Occurrence Of non-Hodgkin Lymphoma Research Articles

Kaposi sarcoma-associated herpesvirus serum DNA and antibodies not associated with subsequent non-Hodgkin lymphoma risk.

Kaposi sarcoma-associated herpes virus (KSHV) infects B-cells and is found in non-Hodgkin lymphoma (NHL) B-cell tumors and could therefore contribute to the occurrence of NHL. We performed a nested case-control study including 155 incident NHL cases and matched noncancer controls. Pre-NHL serum was tested for KSHV DNA and antibodies. Serum KSHV DNA was more common in cases than controls (14% versus 6%, P = 0.03), but after adjustment, the difference was not significant. Epstein-Barr virus serum DNA was similarly unassociated with NHL as were KSHV antibodies. KSHV is not a primary cause of NHL in HIV-infected men who have sex with men.

Pediatric Organ Transplantation and Risk of Premalignant and Malignant Tumors in Sweden

Increased cancer risks are well documented in adult organ transplant recipients. However, the spectrum of malignancies and risk in the pediatric organ transplant population are less well described. We identified all solid organ transplanted patients aged <18 in Sweden between 1970-2007 (n = 536) in the National Patient Register and linked to the Cancer Register. Nationwide rates were used to calculate standardized incidence rate ratios and 95% CI estimating the association between transplant and cancer during maximum 36 years of follow-up. Nearly 7% of pediatric solid organ transplant recipients developed a premalignant or malignant tumor during follow-up. Transplantation was associated with an increased risk of any cancer (n = 24, SIR = 12.5, 95% CI: 8.0-18.6): non-Hodgkin lymphoma (NHL) (n = 13, SIR = 127, 95% CI: 68-217), renal cell (n = 3, SIR = 105, 95% CI: 22-307), vulva/vagina (n = 3, SIR = 665, 95% CI: 137-1934) and nonmelanoma skin cancers (n = 2, SIR = 64.7, 95% CI: 7.8-233.8). NHL typically appeared during childhood, while other tumors were diagnosed during adulthood. Apart from short-term attention toward the potential occurrence of NHL, our results suggest cancer surveillance into adulthood with special attention to skin, kidneys and the female genitalia.

Association of Hodgkin Lymphoma and Non-Hodgkin Lymphoma In the Same Patient. Clinicopathologic Characteristics and Outcome In a Series of 20 Cases

AbstractAbstract 3886The possibility that a non-Hodgkin lymphoma (NHL) is diagnosed either simultaneously or at a different time in patients with Hodgkin lymphoma (HL) has been reported both as single case reports and in small series. However the significance of such an association is still unclear. We searched the database of HL consecutively diagnosed at our Institution in order to identify such cases and to detect any specific clinicopathological or prognostic characteristics. Twenty cases were retrieved representing to our knowledge the largest series reported so far. Fifteen of them were diagnosed over the last ten years and represented 4,6% of the 326 cases of HL diagnosed during the same time period. There were 12 males and 8 females. Median age was 58. It was lower in patients developing HL as the first lymphoma (35 vs 65). HL was diagnosed first in 7 cases and as the second lymphoma in 9 cases. The mean interval between the two diagnoses was longer when HL occurred first (112 vs 60 months). In four patients the two diagnoses were made simultaneously, on the same histologic specimen in two. Histologic diagnoses of NHL included diffuse large B cell in 6, T cell lymphoma in 4 (peripheral unspecified 2, cutaneous 2), follicular in 3, marginal in 3 and lymphocytic in 4 cases each. T cell, marginal and lymphocytic lymphoma were overrepresented in comparison with their general frequency among NHL. No differences emerged regarding the timing of NHL occurrence, except for lymphocytic lymphoma which never occurred after HL. Nodular sclerosis was the most frequent histologic subtype of HL, representing 58% of cases, whereas only two cases (10%) were nodular lymphocyte predominance HL (NLPHL). Immunohistochemistry on Reed Sternberg cells of HL classical type showed CD30+ in 16 (100%) and CD15+ in 10 (63%) of 16 evaluable cases. CD20+ was present in 3/14 classical HL (21%) and in the 2 cases of NLPHL. Clinical presentation of HL was more aggressive than expected with no patient in stage I, 60% of patients in advanced stage (stage II: 8, stage III: 6; stage IV: 6) and 50% with systemic symptoms. There were no differences between cases presenting as first or second lymphoma. Among NHL 15 cases presented in stage III/IV and 6 with systemic symptoms. In seven cases autoimmune abnormalities/disease coexisted, including Raynaud, thyroiditis, cutaneous lupus, and vasculitis. HL patients were treated with ABVD in 11 cases, or with other chemotherapy programs +/− radiotherapy. NHL received treatments according to histology. In composite lymphoma treatment was directed against the more aggressive lymphoma. In spite of the unfavourable presentation, the complete response rate (CRR) in HL was 74% and the overall response rate (ORR) 79%. It was worse (5/8: 63%) when HL presented after NHL. In NHL the CRR was 63% and the ORR 95%. Relapse occurred in 2 HL, in one composite lymphoma (HL+FL > DLBCL) and in 5 NHL. Seven patients died, with active disease in 6 (2 HL, 4 NHL). One patient died of lung cancer. With a median follow up of 6 years, the 5-year and 10-year survival are 83,5% +/−9% and 68%+/−12%, respectively. We conclude that the occurrence of HL and NHL in the same patient is not rare. T-cell, marginal and lymphocytic lymphoma seem to be more frequently associated with HL. Pathologic and immunohistochemical characteristics are otherwise not distinctive. Patients present with advanced disease and systemic symptoms but their response to treatment and overall prognosis seem not worse than that of patients affected by HL as single tumour. The selective association between some histologic types of NHL and HL as well as the possible association with autoimmunity warrants further investigation. Disclosures:No relevant conflicts of interest to declare.

