Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Annals of Internal Medicine, American College of Physicians, Vol. 174, No. 5 ( 2021-05), p. 622-632
    Type of Medium: Online Resource
    ISSN: 0003-4819 , 1539-3704
    RVK:
    Language: English
    Publisher: American College of Physicians
    Publication Date: 2021
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Pediatric Emergency Care Vol. 37, No. 12 ( 2021-12), p. e1531-e1534
    In: Pediatric Emergency Care, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. 12 ( 2021-12), p. e1531-e1534
    Abstract: Children with hemophilia frequently require long-term central venous access devices (CVADs) for regular infusion of factor products. Hemophilia patients are not immunocompromised, but the presence and use of CVADs are associated with infections including bacteremia. Currently, the utility of blood cultures in evaluation of the febrile hemophilia patient with an indwelling CVAD is unknown, nor is optimal empiric antibiotic use. Methods We performed a retrospective cross-sectional study of febrile immunocompetent hemophilia patients with CVADs presenting to a large academic urban pediatric emergency department from 1995 to 2017. We used a natural language processing electronic search, followed by manual chart review to construct the cohort. We analyzed rate of pathogen recovery from cultures of blood in subgroups of hemophilia patients, the pathogen profile, and the reported pathogen susceptibilities to ceftriaxone. Results Natural language processing electronic search identified 181 visits for fever among hemophilia patients with indwelling CVADs of which 147 cases from 44 unique patients met study criteria. Cultures of blood were positive in 56 (38%) of 147 patients (95% confidence interval, 30%–47%). Seventeen different organisms were isolated (10 pathogens and 7 possible pathogens) with Staphylococcus aureus and coagulase-negative Staphylococcus species as the most common. Thirty-four percent of isolates were reported as susceptible to ceftriaxone. Positive blood cultures were more common in cases involving patients with inhibitors (n = 71) versus those without (n = 76), odds ratio, 7.4 (95% confidence interval, 3.5–15.9). This was observed irrespective of hemophilia type. Conclusions Febrile immunocompetent hemophilia patients with indwelling CVADs have high rates of bacteremia. Empiric antimicrobial therapy should be targeted to anticipated pathogens and take into consideration local susceptibility patterns for Staphylococcus aureus.
    Type of Medium: Online Resource
    ISSN: 1535-1815 , 0749-5161
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2053985-X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: British Journal of Haematology, Wiley, Vol. 192, No. 6 ( 2021-03), p. 1092-1096
    Abstract: Diagnosis of pyruvate kinase deficiency (PKD), the most common cause of hereditary non‐spherocytic haemolytic anaemia, remains challenging in routine practice and no biomarkers for clinical severity have been characterised. This prospective study enrolled 41 patients with molecularly confirmed PKD from nine North American centres to evaluate the diagnostic sensitivity of pyruvate kinase (PK) enzyme activity and PK:hexokinase (HK) enzyme activity ratio, and evaluate the erythrocyte PK (PK‐R) protein level and erythrocyte metabolites as biomarkers for clinical severity. In this population not transfused for ≥90 days before sampling, the diagnostic sensitivity of the PK enzyme assay was 90% [95% confidence interval (CI) 77–97%], whereas the PK:HK ratio sensitivity was 98% (95% CI 87–100%). There was no correlation between PK enzyme activity and clinical severity. Transfusion requirements correlated with normalised erythrocyte ATP levels ( r  = 0·527, P  = 0·0016) and PK‐R protein levels ( r  = −0·527, P  = 0·0028). PK‐R protein levels were significantly higher in the never transfused [median (range) 40·1 (9·8–73·9)%] versus ever transfused [median (range) 7·7 (0·4–15·1)%] patients ( P  = 0·0014). The PK:HK ratio had excellent sensitivity for PK diagnosis, superior to PKLR exon sequencing. Given that the number of PKLR variants and genotype combinations limits prognostication based on molecular findings, PK‐R protein level may be a useful prognostic biomarker of disease severity and merits further study.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1475751-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: American Journal of Hematology, Wiley, Vol. 95, No. 10 ( 2020-10)
