Current guidelines support the use of corticosteroids and azathioprine as one possible treatment strategy for idiopathic pulmonary fibrosis (IPF). However, some patients with genetic polymorphisms of thiopurine methyltransferase (TPMT) are at risk of severe azathioprine myelotoxicity.The current authors present the case of an 85-yr-old Caucasian male with IPF who developed diffuse alveolar haemorrhage as a complication of azathioprine-induced myelosuppression.Leukocyte genetic TPMT testing revealed that the patient had homozygous polymorphisms associated with the absence of TPMT activity and severe azathioprine-induced myelotoxicity.Thiopurine methyltransferase deficiency should be considered in patients who develop leukopenia early in treatment with azathiopurine, or who present with severe marrow suppression at usual doses. For centres with equipped laboratories, a dosing suggestion is provided based on thiopurine methyltransferase testing. Even with screening strategies, frequent monitoring of complete blood count and liver biochemistry should remain the mainstay of surveillance for azathioprine toxicity.
Introduction: Heparin induced thrombocytopenia (HIT) is a serious prothrombotic condition, usually triggered by exposure to heparin products with formation of antibodies to platelet factor 4/ heparin polyanion complexes. Diagnostic algorithm for HIT combines clinical scoring (4T score) with time sensitive screening for HIT antibodies (HIT-ab), while serotonin release assay (SRA) is remains the gold standard for confirmatory diagnosis. The rate of utilization of 4T score was low in our institution, resulting in inappropriate orders for HIT-Ab test and subsequent administration of unnecessary alternative anticoagulation (AC) in patients with false positive results. In this project, we designed a structured HIT diagnostic workflow incorporating 4T score calculation in our electronic medical record (EMR) and replaced particle immunofiltration assay (PIFA) with latex immunoturbidometric assay (LIA) in our laboratory for HIT-Ab screening, with an aim to improve the rate of 4T utilization and accuracy of HIT diagnosis in a cost-efficient manner. Methods: In phase I, we performed a retrospective chart review of all patients with PIFA ordered between March 2017-March 2018. Two investigators independently calculated 4T, collected data on results of HIT-Ab, confirmatory SRA tests, and the duration of alternative AC from each record. Any variations in 4T score were resolved by a senior investigator. In phase II, we implemented a new workflow in the EMR incorporating mandatory calculation of 4T score with every order for HIT-Ab test. Our lab started using LIA in place of PIFA. Charts were reviewed on patients with HIT-Ab orders (LIA) from January-June of 2019. Results: On review of data from phase I, we noted that 4T score was documented in only 5 (0.02%) of 170 patients in whom a PIFA test was ordered. Per investigators assessment, 113 (66.4%) patients had low probability (4T ≤ 3), 47 (27.6%) had intermediate probability (4T 4 or 5), and 10 (5.8%) had a high probability (4T ≥ 6) for a diagnosis of HIT. SRA was ordered in 32 patients, although 17 of them had low probability per investigator assessment. PIFA test came back positive in 26 patients, of whom 16 had corresponding SRA results, and three samples were positive for SRA. PIFA was negative in two patients with confirmed HIT (SRA positive). A total of 19 patients received alternate AC in the first phase, 7 of them had low 4T score per our assessment. In phase II, 69 records were found with available LIA results, showing a relative decrease in HIT-Ab orders compared to earlier phase at the six months mark. Documentation of 4T score has been 100% by ordering physicians, a certain improvement from phase I. Investigator calculated 4T score showed low probability in 33 (47.8%) patients, intermediate probability in 31 (44.9%) patients, high probability in 5 (0.07%) patients. LIA was positive in 7 of the 69 ordered tests, 6 of whom scored high/intermediate in the 4T score. HIT diagnosis was confirmed in 3 of these 7 patients with a positive SRA result. During this period, all the 7 of the eight patients who received alternate AC had a high or intermediate probability for HIT as per 4T. Conclusion: Our study demonstrated that the successful implementation of a structured protocol for HIT diagnosis ensured 100% adherence to the calculation and documentation of 4T score by clinicians, and significantly reduced the number of inappropriate HIT-Ab test orders in our institution. Use of alternate AC was also more consistent with the level of probability for HIT. Table Disclosures No relevant conflicts of interest to declare.
Introduction: Multiple myeloma, which accounts for 1% of all cancers, is a hematologic cancer in which clonal plasma-cell proliferation leads to complications and death. Over the recent years, it has shown that the introduction of novel agents, including daratumumab and the incorporation of proteasome inhibitors and immunomodulatory drugs has improved outcomes in patients with multiple myeloma. Daratumumab is a human, CD38-targeting, IgG1κ monoclonal antibody with direct antitumor effects and an immunomodulatory component and has recently shown to improve survival in patients with multiple myeloma. However, there are considerable safety concerns. The purpose of our study is to determine the risk of TD and deaths due to treatment-related adverse events (TRAE) in patients with multiple myeloma treated with daratumumab. Methods: We systematically conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2019. Phase III RCTs utilizing daratumumab in patients with multiple myeloma were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Random effects model was applied. Results: Five phase III RCTs with a total of 3,547 patients with multiple myeloma were eligible. Studies compared daratumumab (D) + bortezomib (V) + melphan (M) + prednisone (P) vs VMP, D + lenalidomide (R) + dexamethasone (d) vs Rd, DVd vs Vd, DVd + thalidomide (T) vs VTd and DRd vs Rd. The randomization ratio was 1:1 in all studies. Daratumumab was utilized in relapsed and refractory multiple myeloma in the POLLUX study (n= 564) and the CASTOR study (n= 480) and as first-line treatment for patients with multiple myeloma in the ALCYONE study (n= 700), the CASSIOPEIA study (n= 1085) and the MAIA study (n= 737). The I2 statistic for heterogeneity was 39, suggesting some heterogeneity among RCTs. TD due to TRAE was noted in 120 (6.77%) vs 179 (10.08%) in control group with RR of 0.68 (95% CI: 0.51 -0.91; P = 0.0009) and RD of -0.03 (95% CI: -0.06 to 0.00; P = 0.02). TD due to infection/ pneumonia was reported in 0.95% vs 0.73% in control group (RR, 1.19; 95% CI: 0.42 -3.34; P = 0.75). Treatment-related deaths were 64 (3.61%) in daratumumab arm vs 77 (4.34%) in control arm. The pooled RR was not statistically significant at 0.86 (95% CI: 0.59 -1.25; P = 0.43). Conclusions: The rate of discontinuation of trial treatment due to adverse events was significantly lower in the daratumumab group (6.77%) than in the control arm (10.08%) with RR of 0.68, favoring daratumumab combination regimen. Furthermore, there was no significant difference in the treatment discontinuation due to pneumonia or infection and treatment-related deaths due to TRAE in the daratumumab group, compared to control arm. Disclosures No relevant conflicts of interest to declare.