Pediatric Kidney Transplantation: Analysis of Donor Age, HLA Match, and Posttransplant Non-Hodgkin Lymphoma: A Collaborative Transplant Study Report

The impact and relationship of donor age, human leukocyte antigen (HLA) matching, and posttransplant non-Hodgkin lymphoma in pediatric kidney recipients are not completely understood. We analyzed Collaborative Transplant Study data from 9209 pediatric kidney transplant recipients to examine the effects of donor age and HLA match on graft survival and the relationship between HLA match and occurrence of non-Hodgkin lymphoma. Survival rates using donors aged 11 to 17, 18 to 34, or 35 to 49 years were similar. Cox regression analysis showed that two HLA-DR mismatches were associated with lower graft survival in transplants performed during 1988 to 1997 (P<0.001) but not during the 1998 to 2007 period (P=0.95). A hierarchical relationship was observed for the effect of increasing numbers of combined HLA-A+B+DR mismatches on graft survival during the 1988 to 1997 (P<0.001) and the 1998 to 2007 period (P<0.001). An association between two HLA-DR mismatches and non-Hodgkin lymphoma was demonstrated by multivariate analysis (hazard ratio for 2 vs. 0-1 DR mismatches 2.04, P=0.021), and the result was consistent during both 10-year periods. We recommend that (1) kidneys from deceased donors up to 49 years be allocated to children, (2) an acceptable HLA-A+B+DR match be attempted in patients with relatively common HLA phenotypes, and (3) transplants with two HLA-DR mismatches be avoided to reduce the risk of posttransplant non-Hodgkin lymphoma.

Non-Hodgkin Lymphoma (NHL) linkage with residence near heavy roads—A case study from Haifa Bay, Israel

The linkage between NHL morbidity and residence near heavy roads is analyzed among the Jewish population of the Haifa Metropolis, Israel. The addresses of 1436 patients (94.5% of all cases, 1995–2004) were geocoded. The geographic distribution of NHL patients was adjusted by the overall density of population in the study area. The analysis indicates steady decline in the “density adjusted” numbers of patients as a function of increasing road distances (P<0.01). Differences between genders/age groups were not found. The much higher occurrence of NHL in areas near main roads may be indicative of disease risks.

Non-Hodgkin's lymphoma--meta-analyses of the effects of corticosteroids and non-steroidal anti-inflammatories

Recent research has focused on the effects of corticosteroids and non-steroidal anti-inflammatory drugs/agents (NSAIDs) on non-Hodgkin's lymphoma (NHL) risk, with inconclusive results. We conducted meta-analyses of data published to date, to ascertain the over-all association between NHL and corticosteroid use, and between NHL and NSAID use. Literature searches were performed to find studies assessing the effects of corticosteroids and/or NSAIDs on NHL risk. We analysed nine case-control studies and one cohort study of the effect of corticosteroids and/or NSAIDs on NHL risk. We performed a formal meta-analysis using summary measures from these studies. The studies contributed 6897 NHL cases and 8881 controls for the corticosteroid analyses, and 5794 NHL cases and 34,707 controls for the NSAID analyses. There was no heterogeneity of the odds ratio (OR) estimates. The overall OR for the effect of corticosteroid exposure on NHL occurrence was not suggestive of an increased risk [OR 1.09, 95% confidence interval (CI) 0.96-1.24]. Similarly, the OR for the effect of NSAIDs on NHL occurrence did not support an increased risk (OR 0.93, 95% CI 0.74-1.14). Our meta-analyses suggest little evidence that corticosteroid or NSAID exposures are themselves risk factors for NHL. Early data linking corticosteroids and/or NSAIDs with NHL may reflect an underlying increased risk of lymphoma in patient populations that use these medications (i.e. autoimmune diseases such as rheumatoid arthritis), and may point to the importance of disease activity in driving NHL risk in these populations.

