Historical review of lymphomas.

Autologous Peripheral Blood Stem Cell Transplantation in Children with Refractory or Relapsed Lymphoma: Results of Children’s Oncology Group Study A5962

Morphologic and immunohistologic studies were performed on a series of 213 lymphoma cases, including CD30-positive anaplastic large cell (ALC) lymphomas (45 cases), other CD30-positive (18 cases) or CD30-negative (72 cases) non-Hodgkin lymphomas (NHL), cases of Hodgkin disease (HD) (73 cases), and an additional 5 cases exhibiting features of both CD30-positive ALC and Hodgkin lymphomas. The aim was to assess differential expression by tumor cells of CD30/BerH2, epithelial membrane antigen (EMA), and other monoclonal antibodies, including BNH9, an epithelial and endothelial marker that has been found to be reactive with ALC lymphoma cells. A significantly greater proportion of cases of ALC lymphoma compared with HD exhibited positive results for CD45, EMA, CD45RO, and CD3 in CD30-positive atypical large cells, whereas Reed-Sternberg cells in HD most frequently coexpressed CD15 and CD30 antigens. ALC lymphoma cells reacted with BNH9 MoAb in 10 of the 42 (23.8%) assessable cases, whereas Reed-Sternberg cells reacted with this antibody in 5 of 73 (6.8%) HD cases. Only 3 of 90 (3.3%) NHL cases had positive results for BNH9; they were CD30-negative high-grade or low-grade lymphomas. It was noteworthy that 9 of 10 BNH9-positive ALC lymphomas also were EMA positive. Four of the five cases with morphologic features intermediate between those of HD and ALC lymphoma showed immunohistologic findings (positive results for CD30 and CD15, negative results for EMA, CD45, and BNH9) similar to those frequently observed in the HD cases; conversely, the remaining case showed a profile (positive results for CD30, CD45, and EMA, negative results for CD15) typically observed in ALC lymphomas. This study suggests that the differential expression of CD45, EMA, and CD15 could be used in the distinction of ALC lymphomas and HD, whereas it seems that BNH9 antibody reactivity may be of diagnostic use only in that it reinforces the diagnostic value of EMA expression in the differentiation of these entities.

Studies associate alcohol consumption, cigarette smoking, and body size with the risk of overall or subtype lymphoma. Current data come mostly from case-control studies or prospective studies with few cases. In the prospective National Institutes of Health-former American Association of Retired Persons (NIH-AARP) Diet and Health Study, the authors assessed the above lifestyle factors via baseline questionnaire among 285,079 men and 188,905 women aged 50-71 years and ascertained histologically confirmed Hodgkin's lymphoma (n = 58) and non-Hodgkin's lymphoma (n = 1,381) cases through linkage with cancer registries from 1995 to 2000. Compared with nondrinkers, alcohol consumers had a lower risk for non-Hodgkin's lymphoma overall (for >28 drinks/week: adjusted relative risk (RR) = 0.77, 95% confidence interval (CI): 0.59, 1.00; p(trend) among drinkers = 0.02) and for its main subtypes. Compared with never smokers, current smokers and recent quitters (<or=4 years ago) had higher risk of Hodgkin's lymphoma (RR = 2.25, 95% CI: 1.04, 4.89; RR = 4.20, 95% CI: 1.94, 9.09, respectively), whereas current or former smokers had lower risk of follicular non-Hodgkin's lymphoma (RR = 0.67, 95% CI: 0.52, 0.86). Severe obesity (body mass index of >or=35: RR = 1.29, 95% CI: 1.02, 1.64) and taller height (RR = 1.19, 95% CI: 1.03, 1.38) were associated moderately with non-Hodgkin's lymphoma. These findings add to the evidence that lifestyle factors and relevant anthropometric characteristics play a role in lymphoma etiology.

