Incidence Patterns and Outcomes for Hodgkin Lymphoma Patients in the United States

Hodgkin lymphoma (HL) demonstrates heterogenous histologic findings, clinical presentation, and outcomes. Using the United States Surveillance, Epidemiology, and End Results (SEER) data we examined relationships between patient characteristics, clinical features at diagnosis, and survival in HL patients. From 2000 to 2007, 16,710 cases were recorded in 17 SEER registries. Blacks and Asians had low incidence (black/white incidence rate ratio (IRR) 0.86, P < .01; Asian/white IRR 0.43, P < .01). The bimodal pattern of incidence was less prominent for black males. Asians and Blacks presented at a mean age of 38 years compared to 42 years for Whites (P < .001). Race was a predictor for survival with HR of 1.19 (95% CI 1.11–1.28) for Blacks. Age was the most important predictor of survival (HR for patients ≥45 years 5.08, 95% CI 4.86–5.31). These current patterns for presentation and outcomes of HL help to delineate key populations in order to explore risk factors for HL and strategies to improve treatment outcomes

Clinical, Molecular, and Environmental Risk Factors for Hodgkin Lymphoma

Epidemiological studies suggest unique occurrence patterns of Hodgkin lymphoma (HL) worldwide. In most Western countries there is a clear bimodal age distribution with an early peak in young adults followed by a second peak in older adults, particularly among males. In the Middle East and Asia, HL is more common in early childhood. There also are marked racial differences in the presentations of HL and HL subtypes, and particular single nucleotide polymorphisms (SNPs) have been identified as etiological factors suggesting that gene-gene and gene-environment interactions are involved. Personal health choices such as exercise and smoking may modify an individual's chances of developing HL. Numerous studies highlight the impact that exposure to Epstein-Barr virus and other environmental factors have on HL risk. Understanding the relative importance of each of these findings and their links to HL development and survival will help clinical researchers expand curative therapies and create preventative strategies for HL

Posttransplant Thrombopoiesis Predicts Survival in Patients Undergoing Autologous Hematopoietic Progenitor Cell Transplantation

AbstractThe frequency and clinical significance of secondary thrombocytopenia following initial engraftment in autologous hematopoietic progenitor cell transplantation (HPCT) is unknown. An institutional review board approved retrospective study of thrombopoiesis was performed in 359 patients transplanted with autologous blood (97%) or marrow (3%) who achieved platelet engraftment to >50,000/μL. Idiopathic secondary posttransplant thrombocytopenia (ISPT) was defined as >50% decline in blood platelets to <100,000/μL in the absence of relapse or sepsis. ISPT occurred at a median of day +35 posttransplant in 17% of patients. Patients with ISPT had similar initial platelet engraftment (median 17 days) versus non-ISPT patients (18 days; P = NS) and recovered platelet counts (median 123,00 K/μL) by day 110 posttransplant. Four factors were independently associated with post-transplant death in a multivariate model: disease status at transplant; the number of prior chemotherapy regimens, failure to achieve a platelet count of >150,000/μL posttransplant, and the occurrence of ISPT. A prognostic score was developed based upon the occurrence of ISPT and posttransplant platelet counts of <150,000/μL. Survival of patients with both factors (n = 25) was poor (15% alive at 5 years); patients with 1 factor (n = 145) had 49% 5-year survival; patients with 0 factors (n = 189) had 72% 5-year survival. Patients who failed to achieve a platelet count of >150,000/μL received significantly fewer CD34+ cells/kg (P < .001), whereas patients with ISPT received fewer CD34+CD38− cells/kg (P = .0006). The kinetics of posttransplant thrombopoiesis is an independent prognostic factor for long-term survival following autologous HPC. ISPT and lower initial posttransplant platelet counts reflect poor engraftment with long-term and short-term repopulating CD34+ hematopoietic stem cells, respectively, and are associated with an increased risk of death from disease relapse

Development of the Lymphoma Enterprise Architecture Database: A caBIG(tm) Silver level compliant System