Incidence of Non-Hodgkin's Lymphoma in Sweden, Denmark, and Finland from 1960 through 2003: an Epidemic That Was

Reports during the early 1990s indicated non-Hodgkin's lymphoma (NHL) as one of the most rapidly increasing malignancies. More recent trends remain poorly characterized, as do the underlying reasons for NHL time trends, in particular, the effect of changes in classification and registration of lymphoproliferative malignancies. Insights into the descriptive epidemiology of NHL may shed light upon its elusive etiology. We used data from the Swedish, Danish, and Finnish national cancer registers to assess the incidences of NHL and other lymphoproliferative malignancies between 1960 and 2004. Using Poisson regression, we estimated the annual rate of change in NHL incidence per decade by sex, age, and country. In Sweden, Denmark, and Finland, the NHL incidence increased in both genders and all age categories by about 4% every year up until the early 1990s. Thereafter, the incidence increased at a slower rate (ages 60-79 years), stabilized (ages 50-59 and > or =80 years), and decreased (ages 0-49 years), respectively, similarly for males and females in the three countries. Time trends of NHL were not reciprocated and explained by trends for other lymphoproliferative malignancies nor explained by trends in NHL as secondary primaries or NHL diagnosed postmortem. The epidemic increase of NHL has recently subsided. Changes in the classification of lymphoproliferative malignancies, or occurrence of NHL as second primaries, only offer a marginal explanation.

441 The influence of interleukin- 10 promoter gene polymorphism on the occurrence of non hodgkin lymphoma (NHL) in subjects infected with hepatitis C virus (HCV)

441 The influence of interleukin- 10 promoter gene polymorphism on the occurrence of non hodgkin lymphoma (NHL) in subjects infected with hepatitis C virus (HCV)

Prevalence and pattern of antinuclear autoantibodies in 347 patients with non-Hodgkin's lymphoma.

The presence of antinuclear autoantibodies (ANA) was investigated in a large cohort of patients with non-Hodgkin's lymphoma (NHL) in order to assess their frequency, specificity and prognostic relevance. ANA were analysed in 347 patients with different histological subgroups of NHL and in 213 controls using an indirect immunofluorescence technique on HEp2 cells. As the appearance of autoantibodies may be found after treatment of NHL, samples were collected at the time of diagnosis of NHL before any therapy. Sixty-six (19%) NHL patients and 12 (5.6%) patients from the control group displayed ANA. The prevalence between the two groups was found to be significantly higher in NHL patients (P < 0.0001) with a marked increased prevalence in follicular and mantle cell lymphoma subgroups. Autoantibodies directed against mitotic proteins or mitotic-associated proteins were found in 6.9% of NHL patients versus 0.5% in the control group (P < 0.001), with a significantly increased incidence in follicular and mantle cell lymphoma subgroups (P < 0.0001). Some 28% of the patients with positive ANA displayed clinical symptoms that could correspond to classical autoimmune manifestations, this frequency appearing to be higher in the marginal zone/mucosa-associated lymphoid tissue lymphoma subgroup. These data demonstrate a significant incidence of ANA before any treatment in NHL occurrence, which seems to be higher in some histological subgroups with particular ANA, such as ANA directed against mitotic proteins or mitotic-associated proteins.

Analysis of Mismatch Repair Defects in the Familial Occurrence of Lymphoma and Colorectal Cancer

Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant disorder featuring familial clustering of colorectal and/or endometrial cancer, and other malignancies. Except for a rare case report, Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) have not been considered part of HNPCC. Recent murine models for HNPCC have shown an increased incidence of B- and T-cell lymphoma, as well as tumors of the gastrointestinal tract and other organ systems, involving defects in genes resulting in faulty mismatch repair (MMR) of DNA. These MMR genes include MLH 1, MSH 2, MSH 3, MSH 6, PMS 1 and PMS 2. We sought to analyze the occurrence of NHL and HD in families with clusters of colorectal cancers (CRC). Probands from 21 kindreds were classified as HNPCC (3), HNPCC-like (5), and HNPCC-variant (13); seen and followed by Clinical Genetics at Memorial Hospital the kindreds were assessed for the occurrence of NHL or HD. Of the 21 pedigrees, a total of 37 patients were identified who were diagnosed with leukemia, lymphoma, or HD. Fourteen of the 37 patients with a diagnosis of NHL or HD were further classified and showed varying histologies ranging from chronic lymphocytic leukemia/small lymphocytic lymphoma (2), mycosis fungoides (1), follicular lymphoma (1), extranodal marginal zone lymphoma of MALT type (2), diffuse large B-cell lymphoma (4), nodular sclerosis HD (3), and mixed cellularity HD (1). Microsatellite instability studies were performed on 6 cases but none showed evidence of replication error repair defects. Immunohistochemical stains performed on paraffin sections from these 6 representative cases showed differential protein expression of MLH1, MSH2, MSH6, and PMS2 when compared to normal reactive tissues from the same patient but showed no significant differences when compared to controls of non-familial, sporadic lymphomas. These results suggest that lymphomas arising in the setting of familial CRC do not bear the molecular hallmarks of HNPCC. Further studies are needed to explain the differential patterns of expression of RER-associated proteins in lymphomas, as well as the association of lymphomas and possibly renal cell cancers in a subset of kindreds in which CRC clustering is evident.

