Characteristics and Outcomes of Alberta Lymphoma Patients with a History of Immunosuppressive therapy for Autoimmune Conditions.

BACKGROUND: Other iatrogenic immunosuppression associated lymphoproliferative disorders (Oii-LPD) is rare subset of lymphoma. There are limited published data on the clinical characteristics and outcomes of this patient population. The primary objective of this study was to describe the clinical characteristics and outcomes of Alberta patients diagnosed with lymphoma following immunosuppressive therapy for autoimmune conditions. Secondary objectives included describing the incidence of Oii-LPD, proportions of subtypes of lymphoma diagnosed and the nature of immunosuppressants used. The outcomes of patients with iatrogenic immunodeficiency-associated diffuse large B cell lymphoma (DLBCL) were compared against a matched control group of patients with de novo DLBCL. PATIENTS AND METHODS: The study is a descriptive retrospective cohort study with a matched historical control comparison for patients with DLBCL. Alberta lymphoma patients, diagnosed from January 2011 to December 2019, with a history of iatrogenic immunosuppression were identified and described. RESULTS: The incidence of Oii-LPD was 1% of total Alberta lymphoma cases. Majority of this cohort were diagnosed with DLBCL (54.9%) and the most common immunosuppressive agents were methotrexate (62%), hydroxychloroquine (42%), and TNF inhibitors (31%). Survival was not different between Oii-LPD DLBCL and de novo DLBCL with 5-year survival rates of 64.1% and 67%, respectively (HR 1.11 [95% CI, 0.64-1.94]). CONCLUSION: Oii-LPD are rare with the most frequent subtype being DLBCL occurring in the setting of methotrexate use. In this population-based analysis, the outcomes of iatrogenic immunodeficiency-associated DLBCL were not significantly different from those of de novo DLBCL patients.

Impact of COVID-19 on the Diagnosis and Management of Multiple Myeloma: Experience from a Canadian Center.

BACKGROUND: The impact of coronavirus disease-19 on the management of multiple myeloma (MM) has been recognized. However, the real effect on clinical outcomes remains poorly understood. OBJECTIVE: We describe a local experience of the management of MM patients and report their outcomes during the current pandemic. METHODS: All consecutive symptomatic MM patients seen at our center since 03/20 were evaluated. RESULTS: A cohort of 156 patients diagnosed from 01/19 to 12/20 was analyzed to interrogate differences in presentation patterns. A total of 553 MM patients were seen and/or treated at Tom Baker Cancer Center in the year of 2020. From those, 47.1% (n = 261) were tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Sixteen patients tested positive and data are presented. In addition, a decrease of 21.7% in the rate of new smoldering MM/MM diagnosis was observed in 2020 as compared to 2019. Further, an increase in deaths was also observed in 2020. CONCLUSIONS: Our study confirms an increase lethality for MM patients infected with SARS-CoV-2. A balance between safety and need for cancer control should be emphasized.

Clinical Pharmacokinetic and Pharmacodynamic Considerations in Treating Non-Hodgkin Lymphoma.

Non-Hodgkin lymphoma (NHL) includes a variety of closely related malignancies that originate from lymphoid precursors. The majority of NHLs are of B-cell lineage, for which traditional therapy involves chemotherapy in combination with the anti-CD20 monoclonal antibody rituximab. Ongoing research into the pathogenesis of NHL subtypes has given rise to the use of novel agents that target specific molecular pathways. While the incidence of NHL extends over a range of ages from pediatric to elderly settings, the majority of diagnoses occur over age 60 years. Increasing the use of concomitant medication coupled with declining organ function among this group of patients creates pharmacokinetic (PK) challenges in administering a number of agents involved in the treatment of NHL. In addition, since many of the new agents are administered orally, there are a number of added PK factors that must be taken into consideration with their prescribing and administration. This article will review the available literature on the PK and pharmacodynamic properties of agents commonly used in the treatment of NHL, and intends to provide information that can assist with properly using these drugs in this setting.

Slow lenalidomide desensitization protocol for patients with multiple myeloma: case series from a single center.