treated with IT and compares them to the rest of patient population. Survival analysis is performed using Kaplan Meier curves; Hazard Ratios (HR) with 95% Confidence Interval (95%CI) are reported to compare the two groups. Result: Patients treated with IT (2 combined with first-line chemotherapy, 14 alone) correspond to 7.5% of the entire study population; they were 9 males and 7 females, with a median age of 62.5 years, mainly current or former-smokers, with an ECOG-performance status 0 in 93.7% of cases. At the cutoff date (December 25th, 2018), after a median follow-up of 35.5 months, no significant differences appear between patients previously treated with IT and the other ones in terms of PFS (5.84 vs 4.31 months, respectively; HR 0.564 [95% CI 0.283-1.122], p-value¼0.1029), and OS (9.37 vs 9.02 months, respectively; HR 1.108 [95% CI 0.393-3.123], p-value¼0.8456). No significant differences have been observed also in disease-control rates (80.0% vs 66.7%, p-value¼0.5436). Conclusion: Despite this report does not show a greater survival expectancy for patients treated with docetaxel/nintedanib and previous IT, it's likely that the small sample size may affect this result. The longer PFS and greater disease-control rate are attractive hints for future evaluations with larger sample sizes, supposing a new therapeutic algorithm for recurrent nsNSCLC patients.
Introduction: Heparin induced thrombocytopenia (HIT) is a severe prothrombotic condition, usually triggered by exposure to heparin products. It is characterized by platelet activation induced by the formation of antibodies to the platelet factor 4 (PF4)/ heparin polyanion complexes. Diagnostic algorithm includes clinical scoring (4T score) alongside serological test for detection of these antibodies (HIT-Ab), while serotonin release assay (SRA) remains the gold- standard for confirmation. The automated latex immunoturbidometric assay (LIA) has recently been FDA approved as a screening tool for HIT and is a potential alternative to the conventional particle immunofiltration assay (PIFA) for time-sensitive detection of HIT-Ab to guide treatment considerations. We recently introduced LIA in our institution. In this study, we present our experience with LIA in comparison to PIFA in the diagnosis of HIT. Methods: We retrospectively reviewed the charts of all the patients on whom a PIFA was ordered between March 2017 and March 2018 in our hospital. We collected information on the results of the PIFA and SRA (if available). We replaced PIFA with LIA for HIT screening. Then, we introduced a structured protocol for diagnosis of HIT in our institution by incorporating 4T scoring alongside LIA order in the electronic medical record (EMR), in December 2018. We reviewed the EMR of all the patients on whom HIT-Ab test (LIA) was ordered between January and June of 2019, and collected similar information as before. All the data were compiled in a single master excel sheet for calculation of performance characteristics (sensitivity, specificity, positive and negative predictive values) for both PIFA and LIA. A patient was considered to have the diagnosis of HIT if the result of SRA was available and positive. Results: In the first phase, a total of 31 orders for SRA was noted against 170 PIFA orders. Five patients had a positive SRA, of whom two were PIFA negative. Half the patients with a negative SRA result were positive for PIFA. Hence, the sensitivity and specificity of PIFA test for our study population were noted to be 60% and 50%, respectively. PIFA had a positive predictive value (PPV) of mere 18.75% for the diagnosis of HIT, whereas the negative predictive value (NPV) was found to be 86.66%. Introduction of structured protocol for HIT diagnosis substantially reduced the number of inappropriate SRA orders in the second phase. On review of data for six months with the new HIT-Ab test LIA, SRA was ordered in only eight patients, to go with 69 orders for the LIA. The result of LIA was positive in all three patients with a positive SRA, whereas it was false positive in four instances. Only one patient was negative for both LIA and SRA during this period. LIA was found to be 100% sensitive and 20% specific for the diagnosis of HIT in our sample. PPV and NPV for LIA were 42.85% and 100%, respectively. Conclusion: The sensitivity and specificity of LIA were found to be 100% and 20%, respectively, in our study population, which is different from the earlier report (Warkentin et al. 2017). The small sample size is a limitation of our study. Higher PPV and NPV for LIA, with its quick turnaround time, make it a useful alternative for the time-sensitive determination of post-test probability for HIT in patients. [HIT- Ab- Heparin Induced Thrombocytopenia Antibody, PIFA- Particle Immunofiltration Assay, LIA- Latex Immunoturbidometric Assay, SRA- Serotonin Release Assay, +ve- Positive, -ve - Negative, PPV- Positive Predictive Value, NPV- Negative Predictive Value] Disclosures No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.