Chronic obstructive pulmonary disease (COPD) poses a significant economic burden on society, and a substantial portion is related to exacerbations of COPD. A literature review of the direct and indirect costs of COPD exacerbations was performed. A systematic search of the MEDLINE database from 1998-2008 was conducted and supplemented with searches of conference abstracts and article bibliographies. Articles that contained cost data related to COPD exacerbations were selected for in-depth review. Eleven studies examining healthcare costs associated with COPD exacerbations were identified. The estimated costs of exacerbations vary widely across studies: $88 to $7,757 per exacerbation (2007 US dollars). The largest component of the total costs of COPD exacerbations was typically hospitalization. Costs were highly correlated with exacerbation severity. Indirect costs have rarely been measured. The wide variability in the cost estimates reflected cross-study differences in geographic locations, treatment patterns, and patient populations. Important methodological differences also existed across studies. Researchers have used different definitions of exacerbation (e.g., symptom- versus event-based definitions), different tools to identify and measure exacerbations, and different classification systems to define exacerbation severity. Unreported exacerbations are common and may influence the long-term costs of exacerbations. Measurement of indirect costs will provide a more comprehensive picture of the burden of exacerbations. Evaluation of pharmacoeconomic analyses would be aided by the use of more consistent and comprehensive approaches to defining and measuring COPD exacerbations.

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TPLL is a rare and aggressive T-cell lymphoid malignancy. It typically presents with leukocytosis, hepatosplenomegaly, lymphadenopathy, and skin involvement. The post-thymic malignant lymphocytes often express CD2, CD3, CD4, CD5, and occasionally CD8. CD52 is also frequently and densely expressed and serves as a therapeutic target for the monoclonal antibody, Alemtuzumab. Inv(14) and chromosome 14 translocations (tchr14) are the most frequent cytogenetic abnormalities contributing to the overexpression of the TCL-1 gene product. This analysis was conducted to update and expand our existing knowledge of this rare disease. To study the demographic characteristics, cytogenetic and molecular signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 91 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathology factors on survival. A search of online databases identified all available comparative studies of Alemtuzumab in TPLL to conduct a meta-analysis using an inverse variance method with a fixed-effects model. The median age was 65 (27-89) years, with a peak incidence between ages 71 and 81. Males were 1.8 times more afflicted than females. The median overall survival of the whole group was 21 months. Sex did not impact the overall survival of the group. When compared to supportive care, chemotherapy significantly improved survival (HR:0.29, p=0.0016). Allogeneic stem cell transplant did not confer any survival advantage. Moreover, the presence of SAMHD1 and JAK-STAT mutations did not affect survival. The median survival of inv(14), tchr14, and TCL-1 expression were 29, 12, and 11 months respectively. When compared to tchr14 and TCL-1 expression combined, inv(14) seems to have a borderline significant survival advantage (HR:0.52, p=0.06). Patients who were treated with Alemtuzumab had higher median survival, though not significant, compared to those who did not (29 vs 12 months, p=0.6). To study further the effect of Alemtuzumab on TPLL survivorship, we conducted a meta-analysis of four retrospective comparative series with a total of 144 patients including ours. Alemtuzumab was found to be significantly associated with a survival benefit in patients with TPLL (HR 0.54, p=0.001). This study presents an updated epidemiologic and clinicopathologic data from a pooled cohort of patients with TPLL. It identifies the potential prognostic impact of inv(14), tchr14, and TCL-1 on survival. Furthermore, it confirms the survival advantage conferred by Alemtuzumab in TPLL. Citation Format: Philip A. Haddad, Kevin Gallagher, Dalia Hammoud. Epidemiology and clinicopathology prognostic factors of T-cell prolymphocytic leukemia: Analysis and met-analysis of updated pooled databases [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5765.

Renal cell carcinomas harboring the t(6;11) (p21;q12) translocation with a specific Alpha(MALAT1)-TFEB gene fusion is a recognized rare subtype of the Microphthalmia Transcription factor (MiT) family of translocation RCC. TBRCC is an indolent disease that occurs at a younger age. Though it may take on a wide spectrum of morphology, TBRCC has been classically characterized by distinctive biphasic morphology with larger epithelioid cells and smaller cells clustered around eosinophilic spheres formed by basement membrane material. This analysis was conducted to update and expand our existing knowledge of this rare disease. In order to study the demographic characteristics, cytogenetic and molecular signatures, survival, and prognostic factors, we compiled a pooled database of 140 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on survival. The median age was 32 (3-78) years with a peak incidence between ages 17 and 30 years. Males and females were afflicted equally. The median overall survival (OS) of the whole group was not reached with more than 78% alive at 10 years. The group's median disease-free survival (DFS) was 96 months. Six percent of this cohort recurred. Among patients who recurred, the median time to recurrence was 24(6-75) months. Sex did not impact OS or DFS. Similarly, the molecular partner of the TFEB gene fusion, Alpha (MALAT1) versus others, did not seem to impact OS or DFS. The presence of necrosis seemed to adversely impact OS (HR:14.3, p<0.0001) and DFS (HR:14.4, p<0.0001). Nuclear grade negatively impacted DFS, the higher the grade the worse the DFS. The presence of eosinophilia, psammoma bodies, and pigmentation did not affect OS or DFS. Similarly, the histologic morphology, biphasic vs others, did not affect OS or DFS. Multivariate analysis revealed older age (HR:1.08, p=0.01) and larger tumor size (HR:10.12, p=0.002) adversely impacted OS. This study presents an updated epidemiologic and clinicopathologic data from a pooled cohort of patients with TBRCC. Age, size, and necrosis were found to adversely impact the OS. However, higher nuclear grade only adversely impacted the cohort's DFS. Citation Format: Philip A. Haddad, Dalia Hammoud, Kevin Gallagher. Epidemiology and clinicopathology prognostic factors of TFEB translocation renal cell carcinoma (TBRCC): Analysis of updated pooled database [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3525.