Lymphomas are the fifth most common cancer in United States with numerous histological subtypes. Integrating existing clinical information on lymphoma patients provides a platform for understanding biological variability in presentation and treatment response and aids development of novel therapies. We developed a cancer Biomedical Informatics Grid™ (caBIG™) Silver level compliant lymphoma database, called the Lymphoma Enterprise Architecture Data-system™ (LEAD™), which integrates the pathology, pharmacy, laboratory, cancer registry, clinical trials, and clinical data from institutional databases. We utilized the Cancer Common Ontological Representation Environment Software Development Kit (caCORE SDK) provided by National Cancer Institute’s Center for Bioinformatics to establish the LEAD™ platform for data management. The caCORE SDK generated system utilizes an n-tier architecture with open Application Programming Interfaces, controlled vocabularies, and registered metadata to achieve semantic integration across multiple cancer databases. We demonstrated that the data elements and structures within LEAD™ could be used to manage clinical research data from phase 1 clinical trials, cohort studies, and registry data from the Surveillance Epidemiology and End Results database. This work provides a clear example of how semantic technologies from caBIG™ can be applied to support a wide range of clinical and research tasks, and integrate data from disparate systems into a single architecture. This illustrates the central importance of caBIG™ to the management of clinical and biological data

Development of Query Strategies to Identify a Histologic Lymphoma Subtype in a Large Linked Database System

Background: Large linked databases (LLDB) represent a novel resource for cancer outcomes research. However, accurate means of identifying a patient population of interest within these LLDBs can be challenging. Our research group developed a fully integrated platform that provides a means of combining independent legacy databases into a single cancer-focused LLDB system. We compared the sensitivity and specifi city of several SQL-based query strategies for identifying a histologic lymphoma subtype in this LLDB to determine the most accurate legacy data source for identifying a specifi c cancer patient population.Methods: Query strategies were developed to identify patients with follicular lymphoma from a LLDB of cancer registry data, electronic medical records (EMR), laboratory, administrative, pharmacy, and other clinical data. Queries were performed using common diagnostic codes (ICD-9), cancer registry histology codes (ICD-O), and text searches of EMRs. We reviewed medical records and pathology reports to confirm each diagnosis and calculated the sensitivity and specificity for each query strategy.Results: Together the queries identified 1538 potential cases of follicular lymphoma. Review of pathology and other medical reports confirmed 415 cases of follicular lymphoma, 300 pathology-verifi ed and 115 verified from other medical reports. The query using ICD-O codes was highly specific (96%). Queries using text strings varied in sensitivity (range 7–92%) and specifi city (range 86–99%). Queries using ICD-9 codes were both less sensitive (34–44%) and specific (35–87%).Conclusions: Queries of linked-cancer databases that include cancer registry data should utilize ICD-O codes or employ structured free-text searches to identify patient populations with a precise histologic diagnosis.Abbreviations: LLDB: Large Linked Database; SEER: Surveillance Epidemiology and End Results; EMR: Electronic Medical Record; ICD-9: International Classifi cation of Diseases (9th revision); ICD-O: International Classifi cation of Diseases for Oncology; AP: Anatomical Pathology; WHO: World Health Organization

Characterizing and prognosticating chronic lymphocytic leukemia in the elderly: prospective evaluation on 455 patients treated in the United States.

BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is \u3e 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites. Patients with CLL were enrolled within 2 months of initiating first line of therapy (LOT1) or a subsequent LOT (LOT ≥ 2). Kaplan-Meier methods were used to evaluate overall survival. CLL- and infection-related mortality were assessed using cumulative incidence functions (CIF) and cause-specific hazards. Logistic regression was used to develop a classification model. RESULTS: A total of 455 E-CLL patients were enrolled; 259 were enrolled in LOT1 and 196 in LOT ≥ 2. E-CLL patients were more likely to receive rituximab monotherapy (19.3 vs. 8.6%; p \u3c 0.0001) and chemotherapy-alone regimens (p \u3c 0.0001) than younger patients. Overall and complete responses were lower in E-CLL patients than younger patients when given similar regimens. With a median follow-up of 3 years, CLL-related deaths were higher in E-CLL patients than younger patients in LOT1 (12.6 vs. 5.1% p = 0.0005) and LOT ≥ 2 (31.3 vs. 21.5%; p = 0.0277). Infection-related deaths were also higher in E-CLL patients than younger patients in LOT1 (7.4 vs. 2.7%; p = 0.0033) and in LOT ≥ 2 (16.2 vs. 11.2%; p = 0.0786). A prognostic score for E-CLL patients was developed: time from diagnosis to treatment \u3c 3 months, enrollment therapy other than bendamustine/rituximab, and anemia, identified patients at higher risk of inferior survival. Furthermore, higher-risk patients experienced an increased risk of CLL- or infection-related death (30.6 vs 10.3%; p = 0.0006). CONCLUSION: CLL- and infection-related mortality are higher in CLL patients aged ≥ 75 years than younger patients, underscoring the urgent need for alternative treatment strategies for these understudied patients. TRIAL REGISTRATION: The Connect CLL registry was registered at clinicaltrials.gov: NCT01081015 on March 4, 2010

Real-world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres.

The clinical course of chronic lymphocytic leukaemia (CLL) is heterogeneous, and treatment options vary considerably. The Connect® CLL registry is a multicentre, prospective observational cohort study that provides a real-world perspective on the management of, and outcomes for, patients with CLL. Between 2010 and 2014, 1494 patients with CLL and that initiated therapy, were enrolled from 199 centres throughout the USA (179 community-, 17 academic-, and 3 government-based centres). Patients were grouped by line of therapy at enrolment (LOT). We describe the clinical and demographic characteristics of, and practice patterns for, patients with CLL enrolled in this treatment registry, providing patient-level observational data that represent real-world experiences in the USA. Fluorescence in&nbsp;situ hybridization (FISH) analyses were performed on 49·3% of patients at enrolment. The most common genetic abnormalities detected by FISH were del(13q) and trisomy 12 (45·7% and 20·8%, respectively). Differences in disease characteristics and comorbidities were observed between patients enrolled in LOT1 and combined LOT2/≥3 cohorts. Important trends observed include the infrequent use of genetic prognostic testing, and differences in patient characteristics for patients receiving chemoimmunotherapy combinations. These data represent experiences of patients with CLL in the USA, which may inform treatment decisions in everyday practice

Charting the future of cancer health disparities research: A position statement from the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138314/1/caac21404_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138314/2/caac21404.pd

Evaluating the impact of eligibility criteria in first-line clinical trials for follicular lymphoma: A MER/LEO cohort analysis

Cancer clinical trial eligibility criteria may create patient populations studied in trials that do not reflect the patient populations treated in the real-world setting. Follicular lymphoma (FL) is an indolent lymphoma with heterogeneous presentations across a broad range of individuals, resulting in many acceptable management strategies. We evaluated how first-line clinical trial eligibility criteria impacted the demographic makeup and outcomes of patients with FL for whom systemic therapy might be considered. We compared the characteristics of 196 patients with FL from a single institution to eligibility criteria from 10 first-line FL trials on clinicaltrials.gov. Next, we tabulated eligibility criteria from 24 first-line FL protocols and evaluated their impact on 1198 patients with FL with stages II to IV disease from the prospective Molecular Epidemiology Resource (MER) and Lymphoma Epidemiology of Outcomes (LEO) cohort studies. We found that 39.8% and 52.7% of patients with FL might be excluded from clinical trials based on eligibility criteria derived from clinicaltrials.gov and protocol documents, respectively. Patients excluded because of renal function, prior malignancy, and self-reported serious health conditions tended to be older. Expanding stage requirement from III-IV to II-IV, and platelet requirement from ≥150 000 to ≥75 000 increased population size by 21% and 8%, respectively, in MER and by 16% and 13%, respectively, in LEO, without impacting patient demographics or outcomes. These data suggest that management of older individuals with FL may not be fully informed by recent clinical trials. Moreover, liberalizing stage and platelet criteria might expand the eligible population and allow for quicker trial accrual without impacting outcomes