Summary Background Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial. We assessed this risk in a ...prospective observational cohort study. Methods 19 486 patients with inflammatory bowel disease, of whom 11 759 (60·3%) had Crohn's disease and 7727 (39·7%) had ulcerative colitis or unclassified inflammatory bowel disease, were enrolled in a nationwide French cohort by 680 gastroenterologists, who reported details of immunosuppressive therapy during the observation period, cases of cancer, and deaths. The risk of lymphoproliferative disorder was assessed according to thiopurine exposure. Median follow-up was 35 months (IQR 29–40). Findings At baseline, 5867 (30·1%) of patients were receiving, 2809 (14·4%) had discontinued, and 10 810 (55·5%) had never received thiopurines. 23 new cases of lymphoproliferative disorder were diagnosed, consisting of one case of Hodgkin's lymphoma and 22 cases of non-Hodgkin lymphoproliferative disorder. The incidence rates of lymphoproliferative disorder were 0·90 per 1000 (95% CI 0·50–1·49) patient-years in those receiving, 0·20/1000 (0·02–0·72) patient-years in those who had discontinued, and 0·26/1000 (0·10–0·57) patient-years in those who had never received thiopurines (p=0·0054). The multivariate-adjusted hazard ratio of lymphoproliferative disorder between patients receiving thiopurines and those who had never received the drugs was 5·28 (2·01–13·9, p=0·0007). Most cases associated with thiopurine exposure matched the pathological range of post-transplant disease. Interpretation Patients receiving thiopurines for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders. Funding Programme Hospitalier de Recherche Clinique National ( AOM05157 ), Association François Aupetit, Délégation Inter-régionale de la Recherche clinique Ile de France-Assistance Publique Hôpitaux de Paris (AP-HP), Ligue contre le Cancer, and Fonds de Recherche de la Société Nationale Française de Gastro-entérologie.
Summary Background More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on ...survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. Methods In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997–99, 2000–02, 2003–05, 2006–08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. Findings We analysed 560 444 cases. From 1997–99 to 2006–08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% 95% CI 40·7–43·4 to 55·4% 54·6–56·2, p<0·0001), follicular lymphoma (58·9% 57·3–60·6 to 74·3% 72·9–75·5, p<0·0001), chronic myeloid leukaemia (32·3% 30·6–33·9 to 54·4% 52·5–56·2, p<0·0001), and acute promyelocytic leukaemia (50·1% 43·7–56·2 to 61·9% 57·0–66·4, p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% 74·1–76·0 to 79·3% 78·4–80·1, p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% 65·1–67·1 to 69·0% 68·1–69·8, p<0·0001), multiple myeloma/plasmacytoma (29·8% 29·0–30·6 to 39·6% 38·8–40·3, p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% 27·7–32·0 to 41·1% 39·0–43·1, p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% 11·9–13·3 to 14·8% 14·2–15·4, p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% 68·7–71·8 to 74·9% 73·8–75·9, p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. Interpretation These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival. Funding Compagnia di San Paolo, Fondazione Cariplo, European Commission, and Italian Ministry of Health.
Changing definitions and classifications of hematologic malignancies (HMs) complicate incidence comparisons. HAEMACARE classified HMs into groupings consistent with the latest World Health ...Organization classification and useful for epidemiologic and public health purposes. We present crude, age-specific and age-standardized incidence rates for European HMs according to these groupings, estimated from 66 371 lymphoid malignancies (LMs) and 21 796 myeloid malignancies (MMs) registered in 2000-2002 by 44 European cancer registries, grouped into 5 regions. Age-standardized incidence rates were 24.5 (per 100 000) for LMs and 7.55 for MMs. The commonest LMs were plasma cell neoplasms (4.62), small B-cell lymphocytic lymphoma/chronic lymphatic leukemia (3.79), diffuse B-cell lymphoma (3.13), and Hodgkin lymphoma (2.41). The commonest MMs were acute myeloid leukemia (2.96), other myeloproliferative neoplasms (1.76), and myelodysplastic syndrome (1.24). Unknown morphology LMs were commonest in Northern Europe (7.53); unknown morphology MMs were commonest in Southern Europe (0.73). Overall incidence was lowest in Eastern Europe and lower in women than in men. For most LMs, incidence was highest in Southern Europe; for MMs incidence was highest in the United Kingdom and Ireland. Differences in diagnostic and registration criteria are an important cause of incidence variation; however, different distribution of HM risk factors also contributes. The quality of population-based HM data needs further improvement.
The survival of patients with diffuse large B-cell lymphoma has increased during the last decade as a result of addition of anti-CD20 to anthracycline-based chemotherapy. Although the trend is ...encouraging, there are persistent differences in survival within and between the USA and European countries suggesting that non-biological factors play a role. Our aim was to investigate the influence of such factors on relative survival of patients with diffuse large B-cell lymphoma. We conducted a retrospective, multicenter, registry-based study in France on 1165 incident cases of diffuse large B-cell lymphoma between 2002 and 2008. Relative survival analyses were performed and missing data were controlled with the multiple imputation method. In a multivariate analysis, adjusted for age, sex and International Prognostic Index, we confirmed that time period was associated with a better 5-year relative survival. The registry area, the medical specialty of the care department (onco-hematology
other), the time to travel to the nearest teaching hospital, the place of treatment (teaching
not-teaching hospital -borderline significance), a comorbidity burden and marital status were independently associated with the 5-year relative survival. Adjusted for first-course treatment, inclusion in a clinical trial and treatment discussion in a multidisciplinary meeting were strongly associated with a better survival outcome. In contrast, socio-economic status (determined using the European Deprivation Index) was not associated with outcome. Despite therapeutic advances, various non-biological factors affected the relative survival of patients with diffuse large B-cell lymphoma. The notion of lymphoma-specific expertise seems to be essential to achieve optimal care management and reopens the debate regarding centralization of these patients' care in hematology/oncology departments.