    Type of Medium: Online Resource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1492749-4
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 949-949
    Abstract: Background: Pyruvate kinase deficiency (PKD) is the most common cause of chronic hereditary non-spherocytic hemolytic anemia. The spectrum of disease in PKD is broad, ranging from an incidentally discovered mild anemia to a severe transfusion-dependent anemia. Splenectomy partially ameliorates the anemia and reduces the transfusion burden in the majority of patients. Because hemoglobin poorly correlates with symptoms in PKD, transfusion requirements are typically used clinically to classify disease severity with those who are regularly transfused despite splenectomy recognized as the most severely affected subgroup. Aim: To compare demographics, complications, and laboratory results between the most severely-affected PKD patients (those that are splenectomized and regularly transfused) with non-regularly transfused splenectomized PKD patients. Methods: After ethics committee approval, patients were enrolled on the PKD Natural History Study, a prospective 30 site international study. All patients had molecularly confirmed PKD. Only splenectomized patients were included in the analysis. Transfusion frequency was observed over a 3-year period. Patients were divided into two groups based on transfusion frequency: the severe phenotype group was defined as those who receive regular transfusions (≥6 discrete red cell transfusion episodes per year) and the control group did not receive regular transfusions. Phenotype stability over the 3-year period was also assessed. Results: 154 splenectomized patients with PKD were included: 30 patients in the severe PKD phenotype group and 124 patients in the comparison PKD group. Results of the analysis comparing the two groups are described in the Table. Severely affected patients were more likely to be female (77% versus 51%, p=0.013), older at the time of splenectomy (median age: 5 versus 3.6, p=0.011), have iron overload (93% vs. 51%, p & lt;0.0001), have received chelation therapy (90% vs. 42%, p & lt;0.0001), and had more lifetime transfusions (median: 77 versus 15, p & lt;0.0001). Rates of other PKD complications including pulmonary hypertension, extramedullary hematopoiesis, liver cirrhosis, endocrinopathy, and bone fracture appear similar between the two groups. Laboratory values, including hemoglobin, total bilirubin, normalized PK enzyme activity, and median absolute reticulocyte count appear similar between the two groups. The underlying genetic mutation patterns (missense mutations versus non-missense mutations) were also similar between the groups. Phenotype stability over time was highly variable: of the patients with a severe phenotype at enrollment, 62% had a severe phenotype during the first follow-up year and 39% had a severe phenotype at the second follow-up year. Conclusions: Patients with PKD who are regularly transfused despite splenectomy appeared to have similar rates of PKD-associated complications (except for iron overload) and similar relevant laboratory values and genotypes when compared to those who are not regularly transfused after splenectomy. The similarity observed between severe phenotype patients and comparison patients with PKD may result from a protective effect of transfusion (e.g. reduction of bone fractures and extramedullary hematopoiesis) or could suggest transfusion-dependence is an artificial signifier of disease severity, reflective of provider practices and patient symptoms rather than an actual distinct phenotype. Transfusion requirements in severe PKD appear to fluctuate significantly over time. Disclosures Al-Samkari: Dova: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Moderna: Consultancy. van Beers:RR Mechatronics: Research Funding; Agios Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Research Funding. Barcellini:Agios: Consultancy, Other: Advisory board; Apellis: Consultancy; Incyte: Consultancy, Other: Advisory board; Bioverativ: Consultancy, Other: Advisory board; Novartis: Research Funding, Speakers Bureau; Alexion: Consultancy, Research Funding, Speakers Bureau. Eber:Agios Pharmaceuticals, Inc.: Consultancy. Glader:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chonat:Alexion: Other: advisory board; Agios Pharmaceuticals, Inc.: Other: advisory board. Kuo:Pfizer: Consultancy; Novartis: Consultancy, Honoraria; Celgene: Consultancy; Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy. Despotovic:Dova: Honoraria; Novartis: Research Funding; Amgen: Research Funding. Kwiatkowski:Celgene: Consultancy; Terumo: Research Funding; Apopharma: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding; Agios: Consultancy; Imara: Consultancy; Novartis: Research Funding. Thompson:Baxalta: Research Funding; Novartis: Consultancy, Research Funding; bluebird bio, Inc.