scholarly journals Clinical Interventions to Prevent Tumour Lysis Syndrome in Hematologic Malignancy: A Multisite Retrospective Chart Review

2019 ◽  
Vol 72 (6) ◽  
Author(s):  
Sarah McKenna ◽  
Alexandra Cheung ◽  
Amanda Wolfe ◽  
Brenda L Coleman ◽  
Michael E Detsky ◽  
...  

ABSTRACTBackground: Tumour lysis syndrome (TLS) occurs when lysis of malignant cells causes electrolyte disturbances and potentially organ dysfunction. Guidelines recommending preventive therapy according to TLS risk are based on low-quality evidence.Objectives: The primary objective was to characterize utilization of TLS preventive strategies through comprehensive description of current practice. Secondary objectives were to determine TLS incidence, to compare use of preventive strategies among intermediate- and high-risk patients, and to describe TLS treatment strategies.Methods: This retrospective chart review examined data for patients with newly diagnosed hematologic malignancy who were admitted to an oncology centre and/or affiliated intensive care unit between October 2015 and September 2016 in Toronto, Ontario, Canada. Results: Fifty-eight patients (29 at intermediate risk, 29 at high risk) were eligible for inclusion. Use of preventive allopurinol, IV bicarbonate, and furosemide was similar between groups. Rasburicase was more frequently used for high-risk patients (3% [1/29] of intermediate-risk patients versus 36% [9/25] of high-risk patients; p = 0.003). In 4 (14%) of the intermediate-risk patients and 2 (8%) of the high-risk patients, TLS developed during the admission. TLS was observed in 10% (1/10) of patients who received preventive rasburicase and 11% (5/44) of those who did not (p > 0.99), and in 9% (4/45) of patients who received preventive IV bicarbonate and 25% (2/8) of those who did not (p = 0.22). Treatment strategies included rasburicase, IV bicarbonate, furosemide, and renal replacement therapy.Conclusions: In this retrospective chart review, rasburicase was more commonly used for high-risk patients, whereas the use of other agents was similar between risk groups. This pattern of use is inconsistent with guidelines, which recommend that all high-risk patients receive rasburicase. There was no difference in TLS incidence between patients who did and did not receive preventive rasburicase or IV bicarbonate. Further prospective studies are needed to inform management of patients with malignancies who are at intermediate or high risk of TLS.RÉSUMÉContexte : Le syndrome de lyse tumorale (SLT) se produit lorsque la lyse de cellules malignes provoque des perturbations électrolytiques et la dysfonction potentielle d’un organe. Les lignes directrices préconisant une thérapie préventive basée sur le risque de SLT se fondent sur des éléments de preuve de piètre qualité.Objectifs : L’objectif principal consistait à décrire l’adoption des stratégies de prévention du SLT en décrivant précisément la pratique actuelle. Les objectifs secondaires consistaient, quant à eux, à déterminer l’incidence du SLT, à comparer l’utilisation des stratégies de prévention pour les patients présentant un risque élevé et moyen et à décrire les stratégies de traitement du SLT.Méthodes : Cet examen rétrospectif a permis d’examiner les données de patients ayant récemment reçu un diagnostic d’hémopathie maligne et ayant été admis dans un centre d’oncologie ou une unité de soins intensifs affiliée, entre octobre 2015 et septembre 2016 à Toronto (Ontario), au Canada.Résultats : Cinquante-huit patients (29 présentant un risque moyen et 29 un risque élevé) étaient admissibles. L’utilisation d’allopurinol à titre préventif, de bicarbonate par voie intraveineuse et de furosémide était similaire d’un groupe à l’autre. Le rasburicase était plus fréquemment utilisé pour les patients présentant un risque élevé (3 % [1/29] de patients présentant un risque moyen contre 36 % [9/25] de patients présentant un risque élevé; p = 0.003). Quatre (14 %) patients présentant un risque moyen et deux (8 %) présentant un risque élevé ont développé un SLT pendant l’admission. Le SLT a été observé chez 10 % (1/10) des patients ayant reçu du rasburicase à titre préventif et chez 11 % (5/44) des patients qui n’en avaient pas reçu (p > 0,99); il a aussi été observé chez 9 % (4/45) des patients ayant reçu du bicarbonate par voie intraveineuse à titre préventif et chez 25 % (2/8) des patients qui n’en avaient pas reçu (p = 0.22). Les stratégies de traitement comprenaient le rasburicase, le bicarbonate par voie intraveineuse, le furosémide et la thérapie de remplacement rénal.Conclusions : Dans cet examen rétrospectif des dossiers, l’usage du rasburicase était plus fréquent pour les patients présentant un risque élevé, tandis que celui d’autres agents était similaire entre les groupes à risque. Ce schéma d’utilisation n’est pas conforme aux lignes directrices, qui recommandent que tous les patients présentant un risque élevé reçoivent du rasburicase. Aucune différence n’est apparue dans l’incidence du SLT parmi les patients ayant reçu du rasburicase ou du bicarbonate par voie intraveineuse à titre préventif et parmi ceux qui n’en avaient pas reçu. Davantage d’études prospectives sont nécessaires pour mieux connaitre la gestion des patients à haut risque ou ceux qui présentent des risques moyens de SLT, mais qui ont des malignités.  