Recent evidence suggests that there is etiologic heterogeneity among the various subtypes of lymphoid neoplasms. However, epidemiologic analyses by disease subtype have proven challenging due to the ...numerous clinical and pathologic schemes used to classify lymphomas and lymphoid leukemias over the last several decades. On behalf of the International Lymphoma Epidemiology Consortium (InterLymph) Pathology Working Group, we present a proposed nested classification of lymphoid neoplasms to facilitate the analysis of lymphoid neoplasm subtypes in epidemiologic research. The proposed classification is based on the World Health Organization classification of lymphoid neoplasms and the International Classification of Diseases–Oncology, Third Edition (ICD-O-3). We also provide a translation into the proposed classification from previous classifications, including the Working Formulation, Revised European-American Lymphoma (REAL) classification, and ICD-O-2. We recommend that epidemiologic studies include analyses by lymphoma subtype to the most detailed extent allowable by sample size. The standardization of groupings for epidemiologic research of lymphoma subtypes is essential for comparing subtype-specific reports in the literature, harmonizing cases within a single study diagnosed using different systems, as well as combining data from multiple studies for the purpose of pooled analysis or meta-analysis, and will probably prove to be critical for elucidating etiologies of the various lymphoid neoplasms.
Medical diagnostic X-rays are an important source of ionizing radiation (IR) exposure in the general population; however, it is unclear if the resulting low patient doses increase lymphoma risk. We ...examined the association between lifetime medical diagnostic X-ray dose and lymphoma risk, taking into account potential confounding factors, including medical history. The international Epilymph study (conducted in the Czech-Republic, France, Germany, Ireland, Italy, and Spain) collected self-reported information on common diagnostic X-ray procedures from 2,362 lymphoma cases and 2,465 frequency-matched (age, sex, country) controls. Individual lifetime cumulative bone marrow (BM) dose was estimated using time period-based dose estimates for different procedures and body parts. The association between categories of BM dose and lymphoma risk was examined using unconditional logistic regression models adjusting for matching factors, socioeconomic variables, and the presence of underlying medical conditions (atopic, autoimmune, infectious diseases, osteoarthritis, having had a sick childhood, and family history of lymphoma) as potential confounders of the association. Cumulative BM dose was low (median 2.25 mGy) and was not positively associated with lymphoma risk. Odds ratios (ORs) were consistently less than 1.0 in all dose categories compared to the reference category (less than 1 mGy). Results were similar after adjustment for potential confounding factors, when using different exposure scenarios, and in analyses by lymphoma subtype and by type of control (hospital-, population-based). Overall no increased risk of lymphoma was observed. The reduced ORs may be related to unmeasured confounding or other sources of systematic bias.We found little evidence that chronic medical conditions confound lymphoma risk and medical radiation associations.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell–related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ...ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell depletion in the blood and a significant reduction in splenic B cells, but these patients did not achieve remission. Moreover, whereas the percentage of circulating regulatory T cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP patients. Interestingly, the ratio of proinflammatory Th1 cells to suppressive Tregs was increased in the spleens of patients who failed RTX therapy. These results indicate that although B cells are involved in ITP pathogenesis, RTX-induced total B-cell depletion is not correlated with its therapeutic effects, which suggests additional immune-mediated mechanisms of action of this drug.
Purpose To prospectively assess the clinical impact of expert review of lymphoma diagnosis in France. Materials and Methods From January 2010 to December 2013, 42,145 samples from patients with newly ...diagnosed or suspected lymphomas were reviewed, according to the 2008 WHO classification, in real time by experts through the Lymphopath Network. Changes in diagnosis between referral and expert review were classified as major or minor according to their potential impact on patient care. Results The 42,145 reviewed samples comprised 36,920 newly diagnosed mature lymphomas, 321 precursor lymphoid neoplasms, 314 myeloid disorders, and 200 nonhematopoietic neoplasms, with 4,390 benign lesions. There were 4,352 cutaneous and 32,568 noncutaneous lymphomas. The most common mature noncutaneous lymphomas were diffuse large B-cell lymphomas (32.4%), follicular lymphomas (15.3%), classic Hodgkin lymphomas (13%), peripheral T-cell lymphomas (6.3%) of which angioimmunoblastic T-cell lymphomas (2.3%) were the most frequent, and mucosa-associated lymphoid tissue lymphomas (5.8%). A diagnostic change between referral and expert review occurred in 19.7% of patients, with an estimated impact on patient care for 17.4% of patients. This rate was significantly higher for patients sent with a provisional diagnosis seeking expert second opinion (37.8%) than for patients sent with a formal diagnosis (3.7%). The most frequent discrepancies were misclassifications in lymphoma subtype (41.3%), with 12.3% being misclassifications among small B-cell lymphoma entities. Fewer than 2% of changes were between benign and malignant lymphoid conditions. Minor changes (2.3%) mostly consisted of follicular lymphoma misgrading and diffuse large B-cell lymphoma subtype misclassification. Conclusion To our knowledge, this study provides the largest ever description of the distribution of lymphoma entities in a western country and highlights how expert review significantly contributes to a precise lymphoma diagnosis and optimal clinical management in a proportion of patients.
Background & Aims: Increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the ...risk of non-Hodgkin’s lymphoma (NHL) subtypes after HCV infection. Methods: The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded. Results: HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio OR, 1.78; 95% confidence interval CI, 1.40–2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44–4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.68–2.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14–5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65–1.60). Conclusions: These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma).
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