Lenalidomide is an immunomodulatory agent that belongs to a family of IMiDs used to treat multiple myeloma. Hypersensitivity and skin reactions are adverse effects of lenalidomide that may lead to discontinuation of its use for multiple myeloma making them contraindicated to other IMiD therapies. Desensitization protocols have been developed to desensitize patients to lenalidomide skin reaction and rash. We report a case series of 5 patients undergoing slow lenalidomide desensitization protocol in an outpatient cancer center setting. Four of the five patients were able to be successfully desensitized to lenalidomide. We also demonstrate safety of using slow lenalidomide desensitization while on combination therapy for control of multiple myeloma.

Medication adherence among adults prescribed imatinib, dasatinib, or nilotinib for the treatment of chronic myeloid leukemia.

BACKGROUND: Oral tyrosine kinase inhibitors are the standard of care for chronic myeloid leukemia. Tyrosine kinase inhibitors are administered in an outpatient setting for an indefinite period which may negatively impact adherence. Non-adherence to tyrosine kinase inhibitors is associated with disease progression. OBJECTIVES: To evaluate the need for adherence-enhancing interventions, this study was designed to determine the proportion of chronic myeloid leukemia patients non-adherent to their tyrosine kinase inhibitor regimen. The secondary objective was to identify the influence of patient characteristics on tyrosine kinase inhibitor adherence. METHODS: Cross-sectional retrospective chart and dispensing record reviews were performed to identify patients receiving a tyrosine kinase inhibitor from 1 June 2010 to 31 January 2012. Adherence was evaluated using the medication possession ratio. RESULTS: A total of 124 patients were included. Thirty-eight (31%) patients were non-adherent to their tyrosine kinase inhibitor regimen. Patients not receiving concurrent medications were more likely to be non-adherent (odds ratio (OR) 2.33, 95% confidence interval (CI) 1.05-5.13, p=0.04). The median medication possession ratio was 0.95 (IQR=0.83-1.07). Median medication possession ratio was lower in patients receiving imatinib compared to dasatinib or nilotinib (0.95 vs. 1.00, p=0.01) and in those less than 50 years old compared to those greater than 50 years old (0.92 vs. 0.97, p=0.02). CONCLUSIONS: Optimal tyrosine kinase inhibitor adherence in chronic myeloid leukemia patients poses a significant obstacle in achieving best possible outcomes while reducing healthcare costs. In this study, one in three chronic myeloid leukemia patients treated with a tyrosine kinase inhibitor were non-adherent to their regimen. Those at higher risk of non-adherence were on no concurrent medications, less than 50 years old, and those treated with imatinib. Active intervention to improve tyrosine kinase inhibitor adherence should be developed, implemented, and evaluated to improve patient outcomes at our center.

Profiling microRNA expression with the Illumina BeadChip platform.

The complex mechanisms involved in the regulation of both gene and protein expressions are still being understood. When microarray technology was first introduced during the early to mid 1990s, they heralded a tremendous opportunity to study transcription on a global scale. Despite this promise, however, one thing that has become clear is that the expression of protein coding genes is not the only aspect of the transcriptome that researchers need pay attention to. Small noncoding RNAs, such as microRNAs, are now known to play a pivotal role in the control of both gene and protein expressions. Each microRNA may act upon a plurality of different targets, which makes the measurement of their expression levels a highly important part of understanding the entire cellular response. It has only been recently, however, that advancements and modifications to microarray technology have allowed us to study these important molecules in a high throughput and parallel manner.

Microarray-based DNA methylation profiling: technology and applications.

This work is dedicated to the development of a technology for unbiased, high-throughput DNA methylation profiling of large genomic regions. In this method, unmethylated and methylated DNA fractions are enriched using a series of treatments with methylation sensitive restriction enzymes, and interrogated on microarrays. We have investigated various aspects of the technology including its replicability, informativeness, sensitivity and optimal PCR conditions using microarrays containing oligonucleotides representing 100 kb of genomic DNA derived from the chromosome 22 COMT region in addition to 12 192 element CpG island microarrays. Several new aspects of methylation profiling are provided, including the parallel identification of confounding effects of DNA sequence variation, the description of the principles of microarray design for epigenomic studies and the optimal choice of methylation sensitive restriction enzymes. We also demonstrate the advantages of using the unmethylated DNA fraction versus the methylated one, which substantially improve the chances of detecting DNA methylation differences. We applied this methodology for fine-mapping of methylation patterns of chromosomes 21 and 22 in eight individuals using tiling microarrays consisting of over 340 000 oligonucleotide probe pairs. The principles developed in this work will help to make epigenetic profiling of the entire human genome a routine procedure.

