To Measure or Not to Measure: Direct Oral Anticoagulant Laboratory Assay Monitoring in Clinical PracticeRead the full article
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Outcomes among Patients with Mantle Cell Lymphoma Post-Covalent BTK Inhibitor Therapy in the United States: A Real-World Electronic Medical Records Study
Purpose. There remains a lack of consensus among experts regarding the optimal therapeutic approach for Mantle cell lymphoma (MCL) after failure of covalent Bruton Tyrosine Kinase inhibitor (cBTKi)-based therapy. This study was designed to examine patient characteristics, current treatment patterns, and clinical outcomes using a real-world database to evaluate how MCL is currently managed post-cBTKi therapy in the U.S. Methods. A large, deidentified U.S. electronic medical record (EMR) oncology database (ConcertAI) with data from January 2011 to July 2021 was utilized for this study. Eligible patients were adults with MCL who had received at least one cBTKi. Descriptive statistics were used to evaluate patient characteristics and treatment patterns. Time-to-event real-world outcomes of duration of therapy, time to next treatment discontinuation, and overall survival was evaluated using the Kaplan–Meier method. Results. A total of 946 patients met eligibility criteria. Of these, 739 (78.1%) discontinued cBTKi treatment before the end of the follow-up period, while the remaining 207 (21.9%) were still receiving cBTKi therapy at the end of the follow-up period. Among those who had discontinued the cBTKi, 352 (47.6%, 352/739) received at least one subsequent (post-cBTKi) treatment. The median duration of the immediate post-cBTKi therapy was 2.6 months (n = 352). Among the 739 patients who discontinued cBTKi treatment, the median time from cBTKi discontinuation to next treatment discontinuation or death was 3.9 months and the median overall survival was 10.3 months. Conclusions. This study demonstrates the poor outcomes experienced by patients after cBTKi therapy. There is an urgent need for safe and effective treatments for patients with recurrent or progressive MCL.
Association of Pulmonary Hypertension and Monoclonal Gammopathy of Undetermined Significance
Objective. To determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with PH as well as precapillary PH. Methods. Olmsted County residents with PH, diagnosed between 1/1/1995 and 9/30/2017, were identified, and age and sex were matched to a normal control group. The PH group and normal control group were then cross-referenced with the Mayo Clinic MGUS database. Charts were reviewed to verify MGUS and PH. Heart catheterization data were then analyzed in these patients for reference to the gold standard for diagnosis. Results. There were 3419 patients diagnosed with PH by echocardiography between 1995 and 2017 in Olmsted County that met the criteria of our study. When the PH group (N = 3313) was matched to a normal control group (3313), a diagnosis of MGUS was significantly associated with PH 10.2% (OR = l.84 [95% CI 1.5–2.2], ), compared with controls 5.8% based on echo diagnosis. Using heart catheterization data (484 patients), a diagnosis of MGUS was associated with PH 13.0% (OR = 3.94 [95% CI 2.28–6.82], ). For pulmonary artery hypertension (N = 222), a diagnosis of MGUS was associated with PH at similar 12.2% (OR = 4.50 [95%CI 1.86–10.90], . Conclusions. There is a higher prevalence of MGUS in patients with PH and precapillary PH compared with normal controls. This association cannot be explained fully by other underlying diagnoses associated with PH. Assessing for this in patients with PH of unclear etiology may be reasonable in the workup of patients found to have PH.
The Efficacy and Safety of Fostamatinib in Elderly Patients with Immune Thrombocytopenia: A Single-Center, Real-World Case Series
Fostamatinib is a small molecule spleen tyrosine kinase (Syk) inhibitor that was approved for the treatment of adult patients with immune thrombocytopenia (ITP) in second-line therapy. Syk inhibition prevents cytoskeletal rearrangements during phagocytosis, allowing platelet survival in ITP. However, fostamatinib treatment in elderly patients with ITP has not been well established. We performed a retrospective review of all elderly patients (age greater than or equal to 65 years) who had started on fostamatinib for the treatment of ITP at a single tertiary care centre to evaluate its efficacy and safety. Seven patients, median age 80 years (range 78–94), four women and three men, all of Caucasian background, with various comorbidities, started fostamatinib 100 mg orally twice daily as second or subsequent line therapy. Patients had a diagnosis of ITP for a median of 6 years (range approximately 6 months–30 years), had six comorbidities (range 2–14), and experienced 2 unique prior lines of ITP therapy (range 1 to 6). Over 1290 days of fostamatinib exposure, two patients required dose escalation to 150 mg orally twice daily, while five patients remained on the initial starting dose of 100 mg twice daily. The median platelet count at the time of initiating fostamatinib was 25 × 109/L (range less than 10–193). The median time to response (defined as any first platelet count greater than or equal to 30 × 109/L) was 19 days (range 0–181 days), with two patients responding rapidly (5 days and 19 days). Two patients required dose escalation and rescue therapy, and these same two patients discontinued fostamatinib after 175 days and 216 days of treatment. Treatment was tolerated in all patients with no thromboembolic events observed. One death was noted and unrelated to treatment. Overall, fostamatinib was effective and safe for the majority of these very elderly patients with ITP.