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Ravindranath:Agios Pharmaceuticals, Inc.: Other: I am site PI on several Agios-sponsored studies, Research Funding. Rothman:Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Agios: Honoraria, Research Funding. Verhovsek:Sickle Cell Awareness Group of Ontario: Membership on an entity's Board of Directors or advisory committees; Sickle Cell Disease Association of Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding; Canadian Haemoglobinopathy Association: Membership on an entity's Board of Directors or advisory committees; Vertex: Consultancy. Kunz:Novartis: Membership on an entity's Board of Directors or advisory committees. Sheth:CRSPR/Vertex: Other: Clinical Trial Steering committee; Apopharma: Other: Clinical trial DSMB; Celgene: Consultancy. London:United Therapeutics: Consultancy; ArQule, Inc: Consultancy. Grace:Novartis: Research Funding; Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3515-3515
    Abstract: Background: Pyruvate Kinase (PK) deficiency is caused by mutations in the PKLR gene leading to chronic hereditary non-spherocytic hemolytic anemia. Diagnostic evaluation can be challenging with falsely normal PK enzyme activity levels in chronically transfused patients, in those with profound reticulocytosis, or in patients with mutations with unusual biochemical properties. Genetic testing can also be complex, as up to 20% of affected patients have new PKLR variants and up to 10% of patients have variants not routinely detected through exon sequencing. The phenotypic spectrum is broad, and biomarkers of clinical severity would be helpful for both prognosis and monitoring. Aims: To describe the correlation of PK enzyme activity, red cell PK (PK-R) protein level, and red cell metabolites [adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG)] with clinical phenotype. To estimate the sensitivity of PK enzyme activity to diagnose PK deficiency in a cohort of patients with genetically confirmed PK deficiency. Methods: Blood samples were collected from a subset of 41 patients enrolled in the PK Deficiency Natural History Study, all with two confirmed PKLR mutations and no red cell transfusions for ≥3 months prior to the blood sample. PK and hexokinase (HK) enzyme activity testing were performed using standard biochemical assays (Beutler 1985) at the Stanford Red Blood Cell Special Studies Laboratory (normal ranges: PK activity: 3.2-6.5 EU/gm Hb, HK activity: 0.14-0.37 EU/gm Hb). Baseline PK-R protein was quantitated by antibody-based capture and detection using a Meso Scale assay and the signal normalized to a control sample without PK deficiency. ATP and 2,3-DPG concentrations (μg/ml) in blood were analyzed using qualified tandem mass spectrometry methods and then normalized for individual hemoglobin (Hb) values (ATP and 2,3-DPG concentrations were converted to g/dL and divided by Hb (g/dL)). Spearman correlation coefficients were calculated to estimate the correlation between continuous variables, and Wilcoxon rank-sum testing was used to assess the association of continuous and binary variables. Results: The median age was 25.3 years (range 1.4-60.4) and 80% of patients were splenectomized (Table). The mean PK enzyme activity level was 1.1 EU/gm Hb with 90% (37/41) of patients with low PK activity. Normal PK activity was observed in 4 patients, 3 of whom had high HK activity and a low PK/HK ratio (normal mean PK/HK ratio 15.6, range: 8.7-22.5), with a sensitivity of 98% (40/41) when both PK activity and PK/HK ratio were used together. There were no correlations between PK enzyme activity and clinical severity indicators, including transfusion status (p=0.3), splenectomy status (p=0.4), or post-splenectomy Hb (r=0.109). Normalized ATP levels were significantly correlated with normalized 2,3-DPG levels (r=0.93) and higher in ever transfused (median=0.0022, range=0.0011-0.0029) compared with never transfused patients (median=0.0012 , range=0.0008-0.0020), (p=0.004). PK-R protein level was inversely correlated with the total number of transfusions prior to enrollment (r= -0.53) and was higher in never transfused (median=40.1%, range=9.8-73.9%) compared