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  • 1
    In: Molecular Diagnosis & Therapy, Springer Science and Business Media LLC, Vol. 26, No. 3 ( 2022-05), p. 333-343
    Type of Medium: Online Resource
    ISSN: 1177-1062 , 1179-2000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 2
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 7896-7897
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 3
    Online Resource
    Online Resource
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 2884-2884
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2884-2884
    Abstract: Background: Aseptic meningitis is a rare and significant complication of intravenous immunoglobulin (IVIg) therapy. The true incidence is unknown as there are a number of case reports and few thorough reviews. Some have suggested the incidence being 0-1% with one reported exception of 11% in the literature. It is important to recognize this condition clinically, as it often mimics infectious meningitis. To determine the true incidence and natural history of IVIg-induced aseptic meningitis, we conducted a retrospective review and case series at a single tertiary care centre by two separate methods. For this study, IVIg-induced aseptic meningitis was defined as: headache with meningismus or a deterioration in mental status after receiving IVIg, with or without accompanying fever, nausea, vomiting, pharyngitis, photophobia, and/or diarrhea (as per the Transfusion Transmitted Injuries Surveillance System of the Public Health Agency of Canada). IVIg headaches alone were not included in our review. Method: We performed a retrospective review of all cases of IVIg-induced aseptic meningitis at London Health Sciences Centre (LHSC) from January 1, 2008 to December 31, 2013. During the study period, the initial method was to evaluate all reported transfusion reactions (as per the Transfusion Reaction Course [TRAC] system for reporting) to identify possible or probable aseptic meningitis due to IVIg. Subsequently, in our second method, we reviewed and cross-referenced all documented IVIg infusions and all lumbar punctures performed at LHSC during the study period. All patients with both IVIg infusions and lumber punctures were identified and further chart review was performed to determine if these patients had aseptic meningitis due to IVIg. We report on our identified cases of IVIg-induced aseptic meningitis, identify the true incidence, and speculate on the natural history of this condition. Results: During our study period, a total of 1921 IVIg infusions (554,566 g) were administered, with major indications being: chronic inflammatory demyelinating polyneuropathy (25.7%), primary immune deficiency (14.1%), other (primarily rheumatologic indications – 13.9%), multifocal motor neuropathy (10.4%), and adult immune thrombocytopenia (7.4%). 8 cases of aseptic meningitis were reported to the transfusion laboratory by the first method, with no additional cases identified by the second method, which gave us an overall incidence of 0.42%. Indications included: aplastic anemia (1/8), immune thrombocytopenia (3/8), chronic inflammatory demyelinating polyneuropathy (1/8), autoimmune hemolytic anemia (1/8), primary immune deficiency (1/8), and myasthenia gravis (1/8). As per our case series, IVIg-induced aseptic meningitis is an uncommon complication of unknown etiology that seems to affect all ages, with no relation to the underlying indication for IVIg. The only predisposing factor seen in our cohort may be a prior exposure to blood products, but other risk factors such as migraines, immune dysregulation, and dose and rate of infusion have been reported in the literature. In this study, patients presented with symptoms within 24-48 hours of IVIg infusion, and were treated with antibiotics initially due to the clinical resemblance and suspicion of bacterial meningitis. However, symptoms self-resolved within 5-7 days. This condition appears to be non-fatal; therefore, treatment is purely supportive, with subsequent IVIg infusions likely requiring premedication or possibly a switch in formulation. Conclusion: In this review of IVIg-induced aseptic meningitis over a 6 year period in a tertiary care centre, we identify a more robust incidence of 0.42% for this condition (consistent with most previous reports). Though this condition can be under-recognized, all possible cases were identified with a rigorous TRAC system for reporting reactions and by using two different methods. Furthermore, we speculate on the natural history of this condition based on our 8 identified cases. Given that this complication can mimic infectious meningitis and cause considerable morbidity, we hope that physicians will be aware of, and recognize, this rare but important complication of IVIg therapy. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 4
    In: Case Reports in Oncology, S. Karger AG
    Abstract: Extramedullary hematopoiesis (EMH) is a rare complication of solid tumor malignancies. We describe the first case of a patient who developed EMH in the pericardium secondary to metastatic gastrointestinal or pancreaticobiliary cancer. A 58-year-old man presented with recurrent episodes of fatigue and shortness of breath and was treated with thoracocentesis and pericardiocentesis for pleural and pericardial effusions, respectively. Owing to a markedly elevated alkaline phosphatase, a bone scan was performed and demonstrated diffuse sclerotic lesions. Evaluation of pleural effusion diagnosed metastatic adenocarcinoma, and cytospin morphology of the pericardial fluid demonstrated EMH. While EMH secondary to solid tumors is commonly suggested to be due to cytokine signaling, we propose the mechanism of EMH in this patient was due to extensive disruption of bone marrow hematopoiesis, similar to what is seen in myeloproliferative neoplasms.
