a Department of Autoimmune Diseases presenting chronic hepatitis C virus (HCV) infection, systemic autoimmune disease, and B cell lymphoma. We analyzed the records of 100 consecutive patients with systemic autoimmune diseases and associated HCV infection seen in our department between 1994 and 2000. We retrospectively investigated the development of B cell malignancies after the diagnosis of HCV related autoimmune disease. Six patients with HCV related systemic autoimmune disease presented B cell non-Hodgkin's lymphoma (NHL). These patients fulfilled the diagnostic criteria for Sjögren's syndrome (n = 4) and polyarteritis nodosa (PAN; n = 2). Four patients were female and 2 male, with a mean age at lymphoma diagnosis of 62 years (range 45-78). The main immunologic markers were hypocomplementemia in all patients and cryoglobulinemia in 5 (83%). Primary extranodal localization of lymphoma was observed in 3 (50%) patients: prostate (n = 1), liver and ovary (n = 1), and ocular annexa (n = 1). Clinically, NHL was classified as indolent lymphoma in 3 patients and aggressive lymphoma in 3. NHL histologic types were diffuse large cell lymphoma (n = 4), extranodal marginal zone B cell lymphoma (n = 1), MALT lymphoma (n = 1), and lymphoplasmacytic lymphoma (n = 1). We describe 6 patients with a triple association of HCV infection, systemic autoimmune disease, and NHL. Characteristics of these patients included a high prevalence of cryoglobulinemia (that clearly contributes to fulfillment of diagnostic criteria for PAN) and an elevated frequency of primary extranodal involvement. We recommend careful evaluation of patients with B cell NHL to detect silent autoimmune or chronic viral diseases. This triple association reinforces the suspected links between autoimmunity, infection, and cancer.
Peral-Cagigal, Beatriz; Galdeano-Arenas, María; Crespo-Pinilla, Juan Ignacio; García-Cantera, José Miguel; Sánchez-Cuéllar, Luis Antonio; Verrier-Hernández, Alberto
The centrofacial angiocentric lymphoma is a rare lymphoid neoplasm, with an often-difficult diagnosis due to the non-specific clinical picture. On many occasions it is necessary to perform various biopsies to reach the correct diagnosis. This lymphoma is an aggressive Non-Hodgkin's (NHL) type, which is normally found in the upper respiratory tract (predominantly in the nasal cavity), and has an ominous prognosis, as the average survival rate is between 12 and 18 months (1). It is predominantly found in subjects of oriental and South American extraction, who are between the ages of 50 and 60 years and with a slight tendency towards males (2:1). This is the case study of a female Ecuadorian patient who was referred to our department with a hemifacial edema, chocolate- like rhinorrhea and nasal respiratory obstruction, which had been treated with antibiotics and anti-inflammatories for a month without success. After performing a number of diagnostic tests, it was found histologically that the patient had an extranodal T-cell lymphoma of the nasal type (also known as T-cell angiocentric lymphoma).
Zelenetz, Andrew D.; Gordon, Leo I.; Wierda, William G.; Abramson, Jeremy S.; Advani, Ranjana H.; Andreadis, C. Babis; Bartlett, Nancy; Byrd, John C.; Czuczman, Myron S.; Fayad, Luis E.; Fisher, Richard I.; Glenn, Martha J.; Harris, Nancy Lee; Hoppe, Richard T.; Horwitz, Steven M.; Kelsey, Christopher R.; Kim, Youn H.; Krivacic, Susan; LaCasce, Ann S.; Nademanee, Auayporn; Porcu, Pierluigi; Press, Oliver; Rabinovitch, Rachel; Reddy, Nishitha; Reid, Erin; Saad, Ayman A.; Sokol, Lubomir; Swinnen, Lode J.; Tsien, Christina; Vose, Julie M.; Yahalom, Joachim; Zafar, Nadeem; Dwyer, Mary; Sundar, Hema
Non-Hodgkin’s lymphomas (NHL) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Mantle cell lymphoma (MCL) accounts for approximately 6% of all newly diagnosed NHL cases. Radiation therapy with or without systemic therapy is a reasonable approach for the few patients who present with early-stage disease. Rituximab-based chemoimmunotherapy followed by high-dose therapy and autologous stem cell rescue (HDT/ASCR) is recommended for patients presenting with advanced-stage disease. Induction therapy followed by rituximab maintenance may provide extended disease control for those who are not candidates for HDT/ASCR. Ibrutinib, a Bruton tyrosine kinase inhibitor, was recently approved for the treatment of relapsed or refractory disease. This manuscript discusses the recommendations outlined in the NCCN Guidelines for NHL regarding the diagnosis and management of patients with MCL. PMID:25190696
Ganzel, Chezi; Pogrebijsky, Galina; Krichevsky, Svetlana; Neuman, Tzahi; Yehuda, Dina Ben
Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) have traditionally been considered as two distinct entities. However, there are rare reports of patients that, over time, develop both diseases. It remains unresolved whether the origin of the two diseases is from the same clone. In this study, we attempted to retrospectively investigate the clinical and molecular aspects of patients who developed both lymphomas. The rearranged immunoglobulin heavy-chain variable region genes from both diagnoses were compared to each other. Twenty-six patients presented with both diagnoses. Twelve had HL as the primary disorder ("HL first" group) and the majority of these (75%) presented with aggressive lymphoma as the second lymphoma. In contrast, in the 11 patients for whom NHL was the primary disorder ("NHL first" group), this was usually (82%) of low-grade histology. Three patients were diagnosed concurrently with both diseases. Mean age at first diagnosis was higher (p = 0.037) in the NHL first group (56.1 years) than in the HL first group (40 years). Mean time between diagnoses was longer (p = 0.026) in the HL first group (9 years) than in the NHL first group (5 years). For 11 patients, diagnostic samples were available for molecular analyses from both diagnoses of HL and NHL. In 6 of these 11 patients, gene rearrangement studies were informative. No patient had the same gene rearrangement identified in both diseases. It seems that development of HL and NHL in one patient, at different time points, reflects, in many cases, separate biologic diseases. Copyright © 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Shaikh, Abubakar Badshaha; Waghmare, Sneha; Koshti-Khude, Supriya; Koshy, Ajit Vergese
The non-Hodgkin's lymphoma (NHLs) is a diverse group of lymphoid neoplasms, prevalence of which increased since three decades. NHL is diverse in the manner of presentation, response to various treatment and prognosis. NHL usually involves not only lymph nodes but also extranodal sites. Usually, oral manifestation of NHL is secondary to the widespread involvement throughout the body. Oral NHL is relatively rare and difficult to diagnose in clinical setting as it presents as local swelling, pain, discomfort and mimics pyogenic granuloma, periodontal disease, osteomyelitis and other malignancies. Sometimes, oral lesion may present as the early disease (primary site). Careful evaluation of patient and proper investigations is required for correct diagnosis so that patient will receive the treatment in early stage which has a good prognosis. Here, we are presenting the case of low-grade B-cell NHL of palate of a 92-year-old man. PMID:27721619
Lee, Suk-Bae; Ham, Byung-Kook; Park, Jeong Mee; Kim, Young Jin; Paek, Kyung-Hee . E-mail: email@example.com
The two genes, named BnNHL18A and BnNHL18B, showing sequence homology with Arabidopsis NDR1/HIN1-like (NHL) genes, were isolated from cDNA library prepared with oilseed rape (Brassica napus) seedlings treated with NaCl. The transcript level of BnNHL18A was increased by sodium chloride, ethephon, hydrogen peroxide, methyl jasmonate, or salicylic acid treatment. The coding regions of BnNHL18A and BnNHL18B contain a sarcolipin (SLN)-like sequence. Analysis of the localization of smGFP fusion proteins showed that BnNHL18A is mainly localized to endoplasmic reticulum (ER). This result suggests that the SLN-like sequence plays a role in retaining proteins in ER membrane in plants. In response to NaCl, hydrogen peroxide, ethephon, and salicylic acid treatments, the protein localization of BnNHL18A was changed. Our findings suggest a common function of BnNHL18A in biotic and abiotic stresses, and demonstrate the presence of the shared mechanism of protein translocalization between the responses to plant pathogen and to osmotic stress.
Lymphoma - Hodgkin; Hodgkin disease; Cancer - Hodgkin lymphoma ... of Hodgkin lymphoma (there are different forms of Hodgkin lymphoma) The stage (where the disease has spread) Whether the tumor is more than ...
Galleze, Assia; Raache, Rachida; Amroun, Habiba; Cherif, Nacera; Fadli, Mohamed; Meçabih, Fethi; Mecheti, Bachira; Belhani, Meriem; Bensenouci, Abdelatif; Abbadi, Mohamed C; Attal, Nabila
Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are the 2 types of lymphoma that represent the third most common childhood malignancy. Multiple etiological factors are involved in lymphoma pathogenesis, including viral infection, immune deficiencies, environmental agents, and genetic factors. Strong arguments supporting a genetic linkage between the susceptibility to lymphomas and human leukocyte antigens (HLA) are reported and give an idea about susceptibility or protection from the disease. Seventy-one cases were included in this study: 36 cases of non-Hodgkin lymphoma and 35 patients with Hodgkin lymphoma. Their ages ranged from 4 to 18 years. The control group consisted of 70 unrelated healthy individuals, with a mean age of 5 to 17 years. The genotype of HLA-A, HLA-B, HLA-DR, and HLA-DQ alleles was typed by means of PCR sequence-specific priming. HLA-B*18, HLA-DRB1*03, *07, and HLA-DQB1*02 were significantly increased in patients with lymphomas when compared with controls, whereas HLA-DRB1*13 and DQB1*03 were significantly decreased when compared with controls. These results indicate that HLA-B*18, DRB1*03, *07, and DQB1*02 may contribute to lymphoma susceptibility, whereas HLA-DRB1*13 and DQB1*03 may confer protection to lymphoma in the Algerian population.
Chen, Zhujun; Xu, Xiaofeng; Hu, Hongfeng; Zhao, Xinmin; Gao, Xiang; Guo, Lin
Lactate dehydrogenase 5 (LDH-5) is one of the major isoenzymes catalyzing the biochemical process of pyruvate to lactate. The purpose of this study was to investigate the expression of serum LDH-5 and test whether this enzyme is regulated by tumor hypoxia and represents a prognostic marker in patients with Non-Hodgkin’s lymphoma (NHL). In this study, LDH-5 levels were detected using agarose gel electrophoresis in NHL patients (n = 266) and non-NHL controls including benign lymphadenectasis (n = 30) and healthy cohorts (n = 233). We also explored the expression of LDH-5 and hypoxia-inducible factor (HIF) 1α in NHL and benign controls by immunohistochemistry and immunofluorescence staining, respectively. Moreover, the role of LDH-5 in the progression of NHL was assessed by multivariate Cox analyses and Kaplan-Meier survival estimates. Serum concentrations of LDH-5 were significantly higher in NHL patients (9.3%) than in benign patients and healthy controls (7.5% and 7.2%, respectively, P<0.01). Application of LDH-5 detection increased the sensitivity of NHL detection, identifying 53.4% of NHL patients as positive, compared with the measurement of total LDH levels (36.5% sensitivity). LDH-5 concentrations increased with clinical stage, extra-nodal site involvement, and WHO performance status of patients with NHL. Exposure to a hypoxic environment induced the expression of LDH-5 and its overexpression correlated with HIF1α cytoplasmic accumulation in NHL cells. In multivariate analyses, LDH-5 was an independent marker for progression-free survival in patients with NHL (P<0.001). Overall, the expression of LDH-5 was elevated in NHL, showing an association with tumor hypoxia and unfavorable prognosis. Thus, LDH-5 emerges as a promising prognostic predictor for NHL patients. PMID:24086384
Machiela, Mitchell J; Lan, Qing; Slager, Susan L; Vermeulen, Roel C H; Teras, Lauren R; Camp, Nicola J; Cerhan, James R; Spinelli, John J; Wang, Sophia S; Nieters, Alexandra; Vijai, Joseph; Yeager, Meredith; Wang, Zhaoming; Ghesquières, Hervé; McKay, James; Conde, Lucia; de Bakker, Paul I W; Cox, David G; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R; De Roos, Anneclaire J; Brooks-Wilson, Angela R; Giles, Graham G; Melbye, Mads; Gu, Jian; Jackson, Rebecca D; Kane, Eleanor; Purdue, Mark P; Vajdic, Claire M; Albanes, Demetrius; Kelly, Rachel S; Zucca, Mariagrazia; Bertrand, Kimberly A; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M; Link, Brian K; Novak, Anne J; Dogan, Ahmet; Asmann, Yan W; Liebow, Mark; Thompson, Carrie A; Ansell, Stephen M; Witzig, Thomas E; Tilly, Hervé; Haioun, Corinne; Molina, Thierry J; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans-Olov; Roos, Göran; Bracci, Paige M; Riby, Jacques; Smith, Martyn T; Holly, Elizabeth A; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M; Severson, Richard K; Tinker, Lesley F; North, Kari E; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J; Villano, Danylo J; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R; Turner, Jenny; Southey, Melissa C; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Boeing, Heiner; Tjønneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Liang, Liming; Park, Ju-Hyun; Chung, Charles C; Weisenburger, Dennis D; Fraumeni, Joseph F; Salles, Gilles; Glenn, Martha; Cannon-Albright, Lisa; Curtin, Karen; Wu, Xifeng; Smedby, Karin E; de Sanjose, Silvia; Skibola, Christine F; Berndt, Sonja I; Birmann, Brenda M; Chanock, Stephen J; Rothman, Nathaniel
Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
Machiela, Mitchell J.; Lan, Qing; Slager, Susan L.; Vermeulen, Roel C.H.; Teras, Lauren R.; Camp, Nicola J.; Cerhan, James R.; Spinelli, John J.; Wang, Sophia S.; Nieters, Alexandra; Vijai, Joseph; Yeager, Meredith; Wang, Zhaoming; Ghesquières, Hervé; McKay, James; Conde, Lucia; de Bakker, Paul I.W.; Cox, David G.; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Giles, Graham G.; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Purdue, Mark P.; Vajdic, Claire M.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Tilly, Hervé; Haioun, Corinne; Molina, Thierry J.; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans-Olov; Roos, Göran; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Boeing, Heiner; Tjønneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C.H.; Liang, Liming; Park, Ju-Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Fraumeni, Joseph F.; Salles, Gilles; Glenn, Martha; Cannon-Albright, Lisa; Curtin, Karen; Wu, Xifeng; Smedby, Karin E.; de Sanjose, Silvia; Skibola, Christine F.; Berndt, Sonja I.; Birmann, Brenda M.; Chanock, Stephen J.; Rothman, Nathaniel
Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22–1.82, P-value = 8.5 × 10−5]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93–3.51, P-value = 4.0 × 10−10). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk. PMID:27008888
Jeon, Young-Woo; Yoon, Jae-Ho; Lee, Sung-Eun; Eom, Ki-Seong; Kim, Yoo-Jin; Kim, Hee-Je; Lee, Seok; Min, Chang-Ki; Lee, Jong Wook; Min, Woo-Sung; Cho, Seok-Goo
Background/Aims: Recently, large cohort studies regarding associations between autoimmune disease and lymphomas have been reported in a few Western countries. However, Asian data concerning autoimmune-related lymphomas are limited. Therefore, we evaluated the clinical characteristics and prognostic factors of patients with autoimmune disease-related non-Hodgkin lymphoma (NHL) in a single center in Korea. Methods: We analyzed the data from 11 patients with autoimmune-related NHL. Patients were categorized into two groups, those with rheumatoid arthritis (RA) and those with non-RA-related NHL. Then patients were re-categorized into a group with methotrexate (MTX) usage and a MTX non-usage group. Histological subtype, MTX duration, autoimmune disease duration, treatment modalities, and other data were collected and analyzed. Results: Our study revealed that older RA patients have a greater likelihood of occurrence of NHL (p = 0.042). We confirmed that MTX duration and cumulative dose of MTX have no significant correlation with autoimmune disease and NHL (p = 0.073). In the management of autoimmune disease-related NHL, all patients were directly treated with systemic chemotherapy instead of employing a wait and watch approach. Overall survival (OS) and progression-free survival (PFS) in all autoimmune disease-related NHL were 100% and 87.5%, with no treatment-related mortality during the 2-year follow-up period of our study. Conclusions: Our study suggests that patients with RA-NHL are characterized by older age at onset compared to those with non-RA-NHL. Also considering of OS and PFS, intensive treatment strategy instead of delayed watchful managements may be required for autoimmune disease-related NHL including of old age group. PMID:27384438
Jeon, Young-Woo; Yoon, Jae-Ho; Lee, Sung-Eun; Eom, Ki-Seong; Kim, Yoo-Jin; Kim, Hee-Je; Lee, Seok; Min, Chang-Ki; Lee, Jong Wook; Min, Woo-Sung; Cho, Seok-Goo
Recently, large cohort studies regarding associations between autoimmune disease and lymphomas have been reported in a few Western countries. However, Asian data concerning autoimmune-related lymphomas are limited. Therefore, we evaluated the clinical characteristics and prognostic factors of patients with autoimmune disease-related non-Hodgkin lymphoma (NHL) in a single center in Korea. We analyzed the data from 11 patients with autoimmune-related NHL. Patients were categorized into two groups, those with rheumatoid arthritis (RA) and those with non-RA-related NHL. Then patients were re-categorized into a group with methotrexate (MTX) usage and a MTX non-usage group. Histological subtype, MTX duration, autoimmune disease duration, treatment modalities, and other data were collected and analyzed. Our study revealed that older RA patients have a greater likelihood of occurrence of NHL (p = 0.042). We confirmed that MTX duration and cumulative dose of MTX have no significant correlation with autoimmune disease and NHL (p = 0.073). In the management of autoimmune disease-related NHL, all patients were directly treated with systemic chemotherapy instead of employing a wait and watch approach. Overall survival (OS) and progression-free survival (PFS) in all autoimmune disease-related NHL were 100% and 87.5%, with no treatment-related mortality during the 2-year follow-up period of our study. Our study suggests that patients with RA-NHL are characterized by older age at onset compared to those with non-RA-NHL. Also considering of OS and PFS, intensive treatment strategy instead of delayed watchful managements may be required for autoimmune disease-related NHL including of old age group.
Friedberg, Jonathan W.
Despite remaining an incurable disease, overall survival improvements have been noted in patients with advanced stage follicular lymphoma. The Follicular Lymphoma International Prognostic Index (FLIPI) is a robust prognostic index in this disease, and continues to provide prognostic information in the rituximab era. Rituximab has significantly changed the management of follicular lymphoma, and the most dramatic impact of rituximab is observed in combination with cytotoxic chemotherapy. However, resistance to rituximab remains a problem, and standard therapy in the rituximab-refractory setting includes radioimmunotherapy, autologous stem cell transplantation, and allogeneic stem cell transplantation. In addition, several novel agents show encouraging activity in FL, including bendamustine, lenalidomide, bortezomib and other proteasome inhibitors, and BCL2 inhibitors. PMID:18760706
Kim, H.D.; Bedetti, C.D.; Boggs, D.R.
Three patients developed non-Hodgkin's lymphoma (NHL) 3 to 6 years after treatment for Hodgkin's disease (HD). In no instance was there evidence of recurrence of HD following the initial chemotherapy or radiotherapy. None of these patients had received both radiation therapy and chemotherapy. All patients responded well to conventional chemotherapy for NHL and are alive at 23 +, 37 +, and 65+ months after that secondary diagnosis. This report, when coupled with at least ten other such reported patients, suggests that NHL may be a relatively uncommon but significant complication of therapy for HD and must be distinguished for recurrence of HD.
Lin, Zhiguang; Chen, Bobin; Xu, Xiaoping; Wang, Xiaoqin; Lin, Guowei
The aim was to determine the clinical and cytogenetic characteristics of non-Hodgkin's lymphoma (NHL) in Shanghai. A retrospective analysis was conducted in 516 patients with NHL. Patient clinical data, including age, sex, diagnosis, immunophenotypes, and karyotypes, were collected. The median age was 58 years. There was a male predominance in all NHL, except extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Patients with B cell NHL (1.5%) expressed CD3. T cell NHL patients (11.5%) expressed CD20. Epstein-Barr virus latent integral membrane protein 1, BCL6, CD10, Bcl-2, CD68, myeloperoxidase, CD99, CD30, CD15, and CD43 were present in various types of NHL. Complex karyotypes accounted for 92.3% of the 73.7% patients with abnormal karyotypes. Immunoglobin heavy chain gene translocation was present in 60.3% of B cell and 23.7% of T/NK cell neoplasms. Understanding the complex clinicopathological and molecular features of NHL may help with prognosis and serve as targets for treatments.
Voulgarelis, Michael; Ziakas, Panayiotis D; Papageorgiou, Aristea; Baimpa, Evangelia; Tzioufas, Athanasios G; Moutsopoulos, Haralampos M
Sjögren syndrome (SS) has been associated with the development of non-Hodgkin lymphoma (NHL). From a cohort of 584 SS patients followed in our department from 1980 to 2010, we retrospectively analyzed 53 consecutive NHL cases. Considerations included histologic type, clinical manifestation and NHL staging, treatment, response rate and overall survival (OS), event-free survival (EFS), and standardized mortality ratio (SMR).Mucosa-associated lymphoid tissue (MALT) lymphomas constituted the majority (59%) of NHL subtypes, followed by nodal marginal zone lymphomas (NMZLs) (15%) and diffuse large B-cell lymphomas (DLBCLs) (15%). Six lymphoma patients died during the median follow-up of 40.8 months. The corresponding age/sex-adjusted SMR of SS with and without NHLs versus the general population was 3.25 (95% confidence interval [CI] 1.32-6.76) and 1.08 (95% CI, 0.79-1.45), respectively. A "watch and wait" policy was adopted for 9 patients with asymptomatic localized salivary MALT lymphomas. Eight patients with limited-stage MALT lymphomas and extraglandular manifestations were treated with rituximab. Ten MALT lymphoma patients with disseminated disease received chemotherapy with or without rituximab. The 3-year OS and EFS in patients with MALT lymphomas was 97% and 78%, respectively. Rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was the chosen therapeutic intervention for patients with DLBCLs. A successful outcome was recorded for this group, with 100% OS and EFS at 3 years. Patients with NMZLs had a less favorable outcome, with a 3-year OS of 80% and EFS of 53%. Our results describe the course and prognosis of SS-associated NHL and highlight the need for a risk-stratified treatment approach.
Bertrand, Kimberly A; Shingala, Janki; Evens, Andrew; Birmann, Brenda M; Giovannucci, Edward; Michaud, Dominique S
Periodontal disease is a chronic inflammatory condition that has been associated with chronic diseases, including cancer. In an earlier prospective cohort analysis within the Health Professionals Follow-Up Study (HPFS), we observed a 31% higher risk of non-Hodgkin lymphoma (NHL) among participants with severe periodontal disease at baseline. Here, we extend the study with an additional 8 years of follow-up, and conduct analyses with updated periodontal disease status and NHL subtypes. The HPFS is an ongoing prospective cohort study of 51,529 men in the USA Between baseline in 1986 and 2012, 875 cases of NHL were diagnosed, including 290 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 85 diffuse large B-cell lymphomas and 91 follicular lymphomas. We performed multivariable Cox proportional hazards regression to evaluate associations of interest. History of periodontal disease at baseline was positively associated with risk of NHL overall (hazard ratio (HR) = 1.26, 95% confidence interval (CI): 1.06-1.49) and CLL/SLL (HR = 1.41, 95% CI: 1.04-1.90). With updated periodontal status, HRs were 1.30 (95% CI: 1.11-1.51) for NHL overall and 1.41 (95% CI: 1.08-1.84) for CLL/SLL. In contrast, after adjusting for periodontal disease, tooth loss was inversely associated with NHL, suggesting that other causes or consequences of tooth loss may have different implications for NHL etiology. Our findings suggest that periodontal disease is a risk factor for NHL. Whether periodontal disease is a direct or indirect cause of NHL, or is a marker of underlying systemic inflammation and/or immune dysregulation, warrants further investigation. © 2016 UICC.
Morton, Lindsay M.; Slager, Susan L.; Cerhan, James R.; Wang, Sophia S.; Vajdic, Claire M.; Skibola, Christine F.; Bracci, Paige M.; de Sanjosé, Silvia; Smedby, Karin E.; Chiu, Brian C. H.; Zhang, Yawei; Mbulaiteye, Sam M.; Monnereau, Alain; Turner, Jennifer J.; Clavel, Jacqueline; Adami, Hans-Olov; Chang, Ellen T.; Glimelius, Bengt; Hjalgrim, Henrik; Melbye, Mads; Crosignani, Paolo; di Lollo, Simonetta; Miligi, Lucia; Nanni, Oriana; Ramazzotti, Valerio; Rodella, Stefania; Costantini, Adele Seniori; Stagnaro, Emanuele; Tumino, Rosario; Vindigni, Carla; Vineis, Paolo; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Cocco, Pierluigi; Foretova, Lenka; Maynadié, Marc; Nieters, Alexandra; Staines, Anthony; Colt, Joanne S.; Cozen, Wendy; Davis, Scott; de Roos, Anneclaire J.; Hartge, Patricia; Rothman, Nathaniel; Severson, Richard K.; Holly, Elizabeth A.; Call, Timothy G.; Feldman, Andrew L.; Habermann, Thomas M.; Liebow, Mark; Blair, Aaron; Cantor, Kenneth P.; Kane, Eleanor V.; Lightfoot, Tracy; Roman, Eve; Smith, Alex; Brooks-Wilson, Angela; Connors, Joseph M.; Gascoyne, Randy D.; Spinelli, John J.; Armstrong, Bruce K.; Kricker, Anne; Holford, Theodore R.; Lan, Qing; Zheng, Tongzhang; Orsi, Laurent; Dal Maso, Luigino; Franceschi, Silvia; La Vecchia, Carlo; Negri, Eva; Serraino, Diego; Bernstein, Leslie; Levine, Alexandra; Friedberg, Jonathan W.; Kelly, Jennifer L.; Berndt, Sonja I.; Birmann, Brenda M.; Clarke, Christina A.; Flowers, Christopher R.; Foran, James M.; Kadin, Marshall E.; Paltiel, Ora; Weisenburger, Dennis D.; Linet, Martha S.; Sampson, Joshua N.
Background Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes. Methods We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case–control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE). Results Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10−4), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10−4). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a
Gaikwad, Harsha Shailesh; Mohindra, Ritin; Sharma, Manjula
Lymphoma is fourth most frequent malignancy diagnosed prenatally (~1:6000 cases), with Hodgkin’s Lymphoma (HL) forming the major chunk. However, in recent times, there has been an increase in occurrence of Non-Hodgkin’s Lymphoma (NHL) due to late child bearing age and high incidence of AIDS-related NHL in developing countries. Managing NHL in pregnancy involves intricate medical, ethical and psychological issues. Diagnostic and treatment delays may influence the prognosis for indolent cases. Seen the complexity of the management decisions associated with NHL, interdisciplinary and individualized approach becomes imperative for each woman. We present a case of 25-year-old G2P0010 at 32 weeks Period of Gestation (PoG) with right sided deep cervical lymphadenopathy, who was diagnosed as aggressive malignant NHL and was subsequently started on chemotherapy after confirmation of diagnosis and eventually had an optimal feto-maternal outcome. The critical appraisal of the accessible data, identification of controversies and unresolved issues and proposal of elucidations about varied facets of NHL in pregnancy are also provided. PMID:28384939
AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chondrosarcoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Nodal Marginal Zone B-cell Lymphoma; Ovarian Sarcoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Uterine Sarcoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small
Gallo, E; Pérez-Gala, S; Navarro, R; Fraga, J; Adrados, M; Arranz, R; García-Diez, A; Aragüés, M
The coexistence of non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) in the same patient, although previously reported, is very unusual. This situation is extremely rare when the first diagnosis is a cutaneous B NHL, and exceptional if there is no personal background of cytostatic treatment. We report a 44-year-old man who developed cutaneous nodules over a period of two years. A marginal zone cutaneous B-cell lymphoma was diagnosed. On staging investigation a mass in the lingual tonsil was found and excision biopsy showed a classical Hodgkin lymphoma.
Alric, Laurent; Besson, Caroline; Lapidus, Nathanael; Jeannel, Juliette; Michot, Jean-Marie; Cacoub, Patrice; Canioni, Danielle; Pol, Stanislas; Davi, Frédéric; Rabiega, Pascaline; Ysebaert, Loic; Bonnet, Delphine; Hermine, Olivier
Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. Methods: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL. Results: The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient. Conclusions: The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection. PMID:27749916
Laurent, Camille; Do, Catherine; Gourraud, Pierre-Antoine; de Paiva, Geisilene Russano; Valmary, Séverine; Brousset, Pierre
Abstract Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) represent a heterogeneous group of malignant lymphoid tumors, which have distinct histological and/or biological characteristics with preferential nodal involvement. However, none of the previous studies have assessed the prevalence of common NHL and HL subtypes at each nodal site of involvement. The aim of our study was to determine the prevalence of HL and NHL subtypes depending on their nodal sites of involvement. We conducted a single-center retrospective study of 938 lymphoma cases diagnosed in the Pathology Department of Toulouse Purpan Hospital in France between 2001 and 2008, taking into account the site that corresponded to the diagnostic biopsy. The most frequent sites were cervical lymph nodes (36.8% of all cases), inguinal lymph nodes (16.4%), axillary lymph nodes (11.9%), and supraclavicular lymph nodes (11%). We found an unexpected association between intraparotid nodes and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and between inguinal nodes and follicular lymphoma. The risk of having classical Hodgkin lymphoma (CHL) was 15 times greater in patients with mediastinal lymphoma compared to those with other sites of involvement. Regarding HL, nodal and extranodal mediastinal sites and supraclavicular nodes were more likely to be involved by nodular sclerosis Hodgkin lymphoma (NSCHL). In addition, intra-abdominal lymph nodes were more frequently involved by lymphocyte depleted Hodgkin lymphoma compared to inguinal nodes where NLPHL predominated. Our study shows that some lymph node sites have a disproportionate prevalence of specific subtypes of lymphoma. Identifying these sites may aid to diagnose and better elucidate the pathogenesis of these tumors. PMID:26107683
Peveling-Oberhag, Jan; Arcaini, Luca; Hansmann, Martin-Leo; Zeuzem, Stefan
There is ample epidemiologic evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin lymphoma (B-NHL). B-NHL subtypes most frequently associated with HCV are marginal zone lymphoma and diffuse large B-cell lymphoma. The most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). In fact, for indolent HCV-associated B-NHL, first-line AVT instead of standard immune-chemotherapy might be considered. Molecular mechanisms of HCV-NHL development are still poorly understood. Three general theories have emerged to understand the HCV-induced lymphomagenesis: (1) continuous external stimulation of lymphocyte receptors by viral antigens and consecutive proliferation; (2) HCV replication in B cells with oncogenic effect mediated by intracellular viral proteins; (3) permanent B-cell damage, e.g., mutation of tumor suppressor genes, caused by a transiently intracellular virus ("hit and run" theory). This review systematically summarizes the data on epidemiology, interventional studies, and molecular mechanisms of HCV-associated B-NHL. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Zhang, X; Miura, R; Nakahachi, A
This was a comparative study of NHL in Jilin Province, China (JPC) and Akita county, Japan (ACJ). A total with 219 cases of their clinical features analyzed. The results indicated that in both areas, B-NHL predominated with a B to T cell ratio of 5.1 : 1 (JPC) and 2.4 : 1 (ACJ) respectively. Histologically B-NHL of defuse large-cell type was most commonly seen, the frequency of which was higher in JPC (61.5%) than in ACJ (37.2%). However, immunoblastic B-NHL was of common occurence in ACJ (26 out of 91 cases). In contrast, immunoblastic lympaoma of T cell lineage was very common in both areas, accounting for a half of all T-NHL. Most of the patients were treated with CHOP or COPP protocol, but the responses differred between the two phenotypes of NHL. Patients with B-NHL responded favorably to chemotherapy, with complete response (CR) in 54 of 70 treated cases (77.0%) in ACJ and 47 of 82 treated cases (57.3%) in JPC. The 3-year disease-free survial rate was 44% and 37%, respectively. The response to treatment in T-NHL patients was inferior with a CR rate of 59% in JPC cases. Only 2 in each series of patients kept the remission over 1 year.
The term "soft skills" encompasses a cluster of personality traits, language abilities, personal habits and, ultimately, values and attitudes. Soft skills complement "harder", more technical, skills, such as being able to read or type a letter, but they also have a significant impact on the ability of people to do their jobs…
The term "soft skills" encompasses a cluster of personality traits, language abilities, personal habits and, ultimately, values and attitudes. Soft skills complement "harder", more technical, skills, such as being able to read or type a letter, but they also have a significant impact on the ability of people to do their jobs…
Ozaltin, Fatih; Yalçin, Bilgehan; Orhan, Diclehan; Sari, Neriman; Caglar, Melda; Besbas, Nesrin; Bakkaloglu, Aysin
Renal involvement is a common finding in non-Hodgkin's lymphoma (NHL). Acute renal failure at initial presentation due to lymphomatous infiltration of the kidneys has been described infrequently. We report a 17-year-old male who presented with acute renal failure due to massive lymphomatous infiltration of the kidneys, which necessitated hemodialysis. The diagnosis of B-cell NHL was established by tru-cut biopsy of the kidneys and the patient had an excellent response to high-dose chemotherapy with no major complication. The presence of extrarenal involvement in the testes and the retroperitoneal lymph nodes made the diagnosis of primary renal lymphoma debatable. However, considering the delay in diagnosis and the high proliferative rate of B-cell NHL, we might postulate that the disease had originated primarily in the kidneys. We recommend that in NHL cases with severe renal involvement, full-dose chemotherapy should be instituted with meticulous clinical and laboratory follow-up in order to improve clinical and renal failure status rapidly and to avoid further dissemination of NHL.
Fadilah, S A W
The incidence of Non-Hodgkin's lymphomas (NHL) is rising worldwide and if not adequately treated carries a high mortality rate. The pattern and frequency of NHL vary in different populations and geographical regions. It has considerable biologic and clinical heterogeneity and a definitive diagnosis can be made only after histopathogical examination. The histology and the extent of the lymphoma are the major determinants of optimal therapeutic regimen and treatment outcome. Additionally, the overall treatment strategies should be tailored according to medical status and preference of the patient. A holistic approach provided by a multi-disciplinary team of health care professionals is the cornerstone of ensuring successful treatment outcome. Importantly, therapy should be expedited and where possible performed in experienced centers. Patients achieving remission would require long-term monitoring for disease recurrence and late effects of cytotoxic chemotherapy and radiotherapy. Hence, clinicians should have a fundamental understanding in the biology and the principles of treatment of NHL. This review provides an evidence-based and systematic approach in designing therapeutic strategies for individual patients with newly diagnosed and relapsed NHL focusing on the common types of NHL with particular reference to the current practice within the local settings. The role of standard and novel therapeutic modalities in treatment will be summarized.
Teras, Lauren R; Patel, Alpa V; Hildebrand, Janet S; Gapstur, Susan M
Results of epidemiologic studies on postmenopausal hormone (PMH) use and non-Hodgkin lymphoma (NHL) are inconsistent. To help clarify this issue, PMH and NHL incidence was examined in the Cancer Prevention Study-II Nutrition Cohort. Between 1992 and 2007, 616 cases of NHL were identified among 67 980 postmenopausal women who were cancer-free at baseline. PMH use was updated during follow-up. Using extended Cox regression, we observed a statistically significant 29% higher risk of NHL for ever unopposed estrogen use compared to never use, which was restricted to follicular lymphoma (current estrogen compared to never use, hazard ratio [HR] = 2.25, 95% confidence interval [CI]: 1.17-4.33) and diffuse large B-cell lymphoma (DLBCL, HR = 1.95, 95% CI: 1.13-3.35). There was no association between current estrogen plus progestin (E + P) use and NHL incidence overall, but a suggested positive association between current E + P use and DLBCL, as well as former E + P use and follicular lymphoma. These results suggest that postmenopausal hormones might play a role in NHL etiology, particularly for follicular lymphoma and DLBCL.
Zhang, Yawei; Sanjose, Silvia De; Bracci, Paige M; Morton, Lindsay M; Wang, Rong; Brennan, Paul; Hartge, Patricia; Boffetta, Paolo; Becker, Nikolaus; Maynadie, Marc; Foretova, Lenka; Cocco, Pierluigi; Staines, Anthony; Holford, Theodore; Holly, Elizabeth A; Nieters, Alexandra; Benavente, Yolanda; Bernstein, Leslie; Zahm, Shelia Hoar; Zheng, Tongzhang
Personal use of hair dye has been inconsistently linked to risk of non-Hodgkin lymphoma (NHL), perhaps because of small samples or a lack of detailed information on personal hair-dye use in previous studies. This study included 4,461 NHL cases and 5,799 controls from the International Lymphoma Epidemiology Consortium 1988-2003. Increased risk of NHL (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.4) associated with hair-dye use was observed among women who began using hair dye before 1980. Analyses by NHL subtype showed increased risk for follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) but not for other NHL subtypes. The increased risks of FL (OR = 1.4, 95% CI: 1.1, 1.9) and CLL/SLL (OR = 1.5, 95% CI: 1.1, 2.0) were mainly observed among women who started using hair dyes before 1980. For women who began using hair dye in 1980 or afterward, increased FL risk was limited to users of dark-colored dyes (OR = 1.5, 95% CI: 1.1, 2.0). These results indicate that personal hair-dye use may play a role in risks of FL and CLL/SLL in women who started use before 1980 and that increased risk of FL among women who started use during or after 1980 cannot be excluded.
Manjunatha, B. S.; Gowramma, R.; Nagarajappa, D.; Tanveer, Ahmed
Non-Hodgkin's lymphoma (NHL) commonly presents as non-tender, enlarged lymph nodes, accompanied by diffuse symptoms of fatigue and low-grade intermittent fever and it is derived predominantly from the cells of the B lymphocyte series. NHL cases occur extra-nodally and in 3% of these cases the initial presentation may be in the oral cavity. Though extra-nodal NHL of the oral cavity is a rare finding, patients with oral lesions of NHL commonly present at the dental clinic in the first instance. A careful clinical evaluation supported by histopathological and other laboratory investigations will help in identifying the disease at an early stage, resulting in better prognosis. Any delay in diagnosis has important implications on the morbidity and mortality of the condition. Due to the rarity of intraoral NHL, we present one such a case with a complaint of tumor-like mass on the gingiva of lower molar region. The lesion was clinically thought as pyogenic granuloma and later diagnosed as extra nodal NHL of the oral cavity. PMID:22368372
Savage, Kerry J; Mottok, Anja; Fanale, Michelle
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma with distinct clinicopathologic features. It is typified by the presence of lymphocyte predominant (LP) cells, which are CD20(+) but CD15(-) and CD30(-) and are found scattered amongst small B lymphocytes arranged in a nodular pattern. Despite frequent and often late or multiple relapses, the prognosis of NLPHL is very favorable. There is an inherent risk of secondary aggressive non-Hodgkin lymphoma (NHL) and studies support that risk is highest in those with splenic involvement at presentation. Given disease rarity, the optimal management is unclear and opinions differ as to whether treatment paradigms should be similar to or differ from those for classical Hodgkin lymphoma (CHL). This review provides an overview of the existing literature describing pathological subtypes, outcome and treatment approaches for NLPHL.
Ali, Sheeraz; Ali, Mussadique; Badar, Farhana; Basit, Abdul; Hameed, Abdul
Anaemia is a common feature of lympho-proliferative disorders and is an important cause of poor quality of life in these patients. When indicated, packed red blood cells (PRBC) units are transfused to treat anaemia. Objective of this study was to identify risk factors associated with PRBC transfusions in lymphoma patients. This was a retrospective study done on Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL) patients who had PRBC transfusions during chemotherapy. Information regarding gender, type of lymphoma, stage, baseline haemoglobin, marrow involvement and total number of PRBC units transfused was collected. A total of 481 patients with diagnosis of HL and NHL were registered during one year period. Out of these, 108 (22.4%) had PRBC transfusions during treatment. HL and NHL patients were 30 (27.8%) and 78 (72.2%) respectively. NHL patients were older than HL (37 vs. 32 years), (p=0.03). HL patients had lower mean haemoglobin 9.3 +/- 2.56 g/dl as compared to NHL 11.33 +/- 2.42 g/dl, (p<0.05). There was significant difference in number of PRBC units transfused based on lymphoma type (NHL 6.74 +/- 5.69 vs. HL 3.97 +/- 3.0 units, p<0.05). Bone marrow involvement resulted in increased transfusion requirements (7.84 +/- 4.36 vs. 5.26 +/- 5.49 units, p<0.05) while stage of disease didn't affected significantly (I/II--4.88 +/- 4.85 and III/IV 6.30 +/- 5.33 units p=0.2). A significant number of lymphoma patients need PRBC transfusions during chemotherapy. NHL patients and bone marrow involvement makes patients at higher risk for transfusions. In places, where blood bank support is not adequate, patients should be informed right from beginning to arrange donors for possible transfusions during chemotherapy.
Vilchez, Regis A.; Lednicky, John A.; Halvorson, Steven J.; White, Zoe S.; Kozinetz, Claudia A.; Butel, Janet S.
Systemic non-Hodgkin lymphoma (S-NHL) is a common malignancy during HIV infection, and it is hypothesized that infectious agents may be involved in the etiology. Epstein-Barr virus DNA is found in <40% of patients with AIDS-related S-NHL, suggesting that other oncogenic viruses, such as polyomaviruses, may play a role in pathogenesis. We analyzed AIDS-related S-NHL samples, NHL samples from HIV-negative patients, peripheral blood leukocytes from HIV-infected and -uninfected patients without NHL, and lymph nodes without tumors from HIV-infected patients. Specimens were examined by polymerase chain reaction analysis with use of primers specific for an N-terminal region of the oncoprotein large tumor antigen ( T-ag ) gene conserved among all three polyomaviruses (simian virus 40 [SV40], JC virus, and BK virus). Polyomavirus T-ag DNA sequences, proven to be SV40-specific, were detected more frequently in AIDS-related S-NHL samples (6 of 26) than in peripheral blood leukocytes from HIV-infected patients (6 of 26 vs. 0 of 69; p =.0001), NHL samples from HIV-negative patients (6 of 26 vs. 0 of 10; p =.09), or lymph nodes (6 of 26 vs. 0 of 7; p =.16). Sequences of C-terminal T-ag DNA from SV40 were amplified from two AIDS-related S-NHL samples. Epstein-Barr virus DNA sequences were detected in 38% (10 of 26) AIDS-related S-NHL samples, 50% (5 of 10) HIV-negative S-NHL samples, and 57% (4 of 7) lymph nodes. None of the S-NHL samples were positive for both Epstein-Barr virus DNA and SV40 DNA. Further studies of the possible role of SV40 in the pathogenesis of S-NHL are warranted.
Vilchez, Regis A.; Lednicky, John A.; Halvorson, Steven J.; White, Zoe S.; Kozinetz, Claudia A.; Butel, Janet S.
Systemic non-Hodgkin lymphoma (S-NHL) is a common malignancy during HIV infection, and it is hypothesized that infectious agents may be involved in the etiology. Epstein-Barr virus DNA is found in <40% of patients with AIDS-related S-NHL, suggesting that other oncogenic viruses, such as polyomaviruses, may play a role in pathogenesis. We analyzed AIDS-related S-NHL samples, NHL samples from HIV-negative patients, peripheral blood leukocytes from HIV-infected and -uninfected patients without NHL, and lymph nodes without tumors from HIV-infected patients. Specimens were examined by polymerase chain reaction analysis with use of primers specific for an N-terminal region of the oncoprotein large tumor antigen ( T-ag ) gene conserved among all three polyomaviruses (simian virus 40 [SV40], JC virus, and BK virus). Polyomavirus T-ag DNA sequences, proven to be SV40-specific, were detected more frequently in AIDS-related S-NHL samples (6 of 26) than in peripheral blood leukocytes from HIV-infected patients (6 of 26 vs. 0 of 69; p =.0001), NHL samples from HIV-negative patients (6 of 26 vs. 0 of 10; p =.09), or lymph nodes (6 of 26 vs. 0 of 7; p =.16). Sequences of C-terminal T-ag DNA from SV40 were amplified from two AIDS-related S-NHL samples. Epstein-Barr virus DNA sequences were detected in 38% (10 of 26) AIDS-related S-NHL samples, 50% (5 of 10) HIV-negative S-NHL samples, and 57% (4 of 7) lymph nodes. None of the S-NHL samples were positive for both Epstein-Barr virus DNA and SV40 DNA. Further studies of the possible role of SV40 in the pathogenesis of S-NHL are warranted.
Ikeda, Tatsuhiko; Bando, Hiroko; Iguchi, Akiko; Tanaka, Yuko; Tohno, Eriko; Hara, Hisato
Non-Hodgkin lymphoma (NHL) of the breast is a rare disease. Herein, we report a rare case of secondary involvement of the breast by NHL in a male patient and the ultrasound imaging findings. A 70-year-old man noticed an induration of the subareolar region of the right breast. He had been diagnosed as having mantle cell lymphoma 5 years before and treated with several series of chemoradiotherapy. On supine examination, palpation revealed bilateral breast enlargement, but detection of a lump was difficult. Ultrasonography showed a hypoechoic non-mass image-forming lesion in the subareolar region of the right breast. The final pathological diagnosis was recurrence of mantle cell lymphoma in the right breast. The diagnosis of malignant lymphoma of the breast by imaging modalities is difficult because there are no specific features. Breast lymphoma should be included with gynecomastia and breast cancer in the differential diagnosis of male patients with breast enlargement.
Cazals-Hatem, D; André, M; Mounier, N; Copin, M C; Divine, M; Berger, F; Bosly, A; Kerneis, Y; Brière, J; Quesnel, B; Diebold, J; Gaulard, P
Between 1987 and 1993, 77 of 2855 lymphomas included in the LNH87 protocol of the GELA as non-Hodgkin lymphoma (NHL) and reviewed by a panel of pathologists had a diagnosis changed to Hodgkin lymphoma (HL). Some of these lymphomas had been initially interpreted as anaplastic large-cell lymphoma Hodgkin-like (ALCL-HL subtype). The purpose of this study was to analyze the histologic pitfalls initially encountered, to define more clearly the diagnostic criteria of lymphomas placed in the gray zone around HL, and to follow the survival of these 77 patients affected with HL and initially treated with NHL regimens. The 77 cases of HL were reviewed by three hematopathologists and immunostained with a large panel of antibodies, including CD30, CD15, CD3, CD20, CD45, CD43, LMP-1, EMA, BNH-9, TiA1, and ALK1. Each case was classified according to the Lukes-Rye system and the British National Lymphoma Investigation (BNLI) grading. The initial clinical presentation of patients was analyzed, and the overall and event-free survival rates of the 77 patients were estimated. Among the 77 HLs, 46 were misinterpreted as NHL by primary individual pathologists (12 as ALCL, 8 as ALCL-HL, 12 as peripheral T-cell lymphoma (PTCL), 6 as B-cell lymphoma, and 8 as unclassifiable NHL). The other 31 cases had been first considered by the panel as consistent with ALCL-HL (n = 18) or with PTCL (n = 13) and were changed later in view of an immunophenotype concordant with HL. Fifty-five percent of the patients completed the full NHL treatment. The 5-year event-free and overall survival rates were 54% and 77%, respectively. The current results indicate that lymphomas initially called ALCL-HL should not be regarded as a variant of ALCL, but as HL. The clinical consequences of misdiagnoses seem to be a lower event-free survival rate compared with that of classical HL, probably because of more relapses of initially inappropriately treated HL.
Landgren, Ola; Tilly, Hervé
Non-follicular indolent subtypes of non-Hodgkin lymphoma (NHL), which include chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL) and marginal zone lymphomas (MZL), are a diverse group of disorders with different presenting features, behaviour patterns and treatment outcomes. Current knowledge of these subtypes is largely based on retrospective analyses. A precise diagnosis can be difficult to achieve, and specific diagnostic criteria are needed to more precisely define some of the rarer indolent tumors, such as nodal and splenic MZLs. Although some subtypes of NHL have a prolonged indolent course, with a good prognosis (e.g. SLL), others (e.g. nodal and splenic MZLs) can rapidly evolve into more aggressive subtypes. In asymptomatic patients, treatment may be deferred until the disease progresses and the patient becomes symptomatic. Universally accepted therapeutic guidelines do not exist, however, and carefully designed, prospective clinical studies are needed to further assess optimal therapeutic approaches for these indolent NHLs.