Eight years after being treated with a new drug for non-Hodgkin's lymphoma, 86 percent of patients were still alive and half had not had a relapse of their disease, according to researchers from the University of Michigan Comprehensive Cancer Center.The patients had follicular lymphoma, a type of cancer that is not considered to be curable using traditional treatments. Even if patients initially respond to treatment, the disease almost always comes back and becomes more difficult to treat.The study followed 76 patients with follicular non-Hodgkin's lymphoma, a cancer of the lymph system, who received the radioimmunotherapy drug Bexxar as their first treatment for the disease. Ninety-five percent of the patients saw their tumors shrink from the treatment and three-quarters of patients went into complete remission. Patients were followed for a median of eight years, and nearly two-thirds have remained in complete remission eight years after treatment."For years we have known radioimmunotherapy such as Bexxar is one of the most effective treatments for patients with relapsed follicular lymphoma. These data show Bexxar is particularly effective when used as a front-line treatment," says Mark Kaminski, M.D., professor of internal medicine at the U-M Medical School. Kaminski presented these results June 4, 2007 at the American Society of Clinical Oncology annual meeting in Chicago."These results compare quite favorably with those achieved with state-of-the-art chemotherapy regimens that take months to deliver. But Bexxar is given as a single treatment, completed within one week, which makes it an extremely convenient regimen for patients," Kaminski says.Non-Hodgkin's lymphoma, the nation's sixth leading cause of cancer death, is a cancer of the lymph system, which is part of the immune system. Follicular lymphoma is the second most common type of non-Hodgkin's lymphoma. Lymphoma spreads easily through the lymph system and the bloodstream and consequently tends to be widespread when it is diagnosed. Traditional treatment often involves intensive chemotherapy, or a combination of chemotherapy and the monoclonal antibody rituximab. These treatments are usually given every three weeks over a span of up to six months and can cause many unpleasant side effects, including nausea, hair loss and infections.Bexxar, whose chemical name is tositumomab and iodine I 131 tositumomab, combines an antibody that seeks out cancer cells, and a radioactive form of the element iodine. When injected, it travels like a guided missile through the bloodstream to bind to a protein found on the surface of the cancerous cells. The radiation zaps these malignant cells with minimal exposure to normal tissues.With the Bexxar therapeutic regimen, a patient receives an injected test dose of radioactive Bexxar, followed one to two weeks later with a custom-tailored therapeutic dose. After that, the therapy is considered complete. The most common side effect is a temporary lowering of blood counts several weeks after the treatment. There is no hair loss and nausea is rare.Kaminski and his colleague Richard Wahl (formerly at U-M and now at Johns Hopkins University) developed the Bexxar regimen, which received approval from the U.S. Food and Drug Administration in June 2003 to treat follicular non-Hodgkin's lymphoma after other treatments have failed. The current results involve Bexxar as a first-line treatment for this disease.In addition to Kaminski and Wahl, U-M study authors were Judith Estes, R.N., a nurse practitioner; Missy Tuck, clinical research coordinator; and Charles Ross, M.D., associate professor of pathology.Funding for the study was from the National Institutes of Health and GlaxoSmithKline. The University of Michigan holds patents for the Bexxar therapeutic regimen, which is marketed by GlaxoSmithKline under a licensing agreement. U-M receives royalties on sales of Bexxar, a portion of which goes to Kaminski and his co-inventors.For information about non-Hodgkin's lymphoma, visit our Non-hodgkins lymphoma web page or call the Cancer AnswerLine at 800-865-1125. For information about Bexxar from its manufacturer, call 877-4-BEXXAR or visit www.bexxar.com.Reference: American Society of Clinical Oncology 43rd annual meeting, June 1-5, 2007, Chicago, Ill. No. 8033.Written by Nicole Fawcett

Lymphoma is the fifth most common type of cancer in the United States, with 74,490 new cases estimated in 2009. Approximately 15% of patients with lymphoma have Hodgkin lymphoma; the remainder have one of the non-Hodgkin lymphomas. The incidence of non-Hodgkin lymphoma has increased steadily over recent decades. This chapter reviews the epidemiology, classification, clinical features, pathology, diagnostic evaluation, staging and prognosis, and treatment of Hodgkin and non-Hodgkin lymphoma. Other topics discussed include the acute and chronic effects of therapy for Hodgkin disease, as well as the subtypes of non-Hodgkin lymphomas, including indolent B cell lymphoma, follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, marginal-zone lymphoma, diffuse large B cell lymphoma (DLBCL), primary central nervous system lymphoma (PCNSL), Burkitt lymphoma, and HIV-related non-Hodgkin lymphoma. Figures illustrate the cellular appearance of Hodgkin lymphoma subtypes and DLBCL, diagnosis of DLBCL subtypes by gene expression, computed tomography and plain chest film in primary mediastinal cell lymphoma, MRI of the brain in PCNSL, and gene expression and gene expression predictors of survival among patients with DLBCL treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine [Oncovin], and prednisone (R-CHOP). Tables describe the Ann Arbor classification and the Cotswold modification for staging of lymphoma; the International Prognostic Score for advanced Hodgkin lymphoma; the World Health Organization classification of hematopoietic neoplasms; chromosomal translocations in non-Hodgkin lymphoma; the Eastern Cooperative Oncology Group performance scale; the International Prognostic Index for aggressive non-Hodgkin lymphoma; and the Follicular Lymphoma International Prognostic Index. This chapter has 185 references. This review contains 9 tables, 7 figures and 185 references

Residence Proximity to Benzene Release Sites Is Associated with Increased Incidence of Non-Hodgkin Lymphoma.