    Type of Medium: Online Resource
    ISSN: 1662-6575
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
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  • 5
    In: Journal of General Internal Medicine, Springer Science and Business Media LLC, Vol. 38, No. 8 ( 2023-06), p. 1828-1833
    Type of Medium: Online Resource
    ISSN: 0884-8734 , 1525-1497
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 6
    Online Resource
    Online Resource
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 5032-5032
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5032-5032
    Abstract: Background:Polycythemia is the most common adverse effect of testosterone replacement therapy (TRT) and may predispose patients to adverse vascular events. Current Canadian guidelines recommend regular laboratory monitoring and discontinuing TRT or reducing the dose if the hematocrit exceeds 54% (hemoglobin ≥180 g/L). This threshold has been interpreted by some physicians and patients to indicate the need for phlebotomy or blood donation while on TRT. Study Design and Methods: We reviewed all male blood donors in Southwestern Ontario at Canadian Blood Services from December 2013 to March 2016 who self-identified or were found on donor screening to be using TRT in any form. Hemoglobin concentration was measured at the time of donation or clinic visit and with each subsequent appointment in repeat donors. Results:We report a case series of 39 patients on TRT who presented for blood donation over a two-year period. The mean hemoglobin at all donor clinic visits was 173 g/L (range 134-205 g/L, n = 108). Hemoglobin concentrations of ≥180 g/L (calculated hematocrit ≥54%) were measured at 25% of appointments. Of the 27 repeat donors, 12 (44%) had persistently elevated hemoglobin levels (≥180 g/L) at subsequent donations. Conclusions: Hemoglobin concentrations were elevated in blood donors on TRT, with a significant number above levels recommended by current guidelines. These data also suggest that repeat blood donation was insufficient to maintain hematocrit below 54%. Our findings raise concerns about persistent risk of vascular events in these donors, particularly when coupled with the misperception by patients and health care providers that donation has abrogated the risks of TRT-induced polycythemia. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 7
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4635-4635
    Abstract: Background: The widespread availability of molecular testing for JAK2 mutations has facilitated the diagnosis of polycythemia vera (PV) but also raises the concern of test overutilization in patients referred for elevated hemoglobin. At our institution, we have observed increased molecular testing in these patients with declining rates of JAK2 mutation positivity, suggesting that a prediction rule could be useful to guide such testing. In this study, we report the derivation and validation of a simple rule using complete blood count (CBC) parameters to predict the likelihood of having a JAK2 mutation in patients referred for elevated hemoglobin. Methods: We examined all patients with elevated hemoglobin (≥160 g/L for women, or ≥165 g/L for men), who underwent JAK2 mutation testing using the Next-Generation Sequencing (NGS)-based Oncomine Myeloid Research Assay (ThermoFisher Scientific, MA, USA), between 2018 and 2021 at the London Health Sciences Centre in Ontario, Canada. We extracted data including age and sex as well as CBC parameters at the time of testing, including hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, platelets and mean corpuscular volume. All CBCs were performed on a Sysmex XN Analyzer (Sysmex Corporation, Japan). In the derivation cohort, JAK2-positive and -negative groups were compared using Student's t-tests or c 2 tests, as appropriate. We dichotomized potentially significant continuous variables at an optimal cut-off point using receiving operating characteristic curves. Potentially significant predictors were evaluated using multiple variable stepwise logistic regression analysis with JAK2 positivity as the dependent variable. The model was evaluated using Hosmer-Lemeshow tests and pseudo-R2 measures. A dichotomous score was derived based on the presence or absence of significant variables and subsequently evaluated and internally validated using logistic regression and c 2 tests using non-parametric bootstrapping with 1000 samples. The model was subsequently validated in the second cohort. Results: The derivation cohort included 308 patients tested between January 9, 2018 and December 19, 2019, and the validation cohort included 223 patients tested between January 7, 2020 and May 12, 2021. The characteristics of both cohorts are shown in Table 1. The final model included platelets above the upper quintile (308 × 10 9/L) and erythrocytes above the upper quartile (6.17 × 10 12/L) and a score of one was assigned to patients with either of these characteristics. The odds ratio for JAK2 positivity in patients with a score of 1 was 14.6 (95% CI 5.5-38.8) compared to those with a score of 0. The model had a sensitivity of 87.8% and a negative predictive value of 97.4% in the derivation cohort, and of 100% for both in the validation cohort. The percentage of JAK2 positive patients in patients with a score of 1 was 28%. The percent of false negatives