Leo, Qi Jie Nicholas; Ollberding, Nicholas J.; Wilkens, Lynne R.; Kolonel, Laurence N.; Henderson, Brian E.; Le Marchand, Loic; Maskarinec, Gertraud
Purpose Obesity increases mortality for several malignancies, but for non-Hodgkin lymphoma (NHL) the association between body mass index (BMI) and survival is unclear. We examined the association of pre-diagnostic BMI with overall and NHL-specific survival in the Multiethnic Cohort (MEC) study of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Caucasians. Methods MEC participants free of NHL at cohort entry and diagnosed with NHL during follow-up were included in the analyses (N=1331). BMI was based on self-reported weight and height at cohort entry and after 6.1 years of cohort entry. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) with BMI as time-varying exposure in relation to all-cause and NHL-specific mortality while adjusting for known confounders. Results The mean age at NHL diagnosis was 70.5 (range 45–89) years. After a mean follow-up of 4.3±3.5 years, 667 deaths including 450 NHL-specific deaths occurred. In multivariable models, obese patients (BMI ≥30.0 kg/m2) had higher all-cause (HR=1.46, 95%CI 1.13–1.87) and NHL-specific (HR=1.77, 95%CI 1.30–2.41) mortality compared to patients with high-normal BMI (22.5–24.9 kg/m2). For overweight patients (BMI=25.0–29.9 kg/m2), the respective HRs were 1.21 (95%CI 0.99–1.49) and 1.36 (95%CI 1.06–1.75). Cases with low-normal BMI (<22.5 kg/m2) experienced a significant 45% higher all-cause and a 40% higher NHL-specific mortality. After stratification by NHL type, the adverse effect of BMI was stronger for chronic lymphocytic leukemia/small lymphocytic lymphoma than for diffuse large B-cell lymphoma and follicular lymphoma. Conclusions Pre-diagnostic BMI may be a suitable prognostic marker for NHL patients. PMID:25070667
Souza, Bruna Maria Bereta; De Vito, Fernanda Bernadelli; Calado, Marianna Licati; Silva, Marcos Vinícius; Oliveira, Leonardo Rodrigues; Rodrigues-Júnior, Virmondes; Moraes-Souza, Helio
This study quantified the perforin and granzyme B in patients with non-Hodgkin lymphoma (NHL) at the time of diagnosis. Protein quantification was performed by flow cytometry. NHL patients had a higher number of cytotoxic T lymphocytes (CTLs) expressing perforin as well as a greater number of activated CTLs than the control group. However, intracellular perforin levels in natural killer cells were lower in the NHL patients compared to the control group. Quantitative real time PCR showed that patients had more expression of perforin and granzyme B transcripts compared to the control group. In addition, patients who had expression of both genes below the median found for the NHL group had lower survival rates. Considering this, we believe that perforin and granzyme B are potential prognostic markers in NHL and thus it is fundamental to pay attention to their expressions in these patients.
Rees, Chris A; Keating, Elizabeth M; Lukolyo, Heather; Danysh, Heather E; Scheurer, Michael E; Mehta, Parth S; Lubega, Joseph; Slone, Jeremy S
Children with human immunodeficiency virus (HIV) have an increased risk of developing Kaposi Sarcoma (KS) and non-Hodgkin lymphoma (NHL) compared to HIV-negative children. We compiled currently published epidemiologic data on KS and NHL among children in sub-Saharan Africa (SSA). Among countries with available data, the median incidence of KS was 2.05/100,000 in the general pediatric population and 67.35/100,000 among HIV-infected children. The median incidence of NHL was 1.98/100,000 among the general pediatric population, while data on NHL incidence among HIV-infected children were lacking. Larger regional studies are needed to better address the dearth of epidemiologic information on pediatric KS and NHL in SSA. © 2016 Wiley Periodicals, Inc.
Karunanayake, Chandima P; Dosman, James A; Pahwa, Punam
Objectives: The objective was to examine the association between non-Hodgkin's lymphoma (NHL) and farming-related activities, gender, pesticides exposure, and exposure to chemicals other than pesticides in Saskatchewan. Materials and Methods: Male and female study participants were taken from two separate case-control studies conducted in Saskatchewan province, Canada. A case was defined as any man or woman aged 19 years and older with a first diagnosis of NHL registered by the Saskatchewan Cancer Agency during the study period. Conditional logistic regression was used to fit the statistical models. Results: Farming exposure and exposure to pesticides-contaminated cloths were related to an increased risk of NHL. Exposure to pesticides was strongly associated with an increased risk of NHL, especially for men. Conclusion: For men, the incidence of NHL was associated with exposure to pesticides after adjusting for other independent predictors. PMID:24872670
Ott, G; Kalla, J; Steinhoff, A; Rosenwald, A; Katzenberger, T; Roblick, U; Ott, M M; Müller-Hermelink, H K
The genetic background of extranodal marginal zone B-cell non-Hodgkin's lymphoma (NHL) of mucosa-associated lymphoid tissue (MALT) type is poorly understood. In contrast to most entities of primary nodal lymphomas, few cytogenetic data are available, and gene rearrangements frequently encountered in and highly characteristic of certain entities of systemic NHL are absent in this type of lymphoma. Recently, it was suggested that MALT-type NHLs are associated with certain numerical chromosome aberrations and especially with trisomy 3. We performed an extensive study using a sensitive double (bicolor) fluorescence in situ hybridization technique for the analysis of trisomies for chromosomes 3, 7, 12, and 18 in 60 samples of low-grade and 45 high-grade MALT-type tumors. In the low-grade cases, trisomy 3 was found in a frequency of only 20%. High-grade lymphomas of MALT type were associated with trisomies 3, 7, 12, and 18 in 36, 20, 18, and 13% of the cases, respectively. Whereas no difference was encountered for trisomy 3 in primary and secondary/simultaneous high-grade lymphomas, +7 and +12 were associated with primary lymphomas, and a +18 was predominantly found in secondary/simultaneous high-grade NHL. These results challenge earlier reports describing a high frequency of +3 in low-grade MALT-type NHL and indicate a possibly different genetic evolution pattern of primary and secondary/simultaneous high-grade lymphomas of primary mucosal origin.
Diumenjo, Maria C; Abriata, Graciela; Forman, David; Sierra, Monica S
The burden of non-Hodgkin lymphoma (NHL) has increased in some Central and South American countries. We describe the current patterns and trends in NHL incidence and mortality in Central and South America. We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries, and national-level cancer mortality data from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and mortality rates (ASMRs) per 100,000 person-years for 2003-2007, and presented distributions by histological subtype. NHL incidence and mortality rates varied between countries by 2-8- and 6-fold, respectively. ASRs per 100,000 ranged from 1.4 to 10.9 among males and 1.3-9.2 among females. Corresponding ASMRs were between 0.5 and 4.8 among males and between 0.5 and 3.0 among females. The highest incidence was observed in Uruguay (males), Ecuador, Peru and Colombia (males). The highest mortality was seen in Uruguay and Costa Rica. Trends in NHL incidence and mortality in Argentina, Brazil, Chile and Costa Rica did not show marked changes. B-cell neoplasms and NHL not otherwise specified (NOS) accounted for 44% and 34% of all NHL cases. Diffuse large B-cell lymphoma, NOS, was the most frequent histological subtype. The geographic variations in NHL rates may partially reflect differences in registration practices, disease classification, diagnostic practice, and death certification quality. There is a need for high-quality data and improvements in the accuracy of NHL histological diagnosis. Given the expected increase in NHL, careful monitoring of rates remains a priority to guide cancer control programs. Copyright © 2016 International Agency for Research on Cancer. Published by Elsevier Ltd.. All rights reserved.
Sandlund, J T; Raimondi, S C
A 19-year-old male was diagnosed with stage III abdominal small noncleaved cell (SNCC) non-Hodgkin lymphoma (NHL). Cytogenetic evaluation of the tumor revealed a complex karyotype which included the t(8;14)(q24;q32), classically associated with this lymphoma histotype, and an extra Y chromosome. After remission was obtained, cytogenetic analysis of bone marrow cells and PHA-stimulated peripheral blood lymphocytes disclosed a normal karyotype except for the persistence of an extra Y chromosome, diagnostic of the XYY syndrome. This is the first reported case of SNCC NHL in an adolescent with the XYY syndrome.
Boccolini, Patricia de M M; Boccolini, Cristiano Siqueira; Chrisman, Juliana de Rezende; Markowitz, Steven B; Koifman, Sergio; Koifman, Rosalina Jorge; Meyer, Armando
Brazil is one of the major pesticide consumers in the world. The continuous exposure to these substances may be etiologically associated with the development of Non-Hodgkin's Lymphoma (NHL). Estimate the correlation between the per capita sales of pesticides in 1985 (exposure) and NHL mortality rates between 1996 and 2005 (outcome), by Brazilian micro-regions. In this ecological descriptive study, the per capita consumption of pesticides in 1985 was used as a proxy of the population exposure to these chemicals in Brazil. All deaths by NHL occurred in the 446 non-urban micro-regions, between 1996 and 2005, among individuals with ages between 20 and 69, of both sexes, were retrieved from the Brazilian Mortality Information System. Micro-regions were then categorized into low, medium, high and very high pesticide consumption, according to the quartiles of per capita consumption of pesticides. NHL mortality rates and rate ratios for each quartile were obtained using the lowest quartile as reference. In addition, the Spearman's correlation coefficient between pesticide consumption and NHL mortality rates was estimated. A moderate correlation between per capita pesticides consumption and standardized mortality rate for NHL was observed (r=0.597). In addition, using the lowest quartile of pesticide consumption as a reference, the higher the quartile of pesticide consumption, the higher was NHL mortality risk: men - (second quartile - MRR=1.69, CI 95% 1.68-1.84; third quartile - MRR=2.41, CI 95% 2.27-2.57; fourth quartile - MRR=2.92, CI 95% 2.74-3.11) and females (second quartile - MRR=1.87, CI 95% 1.69-2.06; third quartile - MRR=2.28, IC 95% 2.10-2.47; fourth quartile - MRR=3.20; CI 95% 2.98-3.43). Our results suggest that pesticide exposure may play a role in the etiology of NHL. Copyright © 2013 Elsevier GmbH. All rights reserved.
Sørensen, Mette; Harbo Poulsen, Aslak; Ketzel, Matthias; Oksbjerg Dalton, Susanne; Friis, Søren; Raaschou-Nielsen, Ole
Exposure to traffic noise may result in stress and sleep disturbances, which have been associated with impairment of the immune system. People with weakened immune systems are known to have a higher risk for non-Hodgkin lymphoma (NHL). We aimed to determine whether traffic noise was associated with risk for NHL in a nationwide case-control study. We identified 2753 cases aged 30-84 years with a primary diagnosis of NHL in Denmark between 1992 and 2010. For each case we selected two random population controls, matched on sex and year of birth. Road traffic and railway noise were calculated, and airport noise was estimated for all present and historical residential addresses of cases and controls from 1987 to 2010. Associations between traffic noise and risk for NHL were estimated using conditional logistic regression, adjusted for disposable income, education, cohabiting status and comorbidity. We found that a 5-year time-weighted mean of road traffic noise above 65 dB was associated with an 18% higher risk for NHL (95% confidence interval (CI) 1.01-1.37) when compared to road traffic noise below 55 dB, whereas for exposure between 55 and 65 dB no association was found (odds ratio: 0.98; 95% CI: 0.88-1.08). In analyzes of NHL subtypes, we found no association between road traffic noise and risk for T-cell lymphoma, whereas increased risks for B-cell lymphoma and unspecified lymphomas were observed at exposures above 65 dB. In conclusion, our nationwide study may indicate that high exposure to traffic noise is associated with higher NHL risk.
Hodgkin's lymphoma (Hodgkin's disease) Overview By Mayo Clinic Staff Hodgkin's lymphoma — formerly known as Hodgkin's disease — is a cancer ... is part of your immune system. In Hodgkin's lymphoma, cells in the lymphatic system grow abnormally and ...
Caporale, Manlio Fabio; Gambino, Giovanni Francesco; Larosa, Fabio Saverio; Del Buono, Angelo; Di Segni, Federico
Summary The non-Hodgkin lymphoma (NHL) is one of the most common shoulder neoplasms, especially the diffuse large B cell lymphoma (DLBCL). We report a rare case of shoulder pain in a 80-year-old man presenting with a six-month history of continuous severe pain to the right shoulder. Routine laboratory studies were normal. Shoulder MRI showed an in-growing inhomogeneous lesion in the anteromedial aspect of the right humeral head extended within the cortical bone of the humerus (osteolitic lesion), next to the surrounding soft tissues. He also underwent shoulder arthroscopy: the intra-articular involvement of the shoulder was therefore excluded. A percutaneous bone biopsy performed on the same day was diagnostic for lymphoma. Three days later, the patient underwent surgical excision of the mass; a reverse shoulder prosthesis was then implanted (Aequalis reversed prosthesis). The patient started chemiotherapy according with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, but did not tolerate it because of the sudden onset of herpes zoster. At 9-month follow-up, the patient is doing well, with fair range of motion, due to the delay of rehabilitation, but no shoulder pain and no evidence of local or systemic recurrence. A painful shoulder may be due to lymphoma even in the absence of classical symptoms. In suspected patients, plain radiographs should be followed by magnetic resonance imaging and bone biopsy. Tumor removal and shoulder arthroplasty can be an effective therapy. Given the devastating side effects of adjuvant chemotherapy, we do not recommend it in elderly patients. PMID:24367786
Herrero-Vicent, Carmen; Machado, Isidro; Illueca, Carmen; Avaria, Amparo; Salazar, Claudia; Hernandez, Abraham; Sandiego, Sergio; Lavernia, Javier
Mantle cell lymphoma (MCL) is an infrequent subtype of non-Hodgkin’s lymphoma (NHL) and represents between 4–8% of adult lymphomas. Recently an increase in its incidence to 1–2 cases/100,000 inhabitants/year has been observed. The first line of treatment is based on chemoimmunotherapy and depends on age and the initial stage at diagnosis. There are no second line or successive treatments. There are currently several drugs available that provide acceptable results. PMID:27110283
Nosari, A; Cantoni, S; Oreste, P; Schiantarelli, C; Landonio, G; Alexiadis, S; Gargantini, L; Caggese, L; Gambacorta, M; Morra, E
We compared the clinical and pathological features of 10 HIV+ CD30+ anaplastic large cell lymphoma (ALCL) patients with 28 HIV+ CD30- non-Hodgkin's lymphoma (NHL) patients. The incidence of ALCL among 38 HIV+ systemic NHL patients was 26%. Clinical features were similar in all the HIV-related NHL cases, but ALCL patients seemed to differ from HIV+ CD30- systemic NHL only in the greater frequency of lung tumours (40% v 21%) without concomitant mediastinal mass, bone marrow (75% v 18%) and gastroenteric involvement (40% v 25%). Among the HIV+ ALCL patients, histologic subtypes did not differ in frequency from ALCL in the general population. The B phenotype was predominant (50%) as in other HIV-related NHL. EBV genoma, studied in all HIV+ ALCL patients, was present in 3/10 by in situ hybridization (ISH) and in 5/10 cases using PCR. The clinical course of lymphomas was similar in CD30 positive and negative NHL patients. Overall survival also was short in our series, particularly in HIV+ ALCL (84 v 188 d), probably because of profound immunodepression of the ALCL patients. Our findings suggest that severe immunodepression due to HIV infection determines-more than any other factor-the clinical features of HIV+ ALCL, making them very similar to those of other high-grade systemic HIV+ NHL.
Silverton, Alexandra; Gunthel, Clifford; Adamski, Marylyn; Mosunjac, Marina; Nguyen, Minh Ly
People living with HIV/AIDS (PLWHA) are at a higher risk of developing non-Hodgkin lymphoma (NHL). The influence of combined antiretrovirals (cART) on the presentation, treatment, and outcomes of HIV-associated NHL (HIV-NHL) warrants further investigation. We performed a retrospective analysis of PLWHA diagnosed with NHL who received care at the Infectious Diseases Ponce de Leon Center in Atlanta, Georgia, from January 1, 2004 to December 31, 2010. Thirty-five patients with HIV-NHL were identified. Among these patients, 7 had Burkitt lymphoma (BL), 20 had diffuse large B cell lymphoma (DLBCL), 7 had plasmablastic lymphoma (PL), and 1 had primary effusion lymphoma (PEL). The majority of patients (82.9%) presented with advanced disease, and 63% were not on ART at diagnosis. Despite having good performance status at presentation, the majority of patients presented with high International Prognostic Index (IPI) scores. There were differences between the histologic subtypes of NHL in regard to treatment, complications, and outcomes. The median CD4 lymphocyte count at diagnosis was 110 cells/mm(3) for patients with DLBCL [interquartile range (IQR): 66, 203], 165 cells/mm(3) for Burkitt lymphoma (IQR: 36, 199), and 98 cells/mm(3) for plasmablastic lymphoma (IQR: 34, 214). Overall, patients completed 67% of planned chemotherapy cycles. Common causes for chemotherapy termination were persistent myelosuppression (18.2%), social factors (22.7%), and disease progression (36.4%). Social factors included lack of transportation, substance abuse, unstable housing, and poor adherence. Two-year overall survival was 40% for all HIV-NHL. Half of the patients with DLBCL (n=10), 42% of patients with PL (n=3), and only 14.3% of patients with BL (n=1) were alive at 2 years. Among the overall survivors at 2 years, 85.7% had CD4 >200 cells/mm(3) and 78.6% had undetectable HIV viral loads (VL) at that time.
Marsan, Felipe Pereira Marcos; Arita, Emiko Saito
Non-Hodgkin's lymphoma (NHL) is a lymphoproliferative disorder, from a subgroup of heterogeneous hematologic malignancies; the term “extranodal” refers to malignant involvement of tissues other than lymph nodes, tonsils, spleen, pharyngeal lymphatic ring, or thymus. Only 0.6% of all NHL are at mandible alone, and it may involve the inferior alveolar canal. We describe a case of bilateral enlargement of the mandibular canal without symptomatology, which was shown in a panoramic radiograph and cone beam computed tomography in a rehabilitation routine exam, as an early sign of primary extranodal NHL. PMID:28299210
Munhoz, Luciana; Marsan, Felipe Pereira Marcos; Arita, Emiko Saito
Non-Hodgkin's lymphoma (NHL) is a lymphoproliferative disorder, from a subgroup of heterogeneous hematologic malignancies; the term "extranodal" refers to malignant involvement of tissues other than lymph nodes, tonsils, spleen, pharyngeal lymphatic ring, or thymus. Only 0.6% of all NHL are at mandible alone, and it may involve the inferior alveolar canal. We describe a case of bilateral enlargement of the mandibular canal without symptomatology, which was shown in a panoramic radiograph and cone beam computed tomography in a rehabilitation routine exam, as an early sign of primary extranodal NHL.
Aminian, Omid; Abedi, Ali; Chavoshi, Farzaneh; Ghasemi, Mohammad; Rahmati-Najarkolaei, Fatemeh
Background Lymphoma is a malignancy, arises from lymphoid tissue. Nowadays, it is the ninth most common cancer in Iran. The risk factors of malignant lymphomas have not well determined, but since 20 years ago till now, too many epidemiological researches have been concerning either Non-Hodgkin Lymphoma (NHL) or Hodgkin's Disease (HD). It is a common usual hypothesis that idiosyncratic reaction to common physical, chemical, and viral agents could lead to lymphoma without obvious immune deficiency. Some occupations has reported to cause increasing "NHL" risks, such as rubber industry, veterinaries, uranium mining, metal working, asbestos exposing, farming, textile industry, and benzene exposing. The roles of ionizing radiation, benzene and other environmental agents have not been clear, because of the lack of confirmed evidences for relation between the occupational and environmental agents with "HD". Methods A case-control study with 150 cases of malignant lymphoma and 150 controls have performed in Tehran. Data have selected through face-to-face interviews about the medical and occupational histories. Results In this study, there was a significantly increased risk for Non-Hodgkin Lymphoma in these occupations; welders, metal workers, founders, aluminium workers OR=4.6 [Confidence Interval (CI): 1.47-14.35] and increased risk for Hodgkin's Disease in drivers OR=2.34 [(CI):0.86-6.35]. We have found out decreased NHL risk in office workers OR=0.54 [(CI):0.29-1.02] and also found out a non-significant increased NHL risk in farmers OR=1.58 [(CI):0.82-3.03]. In this study, we have found no relation between smoking and HD, or NHL. Conclusion The results of this study suggest that several occupations could alter the risk of Non-Hodgkin Lymphoma and Hodgkin's Disease. PMID:25352969
Otter, R.; Bieger, R.; Kluin, P. M.; Hermans, J.; Willemze, R.
In a population-based registry of 580 patients with non-Hodgkin's lymphoma (NHL) 54 patients had a primary gastric lymphoma, 42 an intestinal, 113 a primary extranodal lymphoma localised elsewhere than in the gastrointestinal tract and 371 a primary nodal NHL. Histological specimens were reviewed by a panel of pathologists and classified according to the Kiel classification and the International Working Formulation. The 4-year survival rates for primary gastric, intestinal, other extranodal and nodal NHL ranged from 50 to 60%; the 4-year recurrence-free survival rates were 50%, 35%, 19% and 19%, respectively. Among patients with localised intermediate-grade disease survival for those with gastric NHL was better than for those with intestinal lymphoma. Because it is population-based, our study cohort was not subjected to exclusion due to age, performance scale, etc. and therefore provides a more realistic picture of the occurrence and presentation of as well as prognosis for lymphoma in the population. PMID:2803951
Shome, Durjoy K; George, Sara M; Al-Hilli, Fayek; Satir, Ali A
To determine the clinicopathologic features of malignant lymphomas in Bahraini patients. A retrospective hospital-based study was conducted. All new cases of malignant lymphoma diagnosed during the period January 1996 to December 2001 at the Salmaniya Medical Complex in Bahrain were included in the study. Seventy-two cases met the inclusion criteria. This included 24 (33.3%) cases of Hodgkin's disease (HD) and 48 (66.7%) cases of Non-Hodgkin lymphomas (NHL). A young age at presentation (median 20 years) mixed cellularity histology, lack of extra nodal involvement and rare marrow involvement characterized HD. The majority of NHL showed diffuse high or intermediate grade lesions. A high number of primary extra nodal neoplasms (41.7% of NHL) and frequent involvement of the gastrointestinal tract with Helicobacter pylori-associated gastric lymphomas were notable features among NHL cases. Immunohistochemical staining in 30 cases showed 26 cases (86.7%) of B cell and 4 cases of T cell origin. The study highlights common features that distinguish malignant lymphoma reported from countries of the Arabian Gulf region. This pattern distinguishes them from the disease encountered in the Western world.
Morimoto, Yukiko; Ollberding, Nicholas J; Cooney, Robert V; Wilkens, Lynne R; Franke, Adrian A; Le Marchand, Loïc; Goodman, Marc T; Hernandez, Brenda Y; Kolonel, Laurence N; Maskarinec, Gertraud
Compromised immunity and chronic inflammation are thought to contribute to the development of non-Hodgkin lymphoma (NHL). Because tocopherols protect cells through antioxidant mechanisms, they may play a role in NHL etiology. This nested case-control study within the Multiethnic Cohort examined the association of prediagnostic serum tocopherols levels measured in 271 NHL cases and 538 matched controls by high-pressure liquid chromatography/photodiode array detection with NHL risk. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI). We observed U-shaped associations with NHL for total and α-tocopherols [Ptrend < 0.01 for polynomial terms (3 df)]. The ORs (95% CI) for total tocopherols, which consisted primarily of α-tocopherol, were 0.41 (0.25-0.68), 0.52 (0.32-0.85), 0.39 (0.23-0.65), and 0.78 (0.47-1.29) for the second to fifth quintiles as compared with the first. The risk estimates were similar for α-tocopherol but nonsignificant for β- and γ-tocopherol combined and for γ-tocopherol. Adjustment for serum lipids strengthened the nonlinear associations for total and α-tocopherols. Serum total tocopherol levels were higher for vitamin E supplement users at cohort entry than nonusers (21.32 ± 9.04 vs. 17.72 ± 7.43 μg/mL; P < 0.0001), but supplement use was not associated with NHL risk. No heterogeneity in risk estimates was detected by sex, ethnicity, vitamin E supplement use, or NHL subtype. Circulating tocopherols, at levels likely reflecting adequate dietary intakes, may be protective against NHL, whereas higher intakes from supplementation may not be beneficial. The association between serum tocopherol levels and NHL risk provides possible new insights into the etiology of NHL. ©2013 AACR.
Hofmann, Andreas; Thiesler, Thore; Gerrits, Bertran; Behnke, Silvia; Sobotzki, Nadine; Omasits, Ulrich; Bausch-Fluck, Damaris; Bock, Thomas; Aebersold, Ruedi; Moch, Holger; Tinguely, Marianne; Wollscheid, Bernd
Classical Hodgkin lymphoma (cHL) is characterized by a low percentage of tumor cells in a background of diverse, reactive immune cells. cHL cells commonly derive from preapoptotic germinal-center B cells and are characterized by the loss of B-cell markers and the varying expression of other hematopoietic lineage markers. This phenotypic variability and the scarcity of currently available cHL-specific cell surface markers can prevent clear distinction of cHL from related lymphomas. We applied the cell surface capture technology to directly measure the pool of cell surface exposed proteins in four cHL and four non-Hodgkin lymphoma (NHL) cell lines. More than 1000 membrane proteins, including 178 cluster of differentiation annotated proteins, were identified and allowed the generation of lymphoma surfaceome maps. The functional properties of identified cell surface proteins enable, but also limit the information exchange of lymphoma cells with their microenvironment. Selected candidate proteins with potential diagnostic value were evaluated on a tissue microarray (TMA). Primary lymphoma tissues of 126 different B cell-derived lymphoma cases were included in the TMA analysis. The TMA analysis indicated gamma-glutamyltranspeptidase 1 as a potential additional marker that can be included in a panel of markers for differential diagnosis of cHL versus NHL. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Travis, L.B.; Curtis, R.E.; Boice, J.D. Jr.; Hankey, B.F.; Fraumeni, J.F. Jr. )
The risk of second malignancies following non-Hodgkin's lymphoma (NHL) was estimated in 29,153 patients diagnosed with NHL between 1973 and 1987 in one of nine areas participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Compared with the general population, NHL patients were at a significantly increased risk of developing second cancers (observed/expected (O/E) = 1.18; O = 1231). The O/E ratio increased significantly with time to reach 1.77 in 10-year survivors. Significant excesses were noted for acute nonlymphocytic leukemia (O/E = 2.88), cancers of the bladder (O/E = 1.30), kidney (O/E = 1.47), and lung (O/E = 1.57), malignant melanoma (O/E = 2.44), and Hodgkin's disease (O/E = 4.16). Chemotherapy appeared related to subsequent acute nonlymphocytic leukemia (ANLL) and bladder cancer. Radiation therapy was associated with ANLL and possibly cancers of the lung, bladder, and bone. Malignant melanoma was not clearly related to initial NHL treatment.
Diver, W Ryan; Teras, Lauren R; Gaudet, Mia M; Gapstur, Susan M
Little is known about the risk of non-Hodgkin lymphoma (NHL) in nonsmokers who are exposed to environmental tobacco smoke (ETS). Previous research on NHL and ETS has not included men or examined doses of ETS exposure during childhood. The Cancer Prevention Study II Nutrition Cohort collected information on smoking habits and exposure to ETS during childhood and adulthood. Among 61,326 never-smoking men and women, 884 incident cases of NHL were identified between 1992 and 2009. Multivariable-adjusted relative risks and 95% confidence intervals were calculated using Cox proportional hazards regression to identify associations between ETS and NHL risk. Compared with no exposure to ETS as a child or an adult, childhood and/or adult ETS exposure was not associated with NHL overall. There was a positive association between the number of smokers in the house as a child (P for trend = 0.05) and exposure to 6 or more hours per week of ETS as an adult (relative risk = 2.37, 95% confidence interval: 1.12, 5.04) with follicular lymphoma risk. Adult ETS exposure was associated with a lower risk of diffuse large B-cell lymphoma (relative risk = 0.68, 95% confidence interval: 0.48, 0.97). This study suggests that adult and childhood ETS exposure may affect the risk of NHL, and that the associations differ by histological subtype.
Sergentanis, Theodoros N; Kanavidis, Prodromos; Michelakos, Theodoros; Petridou, Eleni Th
The aim of the present meta-analysis was to examine comprehensively the association between smoking and lymphoma [Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL)] in adults. Eligible studies were identified, and pooled-effect estimates (odds ratios and relative risks) were calculated for ever, current and former smoking, separately by lymphoma subtype and gender. Metaregression analysis with percentage of male patients, mean age, duration (years of smoking), intensity (pack-years and cigarettes per day) and years since quitting was carried out. Out of the 50 eligible articles, 41 used a case-control design (20 143 NHL cases, 4340 HL cases and 61 517 controls), whereas nine used a cohort design (5748 incident NHL cases, 334 HL cases, total cohort size comprising 1 530 833 smokers). Ever smoking was associated with increased risk for NHL [pooled-effect estimate=1.05, 95% confidence interval (CI): 1.00-1.09] mainly because of the association with T-NHL (pooled-effect estimate=1.23, 95% CI: 1.09-1.38). Ever smoking was also associated with increased risk for HL (pooled-effect estimate=1.15, 95% CI: 1.02-1.30); sizeable associations were observed regarding both nodular sclerosis and mixed cellularity subtypes. Although male study arms pointed to predominantly increased risk for HL, metaregression did not confirm the male preponderance. Dose-response patterns were particularly evident for HL. Cigarette smoking seems to be associated with increased lymphoma risk, especially HL and T-NHL. Further well-designed studies seem to be needed so as to investigate the risk thoroughly, especially for T-NHL subentities, and the extent to which confounding may interfere with gender-related disparities.
Paradisi, Roberto; Vicenti, Rossella; Macciocca, Maria; Seracchioli, Renato; Rossi, Stefania; Fabbri, Raffaella
To investigate the ovarian reserve in female lymphoma patients and the potential relationships with the cytokine network. Age-matched control study. Women's university hospital. Seventy-three lymphoma patients (57 with classic Hodgkin lymphoma [HL] and 16 with non-Hodgkin lymphoma [NHL]), approaching our center for ovarian tissue cryopreservation (study group) were compared with 25 age-matched healthy volunteers (control group). Measurements of antimüllerian hormone (AMH), soluble interleukin-2 receptor (SIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) levels. The AMH and cytokine levels of the lymphoma patients and the healthy volunteers were compared. Correlations between AMH with SIL-2R, IL-6, and IL-8 levels were performed. The AMH showed significant lower concentrations in lymphoma patients than in the control group. Higher significant concentrations in lymphoma patients than in control group were found for SIL-2R and IL-6. No differences were observed comparing HL and NHL groups and within the stages of HL group for AMH and all the cytokines analyzed. Finally, significant inverse correlations were observed in lymphoma patients between AMH and SIL-2R, IL-6, and IL-8 levels, but not with TNF-α levels. Positive correlations between SIL-2R with IL-6, and IL-6 with IL-8 were also shown. In patients with HL or NHL at baseline the cytokine network is particularly active and the ovarian reserve is reduced. A strong negative correlation between AMH and SIL-2R, IL-6, and IL-8 has been also evidenced. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
't Mannetje, Andrea; De Roos, Anneclaire J; Boffetta, Paolo; Vermeulen, Roel; Benke, Geza; Fritschi, Lin; Brennan, Paul; Foretova, Lenka; Maynadié, Marc; Becker, Nikolaus; Nieters, Alexandra; Staines, Anthony; Campagna, Marcello; Chiu, Brian; Clavel, Jacqueline; de Sanjose, Silvia; Hartge, Patricia; Holly, Elizabeth A; Bracci, Paige; Linet, Martha S; Monnereau, Alain; Orsi, Laurent; Purdue, Mark P; Rothman, Nathaniel; Lan, Qing; Kane, Eleanor; Costantini, Adele Seniori; Miligi, Lucia; Spinelli, John J; Zheng, Tongzhang; Cocco, Pierluigi; Kricker, Anne
Various occupations have been associated with an elevated risk of non-Hodgkin lymphoma (NHL), but results have been inconsistent across studies. We investigated occupational risk of NHL and of four common NHL subtypes with particular focus on occupations of a priori interest. We conducted a pooled analysis of 10,046 cases and 12,025 controls from 10 NHL studies participating in the InterLymph Consortium. We harmonized the occupational coding using the 1968 International Standard Classification of Occupations (ISCO-1968) and grouped occupations previously associated with NHL into 25 a priori groups. Odds ratios (ORs) adjusted for center, age, and sex were determined for NHL overall and for the following four subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and peripheral T-cell lymphoma (PTCL). We confirmed previously reported positive associations between NHL and farming occupations [field crop/vegetable farm workers OR = 1.26; 95% confidence interval (CI): 1.05, 1.51; general farm workers OR = 1.19; 95% CI: 1.03, 1.37]; we also confirmed associations of NHL with specific occupations such as women's hairdressers (OR = 1.34; 95% CI: 1.02, 1.74), charworkers/cleaners (OR = 1.17; 95% CI: 1.01, 1.36), spray-painters (OR = 2.07; 95% CI: 1.30, 3.29), electrical wiremen (OR = 1.24; 95% CI: 1.00, 1.54), and carpenters (OR = 1.42; 95% CI: 1.04, 1.93). We observed subtype-specific associations for DLBCL and CLL/SLL in women's hairdressers and for DLBCL and PTCL in textile workers. Our pooled analysis of 10 international studies adds to evidence suggesting that farming, hairdressing, and textile industry-related exposures may contribute to NHL risk. Associations with women's hairdresser and textile occupations may be specific for certain NHL subtypes. 't Mannetje A, De Roos AJ, Boffetta P, Vermeulen R, Benke G, Fritschi L, Brennan P, Foretova L, Maynadié M, Becker N, Nieters A
Khelfa, Yousef; Lebowicz, Yehuda; Jamil, Muhammad Omer
Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), accounting for approximately 25% of NHL cases. It is a heterogeneous group of diseases. BCL2, BCL6, and MYC are the most frequent mutated genes in DLBCL. Double-hit lymphoma (DHL) is an aggressive form of DLBCL with an unmet treatment need, in which MYC rearrangement is present with either BCL2 or BCL6 rearrangement. Patients typically present with a rapidly growing mass with B symptoms. DHL has been linked to very poor outcomes when treated with RCHOP chemotherapy. Dual-expressor lymphoma is a form of DLBCL with overexpression of MYC and BCL2/BCL6. There is a paucity of prospective trials evaluating the treatment of DHL. Retrospective series suggest that more aggressive treatment regimens such as DA-EPOCH and hyper CVAD may be more efficacious. However, there remains a lack of consensus regarding optimal treatment for DHL. Further clinical trials, including novel agents, are needed for improvement in outcomes.
El-Galaly, Tarec Christoffer; Hutchings, Martin
Optimal lymphoma management requires accurate pretreatment staging and reliable assessment of response, both during and after therapy. Positron emission tomography with computerized tomography (PET/CT) combines functional and anatomical imaging and provides the most sensitive and accurate methods for lymphoma imaging. New guidelines for lymphoma imaging and recently revised criteria for lymphoma staging and response assessment recommend PET/CT staging, treatment monitoring, and response evaluation in all FDG-avid lymphomas, while CT remains the method of choice for non-FDG-avid histologies. Since interim PET imaging has high prognostic value in lymphoma, a number of trials investigate PET-based, response-adapted therapy for non-Hodgkin lymphomas (NHL). PET response is the main determinant of response according to the new response criteria, but PET/CT has little or no role in routine surveillance imaging, the value which is itself questionable. This review presents from a clinical point of view the evidence for the use of imaging and primarily PET/CT in NHL before, during, and after therapy. The reader is given an overview of the current PET-based interventional NHL trials and an insight into possible future developments in the field, including new PET tracers.
Learning from the failures of drug discovery in B-cell non-Hodgkin lymphomas and perspectives for the future: chronic lymphocytic leukemia and diffuse large B-cell lymphoma as two ends of a spectrum in drug development.
Kubuschok, Boris; Trepel, Martin
Despite substantial recent advances, there is still an unmet need for better therapies in B-cell non Hodgkin lymphomas (B-NHL), especially in relapsed or refractory disease. Many novel targeted drugs have been developed based on a better molecular understanding of B-NHL. Areas covered: This article focuses on chronic lymphocytic leukemia (CLL) as a representative for indolent lymphomas and paradigmatic for the tremendous progress in treating B-NHL on the one hand and diffuse large B-cell lymphoma (DLBCL) as a representative for aggressive lymphomas and paradigmatic for many unsolved problems in lymphoma treatment or the other hand. We highlight salient points in current therapies targeting genetic, epigenetic, immunological and microenvironmental alterations. Possible reasons for drug failure in clinical trials like tumor heterogeneity, clonal evolution and drug resistance mechanisms are discussed. Based thereon, some perspectives for further drug discovery are given. Expert opinion: In view of the pathogenetic complexity of lymphomas, therapies targeting exclusively a single alteration may fail because resistance mechanisms are present either initially or evolve during treatment. Therefore, future therapies in B-NHL may have to target the greatest possible number of genetic, immunological or epigenetic alterations still allowing tolerability and to monitor these alterations during therapy.
Parzen, Jacob S.; Bates, James E.; Milano, Michael T.
Background Survivors of malignant thymoma (MT) are at an increased risk of developing subsequent neoplasms. We compare overall survival (OS) between MT survivors who developed non-Hodgkin’s lymphoma (NHL) or non-small cell lung cancer (NSCLC), and patients with first primary NHL (NHL-1) or NSCLC (NSCLC-1), respectively. Methods Using the population-based Surveillance, Epidemiology, and End Results (SEER) database for 1973 through 2013, 273,313 patients who had NHL-1, 21 patients with MT-NHL, 566,819 patients with NSCLC-1, and 38 patients with MT-NSCLC were identified. Univariate and multivariate models were used to assess the impact of various factors on OS. Results The observed-to-expected ratio among MT patients was 2.63 [95% confidence interval (95% CI), 1.40−4.49; P<0.05] for NHL and 1.90 (95% CI, 1.33–3.63; P<0.05) for lung cancer. On univariate analysis, MT history did not worsen OS for NHL [hazard ratio (HR), 1.46; 95% CI, 0.87–2.47; P=0.16] or NSCLC (HR, 0.89; 95% CI, 0.61–1.29; P=0.53). On multivariate analysis, MT history was found to be an adverse prognostic indicator on OS for NHL (HR, 2.03; 95% CI, 1.20–3.42; P=0.008), but not NSCLC (HR, 0.87; 95% CI, 0.60–1.25; P=0.45). Conclusions Patients who develop NHL after MT have inferior survival than those with first primary NHL. A history of MT does not have an adverse prognostic impact on subsequent NSCLC. Clinicians must be aware of the intrinsic risk for subsequent malignancies after MT and the potential adverse impact of MT history on NHL prognosis but not NSCLC. PMID:28149555
Libra, Massimo; Gloghini, Annunziata; De Re, Valli; Rupolo, Maurizio; Navolanic, Patrick M; Gasparotto, Daniela; Stivala, Franca; Spina, Michele; Boiocchi, Mauro; Carbone, Antonino
Although epidemiologic and experimental data suggest an etiopathogenetic role for both hepatitis C virus (HCV) and Epstein-Barr virus (EBV) infection in development of B-cell non-Hodgkin's lymphoma (NHL), potential interactions between EBV and HCV during progression of B-cell NHL have not yet been fully investigated. In the present study, tumor biopsy specimens from patients with both B-cell NHL and chronic HCV infection (HCV(+)) were analyzed for the presence of EBV-encoded RNA (EBER) by in situ hybridization (ISH). VH and VL gene segments were amplified from tumor biopsy specimen DNA by PCR. EBV infection (EBV(+)) was detected in tumors from 2 of 31 (6%) HCV(+) B-cell NHL patients. Clinical histories of these two EBV(+)/HCV(+) B-cell NHL patients indicated a particularly aggressive course of disease. Chemotherapy failed to induce long lasting remission for either of these EBV(+)/HCV(+) B-cell NHL patients. Amplification of CDR3 of the Ig heavy chain gene from DNA isolated from each EBV(+)/HCV(+) B-cell NHL indicated the presence of monoclonal B-cell expansion. Rearrangement of Ig genes in neoplastic B-cell clones from both EBV(+)/HCV(+) patients was similar to that previously reported for EBV(-)/HCV(+) B-cell NHL patients. Additionally, neoplastic B-cell clones from these two EBV(+)/HCV(+) B-cell NHL patients did not exhibit intraclonal variation. Previous studies have demonstrated that intraclonal variation is common among neoplastic B-cell clones from EBV(-)/HCV(+) patients. EBV infection may have prevented evolution of variant neoplastic B-cell clones by suppressing antibody affinity maturation. Together, these data suggest that EBV infection may cooperate with HCV infection during progression of B-cell NHL in immunocompetent individuals. Such an interaction may accelerate the course of disease in B-cell NHL patients.
Widney, Daniel P; Gui, Dorina; Popoviciu, Laura M; Said, Jonathan W; Breen, Elizabeth C; Huang, Xin; Kitchen, Christina M R; Alcantar, Juan M; Smith, Jeffrey B; Detels, Roger; Martínez-Maza, Otoniel
Background. The homeostatic chemokine, CXCL13 (BLC, BCA-1), helps direct the recirculation of mature, resting B cells, which express its receptor, CXCR5. CXCL13/CXCR5 are expressed, and may play a role, in some non-AIDS-associated B cell tumors. Objective. To determine if CXCL13/CXCR5 are associated with AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Methods. Serum CXCL13 levels were measured by ELISA in 46 subjects who developed AIDS-NHL in the Multicenter AIDS Cohort Study and in controls. The expression or function of CXCL13 and CXCR5 was examined on primary AIDS-NHL specimens or AIDS-NHL cell lines. Results. Serum CXCL13 levels were significantly elevated in the AIDS-NHL group compared to controls. All primary AIDS-NHL specimens showed CXCR5 expression and most also showed CXCL13 expression. AIDS-NHL cell lines expressed CXCR5 and showed chemotaxis towards CXCL13. Conclusions. CXCL13/CXCR5 are expressed in AIDS-NHL and could potentially be involved in its biology. CXCL13 may have potential as a biomarker for AIDS-NHL.
Na, Renhua; Laaksonen, Maarit A; Grulich, Andrew E; Meagher, Nicola S; McCaughan, Geoffrey W; Keogh, Anne M; Vajdic, Claire M
Iatrogenic immunosuppression is a strong risk factor for non-Hodgkin lymphoma (NHL) but the dose-related association between individual immunosuppressive agents and NHL risk is unknown. We conducted a population-based cohort study of 4131 adult Australian liver, heart and lung transplant recipients (1984-2006). We ascertained NHL incidence by probabilistic record linkage between transplant registries and the Australian Cancer Database, and abstracted risk factor data at transplantation and at regular intervals thereafter from medical records. We estimated adjusted hazard ratios (HR) for early (<1 year after transplantation; n = 29) and late (≥1 year; n = 61) NHL using the Fine and Gray proportional subdistribution hazards model that accounted for death as a competing risk. After adjustment for immunosuppression, the risk of both early and late NHL did not significantly differ by organ type. In final models, higher mean daily doses of azathioprine were associated with increased risk of both early [HR 2·20, 95% confidence interval (CI): 1·21-4·01] and late NHL (HR 1·78, 95% CI: 1·12-2·84). There was no association between any other maintenance immunosuppressive agent and NHL risk. This study provides evidence that differences in immunosuppression may explain variation in NHL incidence by organ type, and high doses of azathioprine may independently predict NHL risk. © 2016 John Wiley & Sons Ltd.
Hassler, Melanie R; Schiefer, Ana-Iris; Egger, Gerda
Non-Hodgkin's lymphomas (NHLs) comprise a large and diverse group of neoplasms of lymphocyte origin with heterogeneous molecular features and clinical manifestations. Current therapies are based on standard chemotherapy, immunotherapy, radiation or stem cell transplantation. The discovery of recurrent mutations in epigenetic enzymes, such as chromatin modifiers and DNA methyltransferases, has provided researchers with a rationale to develop novel inhibitors targeting these enzymes. Several clinical and preclinical studies have demonstrated the efficacy of epigenetic drugs in NHL therapy and a few specific inhibitors have already been approved for clinical use. Here, we provide an overview of current NHL classification and a review of the present literature describing epigenetic alterations in NHL, including a summary of different epigenetic drugs, and their use in preclinical and clinical studies.
Perales, M; Cervantes, F; Cobo, F; Montserrat, E
Gaucher's disease is an uncommon disorder which has been reported to be associated with an increased risk of lymphoproliferative disorders, including Non-Hodgkin's lymphoma (NHL). A new instance of such an association is described here. This was a 58 year-old-patient with adult type I Gaucher's disease who, one and a half year after the above diagnosis, presented with supraclavicular lymphadenopathy, massive splenomegaly, prominent retroperitoneal lymphadenopathy and increased serum LDH levels. This led to the diagnosis of large-cell NHL of B-cell type, successfully treated with chemotherapy. The previously published cases of Gaucher's disease associated with NHL as well as the possible mechanisms leading to this association are reviewed here.
Pulte, Dianne; Jansen, Lina; Gondos, Adam; Emrich, Katharina; Holleczek, Bernd; Katalinic, Alexander; Brenner, Hermann
This study provides up-to-date and detailed cancer survival estimates of German patients with non-Hodgkin lymphoma (NHL, International Statistical Classification of Diseases 10th Revision [ICD-10] codes C82-C85) based on data from 11 cancer registries. Period analysis was used to calculate 5-year relative survival in 2002-2006, overall and by gender, age and histology. Comparison was made with patients with NHL in the United States (US) Surveillance, Epidemiology and End Results database in the same time period. Overall 5-year relative survival for patients with NHL in Germany in 2002-2006 was 62.8% and in the US was 65.1%. Survival decreased with age from 81.7% at age 15-49 to 46.5% at age 75+. Survival in the US was 75.3% at age 15-49 and 52% at age 75+. Survival was higher for women than for men, at 65.2% for women and 60.7% for men. Survivals for diffuse B-cell lymphoma and follicular lymphoma, the two most common subtypes of NHL, were 57.3% and 77.5%, respectively. Between 2002 and 2006, overall 5-year relative survival increased by 5.3 percentage points. We conclude that survival for NHL is increasing in Germany in recent years. Survival was higher in Germany than in the US for patients aged 15-49 but lower for older patients.
Barrientos, Jacqueline C
Idelalisib is a first-in-class, oral, selective phosphatidylinositol 3-kinase δ inhibitor that offers a chemotherapy-free option for patients with relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). Clinical trials in iNHL have evaluated idelalisib as monotherapy and as combination therapy with rituximab, bendamustine, and rituximab + bendamustine. When administered to heavily pretreated patients with R/R iNHL, idelalisib monotherapy or combination therapy showed durable antitumor activity accompanied by sustained or improved quality-of-life outcomes. Idelalisib has an acceptable safety profile; however, serious or fatal diarrhea/colitis, hepatoxicity, pneumonitis, and intestinal perforation have occurred in treated patients. Selective inhibition of phosphatidylinositol 3-kinase δ with idelalisib is a valuable addition to available treatment options for patients with iNHL, many of whom do not respond to or cannot tolerate chemoimmunotherapy. Two Phase III, randomized, placebo-controlled trials of idelalisib as combination therapy with rituximab or bendamustine + rituximab and a Phase I trial of idelalisib in combination with the Bruton’s tyrosine kinase inhibitor ONO/GS-4059 in R/R B-cell malignancies are currently ongoing. A Phase III monotherapy trial in previously treated follicular lymphoma or small lymphocytic lymphoma is planned. The development of other kinase inhibitors for the treatment of iNHL raises the potential for new treatment combinations. Additional research is needed to determine optimal therapy (monotherapy vs combination regimens), treatment sequencing, and long-term management. PMID:27274288
Han, Xuesong; Zheng, Tongzhang; Foss, Francine M.; Lan, Qing; Holford, Theodore R.; Rothman, Nathaniel; Ma, Shuangge; Zhang, Yawei
Background Metabolic pathway enzymes, such as Cytochrome P450 (CYP), glutathione S-transferase (GST), and N-Acetyltransferases (NAT) are involved in activation and detoxification of environmental carcinogens as well as drug metabolism. We hypothesized that the genetic variations in such metabolic pathways may affect NHL prognosis and survival. Methodology/Principal Findings Follow-up information of 469 female NHL incident cases diagnosed during 1995-2000 in Connecticut were abstracted from Connecticut Tumor Registry in 2008; survival analyses were conducted using the Kaplan-Meier method, and hazard ratios (HR) were estimated by Cox Proportional Hazard models adjusting for demographic and tumor characteristics which were suggested by previous studies to be determinants of NHL survival. Our results identified nine SNPs from five metabolism genes (CYP2E1, GSTP1, GSTT1, NAT1 and NAT2) that were associated with NHL survival. Specifically, polymorphisms in NAT1 and NAT2 genes were associated with diffuse large B-cell lymphoma survival; polymorphisms in GSTT1 was associated with follicular lymphoma survival; and polymorphisms in CYP2E1, GSTP1 and NAT1 were associated with survival of chronic lymphocytic leukemia/small lymphocytic lymphoma. Conclusions/Significance Our study suggests that genetic polymorphisms in metabolic pathways may help improving the prediction of NHL survival and prognosis. PMID:20029944
Zheng, Rong-Li; Jiang, Yu-Jie; Wang, Xin
Non-Hodgkin’s lymphoma (NHL) is a heterogeneous group of malignancies that originate in lymphatic hematopoietic tissue. Chemotherapy has been used as the main therapy for NHL all the time, and local radiotherapy is also a necessary approach to supplementary treatment. However, resistance of tumor cells to chemo- and radiotherapy often prevent a successful long-term treatment of NHL. MicroRNAs (miRNAs) are a class of approximately 22-nucleotide endogenous non-coding RNAs that play an important regulatory role in gene expression, involving in the process of cell proliferation and differentiation. Alterations of miRNAs have been reported in a variety of human cancers, such as lymphomas, and will critically influence the tumor development and progression. Recently, there is increasing evidence that miRNAs could also influence sensitivity of tumor cells to chemo- and radiotherapy, revealing a crucial role of microRNAs in resistance to anticancer treatment. Therefore, understanding the role of miRNAs in chemo- and radio-resistance of tumor and targeting specific miRNAs will open novel avenues for lymphoma treatment and improve the prognosis of NHL patients. This review outlines the role of miRNAs associated with chemo-and radiotherapy resistance in NHL. PMID:25550890
Merchionne, Francesca; Iacopino, Pasquale; Minoia, Carla; Iacobazzi, Angela; Rana, Antonio; Serrati, Simona; De Tullio, Giacoma; Loseto, Giacomo; Lapietra, Angela; Lucarelli, Annunziata; Guarini, Attilio
Primary gastric non-Hodgkin's lymphomas (PG-NHL) are the most common extranodal lymphomas, representing between 47% and 74% of all gastrointestinal lymphoma cases. In Western countries two histological types, diffuse large B-cell (DLBC) NHL and mucosa-associated lymphoid tissue (MALT) NHL, are more frequently represented, accounting for the majority of gastric tumors after adenocarcinoma. For several years treatment of these PG lymphomas consisted of surgery, chemotherapy and radiotherapy, alone or in combination. In the last two decades however, advances in our understanding of their pathogenesis and biology have changed the treatment strategy, at least as regards the early stages of disease. In addition to making tumor regression possible through the eradication of Helicobacter pylori, which is considered the main pathogenic agent, this understanding has also provided a solid rationale to assess the efficacy of targeted therapy, namely of drugs which interfere with specific molecules expressed by tumor cells or are involved in key growth pathways of these lymphomas. In particular, rituximab, a monoclonal anti-CD20 antibody, radioimmunotherapy, the first-generation proteasome inhibitor bortezomib and lenalidomide have been evaluated. Despite significant antitumor activity in this subset of NHL and manageable toxicity, many questions still remain however about the optimal dose, the best administration schedule and their combination with conventional chemotherapy. This review focuses on the pathogenesis of PG-MALT and DLBC lymphomas, and discusses the results of clinical trials on the impact of new agents on prognosis and survival in these patients, considering also potential new therapautic targets.