2018 ◽  
Vol 103 (2) ◽  
pp. e1.4-e1
Author(s):  
Hutchinson Lauren Jane

Rasburicase is used for the treatment and prophylaxis of hyperuricaemia in patients with haematological malignancy at high risk of tumour lysis syndrome (TLS). It is licensed in both adults and children at a dose of 0.2 mg/kg/day for up to 7 days. In adults off label dosing of 3 mg stat is being used for the prophylaxis of TLS and, whilst not licensed, has been recommended by the British Society for Haematology (BSH) TLS guidelines (Jones et al., 2015). Consequently this has been translated to paediatric use, with our centre using a dose of 0.2 mg/kg (max 3 mg). The aim of this audit is to establish the current prescribing practice for rasburicase within this paediatric oncology centre and ascertain whether its use is in line with BSH recommendations for TLS management in paediatrics.MethodPaediatric patients who had received rasburicase within the previous 12 months were identified via the pharmacy dispensing system. For each patient data was collated from the medical notes, drug chart and blood results. The patient’s risk for TLS was defined, the intended use of rasburicase (treatment or prophylaxis) was established and each patient was assessed for laboratory and clinical signs of TLS according to BSH guidelines.ResultsEleven patients received rasburicase within the previous twelve months. Six were initiated on prophylactic dosing versus five on treatment.Seven out of eleven patients were classed as high risk of TLS, three of which were given a single prophylactic dose of rasburicase and four given treatment.Of the three high risk patients who received rasburicase prophylaxis, one was capped at 3 mg and subsequently converted to treatment due to escalating TLS. This patient received allopurinol concurrently with rasburicase.Three non high risk patients received prophylactic rasburicase. Two showed laboratory signs of TLS and received capped doses of 3 mg. One patient had no access for bloods and was given an uncapped prophylactic dose.The average number of prophylactic doses given per patient was 1.8.Five out of six patients who received treatment rasburicase showed laboratory signs of TLS. The average duration was 4.1 days.ConclusionThe results show inconsistency in the prescribing of rasburicase at this paediatric oncology centre, particularly for TLS prophylaxis. Some patients received capped prophylactic dosing whilst others did not. BSH guidance does not recommend a dose cap of 3 mg in paediatrics due to a lack of evidence whereas the local guideline does. One patient received both allopurinol and rasburicase – the BSH guidance advises this as unnecessary with the potential to reduce the efficacy of rasburicase. TLS treatment with rasburicase was more consistent with five out of six patients being treated in line with BSH guidance and the product license.ReferenceJones GL, Will A, Jackson GH, Webb NJ, Rule S. Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British committee for standards in haematology. Br J Haematol2015;169:661–671.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3274
Author(s):  
Vinson Wai-Shun Chan ◽  
Wei Shen Tan ◽  
Aqua Asif ◽  
Alexander Ng ◽  
Olayinka Gbolahan ◽  
...  