was 2.6% (95% CI 1.1-6.0) and 0 (95% CI 0-2.8) in the derivation and validation cohorts, respectively. The use of this rule to guide molecular testing would have resulted in approximately 60% fewer tests. Conclusion: We developed and validated a simple rule to predict the likelihood of JAK2 mutation positivity in patients with a hemoglobin of 160 or higher, based on CBC parameters with a high negative predictive value (Figure 1). If implemented, this prediction rule could result in a significant reduction in molecular testing avoiding 60% or approximately 100 tests per year at our institution. This approach would be particularly beneficial for broader health system management of hematological malignancies, facilitating the reallocation of resources to emerging higher-yield molecular diagnostic investigation (Kawata et al., BJH 2021). Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 8
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3438-3438
    Abstract: Background: In patients with suspected myelodysplastic syndrome (MDS), ancillary tests including cytogenetics (CG) and molecular diagnostics often support the diagnosis and add prognostic value guiding treatment decisions. Frequently, high-cost new technologies such as next generation sequencing (NGS) are added to the existing test menu without consideration for redundancy or added value. In our institution most patients with suspected MDS or cytopenias of undetermined origin will have conventional CG and NGS routinely ordered in addition to bone marrow (BM) morphology and flow cytometry (FCM). In a previous retrospective study, we evaluated combined NGS and CG in 120 patients and we found that our NGS panel had enhanced diagnostic and prognostic advantages over standard karyotyping. Based on these results, we undertook a quality improvement (QI) project to streamline molecular diagnostic testing, reduce test redundancy, turnaround time and cost. Methods: Between February and June 2019 we prospectively evaluated an "NGS first approach" to investigate patients with suspected MDS or cytopenias of undetermined origin. We assessed BM morphology, FCM, NGS testing (Oncomine Myeloid Research Assay, Thermo-Fisher) and CG for all patients. To assess whether BM aspirates can be used to triage appropriate use of NGS and CG, expert morphologists assigned BM samples to either the NGS/CG group or NGS only group, based exclusively on the presence of morphological abnormalities suggesting the possibility of an MDS. Results: We included 50 patients with suspected MDS or cytopenias of undetermined origin. Of these, 33 (66%) were triaged into the NGS/CG group and the remaining 17 (34%) into the NGS only group. In the NGS/CG group NGS testing revealed DNA mutations in 27 (81.8%) patients, whereas CG showed an abnormal karyotype in 12 (36.4%). Among the 21 patients with normal karyotype, NGS revealed mutations in 17 (81%). Two patients (6%) were identified as MDS by morphological examination and had an abnormal karyotype but negative NGS. Of those assigned to the NGS/CG group, 27 (81.8%) were morphologically diagnosed as either MDS (54.5%), acute myeloid leukemia (AML) (15.2%), MDS/myeloproliferative neoplasms (MPN) (6.1%), or therapy related myeloid neoplasms (t-MNs) - MDS/AML (6.1%). Among the patients assigned to the NGS only group, NGS testing showed no abnormalities in 16 (94.1%) patients. One patient was found to carry a BRAF mutation and subsequently diagnosed with hairy cell leukemia. CG testing showed a normal karyotype in 16 (94.1%) patients. One patient was found to carry an inv(2)(p11.2q13) and was diagnosed as clonal B cell lymphocytosis. Conclusion: We proposed and validated a testing algorithm based on an "NGS first approach" with CG restricted to patients with morphological changes suggestive of MDS, in order to reduce the number of samples karyotyped. Overall, in patients with a morphological diagnosis of MDS, NGS defined genetic abnormalities in more patients (84.2%) compared to CG (47.4%) alone. Additional cytogenetic testing only detected chromosomal abnormalities in less than 10% of MDS cases. Most importantly, nearly no mutations or CG abnormalities were detected in patients without dysplastic features. Based on these results we estimated that we could reduce karyotyping by 10% to 20% for patients presenting with probable MDS or cytopenias of undetermined origin using an "NGS first approach". Further studies are warranted to validate and provide cost saving estimates of this approach. Disclosures Hsia: Amgen: Honoraria; Jansen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 9
    In: Current Oncology, MDPI AG, Vol. 29, No. 10 ( 2022-09-30), p. 7209-7217