Purdue, Mark P.; Freedman, D. Michal; Gapstur, Susan M.; Helzlsouer, Kathy J.; Laden, Francine; Lim, Unhee; Maskarinec, Gertraud; Rothman, Nathaniel; Shu, Xiao-Ou; Stevens, Victoria L.; Zeleniuch-Jacquotte, Anne; Albanes, Demetrius; Bertrand, Kimberly; Weinstein, Stephanie J.; Yu, Kai; Irish, Lonn; Horst, Ronald L.; Hoffman-Bolton, Judith; Giovannucci, Edward L.; Kolonel, Laurence N.; Snyder, Kirk; Willett, Walter; Arslan, Alan A.; Hayes, Richard B.; Zheng, Wei; Xiang, Yong-Bing; Hartge, Patricia
Case-control studies generally suggesting an inverse association between sun exposure and non-Hodgkin lymphoma (NHL) have led to speculation that vitamin D may protect against lymphomagenesis. To examine this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D (25(OH)D) and subsequent NHL risk within 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The authors analyzed measurements from 1,353 cases and 1,778 controls using conditional logistic regression and other methods to estimate the association of 25(OH)D with NHL. No clear evidence of association between categories of 25(OH)D concentration and NHL was observed overall (Ptrend = 0.68) or by sex (men, Ptrend = 0.50; women, Ptrend = 0.16). Findings for other measures (continuous log(25(OH)D), categories of 25(OH)D using sex-/cohort-/season-specific quartiles as cutpoints, categories of season-adjusted residuals of predicted 25(OH)D using quartiles as cutpoints) were generally null, although some measures of increasing 25(OH)D were suggestive of an increased risk for women. Results from stratified analyses and investigations of histologic subtypes of NHL were also null. These findings do not support the hypothesis that elevated circulating 25(OH)D concentration is associated with a reduced risk of NHL. Future research investigating the biologic basis for the sunlight–NHL association should consider alternative mechanisms, such as immunologic effects. PMID:20562184
Boccolini, Patricia de Moraes Mello; Boccolini, Cristiano Siqueira; Chrisman, Juliana de Rezende; Koifman, Rosalina Jorge; Meyer, Armando
To estimate the non-Hodgkin lymphoma (NHL) mortality risk among agricultural workers in Brazil's southern states, we used death certificates to identify cases of NHL between the ages of 20 and 69 years from residents of nonurban municipalities between 1996 and 2005 (n = 1,317). Controls were randomly selected from those whose underlying cause of death did not include neoplasm or hematological diseases and paired with cases by sex, age, year of death, and state of residence (n = 2,634). Odds of being an agricultural worker among cases and controls were estimated by conditional logistic regression, stratified and adjusted by sex, state, education, and race. An increased risk of death by NHL was observed among agricultural workers 20-39 years old (ORadj = 2.06; 95% CI 95%, 1.20-3.14). Our results suggest that the young agricultural workers from southern Brazil were more likely to die of NHL compared to nonagricultural workers.
Wang, Zhiwei; Li, Xiaoguang; Chen, Jin; Jin, Zhengyu; Shi, Haifeng; Zhang, Xiaobo; Pan, Jie; Liu, Wei; Yang, Ning; Chen, Jie
To evaluate the value of computed tomography (CT)-guided core needle biopsy in diagnosis of primary pulmonary lymphoma and its subtypes. A retrospective analysis of the records of all patients with primary pulmonary lymphoma between January 2005 and August 2011 was performed. There were 25 patients referred to the radiology department for CT-guided core needle biopsy. The success rate and complications were assessed. A definitive diagnosis and accurate histologic subtype were obtained in 21 patients with a success rate of 84.0%. Diagnosis was made in the other four patients with bronchoscopy and surgery. Non-Hodgkin lymphoma (NHL) was the diagnosis in all patients. Most subtypes were mucosa-associated lymphoid tissue (MALT) lymphomas (n = 19). The remaining subtypes included three diffuse large B-cell NHLs, two peripheral T-cell lymphomas not otherwise specified, and one anaplastic large cell NHL. The success rate of core needle biopsy was 95% (18 of 19) for MALT lymphomas, 67% (2 of 3) for diffuse large B cell NHLs, and 33% (1 of 3) for other NHLs. The success rate for MALT lymphomas was significantly higher than that of non-MALT lymphomas according to Fisher exact t test (P = .031). No serious complications occurred in any patients. CT-guided core needle biopsy is a reliable procedure to assist in diagnosis and classification of primary pulmonary lymphomas, especially MALT lymphomas. Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.
García Chihuan, Grisley; Fernández Butrón, Ana; Salazar Alejo, Ruth; Frisancho, Oscar; Beltrán, Brady
Plasmablastic lymphoma is an aggressive form of lymphoma diffuse large B cell Lymphoma, initially described in HIV positive patients associated with lesions in the oral cavity. It is about 2% of NHL associated with HIV. This entity currently represents a challenge for the diagnosis and treatment, showing a poor long-term prognosis. This report describes a patient with VIH on HAART and CD4 count in 490 cells/ml associated with Plasmablastic lymphoma that involves rectum and bone marrow. The patient received 6 cycles of EPOCH regimen with complete response.
Tang, Chad; Pachynski, Russell K.; Chin, Robert; Majeti, Ravindra; Weissman, Irving L.
Non-Hodgkin lymphoma (NHL) presents as both localized and disseminated disease with spread to secondary sites carrying a worse prognosis. Although pathways driving NHL dissemination have been identified, there are few therapies capable of inhibiting them. Here, we report a novel role for the immunomodulatory protein CD47 in NHL dissemination, and we demonstrate that therapeutic targeting of CD47 can prevent such spread. We developed 2 in vivo lymphoma metastasis models using Raji cells, a human NHL cell line, and primary cells from a lymphoma patient. CD47 expression was required for Raji cell dissemination to the liver in mouse xenotransplants. Targeting of CD47 with a blocking antibody inhibited Raji cell dissemination to major organs, including the central nervous system, and inhibited hematogenous dissemination of primary lymphoma cells. We hypothesized that anti-CD47 antibody-mediated elimination of circulating tumor cells occurred through phagocytosis, a previously described mechanism for blocking anti-CD47 antibodies. As predicted, inhibition of dissemination by anti-CD47 antibodies was dependent on blockade of phagocyte SIRPα and required macrophage effector cells. These results demonstrate that CD47 is required for NHL dissemination, which can be therapeutically targeted with a blocking anti-CD47 antibody. Ultimately, these findings are potentially applicable to the dissemination and metastasis of other solid tumors. PMID:21828138
Khuroo, Mehnaaz Sultan; Khwaja, Summyia Farooq; Rather, Ajaz; Hassan, Zhahid; Reshi, Ruby; Khuroo, Naira Sultan
Background: The histological categorization of lymphoma has been a source of controversy for many years for both clinicians and pathologists. Clinicopathologic information of gastrointestinal lymphomas in Indian subcontinent is lacking. We studied histopathological spectrum of Primary Gastrointestinal Lymphomas (PGIL) and attempted to classify the G.I. lymphomas based on the recent WHO classification in to major histological types and immunological categories. Material and Methods: This study was done to evaluate the clinicopathological pattern of 100 cases with a histopathological diagnosis of primary gastrointestinal lymphoma at a tertiary care hospital. All patients of primary gastrointestinal lymphomas were included with the help of medical records over a 11-years period that is, January 2005 to December 2015. Results: The study included 100 cases (60 males, 40 females; mean age 51.43 years; age range 4.5-90 years). The disease involved stomach in 82 (82%), small intestine in 8 (8%), large bowel and rectum in 8 (8%), gall bladder in 1 (1%) and oesophagus in 1 (1%). 82 (82%) of the 100 cases were Diffuse Large B cell lymphomas; 12 (12%) were Extra Nodal Marginal Zone Lymphomas (ENMZL of MALT type) 2 (2%) IPSID 2 (2%) of Mantle cell lymphoma morphology, 1 (1%) Burkitt's and 1(1%) enteropathy associated T cell lymphoma. The commonest presenting symptom was abdominal pain. 99 (99%) of 100 tumours were classified as B-cell lymphomas immunohistochemically and majority exhibited monoclonal light chain restriction on kappa/lambda staining. In addition; Burkitt's lymphoma showed positivity for CD 10. One tumour (1%) showed positivity for T-cell markers. The data demonstrated that primary GI NHL is more common among males, mainly in their fifth decade. Abdominal pain is the most common presenting symptom, with stomach being the most commonly involved site. Diffuse large cell lymphoma is the most frequent histologic subtype, followed by extranodal marginal-zone B cell
Bibas, Michele; Antinori, Andrea
HIV-associated lymphoproliferative disorders represent a heterogeneous group of diseases, arising in the presence of HIV-associated immunodeficiency. The overall prevalence of HIV-associated lymphoma is significantly higher compared to that of the general population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART) (1). Moreover, they still represent one of the most frequent cause of death in HIV-infected patients. Epstein–Barr virus (EBV), a γ-Herpesviruses, is involved in human lymphomagenesis, particularly in HIV immunocompromised patients. It has been largely implicated in the development of B-cell lymphoproliferative disorders as Burkitt lymphoma (BL), Hodgkin disease (HD), systemic non Hodgkin lymphoma (NHL), primary central nervous system lymphoma (PCNSL), nasopharyngeal carcinoma (NC). Virus-associated lymphomas are becoming of significant concern for the mortality of long-lived HIV immunocompromised patients, and therefore, research of advanced strategies for AIDS-related lymphomas is an important field in cancer chemotherapy. Detailed understanding of the EBV lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein. PMID:21416008
Hermann, Silke; Rohrmann, Sabine; Linseisen, Jakob; Nieters, Alexandra; Khan, Aneire; Gallo, Valentina; Overvad, Kim; Tjønneland, Anne; Raaschou-Nielsen, Ole; Bergmann, Manuela M; Boeing, Heiner; Becker, Nikolaus; Kaaks, Rudolf; Bueno-de-Mesquita, H Bas; May, Anne M; Vermeulen, Roel C H; Bingham, Sheila; Khaw, Kay-Tee; Key, Timothy J; Travis, Ruth C; Trichopoulou, Antonia; Georgila, Christina; Triantafylou, Dimitra; Celentano, Egidio; Krogh, Vittorio; Masala, Giovanna; Tumino, Rosario; Agudo, Antonio; Altzibar, Jone M; Ardanaz, Eva; Martínez-García, Carmen; Suárez, Marcial Vicente Argüelles; Tormo, Maria José; Braaten, Tonje; Lund, Eiliv; Manjer, Jonas; Zackrisson, Sophia; Hallmans, Göran; Malmer, Beatrice; Boffetta, Paolo; Brennan, Paul; Slimani, Nadia; Vineis, Paolo; Riboli, Elio
Lymphomas belong to the few cancer sites with increasing incidence over past decades, and only a few risk factors have been established. We explored the association between education and the incidence of lymphoma in the prospective EPIC study. Within 3,567,410 person-years of follow-up, 1,319 lymphoma cases [1,253 non-Hodgkin lymphomas (NHL) and 66 Hodgkin lymphomas (HL)] were identified. Cox proportional hazard regression was used to examine the association between highest educational level (primary school or less, technical/professional school, secondary school, university) and lymphoma risk. Overall, no consistent associations between educational level and lymphoma risk were observed; however, associations were found for sub-groups of the cohort. We observed a higher risk of B-NHL (HR = 1.31, 95% CI = 1.02–1.68; n = 583) in women with the highest education level (university) but not in men. Concerning sub-classes of B-NHL, a positive association between education and risk of B cell chronic lymphatic leukaemia (BCLL) was observed only in women. In both genders, the risk of diffuse large B cell lymphoma (DLBCL) was significantly lower for subjects with university degree (HR = 0.46, 95% CI = 0.27–0.79) versus lowest educational level. No association was found for HL. We could not confirm an overall consistent association of education and risk of HL or NHL in this large prospective study; although, education was positively related to the incidence of BCLL and B-NHL (in women) but inversely to incidence of DLBCL. Due to limited number of cases in sub-classes and the large number of comparisons, the possibility of chance findings can not be excluded.
Farawela, Hala; Khorshied, Mervat; Shaheen, Iman; Gouda, Heba; Nasef, Aya; Abulata, Nelly; Mahmoud, Hebat-Allah; Zawam, Hamdy M; Mousa, Somaia M
Hepatitis C virus (HCV) has been postulated to be an etiological agent for lymphoid malignancies. Polymorphisms in oxidative stress genes as; superoxide dismutase (SOD2), glutathione peroxidase (GPX1), catalase (CAT), myeloperoxidase (MPO) and nitric oxide synthase (NOS2) may influence non-Hodgkin's lymphoma (NHL) risk. HCV screening and polymorphisms in these five genes coding for antioxidant enzymes were studied in 100 Egyptian patients with B cell-NHL and 100 controls to clarify the association between HCV infection, oxidative stress genes polymorphisms and B cell-NHL risk. A significantly higher prevalence of HCV infection was detected among NHL patients relative to controls and this carried a 14-fold increased NHL risk (odds ratio (OR)=14.3, 95% confidence interval (CI)=5.4-38.3, p<0.0001). GPX1 and MPO genetic polymorphisms conveyed increase in B-NHL risk (OR=3.3, 95% CI=1.4-7.4, p=0.004 and OR=4.4, 95% CI=1.3-14.2, p=0.009 respectively). Further analyses stratified by HCV infection revealed that concomitant HCV infection and GPX1 gene polymorphism had a synergetic effect on NHL risk with an OR of 15 (95%CI=2.2-69.6, p<0.0001). In addition, combined HCV infection and MPO gene polymorphisms had a pronounced NHL risk (OR=9.2, 95%CI=2.5-33.9, p<0.0001). SOD2, CAT and NOS2 genetic polymorphisms were not found to confer increased NHL risk. This study revealed that HCV infection is a risk factor for NHL in Egypt. Polymorphisms in GPX1 and MPO genes may influence NHL risk in HCV infected Egyptian patients. Larger scale studies are warranted to establish this genetic susceptibility for NHL.
Seelig, Davis M.; Avery, Anne C.; Ehrhart, E. J.; Linden, Michael A.
The non-Hodgkin lymphomas (NHLs) are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma as a comparative, large animal model of human NHL. In alignment with the biologic similarities, the current approach towards the diagnosis and classification of canine lymphoma is based upon the human World Health Organization guidelines. While this approach has contributed to an increasing appreciation of the potential biological scope of canine lymphoma, it has also become apparent that the most appropriate diagnostic philosophy must be multimodal, namely by requiring knowledge of microscopic, immunophenotypic, and clinical features before establishing a final disease diagnosis. This review seeks to illustrate the comparative similarities and differences in the diagnosis of canine lymphoma through the presentation of the microscopic and immunophenotypic features of its most common forms. PMID:28435836
Lam, Clara J.K.; Curtis, Rochelle E.; Dores, Graça M.; Engels, Eric A.; Caporaso, Neil E.; Polliack, Aaron; Warren, Joan L.; Young, Heather A.; Levine, Paul H.; Elmi, Angelo F.; Fraumeni, Joseph F.; Tucker, Margaret A.; Morton, Lindsay M.
Purpose Previous studies have reported that survivors of non-Hodgkin lymphoma (NHL) have an increased risk of developing cutaneous melanoma; however, risks associated with specific treatments and immune-related risk factors have not been quantified. Patients and Methods We evaluated second melanoma risk among 44,870 1-year survivors of first primary NHL diagnosed at age 66 to 83 years from 1992 to 2009 and included in the Surveillance, Epidemiology, and End Results-Medicare database. Information on NHL treatments, autoimmune diseases, and infections was derived from Medicare claims. Results A total of 202 second melanoma cases occurred among survivors of NHL, including 91 after chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 111 after other NHL subtypes (cumulative incidence by age 85 years: CLL/SLL, 1.37%; other NHL subtypes, 0.78%). Melanoma risk after CLL/SLL was significantly increased among patients who received infused fludarabine-containing chemotherapy with or without rituximab (n = 18: hazard ratio [HR], 1.92; 95% CI, 1.09 to 3.40; n = 10: HR, 2.92; 95% CI, 1.42 to 6.01, respectively). Significantly elevated risks also were associated with T-cell activating autoimmune diseases diagnosed before CLL/SLL (n = 36: HR, 2.27; 95% CI, 1.34 to 3.84) or after CLL/SLL (n = 49: HR, 2.92; 95% CI, 1.66 to 5.12). In contrast, among patients with other NHL subtypes, melanoma risk was not associated with specific treatments or with T-cell/B-cell immune conditions. Generally, infections were not associated with melanoma risk, except for urinary tract infections (CLL/SLL), localized scleroderma, pneumonia, and gastrohepatic infections (other NHLs). Conclusion Our findings suggest immune perturbation may contribute to the development of melanoma after CLL/SLL. Increased vigilance is warranted among survivors of NHL to maximize opportunities for early detection of melanoma. PMID:26240221
Jelliffe, A. M.
Twenty patients with non-Hodgkin's lymphoma (NHL) were investigated by diagnostic laparotomy. These patients were seen over a 3 1/2 year period during which a total of 78 patients with NHL were seen. Laparotomy was considered unsuitable in 58 patients, either because widespread disease was easily demonstrated by simpler means or because of their poor general medical condition. Laparotomy revealed more extensive disease in 14 patients. Although laparotomy is proving to be a worthwhile investigative procedure, it is less likely to be useful as a routine investigation than is the case with Hodgkin's disease. Widespread involvement of mesenteric lymph nodes is common and among the 10 patients with a poor histological grade of tumour, 2 with negative laparotomy findings developed disease in the abdomen within 3 months of operation. PMID:1182072
Laurent, Camille; Do, Catherine; Gourraud, Pierre-Antoine; de Paiva, Geisilene Russano; Valmary, Séverine; Brousset, Pierre
Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) represent a heterogeneous group of malignant lymphoid tumors, which have distinct histological and/or biological characteristics with preferential nodal involvement. However, none of the previous studies have assessed the prevalence of common NHL and HL subtypes at each nodal site of involvement. The aim of our study was to determine the prevalence of HL and NHL subtypes depending on their nodal sites of involvement.We conducted a single-center retrospective study of 938 lymphoma cases diagnosed in the Pathology Department of Toulouse Purpan Hospital in France between 2001 and 2008, taking into account the site that corresponded to the diagnostic biopsy. The most frequent sites were cervical lymph nodes (36.8% of all cases), inguinal lymph nodes (16.4%), axillary lymph nodes (11.9%), and supraclavicular lymph nodes (11%). We found an unexpected association between intraparotid nodes and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and between inguinal nodes and follicular lymphoma. The risk of having classical Hodgkin lymphoma (CHL) was 15 times greater in patients with mediastinal lymphoma compared to those with other sites of involvement. Regarding HL, nodal and extranodal mediastinal sites and supraclavicular nodes were more likely to be involved by nodular sclerosis Hodgkin lymphoma (NSCHL). In addition, intra-abdominal lymph nodes were more frequently involved by lymphocyte depleted Hodgkin lymphoma compared to inguinal nodes where NLPHL predominated.Our study shows that some lymph node sites have a disproportionate prevalence of specific subtypes of lymphoma. Identifying these sites may aid to diagnose and better elucidate the pathogenesis of these tumors.
Nair, Reena; Arora, Neeraj; Mallath, Mohandas K
Non-Hodgkin's lymphoma (NHL) is a common hematological malignancy. The age-adjusted incidence rates for NHL in men and women in India are 2.9/100,000 and 1.5/100,000, respectively. These are about one fourth of the incidence rates reported from Western Europe or North America. Within India, the incidence is several-fold higher in urban cancer registries compared to rural areas; the incidence being higher in metropolitan cities and Indian immigrants suggesting that urban lifestyles and economic progress may increase the cancer incidence. Compared to developed nations, the key differences in the presentation in India include: median age of 54 years (almost a decade less), higher male to female ratio, higher proportion of patients with B-symptoms (40-60 vs. 20-30%), poor ECOG performance status (≥2) at diagnosis (50 vs. 20-30%), higher frequency of diffuse large B-cell lymphomas (60-70 vs. <40%), lower frequency of follicular NHL (<20 vs. 30-40%) and T-cell type in 10-20 vs. <10%. The estimated mortality rate due to NHL is higher in India than in North America and Western Europe. Diagnostic and treatment delays, incorrect diagnosis and inappropriate or suboptimal treatment may be possible reasons for the poor outcome. Any improvement in the outcomes for NHL in India will require a nationwide approach, e.g. creation of several regional and district-level centers with expertise in lymphoma management. Collection of data on patient- and disease-related characteristics, treatment outcome, development of infrastructure, centralized review of histopathology subtype, novel treatment protocols, rigorous follow-up, training of staff, and financial support towards treatment could be possible strategies to improve the outcome.
Meytes, D; Leshno, D; Berkowicz, M; Modan, M; Ramot, B
Patients who have recovered from malignant lymphoma are at an increased risk of secondary acute leukemia (AL), and overt AL is frequently preceded by a myelodysplastic syndrome. Although the statistical risk is significant, only a minority of the patients will be so affected. We have reviewed peripheral blood counts of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) treated in the Departments of Hematology at the Edith Wolfson and Chaim Sheba Medical Centers, Israel. Included were only those who went into a complete remission and remained lymphoma free for extended periods. There were 85 patients with HD and 36 with NHL. In both groups peripheral blood counts at diagnosis were within the normal range. A prolonged follow-up (> 4 y), during which no further treatment was given, revealed a sustained increment over time of MCV (delta MCV) both in HD and NHL. A persistent monocytosis in HD patients was also evident. delta MCV was larger in HD. The difference at the end of the follow-up period was as follows: 10.1 fl + 11.8 in HD vs 5.0 fl + 6.2 in NHL, (P < 0.001). In addition, a significant loss of the normal correlation between the MCV and levels of hemoglobin was seen at the last follow-up. The change in MCV was present in all treatment groups, its magnitude increasing from radiotherapy to chemotherapy to combined radio chemotherapy. This trend is in analogy to the risk of secondary AL which is lower in NHL vs HD. Furthermore, it is lowest post radiotherapy and highest when both treatment modalities are used.(ABSTRACT TRUNCATED AT 250 WORDS)
Marcucci, Fabrizio; Spada, Enea; Mele, Alfonso; Caserta, Carmelo Antonio; Pulsoni, Alessandro
Epidemiological studies performed over the last decade have demonstrated a positive association between persistent, hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection and B-cell non-Hodgkin lymphoma (NHL), with HBV-infected patients having a 2-3-fold higher risk to develop NHL than non-infected patients. Moreover, there is evidence that also occult HBV infection (HBsAg-negative, HBV DNA-positive) associates with NHL. An association with HBV infection may exist also for other hematological malignancies, but available evidence is much less persuasive than for NHL. In this review article we will discuss available results on the association between HBsAg-positive HBV infection and NHL, as well as the significance of other serological markers of HBV infection in these subjects. We will also discuss the possible etiopathogenic role of HBV, and propose a multifactorial model for lymphomagenesis. Experimental evidence for multifactorial etiopathogenesis has been obtained in recent years for HBV-associated hepatocellular carcinoma (HCC), and we suggest that a similar model may apply to HBV-associated lymphoma as well. Eventually, we will also address some unresolved questions. Two of these are of particular relevance. First, do HBV-positive NHL patients show regression of their hematologic malignancy upon antiviral therapy? A positive answer would represent a direct demonstration of the necessary etiological role of the virus in the development of NHL, as has been shown previously for HCV-associated lymphomas. Second, if HBV plays a necessary role in lymphomagenesis, then expansion of HBV vaccination is expected to reduce the number of incident NHL cases, even though this effect might become evident only after a long time interval. Studies in those countries which have introduced universal HBV vaccination about two decades ago, like Italy, may soon provide results on this important point. PMID:22432084
Badea, M; Dobrea, Camelia; Badea, Daniela; Genunche-Dumitrescu, Amelia; Mitruţ, P; Duţă, Doriana
The composite lymphoma (CL) is defined by the presence in the same tissue or organ of two distinct histological aspects of non-Hodgkin's lymphoma (NHL), or NHL and Hodgkin's lymphoma (HL). The definition of the CL has evolved, requesting the identification of the immunophenotypic pattern and clonal distinct aspects for the two-lymphoproliferative lesions. We present a case of a 73-year-old farmer who presented with B-symptoms and multiple adenomegaly. The biopsy of a left cervical lymph node reveal a CL: a histological and immunophenotypic aspect of HL-mixed cellularity (CD15+, CD30+, CD20-) and a diffuse small cell infiltrate which meet the criteria for B-CLL (CD20+, CD23+, and CD5+). The lymphocytes in peripheral blood over 15 000/mm(3) and marrow infiltrate with small lymphocytes also sustain the B-CLL diagnosis. The relationship between the two lymphoproliferations is discussed reported to the case above, but also considering the literature data. In most of the cases the two proliferative processes are clonal related which means they have a commune lymphoid progenitor, pre-GC or early-GC with individual detachment and transit through GC (also, the afferent related processes). It is also possible that the two proliferations, which form the composite lesion to have different cellular origins, possibility sustained by the analysis of the IgH rearrangements and of the somatic mutations identified in the two clones. The EBV-role in HL-pathogeny is related to the way of salvage or/and initiation of a clonal process in a GC-cell which has major deletions in the variable part of IgH.
Potts, D. Alan; Fromm, Jonathan R.; Gopal, Ajay K.
Non-Hodgkin lymphomas (NHL) are a heterogeneous group of hematologic malignancies typically treated with multiagent chemotherapy. Rarely, spontaneous remissions can be observed, particularly in more indolent subtypes. The prognosis of aggressive NHL can be predicted using clinical and histopathologic factors. In aggressive B-cell NHL, the importance of MYC and BCL2 proto-oncogene coexpression (as assessed by immunohistochemistry) and high-grade histologic features are particularly noteworthy. We report a unique case of spontaneous remission in a patient with an aggressive B-cell NHL which harbored high-risk histopathologic features, including MYC protein expression at 70–80%, BCL2 protein expression, and morphologic features suggestive of high-grade B-cell lymphoma, NOS (formerly B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma [BCLU]). After undergoing a biopsy to confirm this diagnosis, he opted to forego curative-intent chemotherapy. The single, yet relatively large area of involvement noted on 18F-fluorodeoxyglucose positron emission tomography-computed tomography steadily resolved on subsequent follow-up studies. He remained without evidence of recurrence one year later, having never received treatment. This case emphasizes the potential for spontaneous remission in NHL and demonstrates that this phenomenon can be observed despite contemporary high-risk histopathologic features. PMID:28321348
Zhang, Yiqiu; Li, Beilei; Cai, Liang; Shi, Hongcheng; Hou, Jun
Non-Hodgkin's lymphomas (NHL) quite often present in the neck but are seldom accompanied with cellulitis at the first diagnosis of the disease. We report a 56 year old woman with gradually neck swelling, which was initially treated as cellulitis. After examined by ultrasonography, computed tomography and after pathologically assessments, the diagnosis of large B-cell lymphoma was made. This case highlights the usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET/CT) in staging and assessing treatment response in NHL.
Cherian, Sindhu; Fromm, Jonathan R
Primary mediastinal large B cell lymphoma (PMLBCL) is a B cell non-Hodgkin lymphoma (B-NHL) that shows morphologic, immunophenotypic, and genetic similarities to classical Hodgkin lymphoma (CHL). We evaluated the neoplastic and reactive infiltrate of PMLBCL by flow cytometry (FC). A total of 24 cases of PMLBCL were retrospectively characterized using FC combinations for B-NHL, T-NHL, and CHL. The CHL assay identified the neoplastic population (NP) in all cases, while the B-NHL assay identified the NP in 18 of 24 cases. In four cases, the neoplastic population was retrospectively identified in the B-NHL tube, given the CHL tube-derived immunophenotype. Neoplastic cells of PMLBCL displayed a B cell immunophenotype (CD19/CD20(+) ), with CD40 consistently and brightly expressed. Most cases lacked immunoglobulin light chains, CD10, and CD15; CD30 was frequently expressed. All cases showed expression of CD71 and CD95. The reactive infiltrate in PMLBCL showed increases in T cells relative to reactive tissues. Lower CD4/CD8 ratios in PMLBCL relative to CHL and reactive tissues were also observed. Although not seen as commonly as with CHL, 41% of cases showed a reactive CD3/CD4/CD7(bright) /CD45(bright+) T cell population. Reactive populations seen in PMLBCL were similar to that seen in diffuse large B cell lymphoma, not otherwise specified. FC can detect the NP of PMLBCL and a FC assay for CHL performed better than a B-NHL assay in this regard. The neoplastic cells showed a B cell immunophenotype with over-expression of CD40. The reactive infiltrate in PMLBCL shows unique features including a prominent CD8(+) T cell infiltrate. © 2017 International Clinical Cytometry Society. © 2017 International Clinical Cytometry Society.
Lu, Ting; Yu, Shuang; Liu, Yan; Yin, Congcong; Ye, Jingjing; Liu, Zhi; Ma, Daoxin; Ji, Chunyan
Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of neoplasm in which 90% are B-cell lymphomas and 10% T-cell lymphomas. Although T-helper 17 (Th17) cells have been implicated to be essential in the pathogenesis of autoimmune and inflammatory diseases, its role in B-cell non-Hodgkin's lymphoma (B-NHL) remains unknown. In this study, we observed a significantly decreased frequency of Th17 cells in peripheral blood from B-NHL patients compared with healthy individuals, accompanied with increased Th1 cells. IL-17AF plasma levels were remarkably decreased in B-NHL patients, accompanied with undetectable IL-17FF and unchangeable IL-17AA. Moreover, Th17 and Th1 cells became normalized after one or two cycles of chemotherapy. Interestingly, in B-NHL, circulating Th17 cells frequencies were significantly higher in relapsed patients than those in untreated patients or normal individuals. Meanwhile, there was no statistical difference regarding the frequencies of Th1 cells between relapsed and untreated patients. Taken these data together, circulating Th17 subset immune response may be associated with the response of patients to treatment and with different stages of disease.
Lu, Ting; Yu, Shuang; Liu, Yan; Yin, Congcong; Ye, Jingjing; Liu, Zhi
Non-Hodgkin’s lymphomas (NHLs) are a heterogeneous group of neoplasm in which 90% are B-cell lymphomas and 10% T-cell lymphomas. Although T-helper 17 (Th17) cells have been implicated to be essential in the pathogenesis of autoimmune and inflammatory diseases, its role in B-cell non-Hodgkin’s lymphoma (B-NHL) remains unknown. In this study, we observed a significantly decreased frequency of Th17 cells in peripheral blood from B-NHL patients compared with healthy individuals, accompanied with increased Th1 cells. IL-17AF plasma levels were remarkably decreased in B-NHL patients, accompanied with undetectable IL-17FF and unchangeable IL-17AA. Moreover, Th17 and Th1 cells became normalized after one or two cycles of chemotherapy. Interestingly, in B-NHL, circulating Th17 cells frequencies were significantly higher in relapsed patients than those in untreated patients or normal individuals. Meanwhile, there was no statistical difference regarding the frequencies of Th1 cells between relapsed and untreated patients. Taken these data together, circulating Th17 subset immune response may be associated with the response of patients to treatment and with different stages of disease. PMID:26812681
Benevolo, Giulia; Stacchini, Alessandra; Spina, Michele; Ferreri, Andrés J M; Arras, Marcella; Bellio, Laura; Botto, Barbara; Bulian, Pietro; Cantonetti, Maria; Depaoli, Lorella; Di Renzo, Nicola; Di Rocco, Alice; Evangelista, Andrea; Franceschetti, Silvia; Godio, Laura; Mannelli, Francesco; Pavone, Vincenzo; Pioltelli, Pietro; Vitolo, Umberto; Pogliani, Enrico M
This prospective study compared diagnostic and prognostic value of conventional cytologic (CC) examination and flow cytometry (FCM) of baseline samples of cerebrospinal fluid (CSF) in 174 patients with newly diagnosed aggressive non-Hodgkin lymphoma (NHL). FCM detected a neoplastic population in the CSF of 18 of 174 patients (10%), CC only in 7 (4%; P < .001); 11 patients (14%) were discordant (FCM(+)/CC(-)). At a median follow-up of 46 months, there were 64 systemic progressions and 10 CNS relapses, including 2 patients with both systemic and CNS relapses. Two-year progression-free and overall survival were significantly higher in patients with FCM(-) CSF (62% and 72%) compared with those FCM(+) CSF (39% and 50%, respectively), with a 2-year CNS relapse cumulative incidence of 3% (95% confidence interval [CI], 0-7) versus 17% (95% CI, 0-34; P = .004), respectively. The risk of CNS progression was significantly higher in FMC(+)/CC(-) versus FCM(-)/CC(-) patients (hazard ratio = 8.16, 95% CI, 1.45-46). In conclusion, FCM positivity in the CSF of patients with high-risk NHL is associated with a significantly higher CNS relapse risk and poorer outcome. The combination of IV drugs with a higher CNS bioavailability and intrathecal chemotherapy is advisable to prevent CNS relapses in FCM(+) patients.
Ackova, Darinka Gjorgieva; Smilkov, Katarina; Janevik-Ivanovska, Emilija
Radioimmunotherapy (RIT) of Non-Hodgkin's lymphoma (NHL) is said to be more advantageous compared to unlabelled therapeutic antibodies. To this date, radiolabelled murine anti-CD20 mAbs, Zevalin(®) and Bexxar(®) have been approved for imaging and therapy. A preparation containing rituximab, chimeric mAb radio immunoconjugate suitable for Lu-177 labeling, could provide better imaging and therapeutic profile at the same time. This study was conducted to evaluate prepared lyophilized formulations of two rituximab immune conjugates, intended for immediate Lu-177 labeling, for imaging and therapy. The characterization of the conjugates and demonstration of the integrity of the protein and purity after conjugation and lyophilization was performed by SDS-PAGE, FT-IR and MALDI-TOF-MS. The results showed preserved antibody structure and average of 6.1 p-SCN-Bn-DOTA and 8.8 p-SCN-Bn-DTPA groups per antibody molecule which is suitable for successful labeling. These results support the possibility of developing a "ready-to-label" rituximab immune conjugates for NHL imaging/therapy.
Ackova, Darinka Gjorgieva; Smilkov, Katarina; Janevik-Ivanovska, Emilija
Radioimmunotherapy (RIT) of Non-Hodgkin’s lymphoma (NHL) is said to be more advantageous compared to unlabelled therapeutic antibodies. To this date, radiolabelled murine anti-CD20 mAbs, Zevalin® and Bexxar® have been approved for imaging and therapy. A preparation containing rituximab, chimeric mAb radio immunoconjugate suitable for Lu-177 labeling, could provide better imaging and therapeutic profile at the same time. This study was conducted to evaluate prepared lyophilized formulations of two rituximab immune conjugates, intended for immediate Lu-177 labeling, for imaging and therapy. The characterization of the conjugates and demonstration of the integrity of the protein and purity after conjugation and lyophilization was performed by SDS-PAGE, FT-IR and MALDI-TOF-MS. The results showed preserved antibody structure and average of 6.1 p-SCN-Bn-DOTA and 8.8 p-SCN-Bn-DTPA groups per antibody molecule which is suitable for successful labeling. These results support the possibility of developing a “ready-to-label” rituximab immune conjugates for NHL imaging/therapy. PMID:27980563
Bekelman, Justin E. Yahalom, Joachim
Purpose: Standards for the reporting of radiotherapy details in randomized controlled trials (RCTs) are lacking. Although radiotherapy (RT) is an important component of curative therapy for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), we postulated that RT reporting may be inadequate in Phase III HL and NHL trials. Methods and Materials: We searched PubMed and the Cochrane registry for reports of RCTs involving RT and either HL or NHL published between 1998 and 2007. We screened 133 titles and abstracts to identify relevant studies. We included a total of 61 reports. We assessed these reports for the presence of six quality measures: target volume, radiation dose, fractionation, radiation prescription, quality assurance (QA) process use, and adherence to QA (i.e., reporting of major or minor deviations). Results: Of 61 reports, 23 (38%) described the target volume. Of the 42 reports involving involved-field RT alone, only 8 (19%) adequately described the target volume. The radiation dose and fractionation was described in most reports (54 reports [89%] and 39 reports [64%], respectively). Thirteen reports specified the RT prescription point (21%). Only 12 reports (20%) described using a RT QA process, and 7 reports (11%) described adherence to the QA process. Conclusion: Reporting of RT in HL and NHL RCTs is deficient. Because the interpretation, replication, and application of RCT results depend on adequate description and QA of therapeutic interventions, consensus standards for RT reporting should be developed and integrated into the peer-review process.
Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity, inhibits proliferation, promotes endo-reduplication and induces apoptosis in T-NHL cell lines supporting its importance in PTCL treatment.
Qi, Wenqing; Spier, Catherine; Liu, Xiaobing; Agarwal, Amit; Cooke, Laurence S; Persky, Daniel O; Chen, Deyu; Miller, Thomas P; Mahadevan, Daruka
Peripheral T-cell lymphomas (PTCL) are a diverse group of rare non-Hodgkin lymphomas (NHL) that carry a poor prognosis and are in need of effective therapies. Alisertib (MLN8237) an investigational agent that inhibits Aurora A Ser/Thr kinase has shown activity in PTCL patients. Here we demonstrate that aurora A and B are highly expressed in T-cell lymphoma cell lines. In PTCL patient samples aurora A was positive in 3 of 24 samples and co-expressed with aurora B. Aurora B was positive in tumor cells in 22 of 32 samples. Of the subtypes of PTCL, aurora B was over-expressed in PTCL (NOS) [73%], T-NHL [100%], ALCL (Alk-Neg) [100%] and AITL [100%]. Treatment with MLN8237 inhibited PTCL cell proliferation in CRL-2396 and TIB-48 cells with an IC50 of 80-100nM. MLN8237 induced endo-reduplication in a dose and time dependent manner in PTCL cell lines leading to apoptosis demonstrated by flow cytometry and PARP-cleavage at concentrations achieved in early phase clinical trials. Moreover, inhibition of HisH3 and aurora A phosphorylation was dose dependent and strongly correlated with endo-reduplication. The data provide a sound rationale for aurora inhibition in PTCL as a therapeutic modality and warrants clinical trial evaluation.
Lykken, Jacquelyn M; Horikawa, Mayuka; Minard-Colin, Veronique; Kamata, Masahiro; Miyagaki, Tomomitsu; Poe, Jonathan C; Tedder, Thomas F
Non-Hodgkin lymphoma (NHL) is the most commonly diagnosed hematologic cancer of adults in the United States, with the vast majority of NHLs deriving from malignant B lymphocytes that express cell surface CD20. CD20 immunotherapy (rituximab) is widely used to treat NHL, even though the initial effectiveness of rituximab varies widely among patients and typically wanes over time. The mechanisms through which lymphomas initially resist or gain resistance to immunotherapy are not well established. To address this, a preclinical mouse model system was developed to comprehensively identify lymphoma transcriptomic changes that confer resistance to CD20 immunotherapy. The generation of spontaneous primary and familial lymphomas revealed that sensitivity to CD20 immunotherapy was not regulated by differences in CD20 expression, prior exposure to CD20 immunotherapy, or serial in vivo passage. An unbiased forward exome screen of these primary lymphomas was used to validate the utility of this expansive lymphoma cohort, which revealed that increased lymphoma galectin-1 (Gal-1) expression strongly correlated with resistance to immunotherapy. Genetically induced lymphoma Gal-1 expression ablated antibody-dependent lymphoma phagocytosis in vitro and lymphoma sensitivity to CD20 immunotherapy in vivo. Human NHLs also express elevated Gal-1 compared with nonmalignant lymphocytes, demonstrating the ability of this preclinical model system to identify molecular targets that could be relevant to human therapy. This study therefore established a powerful preclinical model system that permits the comprehensive identification of the dynamic lymphoma molecular network that drives resistance to immunotherapy.
Lykken, Jacquelyn M.; Horikawa, Mayuka; Minard-Colin, Veronique; Kamata, Masahiro; Miyagaki, Tomomitsu; Poe, Jonathan C.
Non-Hodgkin lymphoma (NHL) is the most commonly diagnosed hematologic cancer of adults in the United States, with the vast majority of NHLs deriving from malignant B lymphocytes that express cell surface CD20. CD20 immunotherapy (rituximab) is widely used to treat NHL, even though the initial effectiveness of rituximab varies widely among patients and typically wanes over time. The mechanisms through which lymphomas initially resist or gain resistance to immunotherapy are not well established. To address this, a preclinical mouse model system was developed to comprehensively identify lymphoma transcriptomic changes that confer resistance to CD20 immunotherapy. The generation of spontaneous primary and familial lymphomas revealed that sensitivity to CD20 immunotherapy was not regulated by differences in CD20 expression, prior exposure to CD20 immunotherapy, or serial in vivo passage. An unbiased forward exome screen of these primary lymphomas was used to validate the utility of this expansive lymphoma cohort, which revealed that increased lymphoma galectin-1 (Gal-1) expression strongly correlated with resistance to immunotherapy. Genetically induced lymphoma Gal-1 expression ablated antibody-dependent lymphoma phagocytosis in vitro and lymphoma sensitivity to CD20 immunotherapy in vivo. Human NHLs also express elevated Gal-1 compared with nonmalignant lymphocytes, demonstrating the ability of this preclinical model system to identify molecular targets that could be relevant to human therapy. This study therefore established a powerful preclinical model system that permits the comprehensive identification of the dynamic lymphoma molecular network that drives resistance to immunotherapy. PMID:26888257
Leiba, Merav; Leiba, Adi; Keinan-Boker, Lital; Avigdor, Abraham; Derazne, Estela; Levine, Hagai; Kark, Jeremy D
The age-adjusted annual incidence of non-Hodgkin lymphoma (NHL) has risen worldwide. This trend may be affected by the secular increase in height and the sharp upswing in adolescent overweight; these drive increased insulinlike growth factor 1 and chronic inflammation, which may play an etiologic role. This study examined the association of the body mass index (BMI) and height of adolescents with NHL subtypes, which have been insufficiently evaluated. Health-related data on 2,352,988 Israeli adolescents, aged 16 to 19 years, who were examined between 1967 and 2011 were linked to the Israel National Cancer Registry to derive the NHL incidence up to December 31, 2012 (4021 cases). Cox proportional hazards modeling was used to estimate the multivariate-adjusted hazard ratio (HR) for NHL subtypes associated with the BMI and height of adolescents. Adolescent overweight and obesity were associated with an HR of 1.25 (95% confidence interval [CI], 1.13-1.37; P = 1.14 × 10(-5) ) for NHL in comparison with normal weight. There was a graded association of height with NHL (P = 4.29 × 10(-9) ), with the tallest adolescents (≥ 95th percentile vs 25th to < 50th percentiles [US Centers for Disease Control and Prevention]) exhibiting an HR of 1.28 (95% CI, 1.04-1.56). Marginal zone lymphoma, primary cutaneous lymphoma (PCL), and diffuse large B-cell lymphoma (DLBCL) showed the strongest associations for overweight/obesity, and DLBCL and PCL showed the strongest associations for height. The findings of this large cohort study add to the growing body of evidence showing that higher body weight and taller stature during adolescence are associated with an increased risk of NHL and may modestly contribute to its increasing incidence. Further studies are needed to elucidate the mechanisms linking anthropometric measures and NHL risk. © 2016 American Cancer Society.
Gunnellini, Marco; Falchi, Lorenzo
Mantle cell lymphoma (MCL) comprises 3-10% of NHL, with survival times ranging from 3 and 5 years. Indolent lymphomas represent approximately 30% of all NHLs with patient survival largely dependent on validated prognostic scores. High response rates are typically achieved in these patients with current first-line chemoimmunotherapy. However, most patients will eventually relapse and become chemorefractory with poor outcome. Alternative chemoimmunotherapy regimens are often used as salvage strategy and stem cell transplant remains an option for selected patients. However, novel approaches are urgently needed for patients no longer responding to conventional chemotherapy. Lenalidomide is an immunomodulatory drug with activity in multiple myeloma, myelodisplastic syndrome and chronic lymphoproliferative disorders. In phase II studies of indolent NHL and MCL lenalidomide has shown activity with encouraging response rates, both as a single agent and in combination with other drugs. Some of these responses may be durable. Optimal dose of lenalidomide has not been defined yet. The role of lenalidomide in the therapeutic armamentarium of patients with indolent NHL or MCL will be discussed in the present paper.
Gunnellini, Marco; Falchi, Lorenzo
Mantle cell lymphoma (MCL) comprises 3–10% of NHL, with survival times ranging from 3 and 5 years. Indolent lymphomas represent approximately 30% of all NHLs with patient survival largely dependent on validated prognostic scores. High response rates are typically achieved in these patients with current first-line chemoimmunotherapy. However, most patients will eventually relapse and become chemorefractory with poor outcome. Alternative chemoimmunotherapy regimens are often used as salvage strategy and stem cell transplant remains an option for selected patients. However, novel approaches are urgently needed for patients no longer responding to conventional chemotherapy. Lenalidomide is an immunomodulatory drug with activity in multiple myeloma, myelodisplastic syndrome and chronic lymphoproliferative disorders. In phase II studies of indolent NHL and MCL lenalidomide has shown activity with encouraging response rates, both as a single agent and in combination with other drugs. Some of these responses may be durable. Optimal dose of lenalidomide has not been defined yet. The role of lenalidomide in the therapeutic armamentarium of patients with indolent NHL or MCL will be discussed in the present paper. PMID:22761620
Minoia, Carla; Quero, Carmela; Asselti, Mariaconsilia; Galise, Ida; Marzano, Alessia L; Iacobazzi, Angela; Rana, Antonio; Merchionne, Francesca; Serratì, Simona; De Tullio, Giacoma; Quintana, Giovanni; Casiello, Michela; Maiorano, Eugenio; Simone, Giovanni; Zito, Francesco A; Iacopino, Pasquale; Guarini, Attilio
Angiogenesis is involved in the pathogenesis and progression of non-Hodgkin lymphomas (NHL), and hypoxia-inducible factor-1α (HIF-1α, also termed HIF1A) might contribute to this process. Currently, there is no direct evidence that the clinical progression of indolent NHL is associated with angiogenesis, and the expression of HIF-1α at recurrence is unknown. Matched lymph node biopsies at diagnosis and recurrence of relapsed/refractory indolent NHL patients were analysed by immunohistochemical and morphometric analysis. We observed an increased vascular network and HIF-1α protein expression in the second biopsy, providing direct evidence that angiogenesis is an essential process for disease progression.