Efficacy of COVID-19 Convalescent Plasma Based on Antibody Concentration
Background. Convalescent plasma obtained from individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains neutralizing antibodies to the virus and has been frequently used as a treatment in hospitalized patients with severe COVID-19. Methods. We conducted a retrospective, observational cohort study involving 96 hospitalized patients with severe COVID-19 who were allocated in a 1 : 1 ratio to having received either high antibody concentration convalescent plasma or low antibody concentration convalescent plasma. Quantitative measurements of IgG to the receptor-binding domain (RBD), the S1 subunit of the spike protein, and the SARS-CoV-2 nucleocapsid (N) protein were determined from donor plasma samples. The primary outcome was all-cause mortality within 30 days following convalescent plasma administration in regard to each of the three antibody domains. Results. Within the nucleocapsid antibody domain, death occurred in 22.2% of patients in the low antibody concentration group versus 23.5% in the high antibody concentration group (). Within the RBD antibody domain, death occurred in 22.9% of patients in both the low and the high antibody concentration groups (). Within the S1 subunit antibody domain, death occurred in 27.1% of patients in the low antibody concentration group versus 18.8% in the high antibody concentration group (). Conclusions. No significant differences were observed between low and high concentration convalescent plasma in regard to overall mortality at 30 days, hospital length of stay, number of ventilator days, and subsequent receipt of invasive mechanical ventilation in patients who were previously not receiving mechanical ventilation. Trial Registration. This study was not associated with a clinical trial due to the retrospective nature of study design.
Cystatin C-Based Equations Detect Hidden Kidney Disease and Poor Prognosis in Newly Diagnosed Patients with Multiple Myeloma
Objectives. The aim of this study was to compare the creatinine equations with cystatin C (CysC) equations to define renal impairment (RI) in newly diagnosed multiple myeloma (MM) patients and to analyse the equation that allows for identifying patients with more and worse prognostic factors. Methods. Renal function was evaluated prospectively in 61 patients with newly diagnosed untreated MM employing CKD-EPI and CAPA equations. The comparison was conducted using Bland–Altman graphics and Cohen’s Kappa statistic. Mann–Whitney T and Chi-square tests were used, and univariate and multivariate analyses were carried out. Results. According to the IMWG criteria, 26% of patients showed RI (3 women/13 men) whilst the use of CysC equations allowed us to identify up to 39% of patients (7 women/17 men). The CAPA equation was less biased and dispersed and more sensitive than CKD-EPI-creatinine. Furthermore, univariate analysis unveiled an association between decreased CKD-EPI-CysC and poor prognosis based on R-ISS-3. Conclusions. The IMWG criteria may underestimate kidney disease, mostly in women, which could affect the dose received as well as its toxicity. Altogether, our data suggest that equations that include CysC are more accurate to detect hidden kidney disease, as well as patients with more and worse prognostic factors, in newly diagnosed MM.
Concordance of Peripheral Blood and Bone Marrow Next-Generation Sequencing in Hematologic Neoplasms
Objective. Mutational analysis by next-generation sequencing (NGS) obtained by peripheral blood NGS has been of clinical interest to use as a minimally invasive screening tool. Our study evaluates the correlation between NGS results on peripheral blood and bone marrow in hematolymphoid disease. Method. We evaluated patients who had NGS for presumed hematologic malignancy performed on peripheral blood and bone marrow within a 1-year interval of each other. We excluded cases in which chemotherapy or bone marrow transplant occurred in the interval between the two tests. The concordance across peripheral blood and bone marrow NGS results was assessed by kappa coefficient analysis. Results. A total of 163 patients were studied. Concordance of peripheral blood and bone marrow NGS found in 150 patients (92.0%) with a kappa coefficient of 0.794 (kappa standard error 0.054) and value for testing kappa <0.0001. Myeloid neoplasms showed concordant results in 77/78 cases (98.7%) with a kappa coefficient of 0.916. Lymphoid neoplasms showed concordant results in 26/31 cases (83.9%) with a kappa coefficient of 0.599. Nonneoplastic cases showed concordant results in 47/54 cases (87.0%) with a kappa coefficient of 0.743. Conclusion. Peripheral blood NGS is a reliable tool for mutational analysis and provides a less invasive method for screening and monitoring of the molecular profile.