Search

Background: Treatment with antithymocyte globulin (ATG) is a well-recognized risk factor for the development of post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation, but it is unknown how its use affects overall survival after PTLD. Methods: A total of 114 patients with PTLD and available data on immunosuppressive regimen were included from a nation-wide case series of solid organ transplant recipients in Sweden. Prior use of ATG was correlated to clinical features, PTLD subtype, and survival. Results: A total of 47 (41%) patients had received ATG prior to the diagnosis of PTLD. The ATG-treated patients were more likely to be recipients of hearts or lungs, and less likely of kidneys ( p  < 0.01). They had experienced more acute rejections ( p  = 0.02). The PTLDs arose earlier, median 2.0 vs. 6.6 years post-transplant ( p  = 0.002) and were more often situated in the allograft (32% vs. 7%, p  < 0.001) in patients with prior ATG vs. no ATG treatment. The PTLDs in the ATG group were more often Epstein-Barr virus-positive (80% vs. 40%, p  < 0.001). There were more polymorphic PTLDs (17% vs. 1.5%, p  = 0.004) and less T-cell PTLDs (4% vs. 19%, p  = 0.02) in the ATG group than in the no ATG group. Diffuse large B-cell lymphoma was equally common in patients with and without prior ATG therapy, but the non-germinal center subtype was more frequent in the ATG group ( p  = 0.001). In an adjusted Cox proportional hazards regression model, prior ATG treatment and better performance status were associated with superior overall survival, whereas older age, T-cell subtype of PTLD, presence of B symptoms, and elevated lactate dehydrogenase were associated with inferior overall survival. Patients receiving ATG solely as rejection therapy had superior overall survival compared with those receiving ATG as induction therapy or both ( p  = 0.03). Conclusions: ATG therapy, especially rejection therapy, prior to PTLD development is an independent prognostic factor for superior overall survival after PTLD diagnosis.

Unlabelled: It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination., Material and Methods: Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic influenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal influenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the influenza strains. For the pneumococcal vaccine 14 different serotype-specific anti-capsular antibodies were measured by bead assay xMAP(®)., Results: Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI ≥ 40) to the pandemic-like strain A/California7/2009HINI. After the first and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal flu vaccination SPR against influenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported., Conclusion: A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to influenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.

Background: Epstein-Barr virus (EBV) plays a major role in the development of post-transplant lymphoproliferative disorder (PTLD), but there is an increasing awareness of EBV-negative PTLD. The clinical presentation of EBV-negative PTLD has not been as well characterised as EBV-positive cases. Further, there is limited knowledge on the clinical importance of diffuse large B-cell lymphoma (DLBCL) cell of origin subtype post-transplant., Materials and Methods: We studied the role of EBV, hepatitis C (HCV) and DLBCL subtype in clinical presentation and survival in 135 post-transplant lymphomas diagnosed 1980-2006 in a population-based cohort of 10 010 Swedish solid organ transplant recipients. The lymphomas were re-evaluated according to WHO 2008, examined for EBV, and clinical data were collected from medical records., Results: Lymphoma incidence rate was 159/100 000 person-years and is also reported by lymphoma subtype. EBV-negative lymphomas constituted 48% and were associated with HCV infection (p = 0.02), bone marrow involvement (p < 0.001), and T-cell phenotype (p = 0.002). Among DLBCL, 78% were of non-germinal centre subtype, which was associated with EBV-positivity (69%, p = 0.001), early occurrence (p = 0.03), heart/liver/lung/pancreas recipients (p = 0.02), anti-T-cell globulin (p = 0.001), and tacrolimus treatment (p = 0.02). DLBCL subtypes had similar overall survival. Five-year overall survival was 42% in all treated patients. Independent poor prognostic factors were older age, B symptoms, ECOG 2-4, kidney/pancreas/heart recipients, T-cell lymphoma, and HCV-infection., Conclusions: With long follow-up, a large part of PTLD is EBV-negative, due to a high proportion of T-cell lymphomas and low of polymorphic PTLD. EBV-negative PTLD have a different clinical presentation. HCV may play an aetiological role in late-onset PTLD and was revealed as a new prognostic factor for inferior survival that needs to be confirmed in larger studies. The heavier immunosuppression in non-kidney transplantations seems to play a role in the development of non-germinal centre DLBCL. DLBCL cell of origin subtype lacks prognostic importance in the transplant setting.