Conde, Lucia; Slager, Susan L.; Brooks-Wilson, Angela; Morton, Lindsay; Skibola, Danica R.; Novak, Anne J.; Riby, Jacques; Ansell, Stephen M.; Halperin, Eran; Shanafelt, Tait D.; Agana, Luz; Wang, Alice H.; De Roos, Anneclaire J.; Severson, Richard K.; Cozen, Wendy; Spinelli, John; Butterbach, Katja; Becker, Nikolaus; de Sanjose, Silvia; Benavente, Yolanda; Cocco, Pierluigi; Staines, Anthony; Maynadié, Marc; Foretova, Lenka; Boffetta, Paolo; Brennan, Paul; Lan, Qing; Zhang, Yawei; Zheng, Tongzhang; Purdue, Mark; Armstrong, Bruce; Kricker, Anne; Vajdic, Claire M.; Grulich, Andrew; Smith, Martyn T.; Bracci, Paige M.; Chanock, Stephen J.; Hartge, Patricia; Cerhan, James R.; Wang, Sophia S.; Rothman, Nathaniel; Skibola, Christine F.
Many common genetic variants have been associated with non-Hodgkin lymphoma (NHL), but individual study results are often conflicting. To confirm the role of putative risk alleles in B-cell NHL etiology, we performed a validation genotyping study of 67 candidate single nucleotide polymorphisms within InterLymph, a large international consortium of NHL case-control studies. A meta-analysis was performed on data from 5633 B-cell NHL cases and 7034 controls from 8 InterLymph studies. rs3789068 in the proapoptotic BCL2L11 gene was associated with an increased risk for B-cell NHL (odds ratio = 1.21, P random = 2.21 × 10−11), with similar risk estimates for common B-cell subtypes. PRRC2A rs3132453 in the HLA complex class III region conferred a reduced risk of B-cell NHL (odds ratio = 0.68, P random = 1.07 × 10−9) and was likewise evident for common B-cell subtypes. These results are consistent with the known biology of NHL and provide insights into shared pathogenic components, including apoptosis and immune regulation, for the major B-cell lymphoma subtypes. PMID:23047821
Saraf, Sonali Rajesh; Naphade, Nilesh S; Kalgutkar, Alka D
As in any medical disorder, in non-Hodgkin lymphomas (NHLs) also, precise analysis of causes of death is needed to focus research efforts and improve morbidity and mortality. The aim of this study was to review the clinical presentation, mode of death and the immunophenotype of the autopsy cases of NHL. Autopsy cases wherein NHL was diagnosed, were selected for study. Autopsy cases which were diagnosed as NHL, either antemortem or after autopsy during a 7 years period at a tertiary care referral centre were studied and reviewed. Descriptive statistical analysis used. The autopsy findings seen in eight cases of NHL were reviewed. Except one, all cases were above 40 years age. Infective etiology (62%) followed by cardiorespiratory failure (38%) was the cause of death observed in these patients. In three cases, the antemortem diagnosis of NHL was missed as the patients were being treated for acute febrile illness and were referred late to the Tertiary Care Centre. One of these was a case of extra-nodal primary splenic lymphoma. As NHL present with nonspecific symptoms, these tumours may not be detected in early stages and hence may not be treated appropriately. These patients have weakened immunity and hence are prone to infection and sepsis which can be a major cause of mortality. This autopsy study experience has shown that NHL can masquerade as acute febrile illness which if not detected early and treated adequately can turn fatal.
Baras, Nadia; Dahm, Stefan; Haberland, Jörg; Janz, Martin; Emrich, Katharina; Kraywinkel, Klaus; Salama, Abdulgabar
The increased risk of subsequent primary malignancies (SPM) in survivors of adult-onset Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) remains a challenging clinical problem worldwide. The German cancer registry database, pooled from 14 federal states, was used to calculate the standardized incidence ratio (SIR) and excess absolute risk (EAR) of SPM in 128 587 patients registered with first primary HL/NHL between 1990 and 2012. Conversely, SIRs were also calculated for a subsequent HL/NHL following other first cancers. The risk of developing SPM was significantly increased over twofold for HL survivors (SIR = 2·14, EAR = 51·87 cases/10 000 person-years) and 1·5-fold for NHL survivors (SIR = 1·48, EAR = 55·23) compared with the general German population. For solid cancers, SIRs were significantly elevated (1·6- and 1·4-fold; respectively) and were highest (threefold) in patients below 30 years of age upon initial diagnosis. Overall, SIRs were consistently elevated for lip/oral cavity, colon/rectum, lung, skin melanoma, breast, kidney and thyroid. Significantly increased SIRs for oesophagus, stomach, liver, pancreas, testis, prostate, and brain/central nervous system were observed following NHL only. For certain SPM, SIRs remained significantly elevated more than 10 years following HL/NHL diagnosis. Positive reciprocal associations were demonstrated between HL/NHL and several solid cancers mentioned above; for some, common aetiological mechanisms seem plausible. © 2017 John Wiley & Sons Ltd.
Suthandiram, Sujatha; Gan, Gin Gin; Zain, Shamsul Mohd; Haerian, Batoul Sadat; Bee, Ping Chong; Lian, Lay Hoong; Chang, Kian Meng; Ong, Tee Chuan; Mohamed, Zahurin
An imbalance in folate metabolism can adversely affect DNA synthesis and methylation systems which can lead to susceptibility to non-Hodgkin lymphoma (NHL). Whether single nucleotide polymorphisms (SNPs) and their haplotypes in the methylenetetrahydrofolate reductase (MTHFR) are associated with NHL, remain inconclusive. We investigated the association between MTHFR C677T and A1298C SNPs and NHL risk in a population which is made up of Malay, Chinese and Indian ethnic subgroups. A total of 372 NHL patients and 722 controls were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects failed to demonstrate significant association between the MTHFR C677T and A1298C SNPs with NHL and its subtypes. The results were in agreement with the previous meta-analyses. In the Indian ethnic subgroup however, single locus analysis of MTHFR A1298C appears to confer risk to NHL (Odds ratio (OR) 1.91, 95% confidence interval (95% CI) 1.22-3.00, P=0.006). The risk is almost doubled in homozygous carrier of MTHFR 1298CC (OR 4.03, 95% CI 1.56-10.43, P=0.004). Haplotype analysis revealed higher frequency of CC in the Indian NHL patients compared with controls (OR 1.86, 95% CI 1.18-2.93, P=0.007). There is lack of evidence to suggest an association between MTHFR C677T and A1298C with the risk of NHL in the Malays and Chinese. In the Indians however, the MTHFR A1298C confers risk to NHL. This study suggests ethnicity modifies the relationship between polymorphisms in the folate-metabolizing gene and NHL.
Gathany, Allison H; Hartge, Patricia; Davis, Scott; Cerhan, James R; Severson, Richard K; Cozen, Wendy; Rothman, Nathaniel; Chanock, Stephen J; Wang, Sophia S
Sun exposure and sensitivity, including pigmentation, are associated with risk for non-Hodgkin lymphoma (NHL). One variant in the immune regulatory factor 4 (IRF4) gene (rs12203592) is associated with pigmentation, and a different IRF4 variant (rs12211228) is associated with NHL risk. We evaluated the independent roles of these IRF4 polymorphisms and sun sensitivity in mediating NHL risk and explored whether they are confounded or modified by each other. Genotyping of tag single nucleotide polymorphisms (SNPs) in the IRF4 gene was conducted in 990 NHL cases and 828 controls from a multi-center US study. Measures of sun sensitivity and exposure were ascertained from computer-assisted personal interviews. We used logistic regression to compute odds ratios (OR) and 95% confidence intervals (CI) for NHL in relation to sun exposures, sun exposures in relation to IRF4 genotypes, and NHL in relation to sun exposures. We further assessed the effects of sun exposures in relation to IRF4 genotypes. As previously reported, we found significant associations between IRF4 rs12211228 and NHL and between hair and eye color and NHL. The IRF4 rs12203592 polymorphism (CT/TT genotype) was statistically significantly associated with eye color and particularly with hair color (OR(Light Blonde) = 0.24, 95% CI = 0.11-0.50, overall Chi square p = 0.0002). Analysis of joint effects between eye and hair color with the IRF4 rs12203592 SNP did not reveal statistically significant p-interactions although NHL risk did decline with lighter hair color and presence of the variant IRF4 rs12203592 allele, compared to those without a variant allele and with black/brown hair color. Our data do not statistically support a joint effect between IRF4 and sun sensitivity in mediating risk for NHL. Further evaluation of joint effects in other and larger populations is warranted.
Khelfa, Yousef; Lebowicz, Yehuda
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), representing approximately 25% of diagnosed NHL. DLBCL is heterogeneous disease both clinically and genetically. The 3 most common chromosomal translocations in DLBCL involve the oncogenes BCL2, BCL6, and MYC. Double hit (DH) DLBCL is an aggressive form in which MYC rearrangement is associated with either BCL2 or BCL6 rearrangement. Patients typically present with a rapidly growing mass, often with B symptoms. Extranodal disease is often present. Though there is a paucity of prospective trials in this subtype, double hit lymphoma (DHL) has been linked to very poor outcomes when patients are treated with standard R-CHOP. There is, therefore, a lack of consensus regarding the standard treatment for DHL. Several retrospective analyses have been conducted to help guide treatment of this disease. These suggest that DA EPOCH-R may be the most promising regimen and that achievement of complete resolution predicts better long-term outcomes. PMID:27115017
Hoffmann, Christian; Schommers, Philipp; Wolf, Eva; Müller, Markus; Schultze, Alexander; Krznaric, Ivanka; Stoehr, Albrecht; Wolf, Timo; Fäktenheuer, Gerd; Stier, Bastian; Wyen, Christoph; Hentrich, Marcus
The risk of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) is increased in HIV-infected individuals. We studied the kinetics of lymphocyte subsets in patients who subsequently developed HL or NHL while on virologically suppressive antiretroviral therapy (ART). Using a nested case-control design, cases of HIV+ HL or NHL were selected from two prospective clinical studies. Aviremia was defined as less than 200 HIV-RNA copies/ml for at least 6 months prior to lymphoma diagnosis. Each case was matched to three aviremic HIV+ controls without lymphoma. In the 81 cases (50 HL and 31 NHL), prediagnostic CD4 T cells and CD8 T cells displayed discordant kinetics compared with controls. Within the last and within the next-to-last year preceding HL diagnosis, mean CD4 T cells decreased by -168 and by -2 cells/μl, compared with an increase of +44 and +73 cells/μl in the controls, respectively. Mean CD8 T cells decreased by -352 and -115 cells/μl, compared with nonsignificant changes of -29 and ±0 cells/μl in the controls, respectively. T-cell kinetics demonstrated a marked inter-individual variability. Kinetics of CD4 and CD8 T cells were also discordant between NHL cases and controls. This study on a large number of aviremic patients developing HL and NHL who were carefully matched with controls, gives insights to prediagnostic kinetics of immune parameters. The discordant kinetics of both CD4 and CD8 T cells are already seen 1-2 years prior to lymphoma diagnosis, are more pronounced during the last year and in patients developing HL but are also seen in NHL.
Xu, Yan; Wang, Jin; Yang, Nan; Bai, Ju; Zhang, Peng-Yu; Gu, Liu-Fang; Lei, Bo; Liu, Jie; Wang, Fang-Xia; Huang, Bing-Qiao; Zhang, Wang-Gang; He, Ai-Li; Cao, Xing-Mei; Chen, Yin-Xia; Ma, Xiao-Rong
To explore the effectiveness and safety of combined chemotherapy with pegasparaginase (PEG-Asp) for treatment of patients with acute lymphoblastic leukemia (ALL) and T cell non-Hodgkin's lymphoma (T-NHL) patients. A total of 62 ALL or T-NHL patients were diagnosed and treated in our department and were enrolled in this study. Among them, 22 patients received the combined chemotherapy with PEG-Asp, while the other 40 patients received the standard chemotherapy with L-asparaginase (L-Asp) as the control. Therapeutic effectiveness, adverse effects, duration and expense of hospitalization, treatment-related mortality and survival were evaluated and compared in 2 different groups. In group of combined chemotherapy with PEG-Asp, the overall response rate was 90.91% (20 cases), among them CR rate and PR rate are 77.27% (17 cases) and 13.64% (3 cases), respectively. In the group of standard chemotherapy with L-Asp, the overall response rate was 87.5% (35 cases), among them CR rate and PR rate were 72.5% (29 cases) and 15% (6 cases), respectively. The difference neither between PEG-Asp and L-Asp chemotherapy groups nor between ALL and T-NHL subgroups was significant (P > 0.05). The 6-month and 12-month overall survival rates were not significantly different between the PEG-Asp and L-Asp chemotherapy groups, respectively (P > 0.05). The adverse effects were identified as degree 1-2 according to the WHO criteria of drug toxicity. Neither the adverse effects identified as degree 3-4 nor the treatment-related death were observed. Expect for allergy and hyperglycaemia, the difference of side-effect incidence between the two groups were not significant (P > 0.05). The treatment for all the patients in PEG-Asp chemotherapy group was completed, while the treatment with L-Asp was completed only in 29 cases. Moreover, both average duration and expense of hospitalization after the combined chemotherapy were less than the control. With higher response rate, lower drug toxicity and
Wulczyn, F Gregory; Cuevas, Elisa; Franzoni, Eleonora; Rybak, Agnieszka
Trim-NHL proteins are defined by RING, B-Box and Coiled-coil protein motifs (referred to collectively as the Trim domain) coupled to an NHL domain. The C. elegans, D. melanogaster, mouse and human Trim-NHL proteins are potential and in several cases confirmed, E3 ubiquitin ligases. Current research is focused on identifying targets and pathways for Trim-NHL-mediated ubiquitination and in assessing the contribution of the NHL protein-protein interactiondomain for function and specificity. Several Trim-NHL proteins were discovered in screens for developmental genes in model organisms; mutations in one of the family members, Trim32, cause developmental disturbances in humans. In most instances, mutations that alter protein function map to the NHL domain. The NHL domain is a scaffold for the assembly of a translational repressor complex by the Brat proto-oncogene, a well-studied family member in Drosophila. The link to translational control is common to at least four Trim-NHLs that associate with miRNA pathway proteins. So far, two have been shown to repress (Mei-P26 and Lin41) and two to promote (NHL-2, Trim32) miRNA-mediated gene silencing. In this chapter we will describe structure-function relations for each of the proteins and then focus on the lessons being learned from these proteins about miRNA functions in development and in stem cell biology.
Wulczyn, F Gregory; Cuevas, Elisa; Franzoni, Eleonora; Rybak, Agnieszka
Trim-NHL proteins are defined by RING, B-Box and Coiled-coil protein motifs (referred to collectively as the Trim domain) coupled to an NHL domain. The C. elegans, D. melanogaster, mouse and human Trim-NHL proteins are potential and in several cases confirmed, E3 ubiquitin ligases. Current research is focused on identifying targets and pathways for Trim-NHL-mediated ubiquitination and in assessing the contribution of the NHL protein-protein interaction domain for function and specificity. Several Trim-NHL proteins were discovered in screens for developmental genes in model organisms; mutations in one of the family members, Trim32, cause developmental disturbances in humans. In most instances, mutations that alter protein function map to the NHL domain. The NHL domain is a scaffold for the assembly of a translational repressor complex by the Brat proto-oncogene, a well-studied family member in Drosophila. The link to translational control is common to at least four Trim-NHLs that associate with miRNA pathway proteins. So far, two have been shown to repress (Mei-P26 and Lin41) and two to promote (NHL-2, Trim32) miRNA-mediated gene silencing. In this chapter we will describe structure-function relations for each of the proteins and then focus on the lessons being learned from these proteins about miRNA functions in development and in stem cell biology.
Ferry, Judith A
Lymphomas arising in extranodal sites are intriguing. The types of lymphomas encountered vary widely from one extranodal site to another. For many types of extranodal lymphomas, there are distinctive clinicopathologic features, sometimes including association with an underlying immunodeficiency syndrome, autoimmune disease, infection, or other immunologic disorder, or a predilection to affect patients of certain ethnic origins. Presented below is a review of lymphomas that are encountered most often in extranodal sites.
Rybka, Justyna; Jurczak, Wojciech; Giza, Agnieszka; Paszkiewicz-Kozik, Ewa; Kumiega, Beata; Drozd-Sokołowska, Joanna; Butrym, Aleksandra; Kuliczkowski, Kazimierz; Wróbel, Tomasz
The treatment of patients with relapsed or refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) remains challenging. Gemcitabine is a cytidine analog with a wide spectrum of antitumor activity. Gemcitabine treatment is widely used to treat patients with certain solid tumors and relapsed/refractory hematological malignancies. There are several reports indicating that this compound is active in lymphoid malignancies. In patients with relapsed or refractory HL and NHL, gemcitabine has demonstrated efficacy as a single agent and in combination with other cytostatics. The aim of the study was to analyze the efficacy and toxicity of gemcitabine-based chemotherapy in patients with relapsed or refractory lymphomas. The study evaluated 68 heavily pretreated patients with relapsed/refractory HL and NHL. The median age of the patients was 36 years. All the patients received gemcitabine-based chemotherapy (gemcitabine monotherapy or gemcitabine in combination with other cytostatics). The overall response rate was 46%. Complete response was achieved by 21% of the patients and partial response by 25%. Out of those who responded to gemcitabine treatment, 26 patients proceeded to autologous stem cell transplant. Toxicities connected with gemcitabine therapy occurred in 44% of the patients and included grade 3/4 neutropenia, thrombocytopenia and anemia. The results suggest that gemcitabine-based salvage chemotherapy is effective and well tolerated in patients with relapsed/refractory HL and NHL.
Evens, Andrew M; Advani, Ranjana; Press, Oliver W; Lossos, Izidore S; Vose, Julie M; Hernandez-Ilizaliturri, Francisco J; Robinson, Barrett K; Otis, Stavroula; Nadav Dagan, Liat; Abdallah, Ramsey; Kroll-Desrosiers, Aimee; Yarber, Jessica L; Sandoval, Jose; Foyil, Kelley; Parker, Linda M; Gordon, Leo I; Blum, Kristie A; Flowers, Christopher R; Leonard, John P; Habermann, Thomas M; Bartlett, Nancy L
Lymphoma is the fourth most frequent cancer in pregnancy; however, current clinical practice is based largely on small series and case reports. In a multicenter retrospective analysis, we examined treatment, complications, and outcomes for Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) occurring during pregnancy. Among 90 patients (NHL, n = 50; HL, n = 40), median age was 30 years (range, 18 to 44 years) and median diagnosis occurred at 24 weeks gestation. Of patients with NHL, 52% had advanced-stage versus 25% of patients with HL (P = .01). Pregnancy was terminated in six patients. Among the other 84 patients, 28 (33%) had therapy deferred to postpartum; these patients were diagnosed at a median 30 weeks gestation. This compared with 56 patients (67%) who received antenatal therapy with median lymphoma diagnosis at 21 weeks (P < .001); 89% of these patients received combination chemotherapy. The most common preterm complication was induction of labor (33%). Gestation went to full term in 56% of patients with delivery occurring at a median of 37 weeks. There were no differences in maternal complications, perinatal events, or median infant birth weight based on deferred versus antenatal therapy. At 41 months, 3-year progression-free survival (PFS) and overall survival (OS) for NHL were 53% and 82%, respectively, and 85% and 97%, respectively, for HL. On univariate analysis for NHL, radiotherapy predicted inferior PFS, and increased lactate dehydrogenase and poor Eastern Cooperative Oncology Group performance status (ECOG PS) portended worse OS. For HL patients, nulliparous status and "B" symptoms predicted inferior PFS. Standard (non-antimetabolite) combination chemotherapy administered past the first trimester, as early as 13 weeks gestation, was associated with few complications and expected maternal survival with lymphoma occurring during pregnancy.
Gabellier, Ludovic; Cartron, Guillaume
The use of anti-CD20 monoclonal antibodies (mAbs), such as rituximab, in CD20-positive B-cell malignancies has dramatically improved the outcome of chronic lymphoid leukemia and non-Hodgkin's lymphomas (NHL). However, the occurrence of relapse and development of rituximab-refractory disease highlight the need to develop novel anti-CD20 mAbs, with improved mechanisms of action. Obinutuzumab is the first humanized type II glycoengineered anti-CD20 mAb. In vitro and in vivo data suggested several differences compared with rituximab, including a low level of complement-dependent cytotoxicity and an increased direct nonapoptotic cell death. Moreover, the glycoengineered Fc-linked nonfucosylated oligosaccharide enhanced the Fc-Fcγ receptor (FcγR) IIIa interaction, resulting in improved antibody-dependent cellular cytotoxicity and phagocytosis. Preclinical models suggested that these differences translate into superior survival in murine lymphoma models. Phase I/II trials in monotherapy in relapsed or refractory B-cell NHL demonstrated that obinutuzumab has an acceptable safety profile, infusion-related reactions being the most common adverse event. In rituximab-refractory indolent NHL, the recent randomized phase III GADOLIN study demonstrated an improved median progression-free survival for patients treated with obinutuzumab plus bendamustine rather than bendamustine alone. Further trials are ongoing to determine the role of obinutuzumab as a first-line agent in the treatment of follicular lymphoma.
Yin, Haibing; Zhong, Fei; Ouyang, Yu; Wang, Qiru; Ding, Linlin; He, Song
ADAM12 is a member of a disintegrin and metalloproteinase family and has been reported to participate in the development of variety of tumors. However, the role of ADAM12 in Non-Hodgkin Lymphoma (NHL) has not been investigated. The present study was undertaken to determine the expression and biologic function of ADAM12 in human NHL. First, we constructed a model of cell adhesion in NHL, the mRNA, and protein level of ADAM12 in suspension and the adhesion model was analyzed by RT-PCR and western blot. Then, flow cytometry assay and western blot were used to investigate the mechanism of ADAM12 in the proliferation of NHL cells. In vitro, after using siRNA interfering ADAM12 expression, we performed adhesion assay and cell viability assay to determine the effect of ADAM12 on adhesive rate and drug sensitivity. ADAM12 was lowly expressed in suspended cells and highly expressed in adherent NHL cells. In addition, ADAM12 was positively correlated with the proliferation and apoptosis of NHL cells by regulating the expression of p-AKT and p-GSK-3β. Furthermore, ADAM12 promoted cell adhesion-mediated drug resistance (CAM-DR) in DLBCL via AKT signaling pathway. Our data support a role for ADAM12 in NHL cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in NHL.
Libra, Massimo; Capello, Daniela; Gloghini, Annunziata; Laura, Pasqualucci; Berra, Eva; Cerri, Michaela; Gasparotto, Daniela; Franca, Stivala; De Re, Valli; Gaidano, Gianluca; Carbone, Antonino
Hepatitis C virus (HCV) and aberrant somatic hypermutation (SHM) have each been suggested to contribute to the development of B-cell non-Hodgkin's lymphoma (NHL). The incidence of PIM-1, PAX-5, RhoH/TTF, and c-MYC mutations in tumour biopsy specimens from 32 HCV-infected B-cell NHL patients was analysed to determine whether the extent of aberrant SHM among these patients differed from that previously reported for HCV-negative B-cell NHL patients. Mutation of PIM-1, PAX-5, RhoH/TTF, and c-MYC was detected in 4 (13%), 5 (16%), 4 (13%), and 4 (13%) of 32 samples, respectively. In HCV-positive B-cell NHL patients, the frequency of aberrant SHM was lower than that already found in HCV-negative B-cell NHL patients. This indicates that, unlike B-cell lymphomas from HCV-negative patients, aberrant SHM may not contribute significantly to malignant transformation in HCV-associated B-cell lymphomas. 2005 Pathological Society of Great Britain and Ireland
Yu, Shuang; Yin, Congcong; Li, Peng; Ye, Jingjing; Ma, Daoxin; Ji, Chunyan
T helper (Th) 22 cells play important roles in the pathogenesis of autoimmune and inflammatory diseases, and their function in tumors remains uncertain. In the current study, we investigated the alternations and clinical significance of circulating Th22 cells in patients with B-cell non-Hodgkin's lymphoma (B-NHL). We found that the frequency of Th22 cells was significantly elevated in peripheral blood of newly-diagnosed B-NHL patients, and returned to normal level after chemotherapy. In consistent with increased Th22 frequency, plasma IL-22 and IL-6 levels in B-NHL patients were remarkably increased. Moreover, the increased Th22 frequency was associated with the older age (> 60 yr) and a poorer response to therapy in B-NHL patients. In addition, there existed a statistically positive correlation between circulating Th22 and Th17 frequencies in B-NHL patients. Our data demonstrated that circulating Th22 frequency was associated with the clinical outcome and prognosis of B-NHL patients, indicating that Th22 immune response might play an important role in the development and progression of B-NHL. PMID:27489357
Lu, Ting; Liu, Yan; Yu, Shuang; Yin, Congcong; Li, Peng; Ye, Jingjing; Ma, Daoxin; Ji, Chunyan
T helper (Th) 22 cells play important roles in the pathogenesis of autoimmune and inflammatory diseases, and their function in tumors remains uncertain. In the current study, we investigated the alternations and clinical significance of circulating Th22 cells in patients with B-cell non-Hodgkin's lymphoma (B-NHL). We found that the frequency of Th22 cells was significantly elevated in peripheral blood of newly-diagnosed B-NHL patients, and returned to normal level after chemotherapy. In consistent with increased Th22 frequency, plasma IL-22 and IL-6 levels in B-NHL patients were remarkably increased. Moreover, the increased Th22 frequency was associated with the older age (> 60 yr) and a poorer response to therapy in B-NHL patients. In addition, there existed a statistically positive correlation between circulating Th22 and Th17 frequencies in B-NHL patients. Our data demonstrated that circulating Th22 frequency was associated with the clinical outcome and prognosis of B-NHL patients, indicating that Th22 immune response might play an important role in the development and progression of B-NHL.
Bassig, Bryan A.; Lan, Qing; Rothman, Nathaniel; Zhang, Yawei; Zheng, Tongzhang
The incidence rates of non-Hodgkin lymphoma (NHL) have steadily increased over the last several decades in the United States, and the temporal trends in incidence can only be partially explained by the HIV epidemic. In 1992, an international workshop sponsored by the United States National Cancer Institute concluded that there was an “emerging epidemic” of NHL and emphasized the need to investigate the factors responsible for the increasing incidence of this disease. Over the past two decades, numerous epidemiological studies have examined the risk factors for NHL, particularly for putative environmental and lifestyle risk factors, and international consortia have been established in order to investigate rare exposures and NHL subtype-specific associations. While few consistent risk factors for NHL aside from immunosuppression and certain infectious agents have emerged, suggestive associations with several lifestyle and environmental factors have been reported in epidemiologic studies. Further, increasing evidence has suggested that the effects of these and other exposures may be limited to or stronger for particular NHL subtypes. This paper examines the progress that has been made over the last twenty years in elucidating the etiology of NHL, with a primary emphasis on lifestyle factors and environmental exposures. PMID:23008714
Bhatt, Aadra P.; Jacobs, Sarah R.; Freemerman, Alex J.; Makowski, Liza; Rathmell, Jeffrey C.; Dittmer, Dirk P.; Damania, Blossom
The metabolic differences between B-NHL and primary human B cells are poorly understood. Among human B-cell non-Hodgkin lymphomas (B-NHL), primary effusion lymphoma (PEL) is a unique subset that is linked to infection with Kaposi's sarcoma-associated herpesvirus (KSHV). We report that the metabolic profiles of primary B cells are significantly different from that of PEL. Compared with primary B cells, both aerobic glycolysis and fatty acid synthesis (FAS) are up-regulated in PEL and other types of nonviral B-NHL. We found that aerobic glycolysis and FAS occur in a PI3K-dependent manner and appear to be interdependent. PEL overexpress the fatty acid synthesizing enzyme, FASN, and both PEL and other B-NHL were much more sensitive to the FAS inhibitor, C75, than primary B cells. Our findings suggest that FASN may be a unique candidate for molecular targeted therapy against PEL and other B-NHL. PMID:22752304
Grulich, Andrew E; Vajdic, Claire M; Falster, Michael O; Kane, Eleanor; Smedby, Karin Ekstrom; Bracci, Paige M; de Sanjose, Silvia; Becker, Nikolaus; Turner, Jenny; Martinez-Maza, Otoniel; Melbye, Mads; Engels, Eric A; Vineis, Paolo; Costantini, Adele Seniori; Holly, Elizabeth A; Spinelli, John J; La Vecchia, Carlo; Zheng, Tongzhang; Chiu, Brian C H; Franceschi, Silvia; Cocco, Pierluigi; Maynadié, Marc; Foretova, Lenka; Staines, Anthony; Brennan, Paul; Davis, Scott; Severson, Richard K; Cerhan, James R; Breen, Elizabeth C; Birmann, Brenda; Cozen, Wendy
There is inconsistent evidence that increasing birth order may be associated with risk of non-Hodgkin lymphoma (NHL). The authors examined the association between birth order and related variables and NHL risk in a pooled analysis (1983-2005) of 13,535 cases and 16,427 controls from 18 case-control studies within the International Lymphoma Epidemiology Consortium (InterLymph). Overall, the authors found no significant association between increasing birth order and risk of NHL (P-trend = 0.082) and significant heterogeneity. However, a significant association was present for a number of B- and T-cell NHL subtypes. There was considerable variation in the study-specific risks which was partly explained by study design and participant characteristics. In particular, a significant positive association was present in population-based studies, which had lower response rates in cases and controls, but not in hospital-based studies. A significant positive association was present in higher-socioeconomic-status (SES) participants only. Results were very similar for the related variable of sibship size. The known correlation of high birth order with low SES suggests that selection bias related to SES may be responsible for the association between birth order and NHL.
Chao, Chun; Jacobson, Lisa P; Tashkin, Donald; Martínez-Maza, Otoniel; Roth, Michael D; Margolick, Joseph B; Chmiel, Joan S; Holloway, Marcy N; Zhang, Zuo-Feng; Detels, Roger
The results of many laboratory studies suggest that amphetamine use may lead to altered immune function and cytokine expression, both of which are implicated in HIV-related lymphomagenesis. We examined the hypothesis that use of amphetamines modifies risk of non-Hodgkin lymphoma (NHL) in HIV-infected men in the Multicenter AIDS Cohort Study. Data on amphetamine use were collected every six months during the follow-up period between 1984 and 2002. A total of 171 NHL cases were diagnosed from the 19,250 person-years accrued. Multivariable Cox models were used to estimate the effects of baseline exposures, time-varying recent exposures, and three years lagged exposures on risk of NHL adjusting for potential confounders such as demographics, use of other substances, and risky sexual behaviors. We found that weekly or more frequent use of amphetamines was associated with an increased risk of NHL, with hazard ratios of 1.75 (95% CI = 0.81-3.77) for use at baseline, 4.73 (1.41-15.81) for recent use, and 3.05 (1.19-7.82) for three years prior use. Similar associations were observed when we separately examined systemic NHL and diffuse large B-cell lymphoma. Given these observations, the impact of amphetamines on lymphomagenesis among HIV-infected populations should be assessed more thoroughly.
Baker, Julie A; Weiss, Joli R; Czuczman, Myron S; Menezes, Ravi J; Ambrosone, Christine B; Moysich, Kirsten B
Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of non-Hodgkin lymphoma (NHL), although previous results have been inconsistent. The current study investigated the effects of regular aspirin or acetaminophen use on non-Hodgkin lymphoma risk among 625 individuals with primary, incident NHL and 2512 age and sex matched hospital controls with non-neoplastic conditions who completed a comprehensive epidemiologic questionnaire. Results indicate that regular aspirin use may be associated with decreased NHL risk among men [adjusted odds ratio (aOR) 0.82, 95% confidence interval (CI), 0.65--1.04], but not among women (aOR 0.93, 95% CI, 0.71--1.23). In contrast, regular acetaminophen use was associated with elevated NHL risk among women (aOR 1.71, 95% CI, 1.18--2.50) but not among men (aOR 0.75, 95% CI, 0.48--1.17). Other studies have demonstrated that acetaminophen is associated with transient decreases in DNA repair, and lymphocytes may be particularly susceptible to DNA damage, suggesting a mechanism for the elevated NHL risk observed.
Chao, Mark P
Over the last few decades, advances in immunochemotherapy have led to dramatic improvement in the prognosis of non-Hodgkin’s lymphoma (NHL). Despite these advances, relapsed and refractory disease represents a major treatment challenge. For both aggressive and indolent subtypes of NHL, there is no standard of care for salvage regimens, with prognosis after relapse remaining relatively poor. Nevertheless, there are multiple emerging classes of targeted therapies for relapsed/refractory disease, including monoclonal antibodies, antibody– drug conjugates, radioimmunotherapy, small-molecule inhibitors of cell-growth pathways, and novel chemotherapy agents. This review will discuss treatment challenges of NHL, current available salvage regimens for relapsed/refractory NHL, and the safety and efficacy of novel emerging therapies. PMID:24049458
Okoli, Tracy C; Peer, Cody J; Dunleavy, Kieron; Figg, William D
Indolent Non-Hodgkin Lymphomas (iNHL) are typically B-cell malignancies and are incurable with current standard approaches. Thus, there is a demand for novel agents specific for this group of disorders. In a phase II study published by Gopal et al. in the New England Journal of Medicine, idelalisib, a small molecule inhibitor of PI3Kδ that was FDA approved in July of 2014, was shown to be effective when combined with rituximab in patients who cannot tolerate chemotherapy and as last line therapy in patients with iNHL refractory to 2 prior systemic therapies. Idelalisib demonstrated tolerable diarrhea, fatigue, nausea, pyrexia, and cough. While this novel agent is a clinically significant addition to the iNHL arsenal, further research is needed to determine its most appropriate place in iNHL therapy. PMID:25756507
Oishi, Natsuki; Bagán, José Vicente; Javier, Karla; Zapater, Enrique
Introduction Because of the many HIV-related malignancies, the diagnosis and treatment of lymphoma in patients infected with human immunodeficiency virus are challenging. Objective Here, we review current knowledge of the pathogenesis, epidemiology, symptomatology, diagnosis, and treatment of head and neck lymphomas in HIV patients from a clinical perspective. Data Synthesis Although Hodgkin's lymphoma is not an AIDS-defining neoplasm, its prevalence is ten times higher in HIV patients than in the general population. NHL is the second most common malignancy in HIV patients, after Kaposi's sarcoma. In this group of patients, NHL is characterized by rapid progression, frequent extranodal involvement, and a poor outcome. HIV-related salivary gland disease is a benign condition that shares some features with lymphomas and is considered in their differential diagnosis. Conclusion The otolaryngologist may be the first clinician to diagnose head and neck lymphomas. The increasing survival of HIV patients implies clinical and epidemiological changes in the behavior of this disease. Early diagnosis is important to improve the prognosis and avoid the propagation of HIV infection.
Vlaanderen, Jelle; Lan, Qing; Kromhout, Hans; Rothman, Nathaniel; Vermeulen, Roel
Background The use of occupational cohort studies to assess the association of benzene and lymphoma is complicated by problems with exposure misclassification, outcome classification, and low statistical power. Objective We performed meta-analyses of occupational cohort studies for five different lymphoma categories: Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL). Data extraction We assessed three study quality dimensions to evaluate the impact of study quality variations on meta-relative risks (mRRs): stratification by the year of start of follow-up, stratification by the strength of the reported acute myelogenous leukemia association, and stratification by the quality of benzene exposure assessment. Data synthesis mRRs for MM, ALL, and CLL increased with increasing study quality, regardless of the study quality dimension. mRRs for NHL also increased with increasing study quality, although this effect was less pronounced. We observed no association between occupational benzene exposure and HL. Conclusions Our meta-analysis provides support for an association between occupational benzene exposure and risk of MM, ALL, and CLL. The evidence for an association with NHL is less clear, but this is likely complicated by the etiologic heterogeneity of this group of diseases. Further consideration of the association between benzene and NHL will require delineation of risks by NHL subtype. PMID:20880796
Psyrri, A.; Papageorgiou, S.; Economopoulos, T.
Gastrointestinal lymphoma is the most common form of extranodal lymphoma, accounting for 30%–40% of cases. The most commonly involved site is the stomach (60%–75% of cases), followed by the small bowel, ileum, cecum, colon and rectum. The most common histological subtypes are diffuse large B-cell lymphoma (DLBCL) and marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT). Helicobacter pylori infection has been implicated in the pathogenesis of MALT gastric lymphoma, but its role in gastric diffuse large B-cell non-Hodgkin's lymphoma (NHL) is controversial. The therapeutic approach for patients with gastric NHL has been revised over the last 10 years. Conservative treatment with anthracycline-based chemotherapy alone or in combination with involved-field radiotherapy has replaced gastrectomy as standard therapy in cases with DLBCL. Additionally, MALT lymphomas are mainly treated with antibiotics alone, which can induce lasting remissions in those cases associated with H. pylori infection. Nevertheless, various therapeutic aspects for primary gastric lymphomas are still controversial and several questions remain unanswered. Among others, the role of rituximab, consolidation radiotherapy as well as H. pylori eradication in histological aggressive subtypes warrants better clarification. PMID:18647965
Wang, Rong; Zhang, Yawei; Lan, Qing; Holford, Theodore R.; Leaderer, Brian; Hoar Zahm, Shelia; Boyle, Peter; Dosemeci, Mustafa; Rothman, Nathaniel; Zhu, Yong; Qin, Qin
A population-based case-control study involving 601 incident cases of non-Hodgkin lymphoma (NHL) and 717 controls was conducted in 1996–2000 among Connecticut women to examine associations with exposure to organic solvents. A job-exposure matrix was used to assess occupational exposures. Increased risk of NHL was associated with occupational exposure to chlorinated solvents (odds ratio (OR) = 1.4, 95% confidence interval (CI): 1.1, 1.8) and carbon tetrachloride (OR = 2.3, 95% CI: 1.3, 4.0). Those ever exposed to any organic solvent in work settings had a borderline increased risk of NHL (OR = 1.3, 95% CI: 1.0, 1.6); moreover, a significantly increased risk was observed for those with average probability of exposure to any organic solvent at medium-high level (OR = 1.5, 95% CI: 1.1, 1.9). A borderline increased risk was also found for ever exposure to formaldehyde (OR = 1.3, 95% CI: 1.0, 1.7) in work settings. Risk of NHL increased with increasing average intensity (P = 0.01), average probability (P < 0.01), cumulative intensity (P = 0.01), and cumulative probability (P < 0.01) level of organic solvent and with average probability level (P = 0.02) and cumulative intensity level of chlorinated solvent (P = 0.02). Analyses by NHL subtype showed a risk pattern for diffuse large B-cell lymphoma similar to that for overall NHL, with stronger evidence of an association with benzene exposure. Results suggest an increased risk of NHL associated with occupational exposure to organic solvents for women. PMID:19056833
Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A; Sundquist, Kristina
Infectious etiologies have been hypothesized for Hodgkin and non-Hodgkin lymphoma (HL and NHL) in early life, but findings to date for specific lymphomas and periods of susceptibility are conflicting. We conducted the first national cohort study to examine whether season of birth, a proxy for infectious exposures in the first few months of life, is associated with HL or NHL in childhood through young adulthood. A total of 3,571,574 persons born in Sweden in 1973-2008 were followed up through 2009 to examine the association between season of birth and incidence of HL (943 cases) or NHL (936 cases). We found a sinusoidal pattern in NHL risk by season of birth (p = 0.04), with peak risk occurring among birthdates in April. Relative to persons born in fall (September-November), odds ratios for NHL by season of birth were 1.25 [95% confidence interval (CI), 1.04-1.50; p = 0.02] for spring (March-May), 1.22 (95% CI, 1.01-1.48; p = 0.04) for summer (June-August) and 1.11 (95% CI, 0.91-1.35; p = 0.29) for winter (December-February). These findings did not vary by sex, age at diagnosis or major subtypes. In contrast, there was no seasonal association between birthdate and risk of HL (p = 0.78). In this large cohort study, birth in spring or summer was associated with increased risk of NHL (but not HL) in childhood through young adulthood, possibly related to immunologic effects of delayed infectious exposures compared with fall or winter birth. These findings suggest that immunologic responses in early infancy may play an important role in the development of NHL. © 2014 UICC.
Shivappa, Nitin; Hébert, James R; Taborelli, Martina; Montella, Maurizio; Libra, Massimo; Zucchetto, Antonella; Crispo, Anna; Grimaldi, Maria; La Vecchia, Carlo; Serraino, Diego; Polesel, Jerry
While dietary factors have been shown to play an important etiologic role in non-Hodgkin lymphoma (NHL), little is known about the association between inflammatory properties of diet and NHL risk. We explored the association between the dietary inflammatory index (DII) and NHL risk in a multicenter Italian case-control study conducted between 1999 and 2014. Cases were 536 subjects with incident, histologically confirmed NHL from three areas in Italy. Controls were 984 subjects admitted to the same network of hospitals as the cases for acute, nonmalignant conditions, unrelated to diet. DII scores were computed based on 30 nutrients and food items assessed using a reproducible and validated 78-item food-frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models adjusting for age, total energy intake, and other recognized confounding factors. Subjects in the highest quartile of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of NHL compared with subjects in the lowest quartile (i.e., with the most anti-inflammatory diets) (ORQuartile4vs1 1.61, 95% confidence interval CI 1.07-2.43; p-trend = 0.01). Stratified analyses produced stronger associations between DII and NHL among males (ORQuartile4vs1 2.14; 95% CI 1.25-3.67) with significant heterogeneity (p value = 0.02); when analyzed by histologic subtype, a significant association was observed with diffuse large B-cell lymphoma (ORQuartile4vs1 1.84; 95% CI 1.09-3.10). A pro-inflammatory diet, as indicated by higher DII scores, is associated with elevated odds of NHL, especially among males.
Thakur, Jagdeep S; Minhas, Ravinder S; Mohindroo, Narinder K; Sharma, Dev R; Mohindroo, Shobha; Thakur, Anamika
Background The head and neck are two of the most common sites of extranodal non-Hodgkin's lymphoma (NHL). However, primary tumors of the infratemporal fossa are infrequent, and NHL in this region is extremely rare. Case presentation We present a case of a 41-year-old female that presented with swelling in the right preauricular region that had persisted for the past two years. The patient was diagnosed as having a small lymphocytic NHL. She initially underwent chemo-radiation but reported relapse. The tumor was excised and again the patient underwent chemotherapy. The patient remained symptomatic and developed a second primary squamous cell carcinoma in the right retromolar trigone. Discussion and conclusion We discussed NHL with an emphasis on extranodal manifestations. Extranodal NHL that is limited to a single site can be managed by surgery and regular follow up. To the best of our knowledge, this is only the second case of primary NHL of the infratemporal fossa to be reported in the literature. PMID:19545392
Freeman, Michael D.; Kohles, Sean S.
Polychlorinated biphenyls (PCBs) are synthetic chlorinated hydrocarbons that have extensively polluted the environment and bioaccumulated in the food chain. PCBs have been deemed to be probable carcinogens by the Environmental Protection Agency, and exposure to high levels of PCBs has been consistently linked to increased risk of non-Hodgkin lymphoma (NHL). In the present article we present a forensic epidemiologic evaluation of the causal relationship between NHL and elevated PCB levels via application of the Bradford-Hill criteria. Included in the evaluation is a meta-analysis of the results of previously published case-control studies in order to assess the strength of association between NHL and PCBs, resulting in an odds ratio in which the lowest percentile PCB concentration (quartile, quintile, or tertile) has been compared with the highest percentile concentration in the study groups. The weight-adjusted odds ratio for all PCB congeners was 1.43 with a 95% confidence interval of 1.31 to 1.55, indicating a statistically significant causal association with NHL. Because of the lack of an unexposed comparison group, a rationale for the use of a less than 2.0 relative risk causal contribution threshold is presented herein, including an ecologic analysis of NHL incidence and PCB accumulation (as measured by sales volume) over time. The overall results presented here indicate a strong general causal association between NHL and PCB exposure. PMID:22577404
Karunanayake, Chandima P; McDuffie, Helen H; Dosman, James A; Spinelli, John J; Pahwa, Punam
Background The objective was to study the association between Non-Hodgkin's Lymphoma (NHL) and occupational exposures related to long held occupations among males in six provinces of Canada. Methods A population based case-control study was conducted from 1991 to 1994. Males with newly diagnosed NHL (ICD-10) were stratified by province of residence and age group. A total of 513 incident cases and 1506 population based controls were included in the analysis. Conditional logistic regression was conducted to fit statistical models. Results Based on conditional logistic regression modeling, the following factors independently increased the risk of NHL: farmer and machinist as long held occupations; constant exposure to diesel exhaust fumes; constant exposure to ionizing radiation (radium); and personal history of another cancer. Men who had worked for 20 years or more as farmer and machinist were the most likely to develop NHL. Conclusion An increased risk of developing NHL is associated with the following: long held occupations of faer and machinist; exposure to diesel fumes; and exposure to ionizing radiation (radium). The risk of NHL increased with the duration of employment as a farmer or machinist. PMID:18687133
Rendón-Macías, Mario Enrique; Valencia-Ramón, Edwin A; Fajardo-Gutiérrez, Arturo; Rivera-Flores, Estefanía
We reviewed the childhood lymphomas epidemiological data for the Mexico City metropolitan area (MCMA). Data analysis from children (0-14 years old) diagnosed with lymphoma during the period 1996-2010 was performed at the Mexican Childhood Cancer Registry. Histological subtype was determined according to the International Classification of Childhood Cancer 3 (ICCC-3). Age-adjusted incidence rates were calculated per 1,000,000 children/year by age, gender, and ICCC-3 subtype; trends, by average annual percent change (AAPC). A total of 328 lymphoma cases included in the study had an incidence rate of 11.8, showing a decreasing trend [AAPC: -3.5; CI 95% (-5.9, -1.0)], primarily due to non-Hodgkin lymphomas (NHL) and Hodgkin lymphoma (HL) mixed cellularity subtype. NHL had the major incidence (5.8), with the precursor cell subtype being the most frequent (38.3%). Nodular sclerosis was the most frequent HL subtype. The incidence of Burkitt lymphoma was low (1.3). During the study period, there was an important reduction in the not-otherwise-specified subtype of NHL, which translated into a relative increase in the IIb3 subtype [AAPC: 7.3 (1.2, 13.8)]. Low incidences of NHL and of HL and NHL were found for < 1-year-olds and for 10- to 14-year-olds, respectively. Incidence rates for children in the MCMA, particularly the < 1 and 10-14 age groups, were lower than those for developed countries. The overall male/female ratio was 2.3. There was a trend toward a reduced incidence, for some lymphoma subtypes, in particular for NOS lymphomas, which may be the result of improvement in diagnostic techniques.
Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D.; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M.; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L.; Shea, Thomas C.; Liomba, N. George
There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV. PMID:26934054
Taborelli, Martina; Polesel, Jerry; Montella, Maurizio; Libra, Massimo; Tedeschi, Rosamaria; Battiston, Monica; Spina, Michele; Di Raimondo, Francesco; Pinto, Antonio; Crispo, Anna; Grimaldi, Maria; Franceschi, Silvia; Dal Maso, Luigino; Serraino, Diego
Hepatitis C virus (HCV) has been consistently associated to non-Hodgkin lymphoma (NHL); conversely, few studies have evaluated a comprehensive serological panel of hepatitis B virus (HBV) in NHL etiology. We conducted a case-control study in Italy in 1999-2014, enrolling 571 incident, histologically confirmed NHLs and 1004 cancer-free matched controls. Study subjects provided serum for HCV and HBV testing and for HCV RNA. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were estimated by logistic regression, adjusting for potential confounders. Circulating HCV RNA was detected in 63 (11.1 %) NHL cases and 35 (3.5 %) controls (OR = 3.51, 95 % CI: 2.25-5.47). Chronic HBV infection (i.e., positive to HBV surface antigen - HBsAg(+)) was found in 3.7 % of cases and 1.7 % of controls (OR = 1.95, 95 % CI: 1.00-3.81); a significantly elevated OR was observed for B-cell NHL (2.11, 95 % CI: 1.07-4.15). People with serological evidence of past HCV or HBV infection, vaccination against HBV, or detectable antibodies against HBV core antigen (anti-HBc(+)) alone were not at increased NHL risk. Our results support a role of chronic HCV infection in NHL in Italy and suggest an involvement of HBV infection. Associations were clearest for B-cell NHL and diffuse large B-cell lymphoma. Prevention and treatment of HCV and HBV infection may diminish NHL incidence, notably in areas with high prevalence of hepatitis viruses infection.
Teras, Lauren R; Gapstur, Susan M; Patel, Alpa V; Thun, Michael J; Diver, W Ryan; Zhai, Yusheng; Jacobs, Eric J
Few large prospective studies have examined associations between nonsteroidal anti-inflammatory drug (NSAID) use and non-Hodgkin lymphoma (NHL). We examined the association between NSAID use and NHL incidence among 149,570 participants in the Cancer Prevention Study-II Nutrition cohort. Aspirin and nonaspirin NSAID use were reported at enrollment in 1992 and updated on periodic follow-up questionnaires. During follow-up through 2007, 1,709 incident NHLs were identified. Time-dependent hazard ratios were calculated using extended Cox regression. Compared to no use, current use of 60+ NSAID pills/month (aspirin and nonaspirin NSAIDs combined) was associated with slightly higher NHL incidence (hazard ratio [HR] = 1.26, 95% confidence interval [CI], 1.04-1.53), but no association with frequency of use was observed when NSAID exposure was lagged by approximately 2 years (HR = 1.08, 95% CI, 0.88-1.32). Long duration regular use (current use of 30+ pills/month for ≥5 years) was not associated with NHL incidence (HR = 1.09, 95% CI, 0.91-1.33). In subtype analyses, current use of 60+ NSAID pills/month was associated with follicular lymphoma incidence (HR = 1.87, 95% CI, 1.08-3.24). This association persisted when NSAID exposure was lagged (HR = 1.76, 95% CI, 1.04-2.98) and was similar for aspirin and nonaspirin NSAIDs. The association of current, but not lagged, NSAID use with risk of all NHL could be attributable to use of NSAIDs to relieve symptoms of undiagnosed NHL. However, the association with follicular lymphoma persisted in analyses where NSAID use was lagged and should be investigated further. These findings are particularly important for aspirin as the risks and benefits of prophylactic daily use are weighed.