External factors, such as the coronavirus disease 2019 (COVID-19), can lead to cancellations and backlogs of cancer surgeries. The effects of these delays are unclear. This study summarised the evidence surrounding expectant management, delay radical prostatectomy (RP), and neoadjuvant hormone therapy (NHT) compared to immediate RP. MEDLINE and EMBASE was searched for randomised controlled trials (RCTs) and non-randomised controlled studies pertaining to the review question. Risks of biases (RoB) were evaluated using the RoB 2.0 tool and the Newcastle–Ottawa Scale. A total of 57 studies were included. Meta-analysis of four RCTs found overall survival and cancer-specific survival were significantly worsened amongst intermediate-risk patients undergoing active monitoring, observation, or watchful waiting but not in low- and high-risk patients. Evidence from 33 observational studies comparing delayed RP and immediate RP is contradictory. However, conservative estimates of delays over 5 months, 4 months, and 30 days for low-risk, intermediate-risk, and high-risk patients, respectively, have been associated with significantly worse pathological and oncological outcomes in individual studies. In 11 RCTs, a 3-month course of NHT has been shown to improve pathological outcomes in most patients, but its effect on oncological outcomes is apparently limited.


2019 ◽  
Vol 3 (1) ◽  
pp. 83-95 ◽  
Author(s):  
Haris Ali ◽  
Ibrahim Aldoss ◽  
Dongyun Yang ◽  
Sally Mokhtari ◽  
Samer Khaled ◽  
...  

Abstract Although allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF), data are limited on how molecular markers predict transplantation outcomes. We retrospectively evaluated transplantation outcomes of 110 consecutive MF patients who underwent allo-HCT with a fludarabine/melphalan (Flu/Mel) conditioning regimen at our center and assessed the impact of molecular markers on outcomes based on a 72-gene next-generation sequencing panel and Mutation-Enhanced International Prognostic Scoring System 70+ v2.0 (MIPSS70+ v2.0). With a median follow-up of 63.7 months, the 5-year overall survival (OS) rate was 65% and the nonrelapse mortality (NRM) rate was 17%. In mutational analysis, JAK2 V617F and ASXL1 mutations were the most common. By univariable analysis, higher Dynamic International Prognostic Scoring System scores, unrelated donor type, and very-high-risk cytogenetics were significantly associated with lower OS. Only CBL mutations were significantly associated with lower OS (hazard ratio [HR], 2.64; P = .032) and increased NRM (HR, 3.68; P = .004) after allo-HCT, but CALR, ASXL1, and IDH mutations did not have an impact on transplantation outcomes. Patient classification per MIPSS70 showed worse OS for high-risk (HR, 0.49; P = .039) compared with intermediate-risk patients. Classification per MIPSS70+ v2.0 demonstrated better OS when intermediate-risk patients were compared with high-risk patients (HR, 0.291) and much lower OS when very-high-risk patients were compared with high-risk patients (HR, 5.05; P ≤ .001). In summary, we present one of the largest single-center experiences of Flu/Mel-based allo-HCT, demonstrating that revised cytogenetic changes and MIPSS70+ v2.0 score predict transplantation outcomes, and thus can better inform physicians and patients in making decisions about allo-HCT.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Grinberg ◽  
T Bental ◽  
Y Hammer ◽  
A R Assali ◽  
H Vaknin-Assa ◽  
...  

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.


CJEM ◽  
2019 ◽  
Vol 21 (S1) ◽  
pp. S40
Author(s):  
A. Verma ◽  
A. Kapoor ◽  
J. Kim ◽  
N. Kujbid ◽  
K. Si ◽  
...  

Background: Canadian Stroke Guidelines recommend that Transient Ischemic Attack (TIA) patients at highest risk of stroke recurrence should undergo immediate vascular imaging. Computed tomography angiography (CTA) of the head and neck is recommended over carotid doppler because it allows for enhanced visualization of the intracranial and posterior circulation vasculature. Imaging while patients are in the emergency department (ED) is optimal for high-risk patients because the risk of stroke recurrence is highest in the first 48 hours. Aim Statement: At our hospital, a designated stroke centre, less than 5% of TIA patients meet national recommendations by undergoing CTA in the ED. We sought to increase the rate of CTA in high risk ED TIA patients from less than 5% to at least 80% in 10 months. Measures &amp; Design: We used a multi-faceted approach to improve our adherence to guidelines including: 1) education for staff ED physicians; 2) agreements between ED and radiology to facilitate rapid access to CTA; 3) agreements between ED and neurology for consultations regarding patients with abnormal CTA; and 4) the creation of an electronic decision support tool to guide ED physicians as to which patients require CTA. We measured the rate of CTA in high risk patients biweekly using retrospective chart review of patients referred to the TIA clinic from the ED on a biweekly basis. As a balancing measure, we also measured the rate of CTA in non-high risk patients. Evaluation/Results: Data collection is ongoing. An interim run chart at 19 weeks shows a complete shift above the median after implementation, with CTA rates between 70 and 100%. At the time of submission, we had no downward trends below 80%, showing sustained improvement. The CTA rate in non-high risk patients did also increase. Disucssion/Impact: After 19 weeks of our intervention, 112 (78.9%) of high risk TIA patients had a CTA, compared to 10 (9.8%) in the 19 weeks prior to our intervention. On average, 10-15% of high risk patients will have an identifiable lesion on CTA, leading to immediate change in management (at minimum, an inpatient consultation with neurology). Our multi-faceted approach could be replicated in any ED with the engagement and availability of the same multi-disciplinary team (ED, radiology, and neurology), access to CTA, and electronic orders.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4251-4251
Author(s):  
Angelo Michele Carella ◽  
Gabriella Cirmena ◽  
Gioacchino Catania ◽  
Gianmatteo Pica ◽  
Germana Beltrami ◽  
...  