    Abstract: Background: Since the identification of JAK2 V617F and exon 12 mutations as driver mutations in polycythemia vera (PV) in 2005, molecular testing of these mutations for patients with erythrocytosis has become a routine clinical practice. However, the incidence of myeloid mutations other than the common JAK2 V617F mutation in unselected patients referred for elevated hemoglobin is not well studied. This study aimed to characterize the mutational landscape in a real-world population of patients referred for erythrocytosis using a targeted next-generation sequencing (NGS)-based assay. Method: A total of 529 patients (hemoglobin levels 〉 160 g/L in females or 〉 165 g/L in males) were assessed between January 2018 and May 2021 for genetic variants using the Oncomine Myeloid Research Assay (ThermoFisher Scientific, Waltham, MA, USA) targeting 40 key genes with diagnostic and prognostic implications in hematological conditions (17 full genes and 23 genes with clinically relevant “hotspot” regions) and a panel of 29 fusion driver genes ( 〉 600 fusion partners). Results: JAK2 mutations were detected in 10.9% (58/529) of patients, with 57 patients positive for JAK2 V617F, while one patient had a JAK2 exon 12 mutation. Additional mutations were detected in 34.5% (20/58) of JAK2-positive patients: TET2 (11; 19%), DNMT3A (2;3.4%), ASXL1 (2; 3.4%), SRSF2 (2; 3.4%), BCOR (1; 1.7%), TP53 (1; 1.7%), and ZRSR2 (1; 1.7%). Diagnosis of PV was suspected in 2 JAK2-negative patients based on the 2016 World Health Organization (WHO) diagnostic criteria. Notably, one patient carried mutations in the SRSF2 and TET2 genes, and the other patient carried mutations in the SRSF2, IDH2, and ASXL1 genes. Three JAK2-negative patients with elevated hemoglobin who tested positive for BCR/ABL1 fusion were diagnosed with chronic myeloid leukemia (CML) and excluded from further analysis. The remaining 466 JAK2-negative patients were diagnosed with secondary erythrocytosis and mutations were found in 6% (28/466) of these cases. Conclusion: Mutations other than JAK2 mutations were frequently identified in patients referred for erythrocytosis, with mutations in the TET2, DNMT3A, and ASXL1 genes being detected in 34.5% of JAK2-positive PV patients. The presence of additional mutations, such as ASXL1 mutations, in this population has implications for prognosis. Both the incidence and mutation type identified in patients with secondary erythrocytosis likely reflects incidental, age-associated clonal hematopoiesis of indeterminate potential (CHIP).
    Type of Medium: Online Resource
    ISSN: 1718-7729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 10
    Online Resource
    Online Resource
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 3685-3685
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 3685-3685
    Abstract: Background: Intravenous iron therapy is commonly used in hemodialysis patients but has not been well studied in other patient populations. Intravenous iron has many documented adverse drug reactions and the types and incidence of reactions differ based on the type of intravenous iron therapy used. In Canada, two forms of iron therapy are currently being used: Iron dextran marketed as Infufer or DexIron and iron sucrose marketed as Venofer are available. The general consensus in the literature is that the incidence of serious adverse reactions is relatively low approximately 0.6–0.7% with intravenous iron dextran. The objective of this retrospective chart review was to observe recorded adverse events of iron dextran (Infufer) and iron sucrose (Venofer) in our own non-hemodialysis patients. Methods: 240 non-hemodialysis adult outpatient charts were reviewed. Iron dextran (Infufer) or iron sucrose (Venofer) infusions were recorded from July 20, 2000 to July 13, 2004. For each chart, the patient age, sex, date of birth, past medical history, medications and allergies were recorded. The type of intravenous iron, if premedication was used, and a description of any reaction if it occurred was also recorded. Each adverse reaction was graded on causality, severity, and system classification based on WHO standards done by two investigators virtually blinded to the type of iron therapy used. Results: Of the 240 patient charts reviewed, there were a total of 403 intravenous iron infusions given within the study period. The age of the patients ranged from 19 to 91 with mean age 60.3 +/− 16.3. The majority of our patients were end-stage renal disease peritoneal dialysis patients 187 (78%). 11 (5%) had a history of connective tissue disease or vasculitis, 15 (6%) had a history of asthma, and 84 (35%) used an angiotension converting enzyme inhibitor (ACEI). Only 17 patients (38 total infusions) received premedication. The total number of adverse events of all descriptions was 103 (26%) of the 403 total intravenous iron infusions. This was equally distributed to males 40 out of 156 (26%) and females 63 out of 247 (26%). Of the 365 intravenous therapies not given premedication there were 89 (24%) adverse events. The total number of "certain severe allergic" reactions (CSAs) was 25/403 (6%). In iron dextran (Infufer) a total of 77/295 (26%) ADRs were noted and CSAs of 23/295 (8%). In iron sucrose (Venofer) there was a total of 26/105 (25%) ADRs and 2/105 (2%) CSAs. Of the 295 intravenous iron dextran infusions, 209 had a test dose given. Of these 209, there were 60 ADRs - 25 during the test dose (12%) and 35 (17%) after the test dose. Conclusions: Adverse events and CSAs in our adult outpatient non-hemodialysis patients receiving intravenous iron therapy with either iron dextran (Infufer) and iron sucrose (Venofer) are much higher than previously reported in the literature. There are more ADRs and CSAs in the iron dextran group than the iron sucrose group. Premedication did not appear to reduce ADRs. Having a normal test dose did not preclude to getting ADRs afterwards.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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