Schuurman, H. J.; van Baarlen, J.; Huppes, W.; Lam, B. W.; Verdonck, L. F.; van Unnik, J. A.
The establishment of Clusters of Differentiation for T- and B-lymphoid cells during International Workshops on Human Leukocyte Differentiation Antigens prompted the authors to evaluate the immunophenotypes in 160 cases of non-Hodgkin's lymphoma (NHL). In this group, 130 were of B-lymphocyte lineage (117 by monotypic immunoglobulin expression), and 30 of T-cell lineage. In the B-NHL series the expression of immunoglobulin isotypes, B-cell maturation/differentiation antigens of CD9, CD10, CD19-24, CD37, and CD38 (OKT10), HLA-DR and peanut agglutinin binding showed no significant relationship with histopathologic diagnosis as defined by the Kiel classification. Of the T-cell markers, CD5, CD6, and CD7 showed lineage promiscuity by their presence on some B-NHL. Conversely, the authors grouped the cases according to phenotypes (either CD antigens or immunoglobulin isotypes) which occur in distinct stages of (physiologic) B-cell maturation/differentiation. Eighty-six of the 130 cases could be fitted according to CD phenotype expression. This approach did not yield a significant relationship between phenotype and individual histopathologic categories either. The staging by CD phenotype and by immunoglobulin isotype yielded different results in this respect. Most B-NHL had an intermediate stage of B-cell maturation/differentiation. In the T-NHL series most cases showed a phenotype (CD1-CD8, CD38, TdT, and peanut agglutinin binding capacity) compatible with mature T-lymphocyte characteristics. The exceptions were lymphoblastic convoluted lymphomas, which exhibited an immature immunophenotype. It is concluded that NHL in distinct histopathologic categories are heterogeneous in immunologic phenotypes, and that the immunophenotype of lymphoma cells has no evident association with that of their presumed counterparts in physiologic cell maturation/differentiation. PMID:3310650
Abou-Seif, M A; Rabia, A; Nasr, M
We studied erythrocyte and leukocyte superoxide dismutase and catalase activities, erythrocyte malondialdehyde (MDA) and osmotic fragility and plasma L-ascorbic acid and L-dehydroascorbic acid levels in adult patients with acute lymphoblastic leukemia (ALL), Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) before and after treatment. SOD activity was elevated in leukocytes of ALL and HD patients before treatment, and borderlike-significantly elevated in leukocytes of the same patients after treatment in comparison to the control subjects. SOD activity was not changed in NHL patients before or after chemotherapy. Erythrocyte superoxide dismutase and catalase activities were elevated in the three groups of lymphomas before and after treatment. MDA level and osmotic fragility of red blood cells of patients with lymphomas were increased before and after treatment in comparison to the control group. Plasma L-ascorbic acid concentrations were decreased, whereas L-dehydroascorbic acid concentrations were increased in ALL, HD and NHL patients before and after treatment. There were also significant differences in the activities of the antioxidant enzymes, concentrations of antioxidants, MDA and osmotic fragility in the most of the malignant lymphoma patients. The present data suggest that hematological complications and autoimmune hemolytic anemia might be attributed to the oxidative stress produced by malignant lymphomas.
Davids, Matthew S; Roberts, Andrew W; Seymour, John F; Pagel, John M; Kahl, Brad S; Wierda, William G; Puvvada, Soham; Kipps, Thomas J; Anderson, Mary Ann; Salem, Ahmed Hamed; Dunbar, Martin; Zhu, Ming; Peale, Franklin; Ross, Jeremy A; Gressick, Lori; Desai, Monali; Kim, Su Young; Verdugo, Maria; Humerickhouse, Rod A; Gordon, Gary B; Gerecitano, John F
Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts. Treatment commenced with a 3-week dose ramp-up period for most patients in dose-escalation cohorts and for all patients in safety expansion. Results NHL subtypes included mantle cell lymphoma (MCL; n = 28), follicular lymphoma (FL; n = 29), diffuse large B-cell lymphoma (DLBCL; n = 34), DLBCL arising from chronic lymphocytic leukemia (Richter transformation; n = 7), Waldenström macroglobulinemia (n = 4), and marginal zone lymphoma (n = 3). Venetoclax was generally well tolerated. Clinical tumor lysis syndrome was not observed, whereas laboratory tumor lysis syndrome was documented in three patients. Treatment-emergent adverse events were reported in 103 patients (97%), a majority of which were grade 1 to 2 in severity. Grade 3 to 4 events were reported in 59 patients (56%), and the most common were hematologic, including anemia (15%), neutropenia (11%), and thrombocytopenia (9%). Overall response rate was 44% (MCL, 75%; FL, 38%; DLBCL, 18%). Estimated median progression-free survival was 6 months (MCL, 14 months; FL, 11 months; DLBCL, 1 month). Conclusion Selective targeting of BCL-2 with venetoclax was well tolerated, and single-agent activity varied among NHL subtypes. We determined 1,200 mg to be the recommended single-agent dose for future studies in FL and DLBCL, with 800 mg being sufficient to consistently achieve durable response in MCL. Additional investigations including combination therapy to augment response rates and durability
Bouchikhi, Ahmed Amine; Tazi, Mohamed fadl; Amiroune, Driss; Mellas, Soufiane; El Ammari, Jalaledine; Khallouk, Abdelhak; El fassi, Mohammed Jamal; Farih, Moulay Hassan
Primary bilateral non-Hodgkin's lymphoma (NHL) of the adrenal gland is a very rare entity. Indeed less than 60 cases have been reported in the literature. Hence, we report a case of high-grade lymphoma of both adrenal glands that was found in a young patient of 32 years of age. The patient was admitted in the emergency department of our hospital with a profile of hemorrhagic shock. After stabilization, the imaging investigations demonstrated large bilateral adrenal masses. The CT-scan guided biopsy of both adrenal glands allowed the diagnosis of primary bilateral adrenal NHL. The patient died after the first chemotherapy session. The presence of bilateral adrenal masses associated with a rapid increase of volume should raise the diagnosis of primary adrenal non-Hodgkin's lymphoma. PMID:23304624
Lee, Mu-Hsien; Lin, Yu-Ching; Cheng, Hao-Tsai; Chuang, Wen-Yu; Huang, Hsin-Chih; Kao, Hsiao-Wen
The coexistence of hepatocellular carcinoma (HCC) and non-Hodgkin’s lymphoma (NHL) in the liver is rare. Reports show that these patients have cirrhotic livers or hepatitis virus infections before they develop HCC and NHL. We present a patient with hepatitis B virus infection who was transferred to our hospital with a newly detected liver mass; abdominal computed tomography examination showed one hypodense mass of 7 cm in diameter and multiple mesenteric and mediastinal lymph nodes. A liver tumor biopsy showed a hepatoma, and the pathologic findings from an inguinal lymph node excision showed mantle cell lymphoma. An immunohistochemical stain conﬁrmed that the atypical lymphoid cells within the HCC were positive for the CD20, CD5 and cyclin D1 antigens. Taking these ﬁndings into account, the hepatic tumor was determined to be a HCC inﬁltrated by mantle cell lymphoma. PMID:26668520
Lee, Mu-Hsien; Lin, Yu-Ching; Cheng, Hao-Tsai; Chuang, Wen-Yu; Huang, Hsin-Chih; Kao, Hsiao-Wen
The coexistence of hepatocellular carcinoma (HCC) and non-Hodgkin's lymphoma (NHL) in the liver is rare. Reports show that these patients have cirrhotic livers or hepatitis virus infections before they develop HCC and NHL. We present a patient with hepatitis B virus infection who was transferred to our hospital with a newly detected liver mass; abdominal computed tomography examination showed one hypodense mass of 7 cm in diameter and multiple mesenteric and mediastinal lymph nodes. A liver tumor biopsy showed a hepatoma, and the pathologic findings from an inguinal lymph node excision showed mantle cell lymphoma. An immunohistochemical stain conﬁrmed that the atypical lymphoid cells within the HCC were positive for the CD20, CD5 and cyclin D1 antigens. Taking these ﬁndings into account, the hepatic tumor was determined to be a HCC inﬁltrated by mantle cell lymphoma.
Troy, Jesse D.; Hartge, Patricia; Weissfeld, Joel L.; Oken, Martin M.; Colditz, Graham A.; Mechanic, Leah E.; Morton, Lindsay M.
Prospective studies of lifestyle and non-Hodgkin lymphoma (NHL) are conflicting, and some are inconsistent with case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was used to evaluate risk of NHL and its subtypes in association with anthropometric factors, smoking, and alcohol consumption in a prospective cohort study. Lifestyle was assessed via questionnaire among 142,982 male and female participants aged 55–74 years enrolled in the PLCO Trial during 1993–2001. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards regression. During 1,201,074 person-years of follow-up through 2006, 1,264 histologically confirmed NHL cases were identified. Higher body mass index (BMI; weight (kg)/height (m)2) at ages 20 and 50 years and at baseline was associated with increased NHL risk (Ptrend < 0.01 for all; e.g., for baseline BMI ≥30 vs. 18.5–24.9, hazard ratio = 1.32, 95% confidence interval: 1.13, 1.54). Smoking was not associated with NHL overall but was inversely associated with follicular lymphoma (ever smoking vs. never: hazard ratio = 0.62, 95% confidence interval: 0.45, 0.85). Alcohol consumption was unrelated to NHL (drinks/week: Ptrend = 0.187). These data support previous studies suggesting that BMI is positively associated with NHL, show an inverse association between smoking and follicular lymphoma (perhaps due to residual confounding), and do not support a causal association between alcohol and NHL. PMID:20494998
Bertrand, Kimberly A; Giovannucci, Edward; Rosner, Bernard A; Zhang, Shumin M; Laden, Francine; Birmann, Brenda M
Background: Dietary fat intake may contribute to non-Hodgkin lymphoma (NHL) pathogenesis by influencing carcinogen exposure or through immune modulation.Objective: We aimed to evaluate NHL risk associated with total and specific dietary fat intake.Design: We evaluated associations within the Nurses' Health Study (NHS) (n = 88,598) and the Health Professionals Follow-Up Study (HPFS) (n = 47,531) using repeated validated dietary assessments. We confirmed 1802 incident NHL diagnoses through 2010. Using multivariable Cox proportional hazards models, we estimated hazard ratios (HRs) for all NHL and common subtypes associated with a 1-SD increase in cumulative mean intakes of total, animal, saturated, trans, and vegetable fats and marine fatty acids. We pooled sex-specific HRs using random-effects meta-analysis.Results: Over 24-30 y of follow-up, neither total nor specific dietary fats were significantly associated with NHL risk overall. Higher total, animal, and saturated fat intakes were positively associated with the risk of the chronic lymphocytic leukemia/small lymphocytic lymphoma subtype among women only (253 cases; P-trend ≤ 0.05), driven by strong associations during 1980-1994. From baseline through 1994, among women and men combined, total fat intake was borderline-significantly positively associated with NHL overall (pooled HR per SD: 1.13; 95% CI: 0.99, 1.29) and was significantly associated with diffuse large B cell lymphoma (pooled HR per SD: 1.47; 95% CI: 1.06, 2.05), with similar trends for animal and saturated fat intake. For women only, trans fat was significantly positively associated with all NHL. In contrast, during 1994-2010, there was little evidence for associations of dietary fat intake with NHL overall or by subtype.Conclusion: Previous observations of an increased risk of NHL associated with intakes of total, animal, saturated, and trans fat with 14 y of follow-up did not persist with longer follow-up. © 2017 American Society for Nutrition.
Thacker, Nirav; Bakhshi, Sameer; Chinnaswamy, Girish; Vora, Tushar; Prasad, Maya; Bansal, Deepak; Agarwala, Sandeep; Kapoor, Gauri; Radhakrishnan, Venkatraman; Laskar, Siddharth; Kaur, Tanvir; Rath, G K; Dhaliwal, Rupinder Singh; Arora, Brijesh
Hitherto poor outcomes, paucity of data and heterogeneity in International approach to Pediatric NHL (Non-Hodgkin Lymphoma) prompted the need for guidelines for Indian population with vast variability in access, affordability and infrastructure across the country. These guidelines are based on consensus among the experts and best available evidence applicable to Indian setting. Evaluation of NHL should consist of easily doable and rapid tissue diagnosis (biopsy or flow cytometry of peripheral blood/malignant effusions), St Jude/IPNHLSS (International Pediatric Non-Hodgkin Lymphoma Staging System) and risk grouping with CSF (Cerebro-spinal fluid), bone marrow, whole body imaging [CECT (Contrast enhanced computerized tomography) ± MRI (Magnetic resonance imaging)] and blood investigations for LDH (Lactate dehydrogenase), TLS (Tumor lysis syndrome) and organ functions. Life threatening complications like SVCS (Superior vena cava syndrome)/Mediastinal syndrome and TLS need to pre-empted and promptly managed. All children with poor general condition, co-morbidities, metabolic or obstructive complications should receive a steroid or chemotherapy pro-phase first. For mature B-NHL (B cell - Non-Hodgkin lymphoma), in centres with good infrastructure and methotrexate levels, FAB-LMB-96 (French-American-British/Lymphomes Malins B) or BFM (Berlin-Frankfurt-Münster)-NHL-95 protocols may be used. In centres with limited infrastructure and/or no methotrexate levels; CHOP (Cyclophosphamide-hydroxydaunomycin-oncovin-prednisolone) (early stage) or MCP (Multi-centre protocol)-842 [all stages except CNS (Central nervous system) disease] may be used. Patients with poor early response should have escalated therapy. High-Risk B-NHL will benefit with addition of Rituximab to standard chemotherapy. Radiotherapy (RT) is not warranted. For lymphoblastic lymphoma, in centres with good infrastructure and methotrexate levels, BFM-95 protocol may be used. In centres with limited
Raufi, Alex; Jerkins, James; Lyou, Yung; Jeyakumar, Deepa
Composite lymphoma (CL) is a rare disease with 2 distinct lymphomas concurrently arising in a single patient with an estimated incidence of 1–4.7% of newly diagnosed lymphomas per year. CL most commonly involves 2 B-cell non-Hodgkin lymphomas (NHL) or a B-cell NHL with a Hodgkin lymphoma. Our case is unique in that it was a bilineage CL with both a T-cell and B-cell NHL, which has only been reported in a few case reports. A 49-year-old woman presented with several months of progressive cough, weight loss, dyspnea, and supraclavicular lymphadenopathy. Computed tomographic imaging done upon admission to the hospital found that she had extensive anterior and middle mediastinal lymphadenopathy as well as bilateral supraclavicular lymphadenopathy. The patient underwent an excisional biopsy on the supraclavicular lymph node and was found to have a composite lymphoma involving both a T-cell and B-cell NHL. Her final pathological diagnosis was peripheral T-cell lymphoma and lymphoplasmacytic lymphoma. The patient was found to have stage IIIB disease. Her HIV, hepatitis panel, and tuberculosis tests were all negative. She then underwent chemotherapy with dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab). The patient showed a complete response and was then referred to a bone marrow transplant center for an autologous hematopoietic stem cell transplant. CL is a rare disease composed of at least 2 distinct lymphomas concurrently arising in a single patient. Due to the complexity in having to treat multiple types of lymphoma simultaneously CL presents challenges with treatment and assessing prognosis. PMID:28203178
Shigematsu, N.; Kondo, M.; Kubo, A.; Hashimoto, S.
In 37 patients with seemingly localized non-Hodgkin's lymphoma of the Waldeyer's ring (WR-NHL), lymphangiography (LAG) and/or gallium-67 scans (Ga-67 scans) were done. Before these procedures, 20 patients were diagnosed as Stage I, and 17 as Stage II. LAG was done for 30, and Ga-67 scans for 32, 25 of whom had both. Five patients (16%) were upstaged to Stage III or IV by Ga-67 scans. Only one (3%) had abnormal LAG findings, in whom Ga-67 scans also showed abnormal accumulation in the para-aortic region. Because of this low positive rate, LAG is not recommended for staging of WR-NHL.
Zheng, Tongzhang; Blair, Aaron; Zhang, Yawei; Weisenburger, Dennis D; Zahm, Shelia H
To investigate the association between occupation and the risk of non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), and to test whether the associations may vary by histological type of NHL, we analyzed data from two population-based, case-control studies of NHL performed in Kansas and Nebraska. A total of 555 incident NHL cases, 56 CLL cases, and 2380 population-based controls were included in the analysis. Information on occupation and other confounding factors was collected through telephone interviews. Study pathologists reviewed slides of tumor tissues in all cases. In men, we found an increased risk of NHL and CLL for those working in agricultural, forestry, and logging industries (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2 to 2.1). The OR was 1.9 (95% CI, 1.4 to 2.6) for those producing crops. An increased risk was also observed for industries involving metalworking machinery and equipment (OR, 8.4; 95% CI, 1.4 to 50.6), motor vehicles and motor vehicle equipment (OR, 4.2; 95% CI, 1.3 to 13.9), and telephone communications (OR, 3.1; 95% CI, 1.2 to 8.0), and for teachers (OR, 2.5; 95% CI, 1.0 to 6.5), farmers (OR, 2.0; 95% CI, 1.5 to 2.8), and welders and solderers (OR, 2.9; 95% CI, 1.2 to 6.9). The risks for these associations increased by duration of employment and seem to vary by histological type. Work in the printing and publishing industry was also associated with an increased risk of NHL among women. These data suggest that the workers employed in these industries or occupations experienced an increased risk of NHL and CLL, and the risks associated with these industries or occupations may vary by histological type of NHL.
Malaponte, Grazia; Hafsi, Sameh; Polesel, Jerry; Castellano, Giancarlo; Spessotto, Paola; Guarneri, Claudio; Canevari, Silvana; Signorelli, Santo S; McCubrey, James A; Libra, Massimo
Non-Hodgkin lymphomas (NHL) are a heterogeneous group of lymphoproliferative malignancies with variable patterns of behavior and responses to therapy. NHL development and invasion depend on multiple interactions between tumor cells and non-neoplastic cells. Such interactions are usually modulated by several cytokines. Accordingly, it was demonstrated that matrix-metalloproteinase (MMP)-2 and MMP-9 were activated in human lymphoid cell lines by interleukin-6 (IL-6). The activation of these enzymes is associated with tumor invasion and metastasis in human cancers. MMPs are also activated in several cancers by osteopontin (OPN), a secreted glycoprotein that regulates cell adhesion, migration, and survival. However, it is still unclear if MMPs play a role in NHL development and if their activation is determined by OPN and/or IL-6. In the present study, two groups of 78 NHL patients and 95 healthy donors were recruited for the analysis of OPN, MMP-2, MMP-9 and IL-6.Significant higher circulating levels of MMP-2, MMP-9, OPN and IL-6 were observed in NHL patients when compared to healthy donors. Similar data were obtained by analyzing the activity of both MMP-2 and MMP-9. The multivariate regression model indicates that, in both NHL cases and healthy donors, OPN is associated with the increase of MMP-2 and MMP-9 levels independently of IL-6. These data were first confirmed by “in silico” analyses and then by “in vitro” experiments conducted on peripheral blood mononuclear cells randomly selected from both NHL patients and healthy donors.Overall, our data suggest that the activation of MMPs in NHL development is mostly associated with OPN. However, IL-6 may play an important role in the lymphomagenesis through the activation of other molecular pathways. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.
Change in the diagnosis from classical Hodgkin's lymphoma to anaplastic large cell lymphoma by (18)F flourodeoxyglucose positron emission tomography/computed tomography: Importance of recognising disease pattern on imaging and immunohistochemistry.
Senthil, Raja; Mohapatra, Ranjan Kumar; Sampath, Mouleeswaran Koramadai; Sundaraiya, Sumati
Anaplastic large cell lymphoma (ALCL) is a rare type of nonHodgkin's lymphoma (NHL), but one of the most common subtypes of T-cell lymphoma. It is an aggressive T-cell lymphoma, and some ALCL may mimic less aggressive classical HL histopathlogically. It may be misdiagnosed unless careful immunohistochemical examination is performed. As the prognosis and management of these two lymphomas vary significantly, it is important to make a correct diagnosis. We describe a case who was diagnosed as classical HL by histopathological examination of cervical lymph node, in whom (18)F-flouro deoxyglucose positron emission tomography/computed tomography appearances were unusual for HL and warranted review of histopathology that revealed anaplastic lymphoma kinase-1 negative anaplastic large T-cell lymphoma, Hodgkin-like variant, thereby changing the management.
Martiat, P.; Ferrant, A.; Labar, D.; Cogneau, M.; Bol, A.; Michel, C.; Michaux, J.L.; Sokal, G.
Carbon-11 thymidine (TdR) uptake using positron emission tomography (PET) has been measured in ten patients with non-Hodgkin's lymphoma (NHL). The rate of TdR uptake (mean +/- s.d.) was of 0.009 +/- 0.006 mumol.100 cc-1.min-1 in low-grade NHL. This rate was 0.063 +/- 0.049 mumol.100 cc-1.min-1 in intermediate-grade NHL and 0.159 mumol.100 cc-1.min-1 in a patient with high-grade NHL. Lymphoma radioactivity reached a plateau at 0.42 +/- 0.22%. 100 cc-1 of the injected dose from 10 min after injection. The highest /sup 11/C uptakes were observed in the kidneys and in the liver (3.30 +/- 1.30 and 2.10 +/- 0.05%. 100 cc-1 of the injected dose, respectively). The lymphoma-to-muscle ratio was of 11.8 +/- 1.7, whereas the lymphoma-to-intestine ratio was of 1.5 +/- 0.7. Accordingly, the measurement of (/sup 11/C)TdR uptake in the abdomen may need other imaging methods for adequate interpretation. The results suggest that (/sup 11/C)TdR uptake using PET might be a method for noninvasively measuring cell proliferation in vivo.
Silva, Taísa Domingues Bernardes; Ferreira, Camila Belo Tavares; Leite, Gustavo Boehmer; de Menezes Pontes, José Roberto; Antunes, Héliton S
Lymphoma is a malignant disease with two forms: Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Non-Hodgkin’s lymphoma is diagnosed in extranodal sites in 40% of cases, and the head and neck region is the second most affected, with an incidence of 11–33%, while HL has a very low incidence in extranodal sites (1–4%). The aim of this study was to identify the oral manifestations of lymphoma through a systematic literature review, which we conducted using the PubMed, Lilacs, Embase, and Cochrane Library databases. We found 1456 articles, from which we selected 73. Among the intraoral findings, the most frequent were ulcerations, pain, swelling, and tooth mobility, while the extraoral findings included facial asymmetry and cervical, submandibular, and submental lymphadenopathy. Among the few studies reporting imaging findings, the most cited lesions included hypodense lesions with diffuse boundaries, bone resorptions, and tooth displacements. The publications reviewed highlight gaps in the areas of early detection, diagnosis, and proper treatment. PMID:27594910
Sundquist, Kristina; Sieh, Weiva; Winkleby, Marilyn A.; Sundquist, Jan
Background The incidence of non-Hodgkin lymphoma (NHL) in early life has increased in recent decades, but the relevant risk factors remain largely unknown. We examined perinatal and family risk factors for NHL in childhood through young adulthood. Methods We conducted a national cohort study of 3 571 574 individuals born in Sweden in 1973–2008 who were followed for incidence of NHL through 2009 (ages 0–37 years). Detailed information on perinatal and family characteristics and NHL diagnoses were obtained from national birth and cancer registries. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between perinatal and family variables and NHL; P values are from two-sided tests. Results There were 936 NHL case patients identified in 66.3 million person-years of follow-up. Independent risk factors for NHL included family history of NHL in either a sibling (adjusted HR = 9.84; 95% CI = 2.46 to 39.41; P = .001) or parent (adjusted HR = 2.36; 95% CI = 1.27 to 4.38; P = .007); high fetal growth (for ≥2 SDs relative to 0 to <1 SD from the mean: adjusted HR = 1.64; 95% CI = 1.19 to 2.25; P = .002); older maternal age (adjusted HR for each 5-year increment = 1.11; 95% CI = 1.04 to 1.19; P trend = .004); low birth order (adjusted HR for each increment of one birth = 0.91; 95% CI = 0.84 to 0.99; P trend = .02); and male sex (adjusted HR = 1.58; 95% CI = 1.38 to 1.80; P < .001). Male sex was associated with onset of NHL before 15 years of age but not with later-onset NHL, whereas the other risk factors did not vary by age at diagnosis. No association was found between gestational age at birth, twinning, paternal age, or parental education and NHL. Conclusion In this large national cohort study, family history of NHL, high fetal growth, older maternal age, low birth order, and male sex were independent risk factors for NHL in early life. PMID:22623506
DellaValle, Curt T.; Deziel, Nicole C.; Jones, Rena R.; Colt, Joanne S.; De Roos, Anneclaire J.; Cerhan, James R.; Cozen, Wendy; Severson, Richard K.; Flory, Abigail R.; Morton, Lindsay M.
Purpose To investigate the risk of non-Hodgkin lymphoma (NHL) associated with residential carpet dust measurements of polycyclic aromatic hydrocarbons (PAHs). Methods We evaluated the relationship between residential carpet dust PAH concentrations (benz(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, benzo(k)fluoranthene, chrysene, dibenz(a,h)anthracene, and indeno(1,2,3-c,d)pyrene, and their sum) and risk of NHL (676 cases, 511 controls) in the National Cancer Institute Surveillance Epidemiology and End Results multicenter case–control study. As a secondary aim, we investigated determinants of dust PAH concentrations. We computed odds ratios (OR) and 95 % confidence interval (CI) for associations between NHL and concentrations of individual and summed PAHs using unconditional logistic regression, adjusting for age, gender, and study center. Determinants of natural log-transformed PAHs were investigated using multivariate least-squares regression. Results We observed some elevated risks for NHL overall and B cell lymphoma subtypes in association with quartiles or tertiles of PAH concentrations, but without a monotonic trend, and there was no association comparing the highest quartile or tertile to the lowest. In contrast, risk of T cell lymphoma was significantly increased among participants with the highest tertile of summed PAHs (OR = 3.04; 95 % CI, 1.09–8.47) and benzo(k)fluoranthene (OR = 3.20; 95 % CI, 1.13–9.11) compared with the lowest tertile. Predictors of PAH dust concentrations in homes included ambient air PAH concentrations and the proportion of developed land within 2 km of a residence. Older age, more years of education, and white race were also predictive of higher levels in homes. Conclusion Our results suggest a potential link between PAH exposure and risk of T cell lymphoma and demonstrate the importance of analyzing risk by NHL histologic type. PMID:26573845
Rapisarda, Venerando; Marconi, Andrea; Candido, Saverio; Nicolosi, Daria; Salmeri, Mario; Gangemi, Pietro; Proietti, Lidia; Spandidos, Demetrios A; Bracci, Massimo; Fenga, Cettina; Libra, Massimo
Non-Hodgkin lymphoma (NHL) may occur among hepatitis C virus (HCV)-infected individuals. HCV is one of the most common blood-borne pathogens transmitted from patients to health-care workers (HCWs). The development of NHL among HCV-infected HCWs has recently been shown. To investigate this issue further a tailored health surveillance program was applied to 3,138 HCWs from four Medical Institutions. To this aim, all employees were screened for both anti-HCV antibodies and HCV-related extrahepatic manifestations. The HCV prevalence rate, similar among all the HCW subgroups, was 7.3%. The occurrence of a gastric mucosa-associated lymphoma tissue (MALT) lymphoma, diagnosed in a physician following a long history of HCV chronic infection, was observed. Molecular characterization of MALT tissue indicated that immunoglobuline gene combinations were those usually found among HCV-associated lymphomas. Furthermore, B-cell expansion exhibited t(14;18) translocation, as a genetic abnormality associated with the development of MALT lymphomas from HCV-positive patients. Overall, these findings support the hypothesis that HCV viral infection potentially affects the pathway of transformation and progression of lymphoma cells. The occurrence of B-cell NHL, among HCV-positive HCWs, is an additional reason to apply the standard precautions to reduce the risk of blood-borne pathogen transmission.
RAPISARDA, VENERANDO; MARCONI, ANDREA; CANDIDO, SAVERIO; NICOLOSI, DARIA; SALMERI, MARIO; GANGEMI, PIETRO; PROIETTI, LIDIA; SPANDIDOS, DEMETRIOS A.; BRACCI, MASSIMO; FENGA, CETTINA; LIBRA, MASSIMO
Non-Hodgkin lymphoma (NHL) may occur among hepatitis C virus (HCV)-infected individuals. HCV is one of the most common blood-borne pathogens transmitted from patients to health-care workers (HCWs). The development of NHL among HCV-infected HCWs has recently been shown. To investigate this issue further a tailored health surveillance program was applied to 3,138 HCWs from four Medical Institutions. To this aim, all employees were screened for both anti-HCV antibodies and HCV-related extrahepatic manifestations. The HCV prevalence rate, similar among all the HCW subgroups, was 7.3%. The occurrence of a gastric mucosa-associated lymphoma tissue (MALT) lymphoma, diagnosed in a physician following a long history of HCV chronic infection, was observed. Molecular characterization of MALT tissue indicated that immunoglobuline gene combinations were those usually found among HCV-associated lymphomas. Furthermore, B-cell expansion exhibited t(14;18) translocation, as a genetic abnormality associated with the development of MALT lymphomas from HCV-positive patients. Overall, these findings support the hypothesis that HCV viral infection potentially affects the pathway of transformation and progression of lymphoma cells. The occurrence of B-cell NHL, among HCV-positive HCWs, is an additional reason to apply the standard precautions to reduce the risk of blood-borne pathogen transmission. PMID:23420489
Anderson, Mary Ann; Blombery, Piers; Seymour, John F
Transformed lymphoma is a complex syndrome that encompasses an array of different underlying low-grade lymphoproliferative conditions transforming into more aggressive disease as manifest by morphologic, clinical, and genetic features. Over the last decade, advances in chemoimmunotherapy have led to new options. Knowledge surrounding the genetic changes driving the process of transformation is leading to novel targeted therapies. This article focuses on the transformation of chronic lymphocytic leukemia and follicular lymphoma into diffuse large B-cell lymphoma.
SHERIEF, LAILA M.; ELSAFY, USAMA R.; ABDELKHALEK, ELHAMY R.; KAMAL, NAGLAA M.; YOUSSEF, DOAA M.; ELBEHEDY, RABAB
Non-Hodgkin lymphoma (NHL) accounts for 8–10% of all childhood cancers. NHL collectively represents various lymphoid malignancies with diverse clinicopathological and biological characteristics. In this study, we aimed to describe the epidemiological and clinicopathological characteristics and treatment outcomes of pediatric NHL patients treated at the Pediatric Oncology Unit of Zagazig University Hospital and the Benha Specialized Pediatric Hospital. We conducted a cross-sectional retrospective study by reviewing the medical records of 142 patients admitted with a diagnosis of NHL over a period of 8 years (February, 2004 to February, 2012) in these two Oncology Units. The age at presentation ranged between 2 and 15 years, with a mean ± standard deviation (SD) of 6.1±2.8 years and a male:female ratio of 1.7:1. Abdominal involvement was the most common presentation (73.2%). Burkitt's lymphoma (BL) was the most common NHL subtype (69%), followed by lymphoblastic lymphoma, diffuse large B-cell lymphoma and anaplastic large-cell lymphoma, accounting for 18.3, 10.6 and 2.1% of the cases, respectively. The majority of the patients (88.7%) had been diagnosed with advanced disease (Murphy stage III/IV). Complete remission was achieved in 120 cases (84.5%). A total of 16 patients (11.3%) succumbed to the disease during the first few months and 6 patients (4.2%) remained alive following relapse. The mean follow-up duration ± SD was 34.6±25.1 months (range, 3–84 months). The 5-year overall survival (OS) and event-free survival (EFS) rates were 88.7 and 85.1%, respectively. None of the clinical, epidemiological or pathological variables exhibited a statistically significant association with the OS or EFS. In conclusion, NHL occurs at a younger age, with a higher incidence of BL and advanced-stage disease. The outcome of NHL in our two centers was satisfactory, approaching the international rates. PMID:25469284
Kittivorapart, Janejira; Chinthammitr, Yingyong
Since trephine bone marrow biopsy is an invasive procedure, the identification of a subgroup of patients with Non-Hodgkin lymphoma (NHL) who have a minimal risk of bone marrow involvement would be helpful. This study is aimed to determine the incidence of bone marrow involvement (BMI) by NHL and the predictors of no BMI to not only avoid this invasive procedure but also decrease the cost of investigation. Data from 320 patients with NHL at division of hematology between January 2008 and June 2009 were reviewed and analyzed. The cell types of NHL were classified as B-cell in 283 patients (88.4%), T-cell in 37 patients (11.6%) and incidence of BMI is 24.4% and 18.9% in B- and T-cell, respectively. Factors significantly associated with BMI in univariate analysis were the hepatic and splenic involvement (p = 0.03 and < 0.01, respectively), significant weight loss (p = 0.02), presence of lymphadenopathy (LN) below diaphragm (p = 0.02), anemia (p = 0.001), low percent of blood neutrophil (p < 0.001), high percent of blood lymphocyte (p < 0.001), low absolute neutrophil count (p = 0.002), high absolute lymphocyte count (p = 0.045), low platelet count (p < 0.001), high LDH (p = 0.026), and high alkaline phosphatase (p = 0.020). On the multivariate analysis, factors associated with BMI included LN below diaphragm, anemia, low percent of blood neutrophil and low platelet count. Excluding Burkitt lymphoma and mantle cell lymphoma, NHL patients with no LN below diaphragm, no hepatic & splenic involvement, no significant weight loss, hemoglobin (Hb) >11 g/dL and platelet > 150,000/uL had BMI in 3/78 (3.8%). The incidence of bone marrow involvement in NHL is 23.8%. Excluding Burkitt lymphoma and mantle cell lymphoma, NHL patients with no LN below diaphragm, no hepatic & splenic involvement, no significant weight loss, Hb > 11 g/dL and platelet > 150,000/uL had low risk of BMI.
Jeudy, Jean; Burke, Allen P; Frazier, Aletta Ann
Lymphoma of the heart and pericardium may develop in up to 25% of patients with disseminated nodal disease, but primary cardiac lymphoma is rare. The majority are diffuse large B-cell lymphomas, which arise in immunocompetent older individuals, men twice as often as women. Subsets are found in immunocompromised patients, including those with HIV-AIDS or allograft recipients. Cardiac lymphomas tend to arise in the wall of the right heart, especially right atrium, with contiguous infiltration of epicardium and pericardium. Pericardial implants and effusions are common. The disease is often multifocal in the heart, but cardiac valves are usually spared. Copyright © 2016 Elsevier Inc. All rights reserved.
Voss, Jorine J L P; Ford, Catriona A; Petrova, Sofia; Melville, Lynsey; Paterson, Margaret; Pound, John D; Holland, Pam; Giotti, Bruno; Freeman, Tom C; Gregory, Christopher D
In aggressive non-Hodgkin's lymphoma (NHL), constitutive apoptosis of a proportion of the tumor cell population can promote net tumor growth. This is associated with the accumulation of tumor-associated macrophages (TAMs) that clear apoptotic cells and exhibit pro-oncogenic transcriptional activation profiles characteristic of reparatory, anti-inflammatory and angiogenic programs. Here we consider further the activation status of these TAMs. We compare their transcriptomic profile with that of a range of other macrophage types from various tissues noting especially their expression of classically activated (IFN-γ and LPS) gene clusters - typically antitumor - in addition to their previously described protumor phenotype. To understand the impact of apoptotic cells on the macrophage activation state, we cocultured apoptotic lymphoma cells with classically activated macrophages (M(IFN-γ/LPS), also known as M1, macrophages). Although untreated and M(IFN-γ/LPS) macrophages were able to bind apoptotic lymphoma cells equally well, M(IFN-γ/LPS) macrophages displayed enhanced ability to phagocytose them. We found that direct exposure of M(IFN-γ/LPS) macrophages to apoptotic lymphoma cells caused switching towards a protumor activation state (often referred to as M2-like) with concomitant inhibition of antitumor activity that was a characteristic feature of M(IFN-γ/LPS) macrophages. Indeed, M(IFN-γ/LPS) macrophages exposed to apoptotic lymphoma cells displayed increased lymphoma growth-promoting activities. Antilymphoma activity by M(IFN-γ/LPS) macrophages was mediated, in part, by galectin-3, a pleiotropic glycoprotein involved in apoptotic cell clearance that is strongly expressed by lymphoma TAMs but not lymphoma cells. Intriguingly, aggressive lymphoma growth was markedly impaired in mice deficient in galectin-3, suggesting either that host galectin-3-mediated antilymphoma activity is required to sustain net tumor growth or that additional functions of galectin-3
Voss, Jorine J L P; Ford, Catriona A; Petrova, Sofia; Melville, Lynsey; Paterson, Margaret; Pound, John D; Holland, Pam; Giotti, Bruno; Freeman, Tom C; Gregory, Christopher D
In aggressive non-Hodgkin's lymphoma (NHL), constitutive apoptosis of a proportion of the tumor cell population can promote net tumor growth. This is associated with the accumulation of tumor-associated macrophages (TAMs) that clear apoptotic cells and exhibit pro-oncogenic transcriptional activation profiles characteristic of reparatory, anti-inflammatory and angiogenic programs. Here we consider further the activation status of these TAMs. We compare their transcriptomic profile with that of a range of other macrophage types from various tissues noting especially their expression of classically activated (IFN-γ and LPS) gene clusters – typically antitumor – in addition to their previously described protumor phenotype. To understand the impact of apoptotic cells on the macrophage activation state, we cocultured apoptotic lymphoma cells with classically activated macrophages (M(IFN-γ/LPS), also known as M1, macrophages). Although untreated and M(IFN-γ/LPS) macrophages were able to bind apoptotic lymphoma cells equally well, M(IFN-γ/LPS) macrophages displayed enhanced ability to phagocytose them. We found that direct exposure of M(IFN-γ/LPS) macrophages to apoptotic lymphoma cells caused switching towards a protumor activation state (often referred to as M2-like) with concomitant inhibition of antitumor activity that was a characteristic feature of M(IFN-γ/LPS) macrophages. Indeed, M(IFN-γ/LPS) macrophages exposed to apoptotic lymphoma cells displayed increased lymphoma growth-promoting activities. Antilymphoma activity by M(IFN-γ/LPS) macrophages was mediated, in part, by galectin-3, a pleiotropic glycoprotein involved in apoptotic cell clearance that is strongly expressed by lymphoma TAMs but not lymphoma cells. Intriguingly, aggressive lymphoma growth was markedly impaired in mice deficient in galectin-3, suggesting either that host galectin-3-mediated antilymphoma activity is required to sustain net tumor growth or that additional functions of
Yan, Jin-Song; Chen, Xue-Yu; Li, Wei-Ping; Yang, Yan; Song, Zhen-Lan
Recently, the incidence of non-Hodgkin's lymphoma (NHL) is increasing, in which most are aggressive. It is limited for promoting the efficacy of conventional chemotherapy on NHL. In this study, mouse models of B-cell NHL were established for determining the efficacy and mechanisms of novel therapies. Diffuse large B-cell lymphoma SU-DHL-4 cells and Burkitt's lymphoma Daudi cells were injected into SCID (severe combined immunodeficiency) mice through the tail veins to observe the presentations and requirements for establishing mouse models. The Daudi-cell lymphoma mice were divided into control group and rituximab group, and the latter received treatment of rituximab. The tumor onset and survival time of mice were investigated. The median onset time of SU-DHL-4-cell lymphoma in SCID mice was 39.5 days, which presented cachexia, weight loss, erect hair, tardiness and enlarged tumors in the abdomen, rump or pelvic limb, but without tumor cell infiltration in the liver, spleen or bone marrow. The median onset time of Daudi-cell lymphoma in SCID mice was 30.5 days, which were characterized by paralyzed lower limbs and died about 9.5 days after paralysation. Most organs such as the liver, kidney, spleen and bone marrow were infiltrated by a number of Daudi cells. After treatment of rituximab, Daudi cells presented typical characteristics of apoptosis. The median paralysis time and survival time of mice with Daudi-cell lymphoma were significantly longer in rituximab group than in control group (52.5 days vs. 30.5 days, 76.5 days vs. 40 days, p < 0.05). SCID mouse models of B-cell lymphoma can be successfully established with either SU-DHL-4 cells or Daudi cells.
Hussain, Shehnaz K; Hessol, Nancy A; Levine, Alexandra M; Breen, Elizabeth Crabb; Anastos, Kathryn; Cohen, Mardge; D'Souza, Gypsyamber; Gustafson, Deborah R; Silver, Sylvia; Martínez-Maza, Otoniel
There is increasing evidence that chronic immune activation predisposes to non-Hodgkin lymphoma (NHL). Whether this association exists among women representative of the current HIV epidemic in the United States who are at high risk of HIV-associated NHL (AIDS-NHL), remains to be determined. We conducted a nested case-control study within the Women's Interagency HIV Study with longitudinally collected risk factor data and sera. Cases were HIV-infected women with stored sera collected at three time-windows 3 to 5 years, 1 to 3 years, and 0 to 1 year before AIDS-NHL diagnosis (n = 22). Three to six HIV-infected controls, without AIDS-NHL, were matched to each case on age, race, CD4(+) T-cell count, and study follow-up time (n = 78). ORs and 95% confidence intervals (CI) for the association between one unit increase in log-transformed biomarker levels and AIDS-NHL were computed using random effect multivariate logistic regression models. Elevated levels of sCD27 (OR = 7.21; 95% CI, 2.62-19.88), sCD30 (OR = 2.64; 95% CI, 1.24-5.64), and CXCL13 (OR = 2.56; 95% CI, 1.32-4.96) were associated with subsequent diagnosis of AIDS-NHL overall. Elevated sCD23 was associated with a two to three-fold increased risk of AIDS-NHL in certain subgroups, whereas elevated interleukin 6 was associated with a two-fold increased risk in the 0 to 1 year time-window, only. These findings support the hypothesis that chronic B-cell activation contributes to the development of AIDS-NHL in women. Soluble CD23 (sCD23), sCD27, sCD30, and CXCL13 may serve as biomarkers for AIDS-NHL. ©2013 AACR.
Sinha, Mahua; Rao, Clementina Rama; Premalata, C. S.; Shafiulla, Mohammed; Lakshmaiah, K. C.; Jacob, Linu Abraham; Babu, Govind K.; Viveka, B. K.; Appaji, L.; Subramanyam, Jayshree R.
Context: There is a need to study potential infective etiologies in lymphomas. Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal cell functions, and promote cell division. Epstein–Barr virus (EBV) is known to be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been emphasized. Aims: The aim of this study was to elucidate the association of two potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non-HL (NHL). Settings and Design: In this prospective study, we estimated plasma EBV and HBV DNA in NHL patients. Materials and Methods: Peripheral blood was obtained from newly diagnosed, treatment na ïve, histologically confirmed NHL patients. Plasma EBV DNA was quantified by real-time polymerase chain reaction (PCR) targeting Epstein–Barr Nucleic acid 1 while the plasma HBV DNA was detected using nested PCR targeting HBX gene. In a small subset of patients, follow-up plasma samples post-anticancer chemotherapy were available and retested for viral DNA. Results: Of the 110 NHL patients, ~79% were B-cell NHL and ~21% were T-cell NHL. Plasma EBV-DNA was detected in 10% NHLs with a higher EBV association in Burkitt lymphoma (33.3%) than other subtypes. Pretherapy HBV DNA was detected in 21% NHLs; most of them being diffuse large B-cell lymphoma (DLBCL). Moreover, 42% of DLBCL patients had HBV DNA in plasma. Since all patients were HBV surface antigen seronegative at diagnosis, baseline plasma HBV-DNAemia before chemotherapy was indicative of occult hepatitis B infection. Conclusions: Our findings indicate a significant association of HBV with newly diagnosed DLBCL. PMID:27688607
Han, Xuesong; Zheng, Tongzhang; Lan, Qing; Zhang, Yaqun; Kilfoy, Briseis A; Qin, Qin; Rothman, Nathaniel; Zahm, Shelia H; Holford, Theodore R; Leaderer, Brian; Zhang, Yawei
Oxidative damage caused by reactive oxygen species and other free radicals is involved in carcinogenesis. It has been suggested that high vegetable and fruit intake may reduce the risk of non-Hodgkin lymphoma (NHL) as vegetables and fruit are rich in antioxidants. The aim of this study is to evaluate the interaction of vegetable and fruit intake with genetic polymorphisms in oxidative stress pathway genes and NHL risk. This hypothesis was investigated in a population-based case-control study of NHL and NHL histologic subtypes in women from Connecticut, including 513 histologically confirmed incident cases and 591 randomly selected controls. Gene-vegetable/fruit joint effects were estimated using unconditional logistic regression model. The false discovery rate method was applied to adjust for multiple comparisons. Significant interactions with vegetable and fruit intake were mainly found for genetic polymorphisms on nitric oxide synthase (NOS) genes among those with diffuse large B-cell lymphoma and follicular lymphoma. Two single nucleotide polymorphisms in the NOS1 gene were found to significantly modify the association between total vegetable and fruit intake and risk of NHL overall, as well as the risk of follicular lymphoma. When vegetables, bean vegetables, cruciferous vegetables, green leafy vegetables, red vegetables, yellow/orange vegetables, fruit, and citrus fruits were examined separately, strong interaction effects were narrowed to vegetable intake among patients with diffuse large B-cell lymphoma. Our results suggest that genetic polymorphisms in oxidative stress pathway genes, especially in the NOS genes, modify the association between vegetable and fruit intake and risk of NHL.
He, Jing; Liao, Xiao-Yu; Zhu, Jin-Hong; Xue, Wen-Qiong; Shen, Guo-Ping; Huang, Shao-Yi; Chen, Wei; Jia, Wei-Hua
Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism and DNA synthesis. A number of studies have examined the association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma (NHL) susceptibility; however, the conclusions were contradictory. We searched available publications assessing the polymorphisms of MTHFR and NHL susceptibility from MEDLINE, EMBASE and CBM. Genotype-based mRNA expression analysis was performed using data from 270 individuals with three different ethnicities. Ultimately, a total of 7448 cases and 11146 controls from 25 studies were included for the C677T polymorphism, 6173 cases and 9725 controls from 19 studies for the A1298C polymorphism. Pooled results indicated that neither C677T nor A1298C polymorphism was associated with NHL susceptibility. However, C677T polymorphism showed a statistically significantly increased risk for Caucasians, but a decreased risk for Asians in the subgroup analysis by ethnicity. The same variants may confer increased susceptibility to develop follicular lymphoma (FL). Moreover, A1298C polymorphism was associated with increased NHL risk for Asians. This meta-analysis indicated that C677T polymorphism was associated with altered NHL susceptibility for Caucasians, Asians and FL. Increased NHL risk was also shown for A1298C among Asians. These findings warrant validation in large and well-designed prospective studies. PMID:25146845
Mendez, Miriam; Torrente, Maria; Provencio, Mariano
Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL). Histological transformation (HT) refers to the evolution of a clinically indolent NHL to a clinically aggressive one, defined as those lymphomas in which survival is limited to a few months when untreated. Areas covered: HT is associated with rapid progression of lymphadenopathy, infiltration of extranodal sites, development of systemic symptoms, and elevated serum level of lactate dehydrogenase (LDH). It is frequently related to a poor prognosis, and the median survival after transformation is less than 2 years. Transformation to diffuse large B cell lymphoma (DLBCL) in patients with FL occurs at an annual rate of approximately 3% for the first 15 years, after which the risk of HT falls for reasons that remain unclear. Expert commentary: Although it has long been assumed that transformation reflects the emergence of an aggressive subclone of cells from the primary FL, recent studies suggest that FL transformation might also arise by divergent evolution from a more immature common progenitor cell. Studies on genomic changes and DNA sequencing have shed some light onto the process of transformation. Nowadays, we know that HT is a complex process where several molecular pathways are involved.