Comparative epidemiological analysis of hematological malignancies in adolescents and young adults (AYA) in the United States of America (USA), 1990–2021, with projections to 2040

Efficacy of Fludarabine/Mitoxantrone/Dexamethasone Alternating with CHOP in Bulky Follicular Non-Hodgkin's Lymphoma

BackgroundThe incidence of non-Hodgkin's lymphoma (NHL) has risen steadily during the last few decades in all geographic regions covered by cancer registration for reasons that remain unknown. The aims of this study were to assess the relative contributions of age, period and cohort effects to NHL incidence patterns and therefore to provide clues to explain the increasing incidence.MethodsPopulation and NHL incidence data were provided for the Doubs region (France) during the 1980-2005 period. NHL counts and person-years were tabulated into one-year classes by age (from 20 to 89) and calendar time period. Age-period-cohort models with parametric smooth functions (natural splines) were fitted to the data by assuming a Poisson distribution for the observed number of NHL cases.ResultsThe age-standardised incidence rate increased from 4.7 in 1980 to 11.9 per 100,000 person-years at risk in 1992 (corresponding to a 2.5-fold increase) and stabilised afterwards (11.1 per 100,000 in 2005). Age effects showed a steadily increasing slope up to the age of 80 and levelled off for older ages. Large period curvature effects, both adjusted for cohort effects and non-adjusted (p < 10-4 and p < 10-5, respectively), showed departure from linear periodic trends; period effects jumped markedly in 1983 and stabilised in 1992 after a 2.4-fold increase (compared to the 1980 period). In both the age-period-cohort model and the age-cohort model, cohort curvature effects were not statistically significant (p = 0.46 and p = 0.08, respectively).ConclusionsThe increased NHL incidence in the Doubs region is mostly dependent on factors associated with age and calendar periods instead of cohorts. We found evidence for a levelling off in both incidence rates and period effects beginning in 1992. It is unlikely that the changes in classification (which occurred after 1995) and the improvements of diagnostic accuracy could largely account for the 1983-1992 period-effect increase, giving way to an increased exposure to widely distributed risk factors including persistent organic pollutants and pesticides. Continued NHL incidence and careful analysis of period effects are of utmost importance to elucidate the enigmatic epidemiology of NHL.

Temporal trends and demographic patterns in Hodgkin and non-Hodgkin lymphoma mortality among u.s. adults: A CDC wonder study

The lineage and clonality of Hodgkin's disease (HD) were investigated by analyzing the organization of the immunoglobulin and T-cell receptor beta-chain (T beta) gene loci in 18 cases of HD, and for comparison, in a panel of 103 cases of B- and T-cell non-Hodgkin's lymphomas (NHLs) and lymphoid leukemias (LLs). Sizable clonal B- or T-cell populations, representing greater than or equal to 10% of the pathologic sample, were readily detectable by immunogenotypic analysis in all 103 NHLs and LLs but not in any of the 18 cases of HD. However, extremely minor clonal populations (less than or equal to 1%) were detectable in 3 of 18 cases of HD. We demonstrated that these minor clonal populations do not correspond to Reed-Sternberg (RS) cells since clonal immunoglobulin or T beta gene rearrangements are not detectable in cases of HD containing greater than 25% RS cells. The number of RS cells present in these samples appeared to correlate directly with the pattern of gene rearrangements characteristic of polyclonal T cells. These studies demonstrate that Southern blot hybridization analysis for clonal immunoglobulin and T beta gene rearrangements represents an accurate, objective tool in the differential diagnosis between HD and NHL; that HD is predominantly composed of polyclonal B and T cells; that minor clonal B- or T-cell populations unrelated to RS cells occasionally can be found in HD; and that RS cells do not represent clonal B- or T-cell expansions. Finally, our data preliminarily suggest that RS cells may represent polyclonal T-cell populations.

A critical review of the epidemiology of Agent Orange or 2,3,7,8-tetrachlorodibenzo-p-dioxin and lymphoid malignancies

Lymphoma in Pregnancy: Excellent Fetal Outcomes and Maternal Survival in a Large Multicenter Analysis

To investigate whether the assessment of apoptotic index (AI) from fine needle aspiration (FNA) smears of non-Hodgkin's lymphomas (NHL) is reliable and has potential utility as a criterion to predict histologic grade. AI was independently determined by four cytopathologists as a percentage from routine FNA smears in 96 NHLs and 15 lymphoid hyperplasias. Working formulation (WF) grades from corresponding surgical biopsies were modified to include mantle zone-derived NHLs as intermediate grade and to make diffuse large cell NHL a separate category called "high" grade, whereas WF high grade NHLs were called "very high" grade. Histologic grades were also derived from the Revised European American Lymphoma (REAL) classification. AI was compared with histologic grade using the unpaired, two-tailed Student t test. These data were used to determine potential thresholds for AI that separate lower from higher grade NHLs. Measurements of AI strongly correlated between cytopathologists (median r = .93). Low and intermediate grade NHLs had indistinguishable AIs, whereas higher grade NHLs had significantly higher AIs. Appropriate potential AI thresholds between low or intermediate grade and higher grade NHLs were in the range of 1.5-2.5% (modified WF) and 1-2% (REAL). There is excellent interobserver reliability in the measurement of AI from FNAs of NHLs. Higher AIs distinguish higher from lower grade NHLs. Diffuse large cell NHLs had AIs that were similar to WF high grade NHLs.

Expression of Smac/DIABLO in B-cell non-Hodgkin and Hodgkin lymphomas