with ever transfused patients (median=7.7%, range=0.4%-15.1%), (p=0.0014). Conclusions: In this cohort with a molecularly confirmed diagnosis, PK deficiency was detected by enzyme testing with 98% sensitivity by utilizing both the PK activity and the PK/HK ratio. Although these assays cannot distinguish between heterozygotes and affected patients, the combination of PK activity and the PK/HK ratio is useful as a screening test to determine which patients require genetic testing. There was no correlation between PK enzyme activity and clinical phenotype. PK-R protein and ATP levels were inversely correlated with clinical severity and may be a helpful marker of disease phenotype. Disclosures Al-Samkari: Agios: Consultancy, Research Funding; Moderna: Consultancy; Dova: Consultancy, Research Funding. Glader:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chonat:Alexion: Other: advisory board; Agios Pharmaceuticals, Inc.: Other: advisory board. Thompson:bluebird bio, Inc.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Baxalta: Research Funding. Kuo:Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy. Ravindranath:Agios Pharmaceuticals, Inc.: Other: I am site PI on several Agios-sponsored studies, Research Funding. Rothman:Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Agios: Honoraria, Research Funding. Kwiatkowski:Celgene: Consultancy; Terumo: Research Funding; Imara: Consultancy; Apopharma: Research Funding; Novartis: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding; Agios: Consultancy. Kung:Agios Pharmaceuticals, Inc: Employment, Other: Stakeholder. Kosinski:Agios Pharmaceuticals, Inc: Employment, Other: Stakeholder. London:United Therapeutics: Consultancy; ArQule, Inc: Consultancy. Grace:Novartis: Research Funding; Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 45-46
    Abstract: Introduction: Despite publication of standardized platelet count response definitions by the immune thrombocytopenia (ITP) International Working Group (IWG) in 2009, there remains considerable variability in the definition of platelet count outcomes across ITP studies. Moreover, there is no widely-accepted bleeding scale, health-related quality of life (HRQoL) inventories, or definition of remission for use in ITP patients, all critical outcome measures not addressed in the IWG Report. This heterogeneity makes comparison of response rates and outcomes between studies challenging. Therefore, to better understand current practices and inform future standardization efforts, we performed a systematic review of ITP studies to characterize how these outcomes have been measured in the decade following publication of the IWG Report. Methods: We performed a systematic review of PubMed/MEDLINE-indexed manuscripts published from January 1, 2010 through December 31, 2019 that described a platelet count, bleeding, and/or HRQoL measure in reflection of treatment response in adult and pediatric ITP. Following initial search, two authors (H.A. and R.G.) screened each abstract for inclusion, then read each included full text manuscript to collect outcome measures. Interventional studies with ≥10 patients and observational studies with ≥50 patients were included; manuscripts without abstracts and non-English language manuscripts were excluded. Results: Studies. The PubMed/MEDLINE search revealed 1562 manuscripts; following abstract screening and manuscript review, 168 manuscripts met inclusion criteria for the study. Of the 168 studies, 110 studies evaluated adults, 41 evaluated children, and 17 evaluated both adults and children; 99 were prospective (including 32 randomized trials) and 69 were retrospective observational studies. Platelet Outcomes. 141 studies (including 28 randomized trials, 53 non-randomized prospective studies and 60 retrospective observational studies) reported platelet response outcomes and 11 reported platelet count remission definitions. Of the 141 reporting response outcomes, 61 (43%) used IWG definitions and 80 (57%) did not. Of these 80 studies, there were a total of 21 distinct platelet count outcome definition schemes (Figure 1). The majority of randomized trials (22/28, 79%) and other prospective studies (37/53, 70%) did not use IWG definitions; instead, a plurality of these studies used a Plt ≥50 × 109/L to define a treatment response, without definitions for complete, partial, or minor response. Most retrospective observational studies (39/60, 65%), however, used IWG definitions. Of the 11 studies reporting remission definitions, a