Non-Hodgkin lymphoma and coexisting primary cancers: a retrospective clinical analysis of 10 patients.

The simultaneous occurrence of non-Hodgkin lymphoma (NHL) and primary cancers is rare, and the treatment strategy for both malignancies is unclear. The authors analyzed the clinical records of 10 patients with NHL and coexisting primary cancers. All patients initially had symptoms of NHL, and all carcinomas were found at the initial workup of NHL by chance. The most common primary sites of coexisting cancers were the stomach (six patients) and the colon (two). Histologically, the majority of NHLs were intermediate grade, and all lesions were B-cell type. All primary cancers were adenocarcinoma. Initially, NHL was treated with radiotherapy or chemotherapy. Six primary cancers were resected surgically or endoscopically after the remission of NHL. The remaining four patients received no treatment for primary cancers because of advanced stages or early relapse of NHL. Three patients died of NHL, one died of cancer, and six were still alive, five without evidence of disease and one with disease. The authors conclude that early detection of a coexisting cancer and appropriate treatment after the remission of NHL may increase the possibility of a cure.

Meta-analyses of non-Hodgkin's lymphoma and farming

This study examined the association between non-Hodgkin's lymphoma (NHL) and farming. A series of meta-analyses of peer-reviewed studies was performed using 36 studies published between 1982 and 1997. Prior to the meta-analyses, all the studies were reviewed and evaluated for heterogeneity and publication bias. Combined relative risks (RR) were calculated using the random effect model. The combined RR was 1.10 [95% confidence interval (95% CI) 1.03-1.19] for all the studies and 0.93 (95% CI 0.82-1.06) for studies involving female farmers. Significant heterogeneity was detected for study design and country of study among the studies. Significantly elevated RR values were obtained for case-referent studies (combined RR 1.19, 95% CI 1.06-1.33) and for studies conducted on farmers residing in the United States (combined RR 1.26, 95% CI 1.15-1.37). These findings were not influenced by a publication bias. The findings suggest that male farmers residing in the United States have a slightly elevated risk of contracting NHL. Commonly experienced exposures that might contribute to the occurrence of NHL in this group include infectious microorganisms, herbicides, and insecticides.

Parameters affecting the development of non-Hodgkin's lymphoma in patients with severe human immunodeficiency virus infection receiving antiretroviral therapy.

To investigate the occurrence of non-Hodgkin's lymphoma (NHL) in human immunodeficiency virus (HIV)-infected patients receiving long-term antiretroviral therapy and factors associated with the development of these lymphomas. The charts of 55 patients with advanced HIV infection receiving zidovudine (formerly known as azidothymidine [AZT])-based therapy and 61 patients receiving dideoxyinosine (ddI) were examined for the occurrence of NHL. Stored samples from the AZT-based treatment cohort were examined retrospectively for parameters predictive of the subsequent development of lymphoma. Eight of 55 patients receiving AZT-based therapy developed NHL, yielding an estimated probability of 12% (95% confidence interval [CI], 4.7% to 27.1%) after 24 months, and 29.2% (95% CI, 15.2% to 48.7%) after 36 months. Four of 61 patients receiving ddI developed NHL, yielding a 6.2% (95% CI, 2.1% to 17%) estimated probability after 24 months, and 9.5% (95% CI, 3.6% to 22.8%) after 36 months. The difference between these cohorts was not significant (two-tailed P [P2] = .13). Patients with less than 50 CD4 cells/microL developed NHL at a significantly higher rate (P2 = .0085). This was particularly true for patients who presented with primary CNS lymphoma (PCNSL). For patients receiving AZT-based therapy, pretreatment serum interleukin-6 (IL-6) levels were somewhat higher in those who subsequently developed NHL than in those who did not (P2 = .048). HIV-infected patients with profound immunodeficiency, especially those with less than 50 CD4 cells/microL, are at substantial risk of developing NHL and particularly PCNSL. Additional studies are needed to define the role of other factors such as IL-6 in the pathogenesis of these opportunistic tumors.