Miralles, Pilar; Berenguer, Juan; Ribera, Josep-Maria
With the widespread use of highly active antiretroviral therapy (HAART) the incidence of systemic non-Hodgkin lymphoma (NHL) in patients infected with the Human Immunodeficiency Virus (HIV) has declined. HAART has also modified the clinical manifestations of these tumors, with a lower frequency of involvement of the central nervous system (CNS). Currently, the frequency of meningeal involvement at the time of diagnosis of NHL in HIV-infected patients varies between 3% and 5%. These figures are similar to those observed among immunocompetent hosts. The diagnosis of meningeal lymphoma relies in clinical findings, imaging techniques, and cerebrospinal fluid (CSF) examination. Flow cytometry is a diagnostic technique with a higher sensitivity and specificity than conventional cytology for the diagnosis of meningeal lymphoma. However, flow cytometry is not yet considered to be the gold standard for this purpose. Until recently, most experts recommended neuromeningeal prophylaxis for all HIV-infected patients with aggressive NHL. However, at present this prophylaxis is recommended only in patients with higher risk of CNS relapse according to different sites of involvement, stage and histological subtype. There are different regimens of prophylaxis and treatment for meningeal lymphoma. The drugs most commonly used for this purpose are methotrexate and cytosine arabinoside. However, there are other alternatives such as liposomal cytosine arabinoside that requires fewer spinal taps for drug administration and whose results are very promising. In summary, in the context of an effective HAART, HIV infected patients with NHL have a frequency of CNS involvement by lymphoma similar to that found among immunocompetent hosts. Consequently, indications and regimens for CNS prophylaxis in HIV-infected patients with NHL should not be different than those employed in the general population. Universal CNS prophylaxis should be reserved for the few patients unable to receive an
Chen, Yingtai; Zheng, Tongzhang; Lan, Qing; Foss, Francine; Kim, Christopher; Chen, Xuezhong; Dai, Min; Li, Yumin; Holford, Theodore; Leaderer, Brian; Boyle, Peter; Chanock, Stephen J; Rothman, Nathaniel; Zhang, Yawei
We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m(2), women with BMI more than or equal to 25 kg/m(2) had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 P(forinteraction) = .034) and IL7R (rs1494555 P(forinteraction) = .016) for NHL overall; IL7R (rs1494555 P(forinteraction) = .016) and TNF (1799724 P(forinteraction) = .031) for B-cell lymphoma; and IL5 (rs2069812 P(forinteraction) = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 P(forinteraction) = .006), IL13 (rs20541 P(forinteraction) = .019), and IL7R (rs1494555 P(forinteraction) = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 P(forinteraction) = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 P(forinteraction) = .013) and TNF (1799724 P(forinteraction) = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.
Hayden, Rachel E; Kussaibati, Racha; Cronin, Laura M; Pratt, Guy; Roberts, Claudia; Drayson, Mark T; Bunce, Christopher M
B cell non-Hodgkin lymphomas (B-NHLs) are the most common adult hematological cancers and many remain incurable. Development of chemotherapy regimens is confounded by the prevalence of B-NHL in older, frailer patients and the chemo-protective tumor microenvironment. Although biological therapies such as rituximab have significantly improved outcomes and selective kinase inhibitors are showing promise, the rate of new drug discovery remains disappointing, the treatments expensive and long-term benefits uncertain. An alternative strategy is redeployment of available, inexpensive and non-toxic drugs. Here, we demonstrate the antiproliferative and mitochondrial superoxide (MSO) driven pro-apoptotic activities of bezafibrate (BEZ) and medroxyprogesterone acetate (MPA) against B-NHL cells, with a bias toward MZL, in the presence and absence of the microenvironmental signal CD40L. Our study is the first to confirm the presence of CD40L within the lymph node of B-NHL and its capacity to drive B-NHL proliferation. These findings implicate BEZ + MPA as a potential therapeutic strategy in B-NHL.
Hemminki, K; Försti, A; Sundquist, K; Sundquist, J; Li, X
Many B-cell neoplasms are associated with autoimmune diseases (AIDs) but most evidence is based on a personal rather than a family history of AIDs. Here we calculated risks for non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and multiple myeloma (MM) when family members were diagnosed with any of 44 different AIDs, or, independently, risk for AIDs when family members were diagnosed with a neoplasm. A total of 64 418 neoplasms and 531 155 AIDs were identified from Swedish nationwide health care records. NHL was associated with a family history of five AIDs, all increasing the risk, HL was associated with one AID increasing and three AIDs decreasing the risk while MM had no association. A family history of NHL was associated with eight, HL with seven and MM with seven different AIDs, nine increasing and 13 decreasing the risk. The present family data on B-cell neoplasms and AIDs show an approximately equal number of associations for risk increase and risk decrease, suggesting that inherited genes or gene-environment interactions may increase the risk or be protective. These results differed from published data on personal history of AID, which only report increased risks, often vastly higher and for different AIDs compared with the present data. PMID:28157190
Hemminki, K; Försti, A; Sundquist, K; Sundquist, J; Li, X
Many B-cell neoplasms are associated with autoimmune diseases (AIDs) but most evidence is based on a personal rather than a family history of AIDs. Here we calculated risks for non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and multiple myeloma (MM) when family members were diagnosed with any of 44 different AIDs, or, independently, risk for AIDs when family members were diagnosed with a neoplasm. A total of 64 418 neoplasms and 531 155 AIDs were identified from Swedish nationwide health care records. NHL was associated with a family history of five AIDs, all increasing the risk, HL was associated with one AID increasing and three AIDs decreasing the risk while MM had no association. A family history of NHL was associated with eight, HL with seven and MM with seven different AIDs, nine increasing and 13 decreasing the risk. The present family data on B-cell neoplasms and AIDs show an approximately equal number of associations for risk increase and risk decrease, suggesting that inherited genes or gene-environment interactions may increase the risk or be protective. These results differed from published data on personal history of AID, which only report increased risks, often vastly higher and for different AIDs compared with the present data.
Balhorn, Rod L; Skorupski, Katherine A; Hok, Saphon; Balhorn, Monique Cosman; Guerrero, Teri; Rebhun, Robert B
Therapies using antibodies directed against cell surface proteins have improved survival for human patients with non-Hodgkin's lymphoma (NHL). It is possible that similar immuno-therapeutic approaches may also benefit canine NHL patients. Unfortunately, variability between human and canine epitopes often limits the usefulness of such therapies in pet dogs. The Lym-1 antibody recognizes a unique epitope on HLA-DR10 that is expressed on the majority of human B-cell malignancies. The Lym-1 antibody has now been observed to bind to dog lymphocytes and B-cell NHL. Sequence comparisons and computer modeling of a human and three canine DRB1 proteins identified several orthologs of human HLA-DR10 expressed by dog lymphocytes. Immuno-staining confirmed the presence of proteins containing the Lym-1 epitope on dog lymphocytes and B-cell NHL. In addition, a selective high affinity ligand (SHAL) SH-7139 designed to bind within the Lym-1 epitope of HLA-DR10 was also observed to bind to canine B-cell NHL tissue. This SHAL, which is selectively cytotoxic to cells expressing HLA-DR10 and has been shown to cure mice bearing human B-cell lymphoma xenografts, may prove useful in treating B-cell malignancies in pet dogs.
Yahalom, Joachim; Illidge, Tim; Specht, Lena; Hoppe, Richard T; Li, Ye-Xiong; Tsang, Richard; Wirth, Andrew
Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL). Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL), consolidation after systemic therapy, salvage treatment, or palliation. The wide range of presentations of ENL, involving any organ in the body and the spectrum of histological sub-types, poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies. This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians. Thus far there is a lack of guidelines for the use of RT in the management of ENL. This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL, and to address the technical challenges of simulation, volume definition and treatment planning for the most frequently involved organs. Specifically, detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL. We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU), as has been widely adopted by the field of radiation oncology for solid tumors. Organ-specific recommendations take into account histological subtype, anatomy, the treatment intent, and other treatment modalities that may be have been used before RT. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Yahalom, Joachim; Illidge, Tim; Specht, Lena; Hoppe, Richard T.; Li, Ye-Xiong; Tsang, Richard; Wirth, Andrew
Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL). Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL), consolidation after systemic therapy, salvage treatment, or palliation. The wide range of presentations of ENL, involving any organ in the body and the spectrum of histological sub-types, poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies. This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians. Thus far there is a lack of guidelines for the use of RT in the management of ENL. This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL, and to address the technical challenges of simulation, volume definition and treatment planning for the most frequently involved organs. Specifically, detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL. We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU), as has been widely adopted by the field of radiation oncology for solid tumors. Organ-specific recommendations take into account histological subtype, anatomy, the treatment intent, and other treatment modalities that may be have been used before RT.
Scarantino, C.W.; Greven, K.M.; Buss, D.H.
Single high dose-large field irradiation (SHD-LFI), also described as half-body irradiation (HBI), has previously been reported as an effective modality for the palliation of symptoms in a number of solid tumors. This report concerns the ability of SHD-LFI to produce palliation of symptoms and/or objective response in patients with drug resistant non-Hodgkin's lymphoma (NHL). From 1981 to 1984, 34 patients with advanced drug resistant NHL were treated with SHD-LFI either to the whole abdomen (24 patients) or to the upper half body (10 patients). Overall, 19 of 23 patients achieved symptomatic improvement, while objective response was noted in 23 of 30 patients. We noted subjective and objective response in all histologies, and duration of response was not significantly different. Our results suggest a beneficial role for the early and judicious use of SHD-LFI in NHL.
White, L.; Miller, J.H.; Reid, B.S.
The diagnostic accuracy of abdominal ultrasonography followed by gallium (Ga)-67 scintigraphy in 21 patients, aged 1 to 14 years, appearing with abdominal non-Hodgkin's lymphoma (NHL) was analyzed. All cases were confirmed by biopsy; in a majority (16 patients), the tissue was obtained from an abdominal mass at the time of laparotomy subsequent to the imaging studies. Nineteen satisfactory abdominal ultrasound examinations were performed; 18 were interpreted as characteristic of NHL. Sixteen of these were of masses involving the gastrointestinal tract. All 21 patients had /sup 67/Ga scintigraphy that demonstrated abnormal radionuclide accumulation in the abdomen. In no instance was the final diagnosis different from the one predicted by the combined imaging studies. Ultrasonography is recommended as the initial test in the evaluation of clinical presentations consistent with abdominal NHL to expedite suitable management and prevent inappropriate surgery.
Nabati, Maryam; Yosofnezhad, Keyvan; Taghavi, Morteza; Abbasi, Ali; Ghaemian, Ali
Constrictive pericarditis (CP) is an uncommon post inflammatory disorder. It is described as pericardial thickening, myocardial constriction, and impaired diastolic filling. The most common etiologies are idiopathy, mediastinal radiotherapy, and prior cardiac surgery. Less common etiologies include viral infections, collagen vascular disorders, renal failure, sarcoidosis, tuberculosis, and blunt chest trauma. CP can less commonly be caused by malignancy. We report a very rare case of non-Hodgkin’s lymphoma (NHL) presenting twice with attacks of decompensated heart failure. Echocardiography revealed that CP was responsible for the patient's symptoms as the first manifestation of NHL. Chest computed tomography scan and biopsy findings were compatible with the diagnosis of NHL. The patient received R-CHOP (cyclophosphamide, hydroxydaunorubicin, Oncovin®, and prednisone or prednisolone, combined with the monoclonal antibody rituximab) chemotherapy. Three months later, there was significant improvement in the patient’s symptoms and considerable decrease in pericardial thickness. PMID:27928262
Wolf, Max; Bentley, Mark; Marlton, Paula; Horvath, Noemi; Lewis, Ian D; Spencer, Andrew; Herrmann, Richard; Arthur, Chris; Durrant, Simon; van Kerkhoven, Marilyn; MacMillan, Jamie; Mrongovius, Robert
This study investigated whether pegfilgrastim support would enable on-schedule delivery of dose-dense cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP-14) to elderly patients with non-Hodgkin's lymphoma (NHL). Thirty patients 60 years of age and older with aggressive NHL were evaluated after receiving up to six cycles of CHOP-14 supported with pegfilgrastim. The median age was 68 years (range 61 - 74). Forty-seven per cent of patients received full dose chemotherapy on schedule for all cycles (range 65 - 93). Chemotherapy was delayed in 10 patients and dose reduced in 15 patients. Hematological toxicity was the most common reason for delays and dose reduction. Six of nine patients (67%) achieved a peripheral blood CD34+ count of at least 20 cellsx106 L-1 on day 12 of cycle one. The delivery on schedule of dose-dense CHOP-14 to elderly patients with previously untreated aggressive NHL is safe and efficacious with once per cycle pegfilgrastim support.
Schinasi, Leah; Leon, Maria E.
This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world’s agriculture, were missing in the literature that were reviewed. PMID:24762670
Schinasi, Leah; Leon, Maria E
This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world's agriculture, were missing in the literature that were reviewed.
Vendrame, Elena; Hussain, Shehnaz K; Breen, Elizabeth Crabb; Magpantay, Larry I; Widney, Daniel P; Jacobson, Lisa P; Variakojis, Daina; Knowlton, Emilee R; Bream, Jay H; Ambinder, Richard F; Detels, Roger; Martínez-Maza, Otoniel
HIV infection is associated with a marked increase in risk for non-Hodgkin lymphoma (AIDS-NHL). However, the mechanisms that promote the development of AIDS-NHL are not fully understood. In this study, serum levels of several cytokines and other molecules associated with immune activation were measured in specimens collected longitudinally during 1 to 5 years preceding AIDS-NHL diagnosis, in 176 AIDS-NHL cases and 176 HIV(+) controls from the Multicenter AIDS Cohort Study (MACS). Multivariate analyses revealed that serum levels of immunoglobulin free light chains (FLC), interleukin (IL)-6, IL-10, IP-10/CXCL10, neopterin, and TNF-α were elevated in those HIV(+) individuals who went on to develop AIDS-NHL. In addition, the fraction of specimens with detectable IL-2 was increased and the fraction with detectable IL-4 was decreased in these subjects. These results suggest that long-term, chronic immune activation, possibly driven by macrophage-produced cytokines, precedes development of NHL in HIV(+) individuals. FLC, IL-6, IL-10, IP-10/CXCL10, neopterin, and TNF-α may serve as biomarkers for AIDS-NHL. .
Vendrame, Elena; Hussain, Shehnaz K.; Breen, Elizabeth Crabb; Magpantay, Larry; Widney, Daniel P.; Jacobson, Lisa P.; Variakojis, Daina; Knowlton, Emilee R.; Bream, Jay H.; Ambinder, Richard F.; Detels, Roger; Martínez-Maza, Otoniel
Background: HIV infection is associated with a marked increase in risk for non-Hodgkin lymphoma (AIDS-NHL). However, the mechanisms that promote the development of AIDS-NHL are not fully understood. Methods: In this study serum levels of several cytokines and other molecules associated with immune activation were measured in specimens collected longitudinally during 1-to-5 years preceding AIDS-NHL diagnosis, in 176 AIDS-NHL cases and 176 HIV+ controls from the Multicenter AIDS Cohort Study (MACS). Results: Multivariate analyses revealed that serum levels of immunoglobulin free light chains (FLC), IL-6, IL-10, IP-10/CXCL10, neopterin, and TNFα were elevated in those HIV+ individuals who went on to develop AIDS-NHL. Additionally, the fraction of specimens with detectable IL-2 was increased, and the fraction with detectable IL-4 was decreased, in these subjects. Conclusions: These results suggest that long term, chronic immune activation, possibly driven by macrophage-produced cytokines, precedes development of NHL in HIV+ individuals. Impact: FLC, IL-6, IL-10, IP-10/CXCL10, neopterin, and TNFα may serve as biomarkers for AIDS-NHL. PMID:24220912
Hugo, Frauke; Dittmar, Thomas; Treutler, Eva K; Zänker, Kurt S; Kuehn, Jürgen J
Single cases of clinical observations suggest the efficacy of the Viscum album (VA) extract Iscador P in the treatment of follicular B-Non-Hodgkin's Lymphoma (B-NHL). A previously published study aroused a controversial dispute as it indicated that IL-6 serum levels are elevated following i.v. VA treatment. Increased IL-6 levels have been shown to promote the progression of B-cell neoplasia such as B-NHL. Objective of this study was to investigate whether the VA extract influences the expression of IL-6 and its receptor components in follicular B-NHL cell lines. Follicular B-NHL cell lines (WSU-NHL, DoHH-2) were incubated with clinically relevant doses of VA extract for up to 3 days. At specified time points (6, 24, 48, 72 h) samples were taken and the expression of IL-6 and its receptor components were analysed by real-time-RT-PCR, flow cytometry and ELISA. Treatment of follicular B-NHL cell lines with VA extract did not alter the expression level of IL-6 and its' receptor components at any time and with any of the applied VA extract concentrations. Clinically relevant doses of the VA extract do not trigger an autocrine or paracrine IL-6 loop nor do they initiate IL-6 trans-signalling in follicular B-NHL cell lines.
Khorshied, Mervat Mamdooh; Gouda, Heba Mahmoud; Khorshid, Ola M Reda
Abstract Genetic and environmental factors are involved in the pathogenesis of non-Hodgkin lymphoma (NHL). The present study aimed to investigate the association between cytotoxic T-lymphocyte antigen 4 (CTLA-4) genetic polymorphism, hepatitis C virus (HCV) infection and B-cell NHL risk in Egypt. Genotyping of CTLA-4 single nucleotide polymorphisms (SNPs) was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for 181 adult patients with B-NHL and 200 controls. Our study revealed that CTLA-4 + 49 A/G polymorphism conferred increased risk of B-NHL (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.36-2.565). The prevalence of HCV infection in individuals harboring the mutant genotype + 49 A/G and - 318 C/T SNPs was higher in patients with B-NHL and was associated with increased risk of B-NHL (OR = 2.79, 95% CI = 1.24-6.93 for + 49 A/G and OR = 3.9, 95% CI = 1.01-15.98 for - 318 C/T). In conclusion, some SNPs of CTLA-4 are genetic risk factors for B-NHL. Moreover, this study identified an association of CTLA-4 + 49 A/G and - 318 C/T promoter polymorphisms with HCV infection.
Although the use of monoclonal antibodies as single agents has had a tremendous impact on the care of patients with non-Hodgkin’s lymphoma (NHL), the greatest benefit has been generated by the addition of monoclonal antibodies to conventional cytotoxic chemotherapy. Rituximab is the monoclonal antibody responsible for all clinical improvement noted to date. The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (R-CHOP regimen) improves the response rate, progression-free survival (PFS), and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL). Adding rituximab to CHOP chemotherapy improves response rates and PFS in mantle cell lymphoma (MCL). Finally, the addition of rituximab to a variety of chemotherapy regimens improves the response rates, PFS, and OS in follicular lymphoma (FL). Several other (epratuzumab, bevacizumab, alemtuzumab) monoclonal antibody–chemotherapy combinations are currently under study in NHL. This review will summarize the data supporting the addition of rituximab to chemotherapy in NHL and discuss preliminary data regarding the use of other monoclonal antibodies in combination with chemotherapy. PMID:18381103
Anyadike, Nnaemeka; Rahmani, Rabin
We report a case of non-Hodgkin's lymphoma (NHL) with an unusual initial manifestation as severe hypercholesterolemia and obstructive jaundice in a patient with neurofibromatosis type 1 (NF 1). NHL should be considered in the evaluation of obstructive jaundice alone or in combination with severe hypercholesterolemia. Relief of biliary obstruction led to the resolution of hypercholesterolemia in our 59-year-old male patient, followed by doxorubicin-based chemotherapy for the underlying lymphoma. NF 1 is a genetic condition that results from a defect in a tumor-suppressor gene and it is likely that this led to the development of NHL in our patient. It is important that clinicians are familiar with the gastrointestinal manifestations of NF 1, especially its association with intra-abdominal malignancies, when treating patients with a personal or family history. To the best of our knowledge, this is the first case of NHL presenting initially as severe hypercholesterolemia and it is also one of the few instances where NHL has been reported in association with NF 1. PMID:25093126
Qi, Zhenjia; Wang, Hao; Gao, Guangxun
A meta-analysis was carried out to systematically evaluate the correlation between hepatitis B virus (hepatitis B virus, HBV) infection and risk of non-Hodgkin's lymphoma (non-Hodgkin lymphoma, NHL). We searched Medline, EMBASE, PubMed, Cochrane Library, Chinese Biomedical Literature Database, Chinese Journal Full-text Database, Chinese scientific journals full text databases and collected information about HBV infection and risk of NHL associated case-control studies. Two reviewers extracted useful information which were included in the study independently, and Revman 5.2 was used for meta-analysis. A total of 24 studies were included in this research. Meta-analysis showed that among all of the included studies the heterogeneity were existed (I(2) = 76%, P<0.05). With random effects model the OR was 2.39 (95% CI, 1.93-3.96), indicating infection rate in NHL patients with HBV was higher than that in the control group. Subgroup analysis according to ethnicity suggested that HBV infection were associated with NHL risk both in Asian (OR = 2.46, 95% CI: 2.01, 3.00, P<0.001) and Caucasian (OR = 2.15, 95% CI: 1.37, 3.37, P<0.001) population. HBV infection may increase the risk of NHL, but it still need a large number of experiments and epidemiological studies to verify.
Burdick, Michael J; Macklis, Roger M
Targeted radioimmunotherapy in non-Hodgkin’s B-cell lymphoma (NHL) offers an efficacious therapy and minimal toxicity compared to conventional chemotherapy. Iodine 131 tositumomab (131I-TST) is a murine monoclonal antibody against the CD20 cell surface protein and is directly covalently conjugated to 131I, a radioactive β and γ emitter. While initially approved for use in relapsed, refractory, or transformed low grade B-cell NHL, investigational uses with promising results include autologous stem cell transplant, intermediate grade NHL, and the frontline management of indolent NHL. This review summarizes the 131I-TST literature on mechanism of action, treatment indications, treatment delivery, efficacy, investigational uses, and future prospects. PMID:20616910
Slager, Susan L.; Camp, Nicola J.; Conde, Lucia; Shanafelt, Tait D.; Achenbach, Sara J.; Rabe, Kari G.; Kay, Neil E.; Novak, Anne J.; Call, Timothy G.; Bracci, Paige M.; Sille, Fenna MC; Sanchez, Sylvia; Akers, Nicholas K.; Cunningham, Julie M.; Serie, Daniel J.; McDonnell, Shannon K.; Leis, Jose F.; Wang, Alice H.; Weinberg, J. Brice; Glenn, Martha; Link, Brian; Vachon, Celine M.; Lanasa, Mark C.; Skibola, Christine F.; Cerhan, James R.
Summary A recent meta-analysis of three genome-wide association studies of chronic lymphocytic leukaemia (CLL) identified two common variants at the 6p21.31 locus that are associated with CLL risk. To verify and further explore the association of these variants with other non-Hodgkin lymphoma (NHL) subtypes, we genotyped 1196 CLL cases, 1699 NHL cases, and 2410 controls. We found significant associations between the 6p21.31 variants and CLL risk (rs210134: P=0.01; rs210142: P=6.8×10−3). These variants also showed a trend towards association with some of the other NHL subtypes. Our results validate the prior work and support specific genetic pathways for risk among NHL subtypes. PMID:23025533
Talekar, Mala K; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S
ONC201/TIC10 is a small molecule initially discovered by its ability to coordinately induce and activate the TRAIL pathway selectively in tumor cells and has recently entered clinical trials in adult advanced cancers. The anti-tumor activity of ONC201 has previously been demonstrated in several preclinical models of cancer, including refractory solid tumors and a transgenic lymphoma mouse model. Based on the need for new safe and effective therapies in pediatric non-Hodgkin's lymphoma (NHL) and the non-toxic preclinical profile of ONC201, we investigated the in vitro efficacy of ONC201 in non-Hodgkin's lymphoma (NHL) cell lines to evaluate its therapeutic potential for this disease. ONC201 caused a dose-dependent reduction in the cell viability of NHL cell lines that resulted from induction of apoptosis. As expected from prior observations, induction of TRAIL and its receptor DR5 was also observed in these cell lines. Furthermore, dual induction of TRAIL and DR5 appeared to drive the observed apoptosis and TRAIL expression was correlated linearly with sub-G1 DNA content, suggesting its potential role as a biomarker of tumor response to ONC201-treated lymphoma cells. We further investigated combinations of ONC201 with approved chemotherapeutic agents used to treat lymphoma. ONC201 exhibited synergy in combination with the anti-metabolic agent cytarabine in vitro, in addition to cooperating with other therapies. Together these findings indicate that ONC201 is an effective TRAIL pathway-inducer as a monoagent that can be combined with chemotherapy to enhance therapeutic responses in pediatric NHL. PMID:26030065
Guo, Huan; Bassig, Bryan A; Lan, Qing; Zhu, Yong; Zhang, Yawei; Holford, Theodore R; Leaderer, Brian; Boyle, Peter; Qin, Qin; Zhu, Cairong; Li, Ni; Rothman, Nathaniel; Zheng, Tongzhang
Genetic polymorphisms in DNA repair genes and hair dye use may both have a role in the development of non-Hodgkin lymphoma (NHL). We aimed to examine the interaction between variants in DNA repair genes and hair dye use with risk of NHL in a population-based case-control study of Connecticut women. We examined 24 single nucleotide polymorphisms in 16 DNA repair genes among 518 NHL cases and 597 controls and evaluated the associations between hair dye use and risk of overall NHL and common NHL subtypes, stratified by genotype, using unconditional logistic regression. Women who used hair dye before 1980 had a significantly increased risk of NHL, particularly for the follicular lymphoma (FL) subtype, but not for diffuse large B-cell lymphoma. The following genotypes in combination with hair dye use before 1980 were associated with FL risk: BRCA2 rs144848 AC+CC [odds ratio (OR) (95% confidence interval (CI)) 3.28(1.27-8.50)], WRN rs1346044 TT [OR(95% CI) 2.70(1.30-5.65)], XRCC3 rs861539 CT+TT [OR(95% CI) 2.76(1.32-5.77)], XRCC4 rs1805377 GG [OR(95% CI) 2.07(1.10-3.90)] and rs1056503 TT [OR(95% CI) 2.17(1.16-4.07)], ERCC1 rs3212961 CC [OR(95% CI) 1.93(1.00-3.72)], RAD23B rs1805329 CC [OR(95% CI) 2.28(1.12-4.64)], and MGMT rs12917 CC, rs2308321 AA, and rs2308327 AA genotypes [OR(95% CI) 1.96(1.06-3.63), 2.02(1.09-3.75), and 2.23(1.16-4.29), respectively]. In addition, a significant interaction with risk of overall NHL was observed between WRN rs1346044 and hair dye use before 1980 (p(interaction) = 0.032). Our results indicated that genetic variation in DNA repair genes modifies susceptibility to NHL in relation to hair dye use, particularly for the FL subtype and in women who began using hair dye before 1980. Further studies are needed to confirm these observations.
Lim, Unhee; Gayles, Travis; Katki, Hormuzd A; Stolzenberg-Solomon, Rachael; Weinstein, Stephanie J; Pietinen, Pirjo; Taylor, Philip R; Virtamo, Jarmo; Albanes, Demetrius
Lymphoma patients often exhibit abnormal lipid metabolism. Recent evidence, however, suggests that a decrease in circulating high-density lipoprotein cholesterol (HDL-C) may occur during lymphomagenesis, reflecting underlying etiology such as inflammation. We investigated the relationship between prediagnostic HDL-C and non-Hodgkin lymphoma (NHL) in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. At baseline, serum HDL-C and total cholesterol concentrations from fasting blood, information on diet and lifestyle, and direct measurements of height, weight, and blood pressure were obtained from 27,074 healthy male smokers of ages 50 to 69 years. Cox proportional hazards models with age as underlying time metric was used to estimate relative risks (RR) and 95% confidence intervals (95% CI). We found no association between total or non-HDL cholesterol and the 201 incident NHL cases ascertained during the follow-up (1985-2002), but observed an inverse association between HDL-C and NHL, which changed with length of follow-up. High HDL-C was associated with lower risk of all NHL during the first 10 years (n = 148; RR for 5th versus 1st quintile, 0.35; 95% CI, 0.19-0.62; P(trend) < 0.0001), but not with diagnoses during later follow-up (n = 53; RR, 1.31; 95% CI, 0.55-3.10). The inverse association was similar for NHL subtypes and was not modified by obesity, blood pressure, physical activity, or alcohol intake, but seemed to be stronger in men with lower duration of smoking (P(interaction) = 0.06). Our findings implicate HDL-C as a preclinical indicator of NHL and warrant further prospective investigations for its etiologic contribution.
Switchenko, Jeffrey M.; Bulka, Catherine; Ward, Kevin; Koff, Jean L.; Bayakly, A. Rana; Ryan, P. Barry; Waller, Lance A.; Flowers, Christopher R.
Background Benzene is a known occupational carcinogen associated with increased risk of hematologic cancers, but the relationships between quantity of passive benzene exposure through residential proximity to toxic release sites, duration of exposure, lag time from exposure to cancer development, and lymphoma risk remain unclear. Methods We collected release data through the Environmental Protection Agency’s Toxics Release Inventory (TRI) from 1989 to 2003, which included location of benzene release sites, years when release occurred, and amount of release. We also collected data on incident cases of non-Hodgkin lymphoma (NHL) from the Georgia Comprehensive Cancer Registry (GCCR) for the years 1999–2008. We constructed distance-decay surrogate exposure metrics and Poisson and negative binomial regression models of NHL incidence to quantify associations between passive exposure to benzene and NHL risk and examined the impact of amount, duration of exposure, and lag time on cancer development. Akaike’s information criteria (AIC) were used to determine the scaling factors for benzene dispersion and exposure periods that best predicted NHL risk. Results Using a range of scaling factors and exposure periods, we found that increased levels of passive benzene exposure were associated with higher risk of NHL. The best fitting model, with a scaling factor of 4 kilometers (km) and exposure period of 1989–1993, showed that higher exposure levels were associated with increased NHL risk (Level 4 (1.1–160 kilograms (kg)) vs. Level 1: risk ratio 1.56 [1.44–1.68], Level 5 (>160 kg) vs. Level 1: 1.60 [1.48–1.74]). Conclusions Higher levels of passive benzene exposure are associated with increased NHL risk across various lag periods. Additional epidemiological studies are needed to refine these models and better quantify the expected total passive benzene exposure in areas surrounding release sites. PMID:26949112
Switchenko, Jeffrey M; Bulka, Catherine; Ward, Kevin; Koff, Jean L; Bayakly, A Rana; Ryan, P Barry; Waller, Lance A; Flowers, Christopher R
Benzene is a known occupational carcinogen associated with increased risk of hematologic cancers, but the relationships between quantity of passive benzene exposure through residential proximity to toxic release sites, duration of exposure, lag time from exposure to cancer development, and lymphoma risk remain unclear. We collected release data through the Environmental Protection Agency's Toxics Release Inventory (TRI) from 1989 to 2003, which included location of benzene release sites, years when release occurred, and amount of release. We also collected data on incident cases of non-Hodgkin lymphoma (NHL) from the Georgia Comprehensive Cancer Registry (GCCR) for the years 1999-2008. We constructed distance-decay surrogate exposure metrics and Poisson and negative binomial regression models of NHL incidence to quantify associations between passive exposure to benzene and NHL risk and examined the impact of amount, duration of exposure, and lag time on cancer development. Akaike's information criteria (AIC) were used to determine the scaling factors for benzene dispersion and exposure periods that best predicted NHL risk. Using a range of scaling factors and exposure periods, we found that increased levels of passive benzene exposure were associated with higher risk of NHL. The best fitting model, with a scaling factor of 4 kilometers (km) and exposure period of 1989-1993, showed that higher exposure levels were associated with increased NHL risk (Level 4 (1.1-160kilograms (kg)) vs. Level 1: risk ratio 1.56 [1.44-1.68], Level 5 (>160kg) vs. Level 1: 1.60 [1.48-1.74]). Higher levels of passive benzene exposure are associated with increased NHL risk across various lag periods. Additional epidemiological studies are needed to refine these models and better quantify the expected total passive benzene exposure in areas surrounding release sites. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Hikel, Stephanie Moller; Adams, Kristen; Hinds, David; Moon, Katherine
Background: Although case–control studies conducted to date have largely affirmed the relationship between polychlorinated biphenyls (PCBs) and non-Hodgkin lymphoma (NHL), occupational cohort studies of PCB-exposed workers have been generally interpreted as negative, thereby raising doubts about a potential causal association. A common theme of immune dysregulation unifies many of NHL’s strongest risk factors, and several authors have posited that subclinical immune dysregulation may increase NHL risk by decreasing host resistance, reducing control of cellular proliferation and differentiation, and diminishing tumor surveillance mechanisms. Objectives: The goals of this review were a) to evaluate the epidemiological research examining the association between PCB exposure and NHL and discuss the contribution to the weight of evidence of case–control studies and occupational cohort studies; and b) to summarize the evidence for immune dysregulation as a means by which PCBs may cause NHL. Methods: We performed a literature search using PubMed and seven additional online biomedical and toxicological referencing libraries to identify literature published through August 2011. Discussion and Conclusions: Overall, we conclude that the weight of evidence supports a causal role of PCBs in lymphomagenesis. The strongest epidemiological evidence for the relationship between PCBs and NHL comes from case–control studies conducted among the general population. Epidemiological and toxicological data demonstrating immunosuppressive and inflammatory effects of PCBs further contribute to the weight of evidence by providing a plausible explanation for how PCBs can cause NHL through immune dysregulation. PMID:22552995
Corti, Marcelo; de Dios Soler, Marcela; Bare, Patricia; Villafañe, María F; De Tezanos Pinto, Miguel; Perez Bianco, Raúl; Narbaitz, Marina
Non-Hodgkin lymphomas (NHL) of the B-cell type are the second most common neoplasm among patients with human immunodeficiency virus (HIV) infection and AIDS. Here, we evaluated 48 cases of AIDS-related lymphomas (ARL) diagnosed at the Histopathological Division of the Instituto de Investigaciones Hematológicas of the National Academy of Medicine. Five were females and 43 were males with a median of age of 37 years at the time of the diagnosis. Micrometer sections were prepared and stained with hematoxilin-eosin; immunohistochemical examination for the presence of Epstein-Barr virus (EBV) was carried out in 48/48 cases. Additionally, biotinilated oligonucleotides were used to determine the presence of DNA of the Human Herpes virus type-8 (HHV-8) in 14/14 biopsy smears corresponding to plasmablastic lymphomas (PL). All were fenotype B cell lymphomas with an aggressive course and advanced neoplasm disease at the time of diagnosis. Virological findings showed the strong association between EBV and AIDS-related NHL. According to the histopathological subtype, the EBV genome was detected in 16/21 (76%) diffuse large B cell lymphomas, 1/3 Burkitt lymphoma and 3/4 (75%) of primary central nervous system lymphomas. Globally, EBV genome was detected in 20/28 NHL of this series. Detection of HHV-8 was negative in all cases of PL. Hodgkin lymphoma were more frequent in males 18/20 (90%), with an aggressive clinical course and a significant predominance of the subtypes associated with worse prognosis (90% of cases). We detected a significant association between EBV and HL (90% of cases). We consider that all cases of AIDS related lymphomas should be assessed for the presence of EBV because its presence may play a role in the prognosis.
Taborelli, Martina; Montella, Maurizio; Libra, Massimo; Tedeschi, Rosamaria; Crispo, Anna; Grimaldi, Maria; Dal Maso, Luigino; Serraino, Diego; Polesel, Jerry
Previous studies have provided limited support to the association between tobacco smoking and lymphomas with weak evidence of a dose-response relationship. We investigated the relationship between tobacco smoking and risk of non-Hodgkin lymphomas (NHL) and Hodgkin lymphomas (HL) through logistic regression spline models. Data were derived from an Italian hospital-based case-control study (1999-2014), which enrolled 571 NHLs, 188 HLs, and 1004 cancer-free controls. Smoking habits and other lifestyle factors were assessed through a validated questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression, adjusting for potential confounders. Compared to never smokers, people smoking ≥15 cigarettes/day showed increased risks of both NHL (OR = 1.42, 95% CI: 1.02, 1.97) and HL (OR = 2.47, 95% CI: 1.25, 4.87); the risk was particularly elevated for follicular NHL (OR = 2.43; 95% CI:1.31-4.51) and mixed cellularity HL (OR = 5.60, 95% CI: 1.31, 23.97). No excess risk emerged for former smokers or people smoking <15 cigarettes/day. Spline analyses showed a positive dose-response relationship with significant increases in NHL and HL risks starting from 15 and 21 cigarettes/day, respectively, with the most evident effects for follicular NHL and mixed cellularity HL. Smoking duration was significantly associated with the HL risk only (OR = 2.15, 95% CI: 1.16, 3.99). These findings support a role of tobacco smoking in the etiology of both NHL and HL, providing evidence of a direct association of risk with smoking intensity.
Radiation therapy (RT) is one of the most effective agents available in the treatment of lymphomas. However, it is a local treatment, and today, with systemic treatments assuming a primary role for induction of response, RT is primarily used for consolidation. For advanced stage lymphomas, the indications for the use of RT have been questioned and debated, and proper randomized evidence is sparse. RT has significant long-term side effects, and the very extended RT fields of the past yielded unacceptable toxicity in many patients. Modern advanced imaging and conformal RT techniques now enable treatment of larger and anatomically more challenging target volumes with much less radiation to normal tissues and consequently much lower risks of long-term complications. The modern concept of involved site radiation therapy (ISRT) has now been accepted as standard in lymphomas. In advanced Hodgkin lymphoma (HL), RT to residual disease and/or initial bulk benefits some patients, depending on the chemotherapy regimen used. The more intensive the chemotherapy regimen, the fewer patients benefit from RT. In advanced aggressive non-Hodgkin lymphoma (NHL), most of the evidence comes from the most common type, the diffuse large B cell lymphoma (DLBCL). In patients treated with modern immunochemotherapy, RT to initial bulky disease or extralymphatic involvement is beneficial. For both HL and aggressive NHL, RT to residual masses after systemic treatment is of benefit. The role of PET in the evaluation and indication for RT to residual masses has not been tested in randomized trials. In advanced indolent NHL, very low dose RT offers excellent palliation with very few side effects. Modern RT in advanced lymphomas warrants further evaluation in randomized trials.
Neasham, David; Sifi, Ahlem; Nielsen, Kaspar Rene; Overvad, Kim; Raaschou-Nielsen, Ole; Tjønneland, Anne; Barricarte, Aurelio; González, Carlos A; Navarro, Carmen; Rodriguez Suarez, Laudina; Travis, Ruth C; Key, Tim; Linseisen, Jakob; Kaaks, Rudolf; Crosignani, Paolo; Berrino, Franco; Rosso, Stefano; Mattiello, Amalia; Vermeulen, R C H; Bueno-de-Mesquita, H Bas; Berglund, Göran; Manjer, Jonas; Zackrisson, Sophia; Hallmans, Goran; Malmer, Beatrice; Bingham, Sheila; Khaw, Kay Tee; Bergmann, Manuela M; Boeing, Heiner; Trichopoulou, Antonia; Masala, Giovanna; Tumino, Rosario; Lund, Eiliv; Slimani, Nadia; Ferrari, Pietro; Boffetta, Paolo; Vineis, Paolo; Riboli, Elio
Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.
Burkitt's lymphoma is a very aggressive type of B-cell NHL with replication approaching 100%. Primary gastrointestinal lymphoma is rare. In our case, a 24-year-old male initially presented with symptomatic anemia. He was initially evaluated with colonoscopy and EGD, both of which were unremarkable. A capsule endoscopy was then performed to further evaluate his significant anemia which revealed friable inflamed ulcerated mass in the jejunum. A push enteroscopy was then performed to obtain tissue from the jejunal mass. Biopsy results and immunohistochemical stains were consistent with Burkitt's lymphoma. PET/CT scan revealed only jejunal involvement. Treatment consisted of bowel resection prior to chemotherapy due to concern for perforation with chemotherapy. Patient achieved complete remission after the treatment. PMID:27672459
The role of autologous hematopoietic stem cell transplantation (ASCT) in the management of non-Hodgkin's lymphoma (NHL) is evolving, in the era of novel agents. Multiple histologies and remission stages have been impacted with changing outcomes. In the 1990s, ASCT could cure 50% of relapsed chemosensitive aggressive NHL; now the percentage maybe as low as 20% for patients relapsing within 1 year of completing rituximab-containing induction. Yet recent trials have clarified the value of first remission ASCT for high-grade NHL, the utility of augmented preparative regimens, the efficacy of ASCT in primary CNS lymphoma and in the elderly and analyses have defined strategies to reduce transplant related myeloid malignancies. In addition, optimizing nontransplant induction therapy for mantle cell and double-hit NHL is leading to improved outcomes and a re-examination of the use of ASCT in first complete remission. Caution is needed, however, as delaying transplants may mean that patients will need more morbid allogeneic transplants to achieve long-term control of refractory disease. As an alternative, maintenance therapy trials to improve ASCT outcome in high-risk patients are starting, based on the efficacy of lenolidomide and brentuximab in myeloma and Hodgkin's lymphoma, respectively. In addition, efforts to define early high-risk patients by minimal residual disease (MRD) assessments and genetic profiling, are beginning even for those with "indolent" phenotypes not currently autotransplanted. These efforts should not only refine but also enhance the value of early potentially curative ASCT, especially if novel agents only delay but do not prevent relapse for patients with NHL.
Lee, Eun Kyung; Joo, Eun Hye; Song, Kyung-A; Choi, Bongkum; Kim, Miyoung; Kim, Seok-Hyung; Kim, Sung Joo; Kang, Myung-Soo
Epstein-Barr virus (EBV) infection causes both Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). The present study reveals that EBV-induced HL and NHL are intriguingly associated with a repopulated immune cell profile in humanized mice. Newborn immunodeficient NSG mice were engrafted with human cord blood CD34(+) hematopoietic stem cells (HSCs) for a 8- or 15-wk reconstitution period (denoted (8w)hN and (15w)hN, respectively), resulting in human B-cell and T-cell predominance in peripheral blood cells, respectively. Further, novel humanized mice were established via engraftment of hCD34(+) HSCs together with nonautologous fetal liver-derived mesenchymal stem cells (MSCs) or MSCs expressing an active notch ligand DLK1, resulting in mice skewed with human B or T cells, respectively. After EBV infection, whereas NHL developed more frequently in B-cell-predominant humanized mice, HL was seen in T-cell-predominant mice (P = 0.0013). Whereas human splenocytes from NHL-bearing mice were positive for EBV-associated NHL markers (hBCL2(+), hCD20(+), hKi67(+), hCD20(+)/EBNA1(+), and EBER(+)) but negative for HL markers (LMP1(-), EBNA2(-), and hCD30(-)), most HL-like tumors were characterized by the presence of malignant Hodgkin's Reed-Sternberg (HRS)-like cells, lacunar RS (hCD30(+), hCD15(+), IgJ(-), EBER(+)/hCD30(+), EBNA1(+)/hCD30(+), LMP(+)/EBNA2(-), hCD68(+), hBCL2(-), hCD20(-/weak,) Phospho STAT6(+)), and mummified RS cells. This study reveals that immune cell composition plays an important role in the development of EBV-induced B-cell lymphoma.
The stomach is the most common site involved in primary gastrointestinal lymphoma. Gastric lymphoma originates from the mucosa-associated lymphoid tissue so called MALT. It comprises a group of distinctive clinicopathological entities which are important to take in account for clinical behavior. In recent years, new diagnostic tools and modern modes of treatment have improved their overall prognosis. One of the most exciting recent discoveries is the hypothesis that an infection by a bacterium. Helicobacter pylori has a decisive role in gastric lymphoma.
Yang, Li; Dong, Jianming; Jiang, Shenghua; Shi, Wenyu; Xu, Xiaohong; Huang, Hongming; You, Xuefen; Liu, Hong
Abstract The association between consumption of red and processed meat and non-Hodgkin lymphoma (NHL) remains unclear. We performed a meta-analysis of the published observational studies to explore this relationship. We searched databases in MEDLINE and EMBASE to identify observational studies which evaluated the association between consumption of red and processed meat and risk of NHL. Quality of included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale (NOS). Random-effects models were used to calculate summary relative risk (SRR) and the corresponding 95% confidence interval (CI). We identified a total of 16 case–control and 4 prospective cohort studies, including 15,189 subjects with NHL. The SRR of NHL comparing the highest and lowest categories were 1.32 (95% CI: 1.12–1.55) for red meat and 1.17 (95% CI: 1.07–1.29) for processed meat intake. Stratified analysis indicated that a statistically significant risk association between consumption of red and processed meat and NHL risk was observed in case–control studies, but not in cohort studies. The SRR was 1.11 (95% CI: 1.04–1.18) for per 100 g/day increment in red meat intake and 1.28 (95% CI: 1.08–1.53) for per 50 g/day increment in processed meat intake. There was evidence of a nonlinear association for intake of processed meat, but not for intake of red meat. Findings from our meta-analysis indicate that consumption of red and processed meat may be related to NHL risk. More prospective epidemiological studies that control for important confounders and focus on the NHL risk related with different levels of meat consumption are required to clarify this association. PMID:26559248
Nolen, Brian M.; Breen, Elizabeth Crabb; Bream, Jay H.; Jenkins, Frank J.; Kingsley, Lawrence A.; Rinaldo, Charles R.; Lokshin, Anna E.
Background Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed bead-based immunoassays. Results A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease. PMID:24922518
Engels, Eric A.; Pfeiffer, Ruth M.; Landgren, Ola; Moore, Richard D.
HIV-infected persons treated with highly active antiretroviral therapy (HAART) continue to have elevated risk for non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of NHL among patients at an urban HIV clinic (N=3025). Proportional hazards models identified immunologic and virologic predictors of NHL. Sixty-five NHLs arose during 1989-2006. NHL incidence declined over time. Nonetheless, 51 NHLs (78%) occurred within the HAART era (1996-2006). NHL risk increased with declining CD4 count (p-trend<0.0001) and increasing HIV viral load (p-trend=0.005). In a multivariable model, NHL risk was independently associated with both current CD4 count (hazard ratios 7.7 and 3.8, respectively, for CD4 counts 0-99 and 100-249 vs. 250+ cells/mm3; p-trend<0.0001) and prior time spent with a viral load above 5.00 log10 copies/ml (hazard ratios of 3.4, 2.6, and 6.8, respectively, for 0.1-0.4, 0.5-1.4, and 1.5+ years vs. 0 years; p-trend=0.004). Although serum globulin levels were elevated compared to the general population, NHL risk was unrelated to this B-cell activation marker (p=0.39). Among HIV-infected individuals in the HAART era, NHLs are linked to immunosuppression and extended periods of uncontrolled HIV viremia. The association with high-level viremia could reflect detrimental effects on immune function related to incompletely effective HAART or direct effects on B-cells. PMID:20418723
Chiu, B C-H; Cerhan, J R; Gapstur, S M; Sellers, T A; Zheng, W; Lutz, C T; Wallace, R B; Potter, J D
We investigated the relation of alcohol consumption to risk of non-Hodgkin's lymphoma (NHL) in a cohort of 35 156 lowa women aged 55–69 years who participated in the lowa Women's Health Study in 1986. Alcohol consumption at baseline was obtained using a mailed questionnaire. During the 9-year follow-up period, 143 incident cases of NHL were identified. Higher alcohol consumption was significantly associated with a decreased risk of NHL (P-trend = 0.03). Compared to non-drinkers, multivariate-adjusted relative risks (RRs) were decreased for women with intake of ≤ 3.4 g day−1 (RR = 0.78; 95% confidence interval (CI) 0.51–1.21) and > 3.4 g day−1 (RR = 0.59; 0.36–0.97). The inverse association could not be attributed to one particular type of alcoholic beverage, although red wine (RR = 0.21 for > 2 glasses per month vs non-drinker; 0.05–0.86; P-trend = 0.02) has the most distinct effect. The apparent protective effect was universal regardless of specific NHL grade or Working Formulation subtype, but was most pronounced for nodal NHL (RR = 0.48; 0.26–0.90; P-trend = 0.01) and low-grade NHL (RR = 0.52; 0.21–1.26; P-trend = 0.05). These data suggest that moderate alcohol consumption is inversely associated with the risk of NHL in older women and the amount of alcohol consumed, rather than the type of alcoholic beverages, appears to be the main effect determinant. © 1999 Cancer Research Campaign PMID:10424754
Bibas, Michele; Trotta, Maria Paola; Cozzi-Lepri, Alessandro; Lorenzini, Patrizia; Pinnetti, Carmela; Rizzardini, Giuliano; Angarano, Gioacchino; Caramello, Pietro; Sighinolfi, Laura; Mastroianni, Claudio Maria; Mazzarello, Giovanni; Di Caro, Antonino; Di Giacomo, Cristina; d'Arminio Monforte, Antonella; Antinori, Andrea
A nested case-control study was performed within the Italian cohort of naïve to antiretroviral human immunodeficiency virus (HIV) patients (ICONA) cohort to evaluate the role of serum free light chains (sFLC) in predicting non-Hodgkin's lymphoma (NHL) and Hodgkin lymphoma (HL) in HIV-infected individuals. Of 6513 participants, 86 patients developed lymphoma and 46 of these (NHL, 30; HL, 16) were included in this analysis having stored prediagnostic blood. A total of 46 serum case samples matched 1:1 to lymphoma-free serum control samples were assayed for κ and λ sFLC levels and compared by using conditional logistic regression. Because the polyclonal nature of free light chains (FLCs) was the focus of our study, we introduced the k + λ sum as the measurement of choice and as the primary variable studied. κ + λ sFLC values were significantly higher in patient with lymphoma than in controls, especially when considering samples stored 0-2-year period before the lymphoma diagnosis. In the multivariable analysis, the elevation of sFLC predicted the risk of lymphoma independently of CD4 count, (odd ratio of 16.85 for k + λ sFLC >2-fold upper normal limit (UNL) vs. normal value). A significant reduction in the risk of lymphoma (odd ratio of 0.07 in model with k + λ sFLC) was found in people with low sFLC and undetectable HIV viremia lasting more than 6 months. Our analysis indicates that an elevated polyclonal sFLC is a strong and sensitive predictor of the risk of developing lymphomas, and it is an easy to measure biomarker that merits consideration for introduction in routine clinical practice in people with HIV.
