Post-transplant lymphoproliferative disorders (PTLDs) are potentiallyfatal, often Epstein-Barr virus (EBV)-driven neoplasias developing in immunocompromised hosts. Initial treatment usually consists of a reduction in immunosuppressive therapy and/or rituximab with or without chemotherapy. However, patients who relapse do poorly, and new treatment options are warranted. With the introduction of the immunoconjugate brentuximab vedotin, the CD30 antigen has become an effectively targetable molecule. Therefore, we investigated the frequency and level of CD30 expression in PTLDs. We identified 108 patients with PTLDs diagnosed during 1994-2011, of whom 62 had adequate paraffin-embedded tissue for tissue microarray construction. Immunohistochemical expression of CD30 was consistently detected in all types of PTLD (overall 85.25%), including the monomorphic subtypes, and was correlated with a more favorable outcome. For diffuse large B-cell lymphoma (DLBCL)-type PTLD this was regardless of EBV status, and remained significant in multivariate analysis. Cell-of-origin had no independent prognostic value in our series of DLBCL PTLD.
Post-transplant lymphoproliferative disorder (PTLD) incidence is difficult to determine, mainly because both early and other lesions may go unrecognized and unregistered. Few studies have included systematic pathology review to maximize case identification and decide more accurately PTLD frequency after long-term post-transplantation follow-up. A retrospective population-based cohort study including all kidney transplant recipients at two Danish centres (1990-2011; population covered 3.1 million; 2175 transplantations in 1906 patients). Pathology reports were reviewed for all patient biopsies to identify possible PTLDs. Candidate PTLDs underwent histopathological review and classification. Seventy PTLD cases were identified in 2175 transplantations (3.2%). The incidence rate (IR) after first transplantation was 5.4 cases per 1000 patient-years (95% CI: 4.0-7.3). Most PTLDs were monomorphic (58.5%), or early lesions (21.5%). Excluding early lesions and patients <18 years, IR was 3.7 (95% CI: 2.9-5.5). Ten patients with PTLD were retransplanted, 2 developing further PTLDs. Post-transplant patient survival was inferior in patients with PTLD, while death-censored graft survival was not. Using registry data together with extensive pathological review and long follow-up, a rather high incidence of PTLD was found.
Summary: Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin‐containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population‐based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age‐ and sex‐matched comparators from the background population. Median follow‐up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30–3.68]), with a 10‐year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35–26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43–2.76]), with a 10‐year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43–1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B‐symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work‐up of pulmonary symptoms.
Purpose: Many patients diagnosed with lymphoma are of working age. Cancer patients are known to have a higher risk of sick leave and disability pension, but this has only been delineated for certain subtypes of lymphoma. Therefore, this study aimed at investigating the overall risk of disability pension for all lymphoma subtypes and at quantifying return to work for patients with lymphoma in work before diagnosis. Patients and Methods: Patients aged 18– 60 years with lymphoma in complete remission (CR) diagnosed between 2000 and 2019 were included in the study. Using national registers, each patient was matched with five comparators from the general population with same sex, birth year, and level of Charlson Comorbidity Index. Risk of disability pension was calculated from 90 days after CR or end of treatment with competing events (death, retirement pension, early retirement pension, relapse for patients, or lymphoma diagnosis for comparators). Return to work for patients was calculated annually until 5 years after diagnosis for patients employed before diagnosis. Results: In total, 4072 patients and 20,360 comparators were included. There was a significant increased risk of disability pension for patients with all types of lymphoma compared to the general population (5-year risk difference: 5.3 (95% confidence interval (CI): 4.4;6.2)). Patients with non-Hodgkin lymphoma were more likely to get disability pension than patients with Hodgkin lymphoma (sex- and age-adjusted 10-year risk difference: 2.9 (95% CI: 0.3;5.5)). One year after diagnosis, 24.5% of the relapse-free patients were on sick leave. Return to work was highest 2 years after diagnosis (82.1%). Conclusion: Patients with lymphoma across all subtypes have a significantly higher risk of disability pension. Return to work peaks at 2 years after diagnosis.
Background Posttransplant lymphoproliferative disorder (PTLD) is a feared complication to organ transplantation, associated with substantial morbidity and inferior survival. Risk factors for PTLD include T cell–depleting induction therapy and primary infection or reactivation of Epstein-Barr virus. Possible associations between certain HLA types and the risk of developing PTLD have been reported by other investigators; however, results are conflicting. Methods We conducted a retrospective, population-based study on 4295 Danish solid organ transplant patients from the Scandiatransplant database. Having identified 93 PTLD patients in the cohort, we investigated the association of HLA types with PTLD, Epstein-Barr virus status and time to PTLD onset. The outcomes survival and PTLD were evaluated using Cox regression; mismatching, and the PTLD-specific mortality were evaluated in a competing risk analysis. Results Risk of PTLD was associated with male sex (odds ratio, 1.70; 95% confidence interval, 1.07-2.71), and, in women, HLA-DR13 conferred an increased risk (odds ratio, 3.22; 95% confidence interval, 1.41-7.31). In multivariate analysis, HLA-B45 and HLA-DR13 remained independent predictive factors of PTLD. Mismatching in the B locus was associated with a reduced risk of PTLD (P < 0.001). Overall survival was poor after a PTLD diagnosis and was significantly worse than that in the remaining transplant cohort (P < 0.001). Conclusions Our data indicate risk-modifying HLA associations, which can be clinically useful after transplantation in personalized monitoring schemes. Given the strong linkage disequilibrium in the HLA region, the associations must be interpreted carefully. The large size, virtually complete ascertainment of cases and no loss to follow-up remain important strengths of the study.
Treatment with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is standard treatment for patients suffering from acute promyelocytic leukemia (APL). Peripheral neuropathy is a common sign of arsenic poisoning but reports of peripheral neuropathy from patients treated with ATO for APL are limited. We here present a case of a woman treated with standard regimes of ATRA-ATO for APL, who subsequently developed severe peripheral neuropathy from ATO poisoning.