CpG Island microarray probe sequences derived from a physical library are representative of CpG Islands annotated on the human genome.

An effective tool for the global analysis of both DNA methylation status and protein-chromatin interactions is a microarray constructed with sequences containing regulatory elements. One type of array suited for this purpose takes advantage of the strong association between CpG Islands (CGIs) and gene regulatory regions. We have obtained 20,736 clones from a CGI Library and used these to construct CGI arrays. The utility of this library requires proper annotation and assessment of the clones, including CpG content, genomic origin and proximity to neighboring genes. Alignment of clone sequences to the human genome (UCSC hg17) identified 9595 distinct genomic loci; 64% were defined by a single clone while the remaining 36% were represented by multiple, redundant clones. Approximately 68% of the loci were located near a transcription start site. The distribution of these loci covered all 23 chromosomes, with 63% overlapping a bioinformatically identified CGI. The high representation of genomic CGI in this rich collection of clones supports the utilization of microarrays produced with this library for the study of global epigenetic mechanisms and protein-chromatin interactions. A browsable database is available on-line to facilitate exploration of the CGIs in this library and their association with annotated genes or promoter elements.

Effect of laparoscopic failure on outcome of laparoscopic nissen fundoplication: independent review.

PURPOSE: This study was undertaken to determine whether conversion or early reoperation contributed significantly to the eventual outcome of laparoscopic Nissen fundoplication. PATIENTS AND METHODS: An independent surgeon, blinded to the operative events, administered two general and one system-specific quality of life tools to the first 100 consecutive patients booked for laparoscopic fundoplication in a community hospital, where the open conversion rate was 4 patients/surgeon and the early reoperation rate 1.5 patients/surgeon for the first 20 operations. Patients were also asked about need for medication, dysphagia, satisfaction (analog scale), and whether, if given it to do over, they would opt for surgery again. RESULTS: Of the original 100 patients, 40 were studied an average of 5 years after surgery: 26 completed laparoscopically and 14 with laparoscopic failure (13 conversions and 1 early reoperation). Patient characteristics in the two groups were similar, except that there were more older patients with more fixed intrathoracic hiatus hernias in the failure group. Among the parameters examined, no statistically significant differences could be detected between laparoscopic and converted patients. CONCLUSIONS: General and system-specific quality of life, digestive symptoms, need for medication, patient satisfaction, and willingness to have surgery over again are not altered by conversion or reoperation. Thus, surgeons who have adequate laparoscopic skills, experience with open fundoplication, and training in laparoscopic Nissen fundoplication should feel free to add it to their repertoires provided the likelihood of conversion and reoperation secondary to inexperience is understood by the patient.

Laparoscopic vertical banded gastroplasty: early results with the JOVO procedure.

BACKGROUND: Vertical banded gastroplasty (VBG) is an established treatment for morbid obesity for selected patients. This study seeks to assess the effectiveness of a laparoscopic version, the JOVO procedure, of the VBG. METHODS: An Independent surgeon interviewed all patients, who had had the JOVO procedure at one institution, evaluating weight loss, comorbid conditions, satisfaction and quality of life using the 36-item short-form health survey (SF-36). RESULTS: 14 JOVO procedures were done by two surgeons. Mean body mass index was 44 kg/m2, mean age 30 years and each patient had at least one comorbid condition. Mean operative time was 165 minutes. There was 1 complication, a suspected gastric leak requiring reoperation. Excluding this patient, mean hospital stay was less than 48 hours. Mean weight loss 4 weeks after surgery was 9 kg or 18% of excess weight. Mean excess weight loss of the 5 patients available for 1-year follow-up was 42% at 6 and 85% at 12 months; 1 did not continue to lose weight. All but 1 preoperative comorbid condition resolved or improved. 13 of the 14 patients were fully satisfied. SF-36 scores were high in the 13 that lost weight, especially in physical and social functioning areas. CONCLUSION: The JOVO procedure is safe and reproduces laparoscopically the early weight loss of open VBG with much shorter hospital stay and low complication and failure rates. Longer follow-up and larger numbers are needed.