Pozzato, Gabriele; Mazzaro, Cesare; Dal Maso, Luigino; Mauro, Endri; Zorat, Francesca; Moratelli, Giulia; Bulian, Pietro; Serraino, Diego; Gattei, Valter
Hepatitis C virus (HCV) is a global health problem affecting a large fraction of the world’s population: This virus is able to determine both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, a B-cell “benign” lymphoproliferative disorders, represents the most closely related as well as the most investigated HCV-related extrahepatic disorder. Since this virus is able to determine extrahepatic [non-Hodgkin’s lymphoma (NHL)] as well as hepatic malignancies (hepatocellular carcinoma), HCV has been included among human cancer viruses. The most common histological types of HCV-associated NHL are the marginal zone, the lymphoplasmacytic and diffuse large cell lymphomas. The role of the HCV in the pathogenesis of the B-cell lymphoproliferative disorders is confirmed also by the responsiveness of the NHL to antiviral therapy. The purpose of this review is to provide an overview of the recent literature and a meta analysis of the epidemiology data, to explain the role of HCV in the development of NHL’s lymphoma. Furthermore, the possibility to treat these HCV-related NHL with the antiviral therapy or with other therapeutic options, like chemotherapy, is also discussed. PMID:26807206
Bradshaw, Gabrielle; Sutherland, Heidi G.; Haupt, Larisa M.; Griffiths, Lyn R.
A large number of studies have focused on identifying molecular biomarkers, including microRNAs (miRNAs) to aid in the diagnosis and prognosis of the most common subtypes of non-Hodgkin lymphoma (NHL), Diffuse Large B-cell Lymphoma and Follicular Lymphoma. NHL is difficult to diagnose and treat with many cases becoming resistant to chemotherapy, hence the need to identify improved biomarkers to aid in both diagnosis and treatment modalities. This review summarises more recent research on the dysregulated miRNA expression profiles found in NHL, as well as the regulatory role and biomarker potential of cellular and circulating miRNAs found in tissue and serum, respectively. In addition, the emerging field of research focusing on miRNA single nucleotide polymorphisms (miRSNPs) in genes of the miRNA biogenesis pathway, in miRNA genes themselves, and in their target sites may provide new insights on gene expression changes in these genes. These miRSNPs may impact miRNA networks and have been shown to play a role in a host of different cancer types including haematological malignancies. With respect to NHL, a number of SNPs in miRNA-binding sites in target genes have been shown to be associated with overall survival. PMID:27999330
Blombery, Piers A; Wall, Meaghan; Seymour, John F
The B-cell non-Hodgkin lymphomas (B-NHL) are a diverse group of haematological malignancies which arise from the mature B-lymphocyte compartment. Recently, our understanding of the molecular pathogenesis of these disorders has greatly increased due to technological advances such as high-throughput DNA sequencing techniques. A paradigm of B-NHL pathogenesis has emerged where the normal genetic processes that are central to generating B-cell receptor diversity (somatic hypermutation and class switch/VDJ recombination) also drive the genesis of large-scale, chromosomal-level genetic lesions and smaller-scale gene-level mutations to produce the malignant phenotypes observed. Whilst a significant degree of genetic heterogeneity exists within each B-NHL subtype, the genetic lesions present within each subtype show a degree of convergence on common intracellular signalling, epigenetic and cell cycle pathways. This convergence gives an insight into the key oncogenic drivers of specific B-NHL subtypes and potential targets for therapeutic intervention. This review covers the current understanding of the causative genetic processes of B-NHL, the associated driving molecular lesions and the implications of these findings for the treatment of this group of disorders. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Gonzalez, Quintín H; Heslin, Martin J; Dávila-Cervantes, Andrea; Alvarez-Tostado, Javier; de los Monteros, Antonio Espinosa; Shore, Gregg; Vickers, Selwyn M
J J-pouch (1), and sigmoid colectomy (1). Eighty-seven per cent had negative margins at the time of operation. Twelve patients received postoperative chemotherapy (80%). According to the clinical classification of primary non-Hodgkin lymphoma (NHL) of the gastrointestinal tract (Lugano, 1993) all patients corresponded to stage IE. Mean hospital stay was 6.4 days (range 3-26). There was no surgical mortality and the morbidity rate was 20 per cent (3 patients). One patient had a systemic recurrence (7%) approximately 4 months after surgical resection. Mean follow-up was 31 months (median 2-73). Surgical resection of localized, primary colonic lymphoma provides excellent local disease control and should be considered a primary treatment option. The role of chemotherapy remains controversial depending on the grade, stage, and extension of residual disease.
Bassig, Bryan A; Friesen, Melissa C; Vermeulen, Roel; Shu, Xiao-Ou; Purdue, Mark P; Stewart, Patricia A; Xiang, Yong-Bing; Chow, Wong-Ho; Zheng, Tongzhang; Ji, Bu-Tian; Yang, Gong; Linet, Martha S; Hu, Wei; Zhang, Heping; Zheng, Wei; Gao, Yu-Tang; Rothman, Nathaniel; Lan, Qing
The association between benzene exposure and non-Hodgkin lymphoma (NHL) has been the subject of debate as a result of inconsistent epidemiologic evidence. An International Agency for Research on Cancer (IARC) working group evaluated benzene in 2009 and noted evidence for a positive association between benzene exposure and NHL risk. We evaluated the association between occupational benzene exposure and NHL among 73,087 women enrolled in the prospective population-based Shanghai Women's Health Study. Benzene exposure estimates were derived using a previously developed exposure assessment framework that combined ordinal job-exposure matrix intensity ratings with quantitative benzene exposure measurements from an inspection database of Shanghai factories collected between 1954 and 2000. Associations between benzene exposure metrics and NHL (n = 102 cases) were assessed using Cox proportional hazard models, with study follow-up occurring from December 1996 through December 2009. Women ever exposed to benzene had a significantly higher risk of NHL [hazard ratio (HR) = 1.87, 95% CI: 1.19, 2.96]. Compared with unexposed women, significant trends in NHL risk were observed for increasing years of benzene exposure (p(trend) = 0.006) and increasing cumulative exposure levels (p(trend) = 0.005), with the highest duration and cumulative exposure tertiles having a significantly higher association with NHL (HR = 2.07, 95% CI: 1.07, 4.01 and HR = 2.16, 95% CI: 1.17, 3.98, respectively). Our findings, using a population-based prospective cohort of women with diverse occupational histories, provide additional evidence that occupational exposure to benzene is associated with NHL risk.
Ogura, Michinori; Ando, Kiyoshi; Suzuki, Tatsuya; Ishizawa, Kenichi; Oh, Sung Yong; Itoh, Kuniaki; Yamamoto, Kazuhito; Au, Wing Yan; Tien, Hwei-Fang; Matsuno, Yoshihiro; Terauchi, Takashi; Yamamoto, Keiko; Mori, Masahiko; Tanaka, Yoshinobu; Shimamoto, Takashi; Tobinai, Kensei; Kim, Won Seog
Although initial rituximab-containing chemotherapies achieve high response rates, indolent B-cell non-Hodgkin lymphoma (B-NHL), such as follicular lymphoma (FL), is still incurable. Therefore, new effective agents with novel mechanisms are anticipated. In this multicentre phase II study, patients with relapsed/refractory indolent B-NHL and mantle cell lymphoma (MCL) received vorinostat 200 mg twice daily for 14 consecutive days in a 21-d cycle until disease progression or unacceptable toxicity occurred. The primary endpoint was overall response rate (ORR) in FL patients and safety and tolerability in all patients. Secondary endpoints included progression-free survival (PFS). Fifty-six eligible patients were enrolled; 50 patients (39 with FL, seven with other B-NHL, and four with MCL) were evaluable for ORR, and 40 patients had received rituximab-containing prior chemotherapeutic regimens. For the 39 patients with FL, the ORR was 49% [95% confidence interval (CI): 32·4, 65·2] and the median PFS was 20 months (95% CI: 11·2, 29·7). Major toxicities were manageable grade 3/4 thrombocytopenia and neutropenia. Vorinostat offers sustained antitumour activity in patients with relapsed or refractory FL with an acceptable safety profile. Further investigation of vorinostat for clinical efficacy is warranted.
Morimoto, Yukiko; Ollberding, Nicholas J.; Cooney, Robert V.; Wilkens, Lynne R.; Franke, Adrian A.; Le Marchand, Loïc; Goodman, Marc T.; Hernandez, Brenda Y.; Kolonel, Laurence N.; Maskarinec, Gertraud
Background Compromised immunity and chronic inflammation are thought to contribute to the development of non-Hodgkin lymphoma (NHL). Because tocopherols protect cells through antioxidant mechanisms, they may play a role in NHL etiology. Methods This nested case-control study within the Multiethnic Cohort examined the association of prediagnostic serum tocopherols levels measured in 271 NHL cases and 538 matched controls by high pressure liquid chromatography/photodiode-array detection with NHL risk. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). Results We observed U-shaped associations with NHL for total and α-tocopherols (Ptrend<0.01 for polynomial terms [3 df]). The ORs (95% CI) for total tocopherols, which consisted primarily of α-tocopherol, were 0.41 (0.25–0.68), 0.52 (0.32–0.85), 0.39 (0.23–0.65), and 0.78 (0.47–1.29) for the 2nd-5th quintiles as compared to the 1st. The risk estimates were similar for α-tocopherol but non-significant for β- and γ-tocopherol combined and for δ-tocopherol. Adjustment for serum lipids strengthened the non-linear associations for total and α-tocopherols. Serum total tocopherol levels were higher for vitamin E supplement users at cohort entry than non-users (21.32±9.04 vs 17.72±7.43 μg/mL; P <0.0001), but supplement use was not associated with NHL risk. No heterogeneity in risk estimates was detected by sex, ethnicity, vitamin E supplement use, or NHL subtype. Conclusions Circulating tocopherols, at levels likely reflecting adequate dietary intakes, may be protective against NHL, whereas higher intakes from supplementation may not be beneficial. Impact The association between serum tocopherol levels and NHL risk provides possible new insights into the etiology of NHL. PMID:24045922
Chen, Feifei; Hu, Jiyi; Liu, Ping; Li, Jing; Wei, Zheng; Liu, Peng
Carotenoids may play a protective role in the development of non-Hodgkin lymphoma (NHL), but findings from epidemiological studies on the associations between carotenoid intake and NHL risk are inconsistent. We therefore performed a meta-analysis to systemically evaluate the associations. Eligible studies were identified by a search of PubMed, Web of Science, Embase, and article reference lists. We pooled risk estimates from individual studies using a random-effect model to quantify the associations between intakes of specific carotenoids and NHL risk. A total of 10 (7 case-control and 3 cohort) studies met our inclusion criteria. In the highest versus lowest analyses, intakes of alpha-carotene, beta-carotene, and lutein/zeaxanthin, but not lycopene or beta-cryptoxanthin, were associated with a significant reduced risk of NHL. The estimated summary relative risks (95% confidence intervals) for alpha-carotene, beta-carotene, and lutein/zeaxanthin were 0.87 (0.78-0.97), 0.80 (0.68-0.94), and 0.82 (0.69-0.97), respectively. Subgroup analyses showed that evidence supporting these protective associations was mostly based on studies with a case-control design. In addition, intakes of alpha-carotene and beta-carotene were associated with a significant decreased risk of diffuse large B-cell lymphoma, but not follicular lymphoma or small lymphocytic lymphoma/chronic lymphocytic leukemia. There was a significant inverse dose-response relationship between alpha-carotene intake and NHL risk (13% lower risk per 1000 μg/day increment of intake). In conclusion, our findings suggest that higher intakes of alpha-carotene, beta-carotene, and lutein/zeaxanthin might protect against NHL development. Further cohort studies with a control of plausible confounding are needed to confirm these associations.
Pre-treatment serum levels of interleukin-10, interleukin-12 and their ratio predict response to therapy and probability of event-free and overall survival in childhood soft tissue sarcomas, Hodgkin's lymphomas and acute lymphoblastic leukemias.
Bien, Ewa; Balcerska, Anna; Adamkiewicz-Drozynska, Elzbieta; Rapala, Malgorzata; Krawczyk, Malgorzata; Stepinski, Jan
Deregulated serum IL-10, IL-12 and their reciprocal balance have been stated in malignancies of adults. In children with cancer the issue has not been investigated so far. To determine the diagnostic and prognostic roles of pre-treatment serum levels of IL-10 (Th2 cytokine), IL-12 (Th1) and their ratios (measured by the IL-10 and IL-12p70 ELISA kits; Endogen) in 91 children with soft tissue sarcomas (STS), Hodgkin's lymphomas (HL) and acute lymphoblastic leukemias (ALL). Median IL-10 and IL-12 levels were significantly higher in cancer patients than in healthy controls. Increased IL-10 indicated presence of general symptoms in HL and high risk group in ALL. Elevated IL-10 and IL-10/IL-12 ratios and decreased IL-12 correlated with poor-risk histology in STS, poor response to therapy, relapse and death from cancer. Multivariate analysis identified IL-10/IL-12 ratio>0.14 and IL-12<40 pg/mL as significant predictors for shorter EFS and OS, respectively. Pre-treatment serum levels of IL-10, IL-12 and IL-10/IL-12 balance in children with STS, HL and ALL may be of value as additional prognostic tools to predict the response to therapy and probability of EFS and OS.
Madewell, B R
This article presents an overview of the literature regarding canine malignant lymphoma. It includes a discussion of etiology, classification, systemic manifestations of disease, therapy, and supportive care for patient management.
... as Hodgkin's disease — is a cancer of the lymphatic system, which is part of your immune system. In Hodgkin's lymphoma, cells in the lymphatic system grow abnormally and may spread beyond the lymphatic ...
WU, JINGJING; LI, AIMIN; ZHANG, PENGYU; SUN, ZHENCHANG; HAN, LIJUAN; NAN, FEIFEI; GENG, LI
The aim of the present study was to determine the expression levels of microRNA-503 (miR-503) and the tumor suppressor gene, kangai-1 (KAI1), in B-cell non-Hodgkin's lymphoma (B-NHL). A total of 45 patients with B-NHL (including 29 cases with stage III/IV disease and 16 cases with stage I/II disease) were enrolled in this study. In addition, 26 patients with reactive lymphoid hyperplasia (RLH) were enrolled as the control patients. Reverse transcription-quantitative polymerase chain reaction was performed in order to measure the expression levels of miR-503 in B-NHL and RLH tissues, and to detect the expression levels of miR-503 and KAI1 in peripheral blood samples. In addition, KAI1 expression levels in B-NHL and RLH tissues were detected using western blotting and immunohistochemical analysis. The expression levels of miR-503 were found to be significantly increased in the tissues and peripheral blood of B-NHL patients when compared with those in RLH patients (P<0.05). However, KAI1 was strongly expressed in RLH tissues and weakly expressed in B-NHL tissues. Furthermore, the expression levels of KAI1 were significantly decreased in the tissues and peripheral blood of B-NHL patients when compared with those in the tissues and peripheral blood of RLH patients (P<0.05). The expression levels of miR-503 in the tissues and peripheral blood of patients with stage III/IV B-NHL were significantly higher compared with those with stage I/II B-NHL (P<0.05). By contrast, the expression levels of KAI1 in stage III/IV B-NHL tissues were significantly higher compared with those in stage I/II B-NHL tissues (P<0.05). In conclusion, miR-503 was highly expressed, whereas KAI1 was poorly expressed, in the tissues and peripheral blood of B-NHL patients. Thus, miR-503 may have an application as a novel therapeutic and diagnostic marker in B-NHL patients. PMID:26998012
Mariette, Xavier; Tubach, Florence; Bagheri, Haleh; Bardet, Michel; Berthelot, Jean-Marie; Gaudin, Philippe; Heresbach, Denis; Martin, Antoine; Schaeverbeke, Thierry; Salmon, Dominique; Lemann, Marc; Hermine, Olivier; Raphael, Martine; Ravaud, Philippe
Objective To describe cases of lymphoma associated with anti-TNF therapy, identify risk factors, estimate the incidence and compare risks for different anti-TNF agents. Methods We designed a national prospective registry (RATIO) from 2004 to 2006, for collecting all cases of lymphoma in French patients receiving anti-TNF therapy, whatever the indication. We conducted a case-control analysis including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population used as reference.. Results We collected 38 cases of lymphoma, 31 non-Hodgkin’s lymphoma (NHL) (26 B-cell and 5 T-cell), 5 Hodgkin’s lymphoma (HL) and 2 Hodgkin’s-like lymphoma. Epstein-Barr virus (EBV) was detected in 2 of 2 Hodgkin’s-like lymphoma, 3 of 5 HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: SIR = 4.1 (2.3–7.1) and 3.6 (2.3–5.6) versus 0.9 (0.4– 1.8). The exposure to adalimumab or infliximab versus etanercept was an independent risk factor for lymphoma in the case-control study: odds ratio=4.7 (1.3– 17.7) and 4.1 (1.4–12.5), respectively. The sex and age- adjusted incidence rate of lymphoma was 42.1 per 100,000 patient-years. The standardized incidence ratio (SIR) was 2.4 (95% confidence interval [CI] 1.7–3.2). Conclusion Some lymphomas associated with immunosuppression may occur in patients receiving anti TNF therapy, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy. PMID:19828563
SAGUNA, Carmen; MUT, Ileana Delia; LUPU, Anca Roxana; TEVET, Mihaela; BUMBEA, Horia; DRAGAN, Cornel
ABSTRACT Background: Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory. The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. Material and method: The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, Bucharest Results and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab. PMID:22205891
Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel
Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.
Omodei, Daniela; Acampora, Dario; Russo, Filippo; De Filippi, Rosaria; Severino, Valeria; Di Francia, Raffaele; Frigeri, Ferdinando; Mancuso, Pietro; De Chiara, Anna; Pinto, Antonio; Casola, Stefano; Simeone, Antonio
The roles in brain development. Previous studies have shown the association between OTX2 and OTX1 with anaplastic and desmoplastic medulloblastomas, respectively. Here, we investigated OTX1 and OTX2 expression in Non-Hodgkin Lymphoma (NHL) and multiple myeloma. A combination of semiquantitative RT-PCR, Western blot, and immunohistochemical analyses was used to measure OTX1 and OTX2 levels in normal lymphoid tissues and in 184 tumor specimens representative of various forms of NHL and multiple myeloma. OTX1 expression was activated in 94% of diffuse large B-cell lymphomas, in all Burkitt lymphomas, and in 90% of high-grade follicular lymphomas. OTX1 was undetectable in precursor-B lymphoblastic lymphoma, chronic lymphocytic leukemia, and in most marginal zone and mantle cell lymphomas and multiple myeloma. OTX2 was undetectable in all analyzed malignancies. Analysis of OTX1 expression in normal lymphoid tissues identified a subset of resting germinal center (GC) B cells lacking PAX5 and BCL6 and expressing cytoplasmic IgG and syndecan. About 50% of OTX1(+) GC B cells co-expressed CD10 and CD20. This study identifies OTX1 as a molecular marker for high-grade GC-derived NHL and suggests an involvement of this transcription factor in B-cell lymphomagenesis. Furthermore, OTX1 expression in a subset of normal GC B cells carrying plasma cell markers suggests its possible contribution to terminal B-cell differentiation.
Omodei, Daniela; Acampora, Dario; Russo, Filippo; De Filippi, Rosaria; Severino, Valeria; Di Francia, Raffaele; Frigeri, Ferdinando; Mancuso, Pietro; De Chiara, Anna; Pinto, Antonio; Casola, Stefano; Simeone, Antonio
The roles in brain development. Previous studies have shown the association between OTX2 and OTX1 with anaplastic and desmoplastic medulloblastomas, respectively. Here, we investigated OTX1 and OTX2 expression in Non-Hodgkin Lymphoma (NHL) and multiple myeloma. A combination of semiquantitative RT-PCR, Western blot, and immunohistochemical analyses was used to measure OTX1 and OTX2 levels in normal lymphoid tissues and in 184 tumor specimens representative of various forms of NHL and multiple myeloma. OTX1 expression was activated in 94% of diffuse large B-cell lymphomas, in all Burkitt lymphomas, and in 90% of high-grade follicular lymphomas. OTX1 was undetectable in precursor-B lymphoblastic lymphoma, chronic lymphocytic leukemia, and in most marginal zone and mantle cell lymphomas and multiple myeloma. OTX2 was undetectable in all analyzed malignancies. Analysis of OTX1 expression in normal lymphoid tissues identified a subset of resting germinal center (GC) B cells lacking PAX5 and BCL6 and expressing cytoplasmic IgG and syndecan. About 50% of OTX1+ GC B cells co-expressed CD10 and CD20. This study identifies OTX1 as a molecular marker for high-grade GC-derived NHL and suggests an involvement of this transcription factor in B-cell lymphomagenesis. Furthermore, OTX1 expression in a subset of normal GC B cells carrying plasma cell markers suggests its possible contribution to terminal B-cell differentiation. PMID:19893048
Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...
Mir, Shahnaz Ahmad; Masoodi, Shariq Rashid; Wani, Arshad Iqbal; Ahmad, Syed Nisar; Hameed, Iqra
Primary adrenal lymphomas (PAL) are rare occurrences with only less than 150 cases reported in the literature. Two-thirds of these cases were reported in the last decade due to the advancements in imaging techniques and immunohistochemistry. The non-specific signs and symptoms have resulted in a delayed onset of symptoms and diagnosis of these tumors. Reports of the results of chemotherapy are not gratifying, and most patients die within one year of the diagnosis. We report a 65-year-old male with adrenal non-Hodgkin’s lymphoma (NHL), who presented with hypercalcemia and renal failure. We reviewed all adrenal NHL cases presented with hypercalcemia and attempted to comprehend its etiology and overall survival effect. PMID:28090186
Fernandes, Teresa; Lopes, Alexandra; Santos, Susana; Mafra, Manuela; Rodrigues, António Silva; Botelho de Sousa, Aida
In adults, non-Hodgkin’s lymphoma (NHL) is the second most common neoplasm found in the head and neck region after squamous cell carcinoma. Within this region, primary NHL of the nasopharynx is rare. We report the case of a 28-year-old male diagnosed with a B lymphoblastic lymphoma (CD20−; CD79a+; CD3−; CD10+; PAX5+, CyclinD1−; TdT+) of the nasopharynx extending to the deep and superficial structures of the right hemiface, to the skull base with an intracranial component and a small but detectable bone marrow involvement, who was started on chemotherapy with a complete response. To the best of our knowledge, this is the first case of a primary nasopharynx B-LBL in an adult patient with such aggressive regional spread to be reported in the literature. PMID:20730608
Hosnijeh, Fatemeh Saberi; Heederik, Dick; Vermeulen, Roel
Immune deficiency and altered immunity are among the best characterized and strongest known risk factors of non-Hodgkin lymphomas (NHL). For instance, chronic inflammation or certain disturbances in the immune system are associated with an increased lymphoma risk. Occupational and environmental factors (i.e., dioxin) as well as lifestyle factors (i.e., obesity) may contribute to these risk factors. The precise role of these factors in the etiology of NHL, however, is still not entirely clear. Although the existing epidemiologic studies have not revealed consistent patterns of perturbations of the immune system by these factors, the findings might suggest an adverse impact on both the humoral and cell-mediated immune system.
Tocchini, Cristina; Keusch, Jeremy J; Miller, Sarah B; Finger, Susanne; Gut, Heinz; Stadler, Michael B; Ciosk, Rafal
The mechanisms controlling cell fate determination and reprogramming are fundamental for development. A profound reprogramming, allowing the production of pluripotent cells in early embryos, takes place during the oocyte-to-embryo transition. To understand how the oocyte reprogramming potential is controlled, we sought Caenorhabditis elegans mutants in which embryonic transcription is initiated precociously in germ cells. This screen identified LIN-41, a TRIM-NHL protein and a component of the somatic heterochronic pathway, as a temporal regulator of pluripotency in the germline. We found that LIN-41 is expressed in the cytoplasm of developing oocytes, which, in lin-41 mutants, acquire pluripotent characteristics of embryonic cells and form teratomas. To understand LIN-41 function in the germline, we conducted structure-function studies. In contrast to other TRIM-NHL proteins, we found that LIN-41 is unlikely to function as an E3 ubiquitin ligase. Similar to other TRIM-NHL proteins, the somatic function of LIN-41 is thought to involve mRNA regulation. Surprisingly, we found that mutations predicted to disrupt the association of LIN-41 with mRNA, which otherwise compromise LIN-41 function in the heterochronic pathway in the soma, have only minor effects in the germline. Similarly, LIN-41-mediated repression of a key somatic mRNA target is dispensable for the germline function. Thus, LIN-41 appears to function in the germline and the soma via different molecular mechanisms. These studies provide the first insight into the mechanism inhibiting the onset of embryonic differentiation in developing oocytes, which is required to ensure a successful transition between generations.
Batata, A; Shen, B
Cell suspensions from lymphoid tissue of 82 small lymphocytic lymphoma (SLL), 8 intermediate lymphocytic lymphoma (ILL), 286 other B-non-Hodgkin's lymphoma (B-NHL), and 248 reactive lymphadenopathy (RLA) cases were analyzed to evaluate the diagnostic significance of mouse-rosette (M-rosette) assay, and surface immunoglobulin clonality (SIg) and level of expression. In SLL, 55 were M-rosette positive (67.07%) and 72 SIg positive (87.8%), with weak fluorescence in 63 and strong fluorescence in 9 cases. Of 10 SIg-negative cases, 9 were M-rosette positive; of 27 M-rosette-negative cases, 26 were SIg positive. Seven of the nine cases with strong fluorescence were M-rosette positive. In other B-NHL, 252 were M-rosette negative (88.11%) and 245 SIg positive (85.66%), with strong fluorescence in 211 and weak fluorescence in 34 cases. Thirty-two of the 34 cases with weak fluorescence were M-rosette negative. Of the RLA cases, 213 were M-rosette negative (85.89%) and 1 SIg positive (0.4%). The study demonstrated the independent expression of M-rosettes and SIg in SLL and their complementary role in diagnosis. It showed that positive results for M-rosettes and weak fluorescence are characteristic of SLL, that M-rosette negativity and strong fluorescence are characteristic of other B-NHL, and that M-rosette negativity and polyclonal SIg are characteristic of RLA. In 26 cases with paired data for CD5, M-rosettes, and SIg, a positive result for M-rosettes was superior to CD5 in differentiating SLL from other B-NHL. Intermediate lymphocytic lymphoma frequently showed weak SIg fluorescence and M-rosette negativity.
Witzig, T E; Nowakowski, G S; Habermann, T M; Goy, A; Hernandez-Ilizaliturri, F J; Chiappella, A; Vitolo, U; Fowler, N; Czuczman, M S
Lenalidomide is an oral non-chemotherapy immunomodulator with direct and indirect effects on non-Hodgkin lymphoma (NHL) cells and with single-agent activity in relapsed/refractory aggressive and indolent B-cell NHL, including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma, and follicular lymphoma. Based on the pivotal phase II MCL-001 trial of lenalidomide in heavily pretreated patients with relapsed/refractory MCL, lenalidomide was approved by the US Food and Drug Administration for the treatment of relapsed/refractory MCL after failure of two prior therapies, one of which includes bortezomib, at a recommended starting dose of 25 mg on days 1-21 of each 28-day cycle. Lenalidomide enhanced the survival benefit in combination with rituximab in preclinical models, prompting clinical evaluation of the lenalidomide-rituximab (R2) combination. In phase II trials, lenalidomide 20 mg on days 1-21 in combination with different standard-dose rituximab schedules exhibited promising activity in both first-line and relapsed/refractory disease across multiple B-cell NHL subtypes. The feasibility of combining lenalidomide with immunochemotherapy, including R-CHOP and rituximab-bendamustine, has been demonstrated in phase I/II trials. These latter regimens are currently being evaluated in ongoing phase II and III trials. The role of lenalidomide monotherapy and R2 in maintenance therapy is also being examined. Based on available evidence, a comprehensive review of lenalidomide in all treatment phases of B-cell NHL-relapsed/refractory disease, first-line, and maintenance-is presented here.
Ohmoto, Akihiro; Maeshima, Akiko Miyagi; Taniguchi, Hirokazu; Tanioka, Kensaku; Makita, Shinichi; Kitahara, Hideaki; Fukuhara, Suguru; Munakata, Wataru; Suzuki, Tatsuya; Maruyama, Dai; Kobayashi, Yukio; Tobinai, Kensei
Detection of immunoglobulin light chain restriction (LCR) by flow cytometry (FCM) is a useful tool for B-cell non-Hodgkin lymphoma (B-NHL) diagnosis. Here, we identified B-NHLs without LCR by FCM and investigated the pathological causes for lack of LCR. A total of 89/471 cases (19%) of B-NHL were LCR-negative. The incidence of lack of LCR was 30% both in diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL), and was 6% in follicular lymphoma (FL). In DLBCL cases, low expression of surface membrane light chain (33%), low proportion of lymphoma cells (11%), CD45 negativity (9%), and destruction or sampling error were suggested as reasons for lack of LCR. In MZL cases, the low proportion of lymphoma cells owing to admixture of many reactive germinal centres, and non-detection of plasmacytoid lymphoma cells by CD45 gating might be the reasons. Based on pathological subtypes, the frequency and reasons for lack of LCR by FCM varied.
Bonnefoix, T; Sotto, M F; Gressin, R; Martin, I; Garban, F; Leroux, D; Renversez, J C; Sotto, J J
Twenty-five B-cell-nonHodgkin's lymphomas (B-NHL): 6 lymphocytic, 2 centrocytic, 13 follicular, centrocytic/centroblastic, 2 lymphoplasmocytoid and 2 centroblastic were tested for their ability to acquire features of mature plasma cells under the effect of interferon alpha (final concentration, 600 UI/ml), all-trans-retinoic-acid (ATRA) (final concentration, 10(-6) mol/l) and the association of both. B-NHL cells were negatively purified (>99%) by an immunomagnetic method, cultured for 7 d with or without interferon and ATRA, then stained with anti-CD19, CD20, surface Ig, DR, CD38 and with anti-CD138 (syndecan-1) antibody-recognizing plasma cells. Ig production was estimated in culture supernatants by an ELISA method and changes in cell morphology were investigated on May-Grunwald-Giemsa-stained cytospin preparations. In all cases interferon and ATRA, alone or in association, were able to induce changes in the immunophenotypic profile, associated or not with morphologic changes and induction of Ig secretion. All changes were greatly variable from one to the other B-NHL sample and no relationship could be found between a particular pattern of change and the histological subtype. Interferon alpha was more potent than ATRA in inducing changes. In favour of a differentiation process, we observed a concomitant decrease of DR expression and increase of CD38 expression in 8 cases with interferon alpha, and in 4 cases with ATRA. Although interferon- or ATRA-treated cells did not display cytologic, functional features and changes of the immunophenotypic profile fully compatible with those of terminally differentiated cells, these results suggest a possible transition toward more differentiated elements, especially with interferon alpha.
Haacke, Erlin A; van der Vegt, Bert; Vissink, Arjan; Spijkervet, Fred K L; Bootsma, Hendrika; Kroese, Frans G M
Patients with primary Sjögren's syndrome (pSS) have an increased risk of developing non-Hodgkin's lymphoma (NHL), particularly parotid gland mucosa-associated lymphoid tissue (MALT) lymphomas. Presence of germinal centres (GCs) in labial gland biopsies has been suggested as predictive factor for NHL. We assessed whether presence of GCs is increased in labial gland biopsies from patients with pSS who developed parotid MALT lymphoma, the dominant NHL-subtype in pSS, compared with patients with pSS who did not develop lymphoma. Eleven labial gland biopsies from patients with pSS that were taken prior to parotid MALT lymphoma development were compared with biopsies of 22 matched pSS controls (1:2) who did not develop lymphoma. Biopsies were evaluated for GCs (H&E and Bcl6). Labial gland biopsies of pSS MALT lymphoma patients, revealed GCs in 2/11 (18%) H&E sections and 3/11 (27%) Bcl6 stained sections. In controls, GCs were present in 4/22 (18%) of H&E sections and 5/22 (23%) of Bcl6 stained sections. Presence of GCs in labial gland biopsies does not differ between patients with pSS that develop parotid MALT lymphoma and patients with pSS who do not develop lymphoma. The presence of GCs in labial gland biopsies is therefore not a predictive factor for pSS-associated parotid MALT lymphomas. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Grant, W. B.
The ecological approach is used to investigate dietary and smoking links to lymphoma. International mortality rate data for 1986 and 1994 by gender and age group are compared with national dietary supply values of various food components for up to 10 years prior to the mortality data as well as per capita cigarette consumption rates 5 and 15 years earlier. The non-fat portion of milk, 3-9 years prior to the 1986 mortality data and 4 years prior to the 1994 data, was found to have the highest association with lymphoma, with r as high as 0.89. The results imply that 70 percent of lymphoma mortality may be related to this dietary component. Cigarette smoking in 1980 was found to have a weaker association with 1994 lymphoma mortality rates, being most important for younger men and statistically insignificant for younger women. The non-fat milk result is consistent with both case-control studies and a Norwegian prospective study, and with the often-observed finding that abnormal calcium metabolism, hypercalciuria, and dysregulated calcitriol production are common in normocalcemic patients with non-Hodgkin's lymphoma (NHL). It is hypothesized that excess dietary calcium from milk is a significant risk factor for lymphoma.
Primary cardiac lymphomas represent an extremely rare entity of extranodal lymphomas and should be distinguished from secondary cardiac involvement of disseminated lymphomas belonging to the non-Hodgkin’s classification of blood cancers. Only 90 cases have been reported in literature. Presentation of cardiac lymphomas on imaging studies may not be unambiguous since they potentially mimic other cardiac neoplasms including myxomas, angiosarcoma or rhadomyomas and therefore require multimodality cardiac imaging, endomyocardial biopsy, excisional intraoperative biopsy and pericardial fluid cytological evaluation to establish final diagnosis. Herein we report the case of a 70 y/o immunocompetent Caucasian female with a rapidly progressing superior vena cava syndrome secondary to a large primary cardiac diffuse large B cell lymphoma (NHL lymphoma) almost completely obstructing the right atrium, right ventricle and affecting both mitral and tricuspid valve. The patient had no clinical evidence of disseminated disease and was successfully treated with extensive debulking during open-heart surgery on cardiopulmonary bypass and 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy (R-CHOP). PMID:24422789
Grant, W. B.
The ecological approach is used to investigate dietary and smoking links to lymphoma. International mortality rate data for 1986 and 1994 by gender and age group are compared with national dietary supply values of various food components for up to 10 years prior to the mortality data as well as per capita cigarette consumption rates 5 and 15 years earlier. The non-fat portion of milk, 3-9 years prior to the 1986 mortality data and 4 years prior to the 1994 data, was found to have the highest association with lymphoma, with r as high as 0.89. The results imply that 70 percent of lymphoma mortality may be related to this dietary component. Cigarette smoking in 1980 was found to have a weaker association with 1994 lymphoma mortality rates, being most important for younger men and statistically insignificant for younger women. The non-fat milk result is consistent with both case-control studies and a Norwegian prospective study, and with the often-observed finding that abnormal calcium metabolism, hypercalciuria, and dysregulated calcitriol production are common in normocalcemic patients with non-Hodgkin's lymphoma (NHL). It is hypothesized that excess dietary calcium from milk is a significant risk factor for lymphoma.
Matsuki, Eri; Younes, Anas
Treatment for relapsed/refractory (R/R) Hodgkin and non-Hodgkin lymphoma remains challenging. The introduction of rituximab to B cell non-Hodgkin lymphoma (B-NHL) treatment significantly improved patients' response rate and survival; however, approximately one third of patients with diffuse large B cell lymphoma, the most common B-NHL subtype, still have a relapse or become refractory after first-line therapy. More recently, antibody therapies and small-molecule inhibitors were approved for treating R/R lymphomas; these agents include brentuximab vedotin, ibrutinib, and idelalisib. Immune checkpoint inhibitors and other immune therapies are emerging treatments currently being evaluated in various clinical trials for their efficacy against lymphoid malignancies. Striking results from these treatment modalities have been observed in solid tumors, and evidence is accumulating to support their use in various lymphomas. The most exciting results from immune checkpoint inhibitor therapy have been seen in patients with R/R Hodgkin lymphoma, in whom the overall response rate has reached 60-80 %. Results in NHL are more similar to those seen in other solid malignancies, ranging between 20 and 40 %, depending on the histology. Formal approval of these drugs is being awaited, as are the results of combination therapy with checkpoint inhibitors and other treatment modalities, including conventional chemotherapy, small-molecule inhibitors, and other immune therapies. Although response rates have been promising, attention must be paid to the management of unique immune-related adverse events, which warrant close monitoring in some cases. Identification of biomarkers that predict response or severe adverse events using either the tumor specimen or peripheral blood would aid in selecting patients suited for these types of treatment as well as determining the ideal sequence of treatment within the realm of immune therapies.
Zeng, Weifen; Fu, Kai; Quintanilla-Fend, Leticia; Lim, Megan; Ondrejka, Sarah; Hsi, Eric D
SOX11 expression has been recently shown to be useful in the diagnosis of mantle cell lymphoma (MCL), including cyclin D1-negative MCL with typical morphology. We evaluated SOX11 expression pattern in B-cell non-Hodgkin lymphoma (B-NHL) subtypes to confirm specificity and used it as a feature to identify the first reported cases of cyclin D1-negative blastoid MCL. SOX11 expression was evaluated by immunohistochemistry in 140 cases of mature B-NHL, including 4 cases of suspected blastoid MCL that lacked cyclin D1 expression and 8 cases of CD5-positive diffuse large B-cell lymphoma (DLBL). In addition, 5 cases of B or T lymphoblastic lymphoma were included. Nuclear expression of SOX11 was found in cyclin D1-positive MCL (30/30, 100%) and in a case of cyclin D1-negative MCL with typical morphology. SOX11 was also expressed in Burkitt lymphoma (1/5, 20%) and lymphoblastic lymphoma (2/3 T-LBLs, 2/2 B-LBLs, overall 4/5, 80%), whereas all cases of DLBL (including CD5 DLBL) and other small B-NHL were negative. The 4 suspected cases of blastoid MCL were also SOX11. These cases had a complex karyotype that included 12p abnormalities. We confirmed prior reports that stated that SOX11 nuclear expression was a specific marker for MCL, including cyclin D1-negative MCL with typical morphology. To our knowledge, this is the first report regarding its use in identifying cases of cyclin D1-negative blastoid MCL. Routine use of SOX11 in cases of suspected CD5 DLBL might help identify additional cases of cyclin D1-negative blastoid MCL.
Saba, Nakhle S; Levy, Laura S
Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL) constitutes an aggressive variety of lymphomas characterized by increased extranodal involvement, relapse rate, and resistance to chemotherapy. Protein kinase C-beta (PKCβ) targeting showed promising results in preclinical and clinical studies involving a wide variety of cancers, but studies describing the role of PKCβ in AIDS-NHL are primitive if not lacking. In the present study, 3 AIDS-NHL cell lines were examined: 2F7 (AIDS-Burkitt lymphoma), BCBL-1 (AIDS-primary effusion lymphoma), and UMCL01-101 (AIDS-diffuse large B-cell lymphoma). Immunoblot analysis demonstrated expression of PKCβ1 and PKCβ2 in 2F7 and UMCL01-101 cells, and PKCβ1 alone in BCBL-1 cells. The viability of 2F7 and BCBL-1 cells decreased significantly in the presence of PKCβ-selective inhibitor at half-maximal inhibitory concentration of 14 and 15 μmol/L, respectively, as measured by tetrazolium dye reduction assay. In contrast, UMCL01-101 cells were relatively resistant. As determined using flow cytometric deoxynucleotidyl transferase dUTP nick-end labeling assay with propidium iodide staining, the responsiveness of sensitive cells was associated with apoptotic induction and cell cycle inhibition. Protein kinase C-beta-selective inhibition was observed not to affect AKT phosphorylation but to induce a rapid and sustained reduction in the phosphorylation of glycogen synthase kinase-3 beta, ribosomal protein S6, and mammalian target of rapamycin in sensitive cell lines. The results indicate that PKCβ plays an important role in AIDS-related NHL survival and suggest that PKCβ targeting should be considered in a broader spectrum of NHL. The observations in BCBL-1 were unexpected in the absence of PKCβ2 expression and implicate PKCβ1 as a regulator in those cells.
Pizarro, Alvaro; García, Hernán; Riquelme, Ana; Carmona, Javiera; Cortés, Claudia
Hodgkin lymphomas (HL) and non Hodgkin lymphomas (NHL) are frequently associated to acquired immunodeficiency syndrome in adults. To systematize the clinical features and histological characteristics of lymphomas in AIDS patients, its treatment and outcomes in our institution. Retrospective analysis of patients with HIV-associated lymphoma between January 2001 and December 2008 at the San Borja Arriarán Hospital complex. Information was obtained from 30 patients with NHL and 7 with HL, with a median of 40 years. The majority of tumors were Burkitt lymphoma (47%), diffuse large cell lymphoma B-cell (37%) and NHL of T lineage (10%). There was no CNS or cavities lymphoma. Almost all patients (86.7%) with NHL were treated with CHOP chemotherapy, 57% of those receiving treatment had progression or relapse from complete remission. A rescue chemotherapy was indicated in 4 patients. 73% of patients receiving CHOP, complete 5 to 6 cycles of chemotherapy. The use of CHOP chemotherapy for the subgroup of patients with Burkitt lymphoma achieved low rates of complete remission and frequent relapse and disease progression, showing that CHOP was ineffective in improving survival, especially in high risk patients. We found statistically significant differences in survival according to IPIae (International prognostic Index age-adjusted). Non-Hodgkin lymphoma in HIV patients treated with chemotherapy protocols PAlNDA persists in our environment as a disease with a poor prognosis compared with findings in the international literature. The incorporation of new drugs of proven utility as rituximab and specific schemes chemotherapy could improve these results. The establishment of prognostic groups established by IPIae can guide clinical work for the use of chemotherapy tailored to their specific risk and optimized according to histological type.
Jazirehi, Ali R; Bonavida, Benjamin
Therapeutic strategies for cancer include chemotherapy, immunotherapy, and radiation. Such therapies result in significant short-term clinical responses; however, relapses and recurrences occur with no treatments. Targeted therapies using monoclonal antibodies have improved responses with minimal toxicities. For instance, Rituximab (chimeric anti-CD20 monoclonal antibody) was the first FDA-approved monoclonal antibody for the treatment of patients with non-Hodgkin's lymphoma (NHL). The clinical response was significantly improved when used in combination with chemotherapy. However, a subset of patients does not respond or becomes resistant to further treatment. Rituximab-resistant (RR) clones were used as a model to address the potential mechanisms of resistance. In this chapter, we discuss the underlying molecular mechanisms by which rituximab signals the cells and modifies several intracellular survival/antiapoptotic pathways, leading to its chemo/immunosensitizing activities. RR clones were developed to mimic in vivo resistance observed in patients. In comparison with the sensitive parental cells, the RR clones are refractory to rituximab-mediated cell signaling and chemosensitization. Noteworthy, interference with the hyperactivated survival/antiapoptotic pathways in the RR clones with various pharmacological inhibitors mimicked rituximab effects in the parental cells. The development of RR clones provides a paradigm for studying resistance by other anticancer monoclonal antibodies in various tumor models.
Plosker, Greg L; Figgitt, David P
Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukaemia (CLL). While the optimal use of the drug in many clinical settings has yet to be clarified, two pivotal trials have established rituximab as a viable treatment option in patients with relapsed or refractory indolent NHL, and as a standard first-line treatment option when combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (the most common type of aggressive NHL). The former was a noncomparative trial in relapsed indolent NHL (follicular and small lymphocytic subtypes) with clinical responses achieved in about half of patients treated with rituximab 375 mg/m(2) intravenously once weekly for 4 weeks, which was similar to some of the most encouraging results reported with traditional chemotherapeutic agents. The latter was a randomised comparison of eight cycles of CHOP plus rituximab 375 mg/m(2) intravenously (one dose per cycle) versus CHOP alone in previously untreated elderly patients (60 to 80 years of age) with diffuse large B-cell lymphoma. In this pivotal trial, 2-year event-free and overall survival were significantly higher with rituximab plus CHOP, and there was no increase in clinically significant adverse effects compared with CHOP alone. Treatment with rituximab is generally well tolerated, particularly in terms of adverse haematological effects and serious or opportunistic infections relative to standard chemotherapy. Infusion-related reactions occur in the majority of patients treated with rituximab; these are usually mild to moderate flu-like symptoms that decrease in frequency with subsequent infusions. In approximately 10% of patients, however, severe infusion-related reactions develop (e.g. bronchospasm
Merli, Michele; Carli, Giuseppe; Arcaini, Luca; Visco, Carlo
The association of hepatitis C virus (HCV) and B-cell non-Hodgkin lymphomas (NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment (AT) with interferon (IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study (100 patients) the overall response rate (ORR) after first-line IFN-based AT was 77% (44% complete responses) and responses were sustainable (median duration of response 33 mo). These results were confirmed by a recent meta-analysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response (SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines’ recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents (DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression. PMID:27784957
Sant, Milena; Allemani, Claudia; De Angelis, Roberta; Carbone, Antonino; de Sanjosè, Silvia; Gianni, Alessandro M; Giraldo, Pilar; Marchesi, Francesca; Marcos-Gragera, Rafael; Martos-Jiménez, Carmen; Maynadié, Marc; Raphael, Martine; Berrino, Franco
We explored the influence of morphology on geographic differences in 5-year survival for non-Hodgkin lymphoma (NHL) diagnosed in 1990-1994 and followed for 5years: 16,955 cases from 27 EUROCARE-3 cancer registries, and 22,713 cases from 9 US SEER registries. Overall 5-year relative survival was 56.1% in EUROCARE west, 47.1% in EUROCARE east and 56.3% in SEER. Relative excess risk (RER) of death was 1.05 (95% confidence interval (CI) 1.01-1.10) in EUROCARE west, 1.52 (95% CI 1.44-1.60) in EUROCARE east (SEER reference). Excess risk of death was significantly above reference (diffuse B lymphoma) for Burkitt's and NOS lymphoma; not different for lymphoblastic and other T-cell; significantly below reference (in the order of decreasing relative excess risk) for NHL NOS, mantle cell/centrocytic, lymphoplasmacytic, follicular, small lymphocytic/chronic lymphocytic leukaemia, other specified NHL and cutaneous morphologies. Interpretation of marked variation in survival with morphology is complicated by classification inconsistencies. The completeness and standardisation of cancer registry morphology data needs to be improved.
Gabellier, Ludovic; Cartron, Guillaume
The use of anti-CD20 monoclonal antibodies (mAbs), such as rituximab, in CD20-positive B-cell malignancies has dramatically improved the outcome of chronic lymphoid leukemia and non-Hodgkin’s lymphomas (NHL). However, the occurrence of relapse and development of rituximab-refractory disease highlight the need to develop novel anti-CD20 mAbs, with improved mechanisms of action. Obinutuzumab is the first humanized type II glycoengineered anti-CD20 mAb. In vitro and in vivo data suggested several differences compared with rituximab, including a low level of complement-dependent cytotoxicity and an increased direct nonapoptotic cell death. Moreover, the glycoengineered Fc-linked nonfucosylated oligosaccharide enhanced the Fc–Fcγ receptor (FcγR) IIIa interaction, resulting in improved antibody-dependent cellular cytotoxicity and phagocytosis. Preclinical models suggested that these differences translate into superior survival in murine lymphoma models. Phase I/II trials in monotherapy in relapsed or refractory B-cell NHL demonstrated that obinutuzumab has an acceptable safety profile, infusion-related reactions being the most common adverse event. In rituximab-refractory indolent NHL, the recent randomized phase III GADOLIN study demonstrated an improved median progression-free survival for patients treated with obinutuzumab plus bendamustine rather than bendamustine alone. Further trials are ongoing to determine the role of obinutuzumab as a first-line agent in the treatment of follicular lymphoma. PMID:27054024
Canine lymphoma has served as the ''workhorse'' for the development of veterinary oncology and as an important animal model for human non-Hodgkins lymphomas. Significant advances have been achieved in understanding the biological behavior of the disease and in its treatment. Although it is unlikely that a cure for lymphoma will be achieved, owners should be encouraged to treat their pets, provided they understand that only prolonged remissions and survivals are likely to result. Cooperative studies, employing large numbers of dogs, are needed to optimize and refine the classification scheme to provide a system with diagnostic and prognostic correlates and derive maximum benefit from therapeutic regimens. Such studies need to be prospective in nature, with a solid statistical base incorporated into their design. Rather than being content with what we have accomplished to date in treatment of canine lymphoma, the opportunity exists for the veterinary profession to make further significant contributions to the understanding and treatment of lymphoma in the dog. 10 refs., 4 tabs.