platelet count of ≥100 × 109/L with or without treatment over a time period of ≥6 months was the most commonly used definition of remission, although a minority of studies used thresholds of ≥50 × 109/L or ≥150 × 109/L. Bleeding Outcomes. Bleeding outcomes were reported in a systematic fashion in only a minority of studies (67/168, 36%), which used a total of 21 distinct bleeding outcome reporting schemes. A plurality of adult studies used the WHO Bleeding Scale and a plurality of pediatric studies used the Buchanan and Adix Score, Figure 2. HRQoL Outcomes. HRQoL outcomes were reported in a small minority of studies (15/168, 9%), which used a total of 8 different HRQoL instruments (6 adult instruments and 2 pediatric instruments), Table. Conclusions: Despite prior attempts to standardize evaluation of platelet response to treatment in ITP, there remains wide variability in the definition of both treatment response and remission. In particular, most prospective and randomized studies published following release of the 2009 IWG report have used study-specific platelet count response thresholds, whereas retrospective observational studies were much more likely to adopt the IWG-recommended platelet response definitions. Despite the fact that ITP is a bleeding disorder and its impact on HRQoL has been well-documented, most ITP studies published in the past decade did not evaluate bleeding in any systematic way and fewer still evaluated the impact of treatment on HRQoL. Further standardization of platelet count, bleeding, and HRQoL outcomes in both pediatric and adult ITP is greatly needed, especially for future randomized trials, to allow for more meaningful comparison of response rates and efficacy between studies. Disclosures Al-Samkari: Agios: Consultancy, Research Funding; Argenx: Consultancy; Amgen: Research Funding; Dova: Consultancy, Research Funding; Rigel: Consultancy. Arnold:Novartis: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Principia: Consultancy. Grace:Novartis: Research Funding; Dova: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Agios: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 8159-8160
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Online Resource
    Online Resource
    American Society of Hematology ; 2021
    In:  Blood Vol. 137, No. 7 ( 2021-02-18), p. 888-895
    In: Blood, American Society of Hematology, Vol. 137, No. 7 ( 2021-02-18), p. 888-895
    Abstract: Hereditary hemorrhagic telangiectasia (HHT) management is evolving because of the emergence and development of antiangiogenic therapies to eliminate bleeding telangiectasias and achieve hemostasis. This progress is reflected in recent clinical recommendations published in the Second International Guidelines for the Diagnosis and Treatment of HHT, in which systemic therapies including antiangiogenics and antifibrinolytics are now recommended as standard treatment options for bleeding. This review highlights the new recommendations especially relevant to hematologists in managing bleeding, anticoagulation, and anemia in patients with HHT.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Online Resource
    Online Resource
    American Society of Hematology ; 2021
    In:  Blood Vol. 138, No. Supplement 1 ( 2021-11-05), p. 584-584
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 584-584
    Abstract: INTRODUCTION: Chemotherapy-induced thrombocytopenia (CIT) is a common complication of cancer therapy. Due to the lack of FDA-approved therapies for CIT and clear limitations of platelet transfusions, clinicians often must choose between reducing dose intensity, delaying treatment, switching to an alternative regimen less prone to thrombocytopenia, or even discontinuing therapy altogether. Lower overall survival in CIT is associated with bleeding complications in patients proceeding with chemotherapy as well as patients managed with reductions in relative dose intensity of chemotherapy due to dose reduction and/or treatment delay. Although there are no current FDA-approved therapies for CIT, evidence has emerged supporting use of romiplostim to treat CIT. However, predicting clinical response to romiplostim before initiation is not currently possible due to the lack of a known predictive biomarker. Baseline endogenous TPO levels may, however, be a predictive biomarker for response to thrombopoietin receptor agonists. Prior studies have demonstrated the utility of baseline TPO level to predict romiplostim response in ITP and avatrombopag response in