Abstract Abstract 4251 Kinase domain (KD) mutations are associated with resistance to Imatinib in CP-CML but their incidence and prognostic significance before any treatment are unclear. To assess if KD mutations at diagnosis may have prognostic significance, we have recently reviewed (before treatment with Imatinib) the mutation status of 45 patients,of whom low risk: 24 patients; intermediate risk: 8 patients; high risk: 13 patients, according to Sokal/Euro. We found that a) no patient with low and intermediate risk showed KD mutations at diagnosis; b) 4/13 high risk patients showed the following mutations at diagnosis: S265R, E255K, F359Y and E255V/E258V; other 5 patients developed mutations during Imatinib treatment (E255V, T315I, E255V/E258V, H396R and D248-274). All patients with low-intermediate risk are alive and well at a median of 44 months (range, 15-71 months). On the contrary, 3/4 high risk patients with KD mutations at diagnosis progressed and died of blastic evolution at 23, 33 and 69 months despite Nilotinib and Dasatinib therapy. Other 3/5 high risk patients who developed mutations under Imatinib, died of blastic evolution at 22, 23 and 43 months despite Nilotinib and Dasatinib treatment. Seven high risk patients are alive under Imatinib between 4 and 51 months. In conclusion, the KD mutations at diagnosis were frequent in high Sokal/Euro risk group supporting the concept that such mutations could be related to the basic biology of the disease. These data, if confirmed, could modify our approach to high risk patients with KD mutation at diagnosis, i.e. utilizing second/third TKI generation earlier during the disease and, in selected cases, reconsidering allografting earlier before leukemic evolution make such procedure useless. Disclosures: No relevant conflicts of interest to declare.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1577-1577
Author(s):  
Deesha Sarma ◽  
So Yeon Kim ◽  
David H. Henry

1577 Background: Venous thromboembolism (VTE) poses a significant health risk to cancer patients and is one of the leading causes of death among this population. The most effective way to prevent VTE and reduce its prominence as a public health burden is by identifying high-risk patients and administering prophylactic measures. In 2008, Khorana et al. developed a model that classified patients by risk based on clinical factors. Methods: We conducted a retrospective study to test this model’s efficacy, on 150 patients with cancer receiving chemotherapy at an outpatient oncology clinic between January 1 and August 1, 2011. We aggregated data and assigned points based on the five factors in the Khorana model: site of cancer with 2 points for very high-risk site and 1 point for high-risk site, 1 point each for leukocyte counts more than 11 x 109/L, platelet counts greater than 350 X 109/L, hemoglobin levels less than 100 g/L and/or the use of erythropoiesis-stimulating agents, and BMI greater than 35 kg/m2 (Khorana et al., Blood 2008). Based on this scoring system, patients with 0 points were grouped into the low-risk category, those with 1-2 points were considered intermediate-risk, and those with 3-4 points were classified as high-risk. Results: As shown in the table, VTE incidence for the low-risk group was 1.9%, intermediate-risk group was 3.9%, and high-risk group was 9.1%. Conclusions: High-risk patients were about 4.5 times more likely to develop a VTE than low risk patients. These results provide valuable insight in determining which patients might benefit from prophylaxis and in motivating the design of prospective clinical trials that assess the VTE predictive model in various ambulatory cancer settings. [Table: see text]


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