Ellin, Fredrik; Landström, Jenny; Jerkeman, Mats; Relander, Thomas
Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas, but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, as well as the outcome of these patients, in a large population-based cohort of patients with PTCL. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis, disease characteristics at diagnosis independently associated with an increased risk for later CNS involvement were involvement of more than 1 extranodal site (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.07-6.29; P = .035) and skin (HR, 3.51; 95% CI, 1.26-9.74; P = .016) and gastrointestinal involvement (HR, 3.06; 95% CI, 1.30-7.18; P = .010). The outcome of relapsed/refractory patients was very poor, and CNS involvement was not associated with a significantly worse outcome compared with relapsed/refractory patients without CNS involvement in multivariable analysis (HR, 1.6; 95% CI, 0.96-2.6; P = .074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease.
Intragumtornchai, Tanin; Bunworasate, Udomsak; Wudhikarn, Kitsada; Lekhakula, Arnuparp; Julamanee, Jakrawadi; Chansung, Kanchana; Sirijerachai, Chittima; Norasetthada, Lalita; Nawarawong, Weerasak; Khuhapinant, Archrob; Siritanaratanakul, Noppadol; Numbenjapon, Tontanai; Prayongratana, Kannadit; Chuncharunee, Suporn; Niparuck, Pimjai; Suwanban, Tawatchai; Kanitsap, Nongluk; Wongkhantee, Somchai; Pornvipavee, Rutchanid; Wong, Peerapon; Makruasi, Nisa; Wannakrairot, Pongsak; Assanasen, Thamathorn; Sukpanichnant, Sanya; Boonsakan, Paisarn; Kanoksil, Wasana; Ya-In, Charin; Kayasut, Kanita; Mitranun, Winyu; Warnnissorn, Naree
Systemic reports on the descriptive epidemiology of non-Hodgkin lymphoma (NHL) from Southeast Asia are scarce. A nationwide multi-institutional registry was conducted to compare the histopathology, clinical features, and survival of Thai adult patients with NHL using large registries, especially those from Far East Asia (FEA). Using a web-based registry system, 13 major medical centers from the 4 geographic regions of Thailand prospectively collected, from 2007 to 2014, the diagnostic pathology, according to the World Health Organization classification, 2008, clinical features and survival of 4056 patients who were newly diagnosed with NHL. The median age of the patients was 56 years (range, 16-99 years). The male-to-female ratio was 1.3:1. From the total of 4056 patients, T/NK-cell lymphoma (TNKCL) accounted for 12.6% of cases, and 5.1% had human immunodeficiency virus-associated lymphoma. The four leading histological subtypes were diffuse large B-cell lymphoma, not otherwise specified (58.1%); follicular lymphoma (5.6%); extranodal mucosa-associated lymphoid tissue lymphoma (5.2%); and peripheral T-cell lymphoma, not otherwise specified (4.0%). With a median follow-up duration of 46.1 months, the median overall survival of B-cell NHL was significantly longer than that of patients with TNKCL (76.5 vs 28.8 months, P = .0001). Compared to FEA, the Thai registry had an approximately one-half lower relative frequency of TNKCL; the prevalence of extranodal mucosa-associated lymphoid tissue lymphoma was much lower than in Korea, and the frequency of extranodal TNKCL, nasal type, was strikingly low compared to China. It is concluded that while the median age of Thai patients with NHL was approximately a decade younger than for Caucasians, the long-term survival rates for most histological subtypes were comparable. While the histological distribution generally complied with the characteristic Asian features, some differences from FEA were observed.
Ferrucci, PF; Vanazzi, A; Crosta, C; Pruneri, G; Grana, C; Bartolomei, M; Paganelli, G; Martinelli, G
Treatment modalities for resistant/relapsing gastric mucosa associated lymphoid tissue (MALT) non-Hodgkin’s lymphoma (NHL) are not yet well standardized. In the past, most patients were treated surgically with a gastrectomy, while, more recently, radiotherapy and systemic approaches (chemotherapy and immunotherapy) have been used with improving results. Here, we report the case of a patient affected by MALT NHL resistant to antibiotics, chemotherapy and immunotherapy, who achieved a durable complete remission after radio-immunotherapy treatment with Zevalin (90Y ibritumomab-tiuxetan), administered in a single-standard dose. This observation must be confirmed on a larger series but suggests that radio-immunotherapy may be a valid approach in treating relapsing MALT NHL patients, or those resistant to conventional therapies, so avoiding more aggressive and toxic approaches. PMID:22275968
Corazzelli, Gaetano; Frigeri, Ferdinando; Arcamone, Manuela; Aloj, Luigi; Capobianco, Gaetana; Becchimanzi, Cristina; Morelli, Emanuela; Volzone, Francesco; Marcacci, Gianpaolo; Russo, Filippo; De Filippi, Rosaria; Lastoria, Secondo; Pinto, Antonio
Patients with recurring T-cell non-Hodgkin lymphoma (T-NHL) are incurable and candidate for investigational agents. Here, we report on five patients with T-NHL refractory to multiple chemotherapy lines, including in all cases alkylators and gemcitabine, who received the third-generation chloroethylnitrosourea fotemustine at a dose of 120 mg/m(2) every 21 d, up to eight courses. Median actual dose intensity was 79%; toxicity was manageable and mainly hematological. One complete remission, one partial remission, two protracted disease stabilization, and one transient, minor response were achieved. Time to progression ranged from 48 to 240+ d. This is the first evidence ever reporting the activity of fotemustine in end-stage T-NHL. Formal studies with this agent are warranted in T-cell malignancies.
Corazzelli, Gaetano; Frigeri, Ferdinando; Arcamone, Manuela; Aloj, Luigi; Capobianco, Gaetana; Becchimanzi, Cristina; Morelli, Emanuela; Volzone, Francesco; Marcacci, Gianpaolo; Russo, Filippo; De Filippi, Rosaria; Lastoria, Secondo; Pinto, Antonio
Patients with recurring T-cell non-Hodgkin lymphoma (T-NHL) are incurable and candidate for investigational agents. Here, we report on five patients with T-NHL refractory to multiple chemotherapy lines, including in all cases alkylators and gemcitabine, who received the third-generation chloroethylnitrosourea fotemustine at a dose of 120 mg/m2 every 21 d, up to eight courses. Median actual dose intensity was 79%; toxicity was manageable and mainly hematological. One complete remission, one partial remission, two protracted disease stabilization, and one transient, minor response were achieved. Time to progression ranged from 48 to 240+ d. This is the first evidence ever reporting the activity of fotemustine in end-stage T-NHL. Formal studies with this agent are warranted in T-cell malignancies. PMID:21752099
Selva, R La; Violetti, S Alberti; Delfino, C; Grandi, V; Cicchelli, S; Tomasini, C; Fierro, M T; Berti, E; Pimpinelli, N; Quaglino, P
The term “Primary Cutaneous B-Cell Lymphoma” (PCBCL) comprehends a variety of lymphoproliferative disorders characterized by a clonal proliferation of B-cells primarily involving the skin. The absence of evident extra-cutaneous disease must be confirmed after six-month follow-up in order to exclude a nodal non-Hodgkin's lymphoma (NHL) with secondary cutaneous involvement, which may have a completely different clinical behavior and prognosis. In this article, we have summarized the clinico-pathological features of main types of PCBCL and we outline the guidelines for management based on a review of the available literature. PMID:28400634
effects in human NHL xenografts. We also have the c apacity to use small animal immuno-positron emission tomography (iPET). IP ET is a new, sop...CLL, mantle cell:Karpas 519, figure 6. CD22 Binding Peptide 41 Treatment of Differnt Lymphoma cell Lines (Figure 6) 0 20 40 60 80 100 120 Jurkat...the anti- CD22 mAb HB22.7 to B cells. Thus we used a flow cytometry-based assay to examine the effects of peptide 41 on HB22.7 binding to B cells
Tang, Hui; Micallef, Ivana N. M.; Ansell, Stephen M.; Link, Brian K.; Inwards, David J.; Porrata, Luis F.; Johnston, Patrick B.; Colgan, Joseph P.; Markovic, Svetomir N.; Nowakowski, Grzegorz S.; Thompson, Carrie A.; Allmer, Cristine; Maurer, Matthew J.; Gupta, Mamta; Weiner, George; Hohl, Ray; Kurtin, Paul J.; Ding, Husheng; Loegering, David; Schneider, Paula; Peterson, Kevin; Habermann, Thomas M.; Kaufmann, Scott H.
A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib was conducted in 93 adult patients with relapsed or refractory lymphoma. Patients received tipifarnib 300 mg twice daily on days 1-21 of each 28-day cycle. The median number of prior therapies was 5 (range, 1-17). For the aggressive B-cell, indolent B-cell, and T-cell and Hodgkin lymphoma (HL/T) groups, the response rates were 17% (7/42), 7% (1/15), and 31% (11/36), respectively. Of the 19 responders, 7 were diffuse large B-cell non-Hodgkin lymphoma (NHL), 7 T-cell NHL, 1 follicular grade 2, and 4 HL. The median response duration for the 19 responders was 7.2 months (mean, 15.8 months; range, 1.8-62), and 5 patients in the HL/T group are still receiving treatment at 29-64+ months. The grade 3/4 toxicities observed were fatigue and reversible myelosuppression. Correlative studies suggest that Bim and Bcl-2 should be examined as potential predictors of response in future studies. These results indicate that tipifarnib has activity in lymphoma, particularly in heavily pretreated HL/T types, with little activity in follicular NHL. In view of its excellent toxicity profile and novel mechanism of action, further studies in combination with other agents appear warranted. This trial is registered at www.clinicaltrials.gov as #NCT00082888. PMID:21725056
Mendes, José; Gonçalves, Ana Cristina; Alves, Raquel; Jorge, Joana; Pires, Ana; Ribeiro, Ana; Sarmento-Ribeiro, Ana Bela
Non-Hodgkin Lymphoma (NHL) constitutes a very heterogeneous group of diseases with different aggressiveness. Diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma (BL) are two clinically aggressive lymphomas from the germinal center, very heterogeneous and with different genetic signatures. Several intracellular pathways are involved in lymphomagenesis, being BCR/PI3K/AKT/mTOR and RAS/RAF pathways the most frequently ones. In this context the therapeutic potential of a mTOR inhibitor--everolimus--and a RAS/RAF pathway inhibitor--L744,832--was evaluated in two NHL cell lines. Farage and Raji cells were cultured in the absence and presence of several concentrations of everolimus and L744,832 in monotherapy and in combination with each other, as well as in association with the conventional chemotherapy drug vincristine. Our results show that everolimus and L744,832 induce antiproliferative and cytotoxic effect in a time-, dose-, and cell line-dependent manner, inducing cell death mainly by apoptosis. A potentiation effect was observed when the drugs were used in combination. In conclusion, the results suggest that everolimus and L744,832, alone or in combination, could provide therapeutic benefits in these subtypes of NHL.
Oerlemans, Simone; Mols, Floortje; Nijziel, Marten R; Lybeert, Marnix; van de Poll-Franse, Lonneke V
Cancer survivors are at risk of experiencing adverse physical and psychosocial effects of their cancer and its treatment. Both Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) survivors face problems that can affect their health-related quality of life (HRQoL). The authors systematically reviewed the literature on HRQoL among HL and NHL survivors. A PubMed and PsychINFO literature search for original articles published until May 2011 was performed. Twenty-four articles, which met the predefined inclusion criteria, were subjected to a quality checklist. HL survivors showed the most problems in (role) physical, social and cognitive functioning, general health, fatigue and financial problems. In addition, HL survivors treated with a combination of therapies, with older age and female sex reported worse HRQoL. NHL survivors showed the most problems in physical functioning, appetite loss, vitality and financial problems. Having had chemotherapy was negatively associated with HRQoL, but no differences in chemotherapy regimens were found. Furthermore, in NHL survivors not meeting public exercise guidelines, HRQoL is low but can be improved with more exercise. More research on the longitudinal comparison between HL and NHL survivors and healthy controls should be performed in order to better understand the long-term (side) effects of treatment on HRQoL and possibilities to alleviate these.
Brewer, Jerry D.; Shanafelt, Tait D.; Khezri, Farzaneh; Sosa Seda, Ivette M.; Zubair, Adeel S.; Baum, Christian L.; Arpey, Christopher J.; Cerhan, James R.; Call, Timothy G.; Roenigk, Randall K.; Smith, Carin Y.; Weaver, Amy L.; Otley, Clark C.
Background Cutaneous malignancy is associated with worse outcomes in patients with chronic lymphocytic leukemia (CLL). Objective To identify the incidence and recurrence rate of nonmelanoma skin cancer (NMSC) in patients with non-Hodgkin lymphoma (NHL). Methods NMSC incidence was calculated and Cox proportional hazard models were used to evaluate associations with risk of recurrence for patients with NHL between 1976 and 2005 who were in the Rochester Epidemiology Project research infrastructure. Results We identified 282 patients with CLL or small lymphocytic lymphoma and 435 with non-CLL NHL. The incidence of BCC and SCC was 1,829.3 (95% CI, 1,306.7-2,491.1) and 2,224.9 (95% CI, 1,645.9-2,941.6), respectively, in patients with CLL. The cumulative recurrence rate at 8 years after treatment with Mohs micrographic surgery was 8.3% (95% CI, 0.0%-22.7%) for BCC and 13.4% (95% CI, 0.0%-25.5%) for SCC in patients with CLL. Limitations This was a retrospective cohort study. Conclusions After Mohs micrographic surgery and standard excision of NMSC, patients with NHL had a skin cancer recurrence rate that was higher than expected. Careful treatment and monitoring of patients with NHL and NMSC are warranted. PMID:25479909
Kalathingal, S; Capes, J; Kurago, Z
A very unusual radiographic presentation of non-Hodgkin lymphoma (NHL) involving the maxilla is described. The patient was initially managed with antibiotics prescribed to treat what was thought to represent an odontogenic infection. After unsuccessful antibiotic therapy, the patient was referred to an oral surgery clinic where CBCT was performed. CBCT revealed an atypical generalized sclerosis of the affected bone rather than the usual lytic radiographic pattern associated with NHL. Destruction of the sinus floor with infiltration of the sinus was also present. This rare radio-opaque radiographic presentation is described in detail together with the clinical presentation and histopathological findings. The important radiographic features suggesting malignancy that were present in this atypical case of NHL are discussed. A differential diagnosis highlighting the differences between NHL, osteomyelitis and osteosarcoma is also provided. PMID:25421808
Fernández-Álvarez, Rubén; Sancho, Juan-Manuel; Ribera, Josep-María
Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin lymphoma that commonly occurs in human immunodeficiency virus (HIV)-positive individuals, and affects oral sites. Occasionally, it has been described in HIV-negative patients and involving non-oral sites. Pathologically, PBL is a high-grade B-cell lymphoma that displays the immunophenotype of a terminally differentiated B-lymphocyte with loss of B-cell markers (CD20) and expression of plasma-cell antigens. Epstein-Barr virus infection and MYC rearrangements are frequently observed. Treatment of PBL is challenging because of the lack of established treatment and poor outcomes, with median survival times shorter than one year. In this review, we discuss the clinical and epidemiologic spectrum of PBL as well as its distinct pathological features. Finally, we summarize the currently available approaches for the treatment of patients with PBL.
Vilaine, Françoise; Kerchev, Pavel; Clément, Gilles; Batailler, Brigitte; Cayla, Thibaud; Bill, Laurence; Gissot, Lionel; Dinant, Sylvie
The complex process of phloem sugar transport involves symplasmic and apoplasmic events. We characterized Arabidopsis thaliana lines ectopically expressing a phloem-specific gene encoding NDR1/HIN1-like26 (NHL26), a putative membrane protein. NHL26 overexpressor plants grew more slowly than wild-type plants, accumulated high levels of carbohydrates in mature leaves, and had a higher shoot biomass, contrasting with slower root growth and a lower seed yield. Similar effects were observed when NHL26 was overexpressed in companion cells, under the control of a companion cell-specific promoter. The soluble sugar content of the phloem sap and sink organs was lower than that in the wild type, providing evidence of a sugar export defect. This was confirmed in a phloem-export assay with the symplastic tracer carboxyfluorescein diacetate. Leaf sugar accumulation was accompanied by higher organic acid, amino acid, and protein contents, whereas analysis of the metabolite profile of phloem sap exudate revealed no change in amino acid or organic acid content, indicating a specific effect on sugar export. NHL26 was found to be located in the phloem plasmodesmata and the endoplasmic reticulum. These findings reveal that NHL26 accumulation affects either the permeability of plasmodesmata or sugar signaling in companion cells, with a specific effect on sugar export.
Loedige, Inga; Gaidatzis, Dimos; Sack, Ragna; Meister, Gunter; Filipowicz, Witold
TRIM-NHL proteins are conserved regulators of development and differentiation but their molecular function has remained largely elusive. Here, we report an as yet unrecognized activity for the mammalian TRIM-NHL protein TRIM71 as a repressor of mRNAs. We show that TRIM71 is associated with mRNAs and that it promotes translational repression and mRNA decay. We have identified Rbl1 and Rbl2, two transcription factors whose down-regulation is important for stem cell function, as TRIM71 targets in mouse embryonic stem cells. Furthermore, one of the defining features of TRIM-NHL proteins, the NHL domain, is necessary and sufficient to target TRIM71 to RNA, while the RING domain that confers ubiquitin ligase activity is dispensable for repression. Our results reveal strong similarities between TRIM71 and Drosophila BRAT, the best-studied TRIM-NHL protein and a well-documented translational repressor, suggesting that BRAT and TRIM71 are part of a family of mRNA repressors regulating proliferation and differentiation.
Ram, Ron; Gooley, Ted A.; Maloney, David G.; Press, Oliver W.; Pagel, John M.; Petersdorf, Stephen H.; Shustov, Andrei R.; Flowers, Mary E.D.; O’Donnell, Paul; Sandmaier, Brenda M.; Storb, Rainer F.; Gopal, Ajay K.
Reduced-intensity-conditioning (RIC) prior to allogeneic hematopoietic cell transplantation (HCT) is increasingly employed as a potentially curative option for patients with advanced lymphoma; however relapse remains a major challenge. Unfortunately, little data exist on the outcomes, predictors of survival, and results of specific management strategies of such individuals. One-hundred-one consecutive relapses occurred and were evaluated in 280 lymphoma patients following RIC-HCT. Characteristics included: aggressive non-Hodgkin lymphoma (NHL) (n=42), indolent NHL (n=33) and Hodgkin’s Lymphoma (HL) (n=26). Median time to relapse was 90 (range 3 - 1275) days and graft-versus-host-disease at relapse was present in 56 (55%) patients. Interventions following relapse included no therapy (n=14), withdrawal of immunosuppression alone (n=11), chemoradiotherapy (n=60), and donor lymphocyte infusion/second HCT (n=16). Overall survival (OS) at 3 and 5 years following relapse was 33% (95%CI 23-44%) and 23% (95%CI 13-34%), respectively. Aggressive NHL (vs indolent disease, HR=2.29, p=.008) and relapse <1 month after HCT (vs >6 months HR=3.17 p=.004) were each associated with increased mortality. Estimated 3-year OS after relapse for aggressive, indolent and HL was 16% (95%CI 5-32%), 40% (95%CI 19-61%) and 47% (95%CI 29-64%), respectively. The 1-year survival for patients relapsing within 1 month of HCT was 24% as compared to 52%, 74%, and 77%, for those relapsing at 1-3 months, 3-6 months, and >6 months after HCT. We conclude that despite relapse of lymphoma after RIC-HCT, some patients can experience prolonged survival with better post-relapse outcomes occurring in patients with indolent NHL, HL or late relapse. PMID:21536145
Gil, Veronica S.; Howell, Louise; Zhang, Jiyuan; Kim, Chae H.; Stengel, Sven; Vega, Francisco; Zelent, Arthur
ABSTRACT Histone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (Eμ). Here, we report that the Eμ-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD) with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of Eμ-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors. PMID:27799148
Schmidt, Laura C.; Roolf, Catrin; Pews-Davtyan, Anahit; Rütgen, Barbara C.; Hammer, Sabine; Willenbrock, Saskia; Sekora, Anett; Rolfs, Arndt; Beller, Matthias; Brenig, Bertram; Nolte, Ingo; Junghanss, Christian
Protein kinase inhibitors are widely used in chemotherapeutic cancer regimens. Maleimide derivatives such as SB-216763 act as GSK-3 inhibitor targeting cell proliferation, cell death and cell cycle progression. Herein, the two arylindolylmaleimide derivatives PDA-66 and PDA-377 were evaluated as potential chemotherapeutic agents on canine B-cell lymphoma cell lines. Canine lymphoma represents a naturally occurring model closely resembling the human high-grade non-Hodgkin's lymphoma (NHL). PDA-66 showed more pronounced effects on both cell lines. Application of 2.5μM PDA-66 resulted in a significant induction of apoptosis (approx. 11 %), decrease of the metabolic activity (approx. 95 %), anti-proliferative effect (approx. 85 %) and cell death within 48h. Agent induced mode of action was characterized by whole transcriptome sequencing, 12 h and 24 h post-agent exposure. Key PDA-66-modulated pathways identified were cell cycle, DNA replication and p53 signaling. Expression analyses indicated that the drug acting mechanism is mediated through DNA replication and cycle arrest involving the spindle assembly checkpoint. In conclusion, both PDA derivatives displayed strong anti-proliferation activity in canine B-cell lymphoma cells. The cell and molecular PDA-induced effect characterization and the molecular characterization of the agent acting mechanism provides the basis for further evaluation of a potential drug for canine lymphoma serving as model for human NHL. PMID:27177088
Reddy, Srikanth; Kumar, Ashish; Allugolu, Rajesh; Uppin, Megha; Ramgopal, Keshav
Lesions occupying the anterior cranial fossa may arise de novo or are extensions from the sino-nasal areas with a handful of differentials in either group. The imaging findings, though to a large extent standardized are not full proof. Primary central nervous system lymphoma and sino-nasal lymphoma are uncommon variants of extranodal non-Hodgkin's lymphoma (NHL). We encountered a 35-year-old lady presenting with headache and seizures with a mass lesion involving the ethmoids with invasion into the anterior cranial fossa diagnosed as T-cell extranodal NHL. Gross total resection and reconstruction of the skull base were done. She was treated with chemotherapy and radiotherapy and is doing well at 6 months follow-up. This is the first report of a sino-nasal T-cell lymphoma invading the brain-parenchyma in an immuno-competent person. Sino-nasal primary T-cell lymphoma presenting as skull base pathology should form an essential differential diagnosis along with other routine lesions of anterior cranial fossa. Since these lesions have a good response to chemo and radiotherapy, a trans-nasal biopsy may obviate the need of a craniotomy if neurosurgeons are aware of this rare entity. PMID:25685223
Maziarz, Richard T.; Wang, Zhiwei; Zhang, Mei-Jie; Bolwell, Brian J.; Chen, Andy I.; Fenske, Timothy S.; Freytes, Cesar O.; Gale, Robert Peter; Gibson, John; Hayes-Lattin, Brandon M.; Holmberg, Leona; Inwards, David J.; Isola, Luis M.; Khoury, H. Jean; Lewis, Victor A.; Maharaj, Dipnarine; Munker, Reinhold; Phillips, Gordon L.; Rizzieri, David A.; Rowlings, Philip A.; Saber, Wael; Satwani, Prakash; Waller, Edmund K.; Maloney, David G.; Montoto, Silvia; Laport, Ginna G.; Vose, Julie M.; Lazarus, Hillard M.; Hari, Parameswaran N.
SUMMARY Pre-existing central nervous system (CNS) involvement may influence referral for autologous haematopoietic cell transplantation (AHCT) for patients with non-Hodgkin lymphoma (NHL). The outcomes of 151 adult patients with NHL with prior secondary CNS involvement (CNS+) receiving an AHCT were compared to 4688 patients without prior CNS lymphoma (CNS−). There were significant baseline differences between the cohorts. CNS+ patients were more likely to be younger, have lower performance scores, higher age-adjusted international prognostic index scores, more advanced disease stage at diagnosis, more aggressive histology, more sites of extranodal disease, and a shorter interval between diagnosis and AHCT. However, no statistically significant differences were identified between the two groups by analysis of progression-free survival (PFS) and overall survival (OS) at 5 years. A matched pair comparison of the CNS+ group with a subset of CNS− patients matched on propensity score also showed no differences in outcomes. Patients with active CNS lymphoma at the time of AHCT (n=55) had a higher relapse rate and diminished PFS and OS compared with patients whose CNS lymphoma was in remission (n=96) at the time of AHCT. CNS+ patients can achieve excellent long-term outcomes with AHCT. Active CNS lymphoma at transplant confers a worse prognosis. PMID:23829536
Fernandez, H F; Escalón, M P; Pereira, D; Lazarus, H M
High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard approach for chemosensitive, relapsed aggressive non-Hodgkin's lymphoma (NHL). Various conditioning regimens have been used as treatment before ASCT and disease-free (DFS) and overall survival (OS) rates range from 34 to 60% and 26 to 46%, respectively. To date, few comparative randomized trials have been performed and no regimen has demonstrated superiority to another. Reduction of disease relapse remains the major hurdle for improving patient outcome and in vitro and in vivo purging of lymphoma cells has not necessarily enhanced results. Rituximab pre-mobilization and post-transplant appear to provide better response rates with OS approaching 87-91% at 2-3 years. Newer approaches with radioimmunotherapy may raise DFS to 78% and OS to 93%, albeit with short follow-up. Advances in the conditioning regimens and supportive care have reduced transplant-related mortality to less than 10%. In this review we discuss commonly utilized conditioning regimens, describe their pros and cons and address purging and present conditioning strategies. Owing to the poor outcome with conventional chemotherapy in mantle cell, Burkitt's and T-cell lymphoma, we propose the standard approach of front-line ASCT for these high-risk lymphoma patients. Finally, we will present novel strategies, which can enhance the anti-lymphoma effect, at the same time reducing toxicity, to improve the outcome of ASCT in NHL patients.
Rabii, Redouane; Mezzour, Mohamed Hicham; Guessous, Hicham; Essaki, Hicham; Joual, Abdenbi; Rachid, Mohamed; Quessar, Asmaa; Benchekroun, Said; El Mrini, Mohamed
The authors report a case of urogenital lymphoma with multiple sites in a patient presenting with oligo-anuria. Clinical examination revealed a hard hypogastric and prostatic mass and an enlarged left scrotum. Abdominopelvic and scrotal ultrasound demonstrated a prostatic tumour, a hypogastric mass, hepatic nodular lesions and coeliac lymphadenopathy with bilateral ureterohydronephrosis and a heterogeneous intrascrotal mass in contact with the lower pole of the left testis. The laboratory assessment revealed severe renal failure. After a haemodialysis session and ultrasound-guided right percutaneous nephrostomy, pelvic magnetic resonance imaging (MRI) showed a very large pelvic mass between the bladder and the rectum and transrectal biopsy of the mass confirmed the diagnosis of high-grade malignant non-Hodgkin's lymphoma (NHL) with a type B lymphoblastic phenotype. Treatment consisted of chemotherapy according to the LMB 93 protocol. The course was favourable with return of normal renal function and complete remission 1 month after induction. The patient is currently in complete remission with a follow-up of 12 months. In the light of this case and a review of the literature, the authors discuss the diagnostic, therapeutic and prognostic aspects of this rare site of lymphoma.
Talaat, Roba M; Abdel-Aziz, Amal M; El-Maadawy, Eman A; Abdel-Bary, Naser
Given the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin's lymphoma (NHL), this pilot study was designed to investigate the impact of CD38 (184C/G; rs6449182) and IL-6 (-174 G/C; rs1800795) gene polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma (DLBCL); major types of NHL. To the best of our knowledge, this study is the first one that examines CD38 polymorphism in the NHL. Genotyping polymorphism is performed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) for CD38 and Mutagenically separated PCR (MS-PCR) for IL-6 in 100 Egyptian NHL patients with DLBCL subtype and 119 normal controls. The serum level of IL-6 was measured using Enzyme-linked immunosorbent assay (ELISA). CD38 (184C/G) genotype is significantly increased in NHL patients (p < 0.01), while the GG genotype is significantly increased in controls (p < 0.05). Only two genotypes were found (GG and GC) in IL-6 (-174), no CC in our NHL patients and only one case in the controls. Insignificant change in IL-6 (-174 G/C) genotypes was recorded. Significantly increased serum IL-6 (p < 0.05) was positively correlated (r = 0.17; p < 0.05) with the disease. Taken together, our data stressed the importance of CD38 gene polymorphism in developing DLBCL. Our pilot study indicates that CD38 (184) CG genotype might play a role in DLBCL susceptibility in Egyptians. Additional prospective studies on larger population are needed to confirm our findings.
‘t Mannetje, Andrea; De Roos, Anneclaire J.; Boffetta, Paolo; Vermeulen, Roel; Benke, Geza; Fritschi, Lin; Brennan, Paul; Foretova, Lenka; Maynadié, Marc; Becker, Nikolaus; Nieters, Alexandra; Staines, Anthony; Campagna, Marcello; Chiu, Brian; Clavel, Jacqueline; de Sanjose, Silvia; Hartge, Patricia; Holly, Elizabeth A.; Bracci, Paige; Linet, Martha S.; Monnereau, Alain; Orsi, Laurent; Purdue, Mark P.; Rothman, Nathaniel; Lan, Qing; Kane, Eleanor; Costantini, Adele Seniori; Miligi, Lucia; Spinelli, John J.; Zheng, Tongzhang; Cocco, Pierluigi; Kricker, Anne
Background: Various occupations have been associated with an elevated risk of non-Hodgkin lymphoma (NHL), but results have been inconsistent across studies. Objectives: We investigated occupational risk of NHL and of four common NHL subtypes with particular focus on occupations of a priori interest. Methods: We conducted a pooled analysis of 10,046 cases and 12,025 controls from 10 NHL studies participating in the InterLymph Consortium. We harmonized the occupational coding using the 1968 International Standard Classification of Occupations (ISCO-1968) and grouped occupations previously associated with NHL into 25 a priori groups. Odds ratios (ORs) adjusted for center, age, and sex were determined for NHL overall and for the following four subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and peripheral T-cell lymphoma (PTCL). Results: We confirmed previously reported positive associations between NHL and farming occupations [field crop/vegetable farm workers OR = 1.26; 95% confidence interval (CI): 1.05, 1.51; general farm workers OR = 1.19; 95% CI: 1.03, 1.37]; we also confirmed associations of NHL with specific occupations such as women’s hairdressers (OR = 1.34; 95% CI: 1.02, 1.74), charworkers/cleaners (OR = 1.17; 95% CI: 1.01, 1.36), spray-painters (OR = 2.07; 95% CI: 1.30, 3.29), electrical wiremen (OR = 1.24; 95% CI: 1.00, 1.54), and carpenters (OR = 1.42; 95% CI: 1.04, 1.93). We observed subtype-specific associations for DLBCL and CLL/SLL in women’s hairdressers and for DLBCL and PTCL in textile workers. Conclusions: Our pooled analysis of 10 international studies adds to evidence suggesting that farming, hairdressing, and textile industry–related exposures may contribute to NHL risk. Associations with women’s hairdresser and textile occupations may be specific for certain NHL subtypes. Citation: ‘t Mannetje A, De Roos AJ, Boffetta P, Vermeulen R, Benke G
Greve, J; Bas, M; Schipper, J; Hoffmann, T K
A Non-Hodgkin Lymphoma (NHL) represents nearly three percent of all malignant tumors. Thirty to fourty percent of the lymphomas are located extra-nodal. Within the head and neck region they might occur in the tonsils, tongue base or the sinuses, the larynx and the pharynx. A cutaneous manifestation is rare. We report on an extranodal B-cell-lymphoma of the ear in a young woman. She reported on a piercing of the pinna months before with a subsequent infection. This infection led to the development of a massive ear tumor. Histologic examination resulted in the final diagnosis. In spite of the considerable extent of the lymphoma there was no systemic manifestation and a total remission was induced by chemotherapy before adjuvant radiation.
The role of bone marrow biopsy and FDG-PET/CT in identifying bone marrow infiltration in the initial diagnosis of high grade non-Hodgkin B-cell lymphoma and Hodgkin lymphoma. Accuracy in a multicenter series of 372 patients.
Chen-Liang, Tzu-Hua; Martin-Santos, Taida; Jerez, Andres; Senent, Leonor; Orero, Maria Teresa; Remigia, Maria Jose; Muiña, Begoña; Romera, Marta; Fernandez-Muñoz, Hermogenes; Raya, Jose M; Fernandez-Gonzalez, Marta; Lancharro, Aima; Villegas, Carolina; Carlos Herrera, Juan; Frutos, Laura; Luis Navarro, Jose; Uña, Jon; Igua, Carolina; Sanchez-Vaño, Raquel; Cozar, Maria Del Puig; Contreras, Jose; Sanchez-Blanco, Jose Javier; Perez-Ceballos, Elena; Ortuño, Francisco Jose
Bone marrow infiltration (BMI), categorized as an extra-nodal site, affects stage and is associated with poor prognosis in newly diagnosed lymphoma patients. We have evaluated the accuracy of PET/CT and bone marrow biopsy (BMB) to assess BMI in 372 lymphoma patients [140 Hodgkin Lymphoma (HL) and 232 High Grade B-cell non-Hodgkin Lymphoma (HG B-NHL), among them 155 Diffuse Large B-Cell Lymphoma (DLCL)]. For HL cases, and taking into account PET/CT, sensitivity, negative predictive value (NPV) and accuracy were 96.7, 99.3, and 99.3% while those of BMB were 32.3, 83.8, and 85%, respectively. For HG B-NHL and considering PET/CT, sensitivity, NPV, and accuracy were 52.7, 81.7, and 84.1%, while those of BMB were 77.6, 90.2, and 90.7%, respectively. In the HG B-NHL group, 25 patients would have been under-staged without BMB. These results lead us to recommend PET/CT and the avoidance of BMB to assess BMI in HL. In the case of HG B-NHL, bone marrow status should be assessed firstly by means of PET/CT; only in either focal or diffuse PET/CT with low borderline SUV max values or in negative cases, should BMB be carried out afterwards. In the HG B-NHL setting and at the present moment, both techniques are complementary. © 2015 Wiley Periodicals, Inc.
Fallahzadeh, Hosein; Cheraghi, Maria; Amoori, Neda; Alaf, Mehrangiz
While the incidence of non-Hodgkins lymphoma (NHL) has been rising worldwide, the reasons remain undefined. Recent research has focused on effect of red andf processed meat intake as a risk factor, but with inconclusive results. We therefore conducted a meta-analysis of data published to date, to ascertain the overall association between intake and NHL. A published literature search was performed through Pubmed, Cochrane Library, Medline, and Science Citation Index Expanded databases for articles published in English. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random or fixed effects models. Heterogeneity was assessed using Chi-square and I2 statistics. Dissemination bias was evaluated by funnel plot analysis.We performed a formal meta-analysis using summary measures from these studies. In total, 11 published studies were included in the final analysis. The combined analysis revealed that there was significant association between the red meat and NHL risk (OR=1.10, 95%CI: 1.02 to 1.19, p=0.01). Additionally, there was showed significance association between processed red meat and NHL risk (OR=1.17, 95%CI: 1.06 to 1.29, p=0.001). In subgroup analysis, a statistical significant association was noted between diffuse large B-cell lymphoma (DLBCL) (OR=1.20, 95%CI: 1.04 to 2.37, P=0.01) and red meat intake. In this meta-Analysis, there was evidence for association between consumption of red meat, or processed meat and risk of NHL, particularly with the DLBCL subtype in the red meat case.
Caruso, Vanesa; Di Castelnuovo, Augusto; Meschengieser, Susana; Lazzari, Maria A; de Gaetano, Giovanni; Storti, Sergio; Iacoviello, Licia; Donati, Maria Benedetta
Thrombotic complications in hematologic malignancies have important clinical implications. In this meta-analysis we sought to obtain accurate estimates of the thrombotic risk in lymphoma patients. Articles were searched in electronic databases and references. Eighteen articles were identified (29 cohorts, 18 018 patients and 1149 events). Pooled incidence rates (IRs) were calculated by the use of a method based on the exact maximum likelihood binomial distribution. The global IR of thrombosis was 6.4% (95% confidence interval [CI] 6.0%-6.8%). The global IRs of venous or arterial events were 5.3% (95% CI, 5.0%-5.7%) and 1.1% (95% CI, 0.9%-1.2%), respectively. The IR of thrombosis observed in subjects with non-Hodgkin lymphoma (NHL) was 6.5% (95% CI, 6.1%-6.9%), significantly greater than that observed for patients with Hodgkin lymphoma (4.7%; 95% CI, 3.9%-5.6%). Within NHL, patients with high-grade disease had a greater risk of events (IR 8.3%; 95% CI, 7.0%-9.9%) than low-grade disease (IR 6.3%; 95% CI, 4.5%-8.9%). This meta-analysis shows that the IR of thrombosis in lymphoma patients is quite high, especially in those with NHL at an advanced stage of the disease. These results may help better defining lymphoma populations at high thrombotic risk, to whom prophylactic approaches could be preferentially applied.
Autologous hematopoietic stem cell transplantation in elderly patients (≥ 70 years) with non-Hodgkin's lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study.
Hermet, E; Cabrespine, A; Guièze, R; Garnier, A; Tempescul, A; Lenain, P; Bouabdallah, R; Vilque, J P; Frayfer, J; Bordessoule, D; Sibon, D; Janvier, M; Caillot, D; Biron, P; Legros, L; Choufi, B; Drenou, B; Gorin, N C; Bilger, K; Tamburini, J; Soussain, C; Brechignac, S; Bay, J O
Limited data is available on the feasibility of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) in elderly patients over 70 years of age with non-Hodgkin's lymphoma (NHL). In the setting of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) group, we retrospectively analyzed 81 consecutive patients with NHL over 70 years of age who received AHSCT. The median age at AHSCT was 72.3 years [70-80]. Patients' were diagnosed with diffuse large B-cell lymphoma (n=40), follicular lymphoma (n=16), mantle cell lymphoma (n=15), T-cell lymphoma (n=5), and other (n=5). Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was 0 in 73% of patients. Main conditionings were BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=61) and melphalan alone (n=14). Median delays to reach 0.5×10⁹/L neutrophils and 20 × 10(9)/L platelets were of 12 [9-76] days and 12 [0-143] days, respectively. One hundred day and one year cumulative incidence of NRM was 5.4% and 8.5%, respectively. The main cause of death remains relapse. In conclusion, this study revealed that AHSCT seemed to be acceptable in patients over 70 years of age with NHL. Patient age is not a limiting factor if clinical condition is adequate. Copyright © 2015 Elsevier Inc. All rights reserved.
He, Song; Huang, Yuejiao; Wang, Yuchan; Tang, Jie; Song, Yan; Yu, Xiafei; Ma, Jing; Wang, Shitao; Yin, Haibing; Li, Qiuyue; Ji, Lili; Xu, Xiaohong
Mounting evidence has proved that cellular adhesion confers resistance to chemotherapy in multiple lymphomas. The molecular mechanism underlying cell adhesion-mediated drug resistance (CAM-DR) is, however, poorly understood. In this study, we investigated the expression and biologic function of histamine-releasing factor (HRF) in non-Hodgkin lymphomas (NHLs). Clinically, by immunohistochemistry analysis we observed obvious up-regulation of HRF in NHLs including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and natural killer (NK)/T-cell lymphoma. Functionally, overexpression and knockdown of HRF demonstrated the antiapoptotic effect of HRF in NHL cells, which may be associated with activation of the p-CREB/BCL-2 signaling pathway. Moreover, cell adhesion assay demonstrated that adhesion to fibronectin (FN) or HS-5 up-regulated HRF expression, while knockdown of HRF resulted in decreased cell adhesion, which led to reversed CAM-DR. Our finding supports the role of HRF in NHL cell apoptosis, adhesion and drug resistance, and may provide a clinical therapeutic target for CAM-DR in NHL.
Pan, Jing; Jiang, Chun-Mei; Srivastava, Renu; Li, Bei; Zhu, Lu-Ying; Su, Hong-Yan; Gao, Xiao-Shu; Liu, Hua; Yu, Xiang; Yang, Lei; Cheng, Xian-Hao; Zhang, Hong-Xia
NHL (NDR1/HIN1-like) genes play crucial roles in pathogen induced plant responses to biotic stress. Here, we report the possible function of NHL6 in plant response to abscisic acid (ABA) and abiotic stress. NHL6 was highly expressed in non-germinated seeds, and its expression was strongly induced by ABA and multiple abiotic stress signals. Loss-of-function of NHL6 decreased sensitivity to ABA in the early developmental stages including seed germination and post-germination seedling growth of the nhl6 mutants. However, overexpression of NHL6 increased sensitivity to ABA, salt and osmotic stress of the transgenic plants. Further studies indicated that the increased sensitivity in the 35S::NHL6 overexpressing plants could be a result of both ABA hypersensitivity and increased endogenous ABA accumulation under the stress conditions. It was also seen that the ABA-responsive element binding factors AREB1, AREB2 and ABF3 could regulate NHL6 expression at transcriptional level. Our results indicate that NHL6 plays an important role in the abiotic stresses-induced ABA signaling and biosynthesis, particularly during seed germination and early seedling development in Arabidopsis. PMID:26849212
Bao, Yan; Song, Wei-Meng; Pan, Jing; Jiang, Chun-Mei; Srivastava, Renu; Li, Bei; Zhu, Lu-Ying; Su, Hong-Yan; Gao, Xiao-Shu; Liu, Hua; Yu, Xiang; Yang, Lei; Cheng, Xian-Hao; Zhang, Hong-Xia
NHL (NDR1/HIN1-like) genes play crucial roles in pathogen induced plant responses to biotic stress. Here, we report the possible function of NHL6 in plant response to abscisic acid (ABA) and abiotic stress. NHL6 was highly expressed in non-germinated seeds, and its expression was strongly induced by ABA and multiple abiotic stress signals. Loss-of-function of NHL6 decreased sensitivity to ABA in the early developmental stages including seed germination and post-germination seedling growth of the nhl6 mutants. However, overexpression of NHL6 increased sensitivity to ABA, salt and osmotic stress of the transgenic plants. Further studies indicated that the increased sensitivity in the 35S::NHL6 overexpressing plants could be a result of both ABA hypersensitivity and increased endogenous ABA accumulation under the stress conditions. It was also seen that the ABA-responsive element binding factors AREB1, AREB2 and ABF3 could regulate NHL6 expression at transcriptional level. Our results indicate that NHL6 plays an important role in the abiotic stresses-induced ABA signaling and biosynthesis, particularly during seed germination and early seedling development in Arabidopsis.
Thompson, Carrie A.; Habermann, Thomas M.; Wang, Alice H.; Vierkant, Robert A.; Folsom, Aaron R.; Ross, Julie A.; Cerhan, James R.
Antioxidant nutrients found in fruits, vegetables, and other foods are thought to inhibit carcinogenesis and to influence immune status. We evaluated the association of these factors with risk of NHL overall and for diffuse large B-cell (DLBCL) and follicular lymphoma specifically in a prospective cohort of 35,159 Iowa women aged 55–69 years when enrolled at baseline in 1986. Diet was ascertained using a validated semi-quantitative food frequency questionnaire. Through 2005, 415 cases of NHL (including 184 DLBCL and 90 follicular) were identified. Relative risks (RRs) and 95% confidence intervals (CI) were estimated using Cox regression, adjusting for age and total energy. The strongest associations of antioxidants with risk of NHL (RR for highest versus lowest quartile; p for trend) were observed for dietary vitamin C (RR=0.78; p=0.044), α-carotene (RR=0.71; p=0.015), proanthocyanidins (RR=0.70; p=0.0024), and dietary manganese (RR=0.62; p=0.010). There were no associations with multivitamin use or supplemental intake of vitamins C, E, selenium, zinc, copper or manganese. From a food perspective, greater intake of total fruits and vegetables (RR=0.69; p=0.011), yellow/orange (RR=0.72; p=0.015) and cruciferous (RR=0.82; p=0.017) vegetables, broccoli (RR=0.72; p=0.018), and apple juice/cider (RR=0.65; p=0.026) were associated with lower NHL risk; there were no strong associations for other antioxidant-rich foods, including whole grains, chocolate, tea or nuts. Overall, these associations were mainly observed for follicular lymphoma, and were weaker or not apparent for DLBCL. In conclusion, these results support a role for vegetables and perhaps fruits, and associated antioxidants from food sources, as protective factors against the development of NHL and follicular lymphoma in particular. PMID:19685491
Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19).
Herold, M; Schulze, A; Niederwieser, D; Franke, A; Fricke, H J; Richter, P; Freund, M; Ismer, B; Dachselt, K; Boewer, C; Schirmer, V; Weniger, J; Pasold, R; Winkelmann, C; Klinkenstein, C; Schulze, M; Arzberger, H; Bremer, K; Hahnfeld, S; Schwarzer, A; Müller, C; Müller, Chr
The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.
Kobayashi, Ryoji; Sunami, Shosuke; Mitsui, Tetsuo; Nakazawa, Atsuko; Koga, Yuhki; Mori, Takeshi; Tanaka, Fumiko; Ueyama, Jun-ichi; Osumi, Tomoo; Fukano, Reiji; Ohki, Kentaro; Sekimizu, Masahiro; Mori, Tetsuya
Results of pediatric lymphoma treatment have improved markedly over the past 30 years. In Hodgkin's lymphoma, the 5 year event-free survival (EFS) was 81.5% in a retrospective study. In the ALB-NHL03 study, the 5 year EFS according to clinical stage in patients with lymphoblastic T-cell lymphoma (T-LBL) was 70.6% for stage III and 88.9% for stage IV. In mature B-cell lymphoma, the B-NHL03 study indicated that the 4 year EFS according to treatment group was 94% for group 1, 98% for group 2, 84% for group 3, and 78% for group 4. Moreover, the 2 year EFS rate was 81% in Japanese advanced stage patients based on the international ALCL99 study. Thus, EFS >80% was achieved in any subtype of pediatric lymphoma. With regard to refractory or recurrent lymphoma, however, treatment methods for improvement of the survival rate in these patients still need to be developed. Also the difference between child, and adolescent and young adult patients still needs to be clarified, and treatment protocols developed. Although lymphoma treatment does not greatly change according to country, it does differ between other countries and Japan for some subtypes of lymphoma. In particular, the results of treatment of stage III T-LBL in Japan are worse than those in the USA and Europe. The priority in future studies will be to collect data on these differences, and the reasons for these differences. © 2015 Japan Pediatric Society.
Kent, Erin E; Breen, Nancy; Lewis, Denise R; de Moor, Janet S; Smith, Ashley Wilder; Seibel, Nita L
Improvement in US survival rates among adolescents and young adults (AYAs, ages 15 through 39 years inclusive) diagnosed with non-Hodgkin lymphoma (NHL) has been documented over the last two decades. We examined national trends in survival disparities for AYAs with NHL by race/ethnicity and socioeconomic status (SES, county-level poverty) to further understand NHL and to begin monitoring health outcome disparities for this disease. Surveillance Epidemiology and End Results data were used to calculate 5-year relative survival rates of AYAs diagnosed with NHL from 1992 to 2007 and followed through 2011. Absolute and relative disparities were computed using HD*Calc. Whether a significant linear trend was present was evaluated using Joinpoint. Analyses were replicated after excluding individuals with known HIV infection. The study sample included 9,573 total and 7,121 non-HIV cases of NHL. Five-year survival rates improved for all groups over time. Significant decreases were found in absolute disparities for race/ethnicity (non-HIV), in relative disparities for SES (total) and race/ethnicity (total and non-HIV) (all p < 0.05). Survival rates of non-Hispanic Blacks and Hispanics remained below than those of non-Hispanic Whites throughout the time period. Absolute and relative disparities in 5-year survival narrowed for AYAs with NHL over the time period. To continue to promote this trend, future research should investigate factors, particularly diagnostic delays and barriers to care, which continue to contribute to SES and racial/ethnic differences in survival. These factors may be particularly relevant to identify given the recent Affordable Care Act, which is designed to increase access to medical services, particularly for young adults.
Lybeert, M L; Meerwaldt, J H; Deneve, W
Sixty-eight patients received fractionated low dose total body irradiation (LTBI) as treatment for non-Hodgkin lymphoma (NHL) at the Rotterdamsch Radio-Therapeutisch Instituut (RRTI) in the period 1973-1979. Ninety percent (61/68) of these patients had advanced disease (Stage III + IV). According to current malignancy grade classifications, 34 patients had low grade NHL, 10 intermediate, and 19 high grade. In 5 cases no exact grading was possible. LTBI was given 3 times a week, midline dose 0.1 Gy, using 6 or 25 MeV photons to a mean total dose of 1.78 Gy. Initial response rate for low, intermediate, and high grade NHL was resp. 84, 42, and 40%. The main prognostic factor for sur