thrombocytopenia of chronic liver disease. Because measurement of TPO level prior to romiplostim treatment of CIT is standard at our institution, we investigated the utility of baseline TPO level to predict romiplostim response in CIT. METHODS: We performed an observational study of patients age ≥18 years who had TPO levels measured and received romiplostim for the treatment of CIT. For each weekly on-romiplostim platelet (Plt) count assessment, clinical response was defined as Plt ≥75×10 9/L and ≥30×10 9/L above pretreatment baseline. Overall, moderate, and superior classes of treatment response were defined based on response fraction (RF) of weekly Plt assessments meeting clinical response criteria (RF & gt;0, ≥ 0.6, and ≥ 0.8, respectively). Median TPO levels were compared in those patients with and without a moderate response or a superior response using the Mann-Whitney U test. A generalized linear model was used to model the logit transformation of RF to predict response fraction based on TPO level. Receiver operating characteristic (ROC) analysis was performed to identify TPO level thresholds for optimal discrimination of those who achieved moderate and superior responses from those who did not. RESULTS: Patients: 63 patients met inclusion criteria. Baseline patient characteristics are detailed in TABLE 1. Relation of TPO Level and Romiplostim Response: Median (IQR) TPO level was lower in patients who achieved a moderate response to romiplostim versus those who did not, 234 (135-1085) pg/mL versus 665 (244-1970) pg/mL (P=0.034) and lower still in patients who achieved a superior response versus those who did not, 212 (91-690) pg/mL versus 559 (173-1851) pg/mL (P=0.023) (FIGURE 1). A generalized linear model demonstrated a significantly higher predicted response fraction as TPO level declined (P=0.036, Figure 2). TPO level was significantly correlated with lowest effective romiplostim dose (r=0.27, P=0.049). Optimal TPO Thresholds for Predicting Response: Utilizing Youden's index, the optimally discriminant TPO level threshold for moderate response to romiplostim was ≤457 pg/mL, which predicted a 61% probability of response in those with a TPO level ≤457 pg/mL and a 65% probability of non-response in those with a TPO level & gt;457 pg/mL (Figure 3A). The optimally discriminant TPO level threshold for superior response to romiplostim was ≤260 pg/mL, which predicted a 59% probability of response in those with a TPO level ≤260 pg/mL and a 70% probability of non-response in those with a TPO level & gt;260 pg/mL (Figure 3B). A near trivial response rate was associated with extreme TPO elevations (e.g., 7% for TPO level & gt;1978 pg/mL, Figure 3). CONCLUSION: Lower TPO levels predict for a higher likelihood and depth of response to romiplostim in CIT, extreme TPO elevations predict strongly for non-response, and higher doses of romiplostim may be needed in patients with moderate TPO elevations to achieve a response. Considering the significant impact of CIT on patient outcomes as a result of treatment delays and dose reductions, baseline serum TPO level in patients with CIT may be a clinically useful biomarker in predicting response to romiplostim, and therefore potentially useful in guiding patient selection and dosing. Figure 1 Figure 1. Disclosures Kuter: Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, CRICO, Daiichi Sankyo, Dova, Genzyme, Immunovant, Incyte, Kyowa-Kirin, Merck Sharp Dohme, Momenta, Novartis, Pfizer, Principia, Protalex, Protalix, Rigel: Consultancy, Other: grant support and consulting fees; Up-to-Date: Patents & Royalties: Up-To-Date; Rubius: Current equity holder in publicly-traded company; Platelet Disorder Support Association: Membership on an entity's Board of Directors or advisory committees; Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol Myers Squibb (BMS), Immunovant, Kezar, Principia, Protalex, Rigel, Takeda (Bioverativ), UCB: Research Funding. Al-Samkari: Novartis: Consultancy; Rigel: Consultancy; Moderna: Consultancy; Argenx: Consultancy; Amgen: Research Funding; Dova/Sobi: Consultancy, Research Funding; Agios: Consultancy, Research Funding. OffLabel Disclosure: Romiplostim is a thrombopoietin-receptor agonist (TPO-RA) used off-label for chemotherapy-induced thrombocytopenia. TPO-RAs are well-established in the treatment of numerous etiologies of thrombocytopenia, including immune thrombocytopenia (ITP), aplastic anemia, and thrombocytopenia of chronic liver disease.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages