Myeloproliferative (MPN) Symptom Burden Response Thresholds: Assessment Of MPN-SAF TSS Quartiles As Potential Markers Of Symptom Response

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4067-4067 ◽  
Author(s):  
Robyn M. Emanuel ◽  
Amylou Constance Dueck ◽  
Holly Lynn Geyer ◽  
Jean-Jacques Kiladjian ◽  
Stephanie Slot ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Symptom Burden ◽  
Symptom Assessment ◽  
Response To Therapy ◽  
Risk Scores ◽  
Individual Risk ◽  
Advisory Committees ◽  
Symptom Response ◽  
History Of ◽  
Response Thresholds

Abstract Background We have previously reported on the significant, but heterogeneous baseline MPN symptom burden among an international sample of MPN patients (including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)) utilizing the MPN Symptom Assessment Form (MPN-SAF) and the derivative Total Symptom Score (MPN-SAF TSS). Recent clinical trials have sought to determine optimal MPN symptom response criteria, such as absolute 10 point improvement in MPN SAF TSS for ET/PV (ELN Criteria, Barosi et. al. Blood 2013) and 50% reduction in MPN-SAF TSS for MF (IWG-MRT, Tefferi et. al. Blood 2013). We sought to determine the role of improvement in MPN-SAF TSS quartiles as potential thresholds to assess symptomatic response to therapy. Methods Utilizing prospectively gathered MPN-SAF TSS (Emanuel et. al. JCO 2012) in patients we assessed potential thresholds of response by evaluating quartile thresholds for severity of symptom burden. The MPN-SAF TSS was scored as the average of 10 symptoms (individual symptoms scores of 0-10, with a total score of 0 (best) to 100 (worst)). MPN-SAF TSS quartiles were identified by the percentage of scores between 0-24% (quartile 1 (Q1)), 25-49% (quartile 2 (Q2)), 50-74% (quartile 3 (Q3)), 75-100% (quartile 4 (Q4)). Results MPN-SAF TSS Quartiles: MPN-SAF TSS quartiles were identified among 1858 MPN patients (ET N=775, PV N=654, and MF N=423). Overall MPN-SAF TSS scores of 0 - 7 were designated as Q1, 8 - 17 as Q2, 18 - 31 as Q3, and ≥ 32 was as Q4. MPN-SAF TSS scores were significantly different between clusters (p<0.001). Associations Between Quartiles and Demographic/ Disease Factors: As quartiles increased, the proportion of PV and ET patients diminished and MF increased (Table 1, p<0.001). Cytopenias and transfusion dependence increased in prevalence in the higher quartiles (p<0.001). A history of prior thrombosis was also significantly more prevalent in the quartiles with highest symptom burden (p<0.001). The prevalence of women was significantly higher among the more symptomatic quartiles females 48.9% Q1, 49.4% Q2, 58.4% Q3, and 60.1% Q4; p<0.001). Associations Between Individual Symptoms and MPN-SAF TSS Quartiles: All individual symptoms measured in the MPN-SAF TSS were significantly worse in quartiles as they increased (p<0.0001). Evaluation of Prognostic Scoring and MPN-SAF TSS Quartiles: Comparison of each patients individual risk score (IPSET, PV, DIPSS for MF) and worsening symptom quartile showed the highest correlation with MF patients (DIPSS) (Table 1). However, ET and PV risk scores were not surrogates for symptom burden by quartile. Conclusions Distribution of MPN patient symptomatic burden by MPN-SAF TSS quartiles provides an easy-to-calculate method to cluster and analyze MPN patients of similar burden. Although MF patients are most prevalent in the most severe quartile of MPN symptomatology it is notable that Q4 has many patients with PV and ET. Future prospective efforts are ongoing to assess the potential of using changes in quartile (i.e. improving from Q3 to Q1) as potential symptomatic response thresholds. Disclosures: Etienne: novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Shire: Speakers Bureau; Celgene: Honoraria; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vannucchi:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria.

scholarly journals Unmet Needs for Symptom Control in Essential Thrombocythemia with Front Line Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5175-5175
Author(s):  
Holly Geyer ◽  
Robyn M. Scherber ◽  
Heidi Kosiorek ◽  
Amylou C. Dueck ◽  
Jean-Jacques Kiladjian ◽  
...  
Keyword(s):  
High Risk ◽  
Blood Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Symptom Burden ◽  
Red Blood Cell Transfusion ◽  
Risk Scores ◽  
Advisory Committees ◽  
Transfusion Requirements ◽  
History Of

Abstract Background: Thrombotic and hemorrhagic complications are commonly encountered in uncontrolled essential thrombocythemia (ET). Both anagrelide and hydroxyurea (HU) have proven efficacious in cytoreduction as well as reducing these events and remain first line therapy for most high-risk ET patients. Independent of their role in risk-reduction, little is known about how these therapies impact patient symptomatology or quality of life. In this study, we compared the clinical and symptomatic profiles of ET patients receiving HU or anagrelide against patients with no previous experience with these agents. Methods: Data was assessed from a prospectively collected international database of ET patients in which demographics, disease features, and ET symptoms utilizing the myeloproliferative neoplasm symptom assessment form (MPN-SAF; Scherber et al, 2011). The MPN-SAF includes the patient's perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Total symptom score (TSS) was computed based on symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. ET risk scores were calculated using the IPSET scoring algorithm (Passamonti 2012). Thrombocytopenia was defined as a platelet count <100 x 10(9)/L, anemia was defined as hemoglobin<10 g/dL and leukopenia was defined as a white blood cell count <4.0 x 10(9)/L. Associations between the MPN-SAF individual symptoms were investigated using chi-square test for categorical data and ANOVA F-test for continuous variables. Results Hydroxyurea vs. HU Naive A total of 402 ET patients with active HU use were compared to 392 ET patients with no history of HU use. Patients using HU were older (63.5 years vs. 52.3 years, p<0.001) and had a greater concentration of both high risk (24.9% vs. 11.4%, p=0.001) and intermediate risk (53.9% vs 38.4%, p<0.001) patients. They also had a higher rate of prior thrombosis (29.8% vs 11.3%, p<0.001) and leukopenia (10.1% vs. 3.0%, p<0.001). No differences were noted between gender, a history of prior hemorrhage, red blood cell transfusion requirements, or the presence of anemia/thrombocytopenia. In comparing symptom profiles, no significant differences were noted between TSS or individual symptoms with the exception of slightly more severe cough in HU patients (1.5 vs. 1.1, p=0.02, Figure 1). Anagrelide vs. Anagrelide Naive A total of 49 ET patients with active anagrelide use were compared to 794 ET patients with no history of anagrelide use. Patients using anagrelide had a longer mean disease duration (8.1 years vs. 5.8 years) and were more anemic (9.1% vs. 1.2%, p<0.001). No differences were noted between age, gender, risk scores, the presence of leukopenia/thrombocytopenia, a history of prior thrombosis or hemorrhage complications or red blood cell transfusion requirements. Additionally, there were no significant differences between TSS or individual symptom items (Figure 1). HU vs. Anagrelide A total of 402 patients currently using HU were compared to 39 patients currently using anagrelide. Overall, HU users were slightly older (63.5 years vs. 55.1 years, p<0.001) with a greater population of patients meeting high risk criteria (24.9% vs. 2.8%, p=0.002) and having a history of prior thrombosis (29.8% vs. 12.8%, p=0.02). Patients receiving anagrelide had a slightly longer disease duration (8.2 years vs. 6.0 years, p=0.0446). In comparing symptom profiles, no differences were noted in TSS or individual symptom items between cohorts. Discussion In this retrospective analysis, it does not appear cytoreduction with either HU and/or anagrelide has a significant impact on ET symptom burden despite reducing vascular events. Importantly, the higher risk scores in HU patients did not translate directly into greater patient symptomatology supporting previous studies demonstrating a poor association between these two items. Prospective trials measuring ET symptom change, in the setting of randomized trials will better quantify impact of cytoreduction on symptom burden as well as quantify impact of newer agents such as interferon or jak inhibition. Figure 1. Symptom Comparisons Between HU, Anagrelide and Other Therapy Figure 1. Symptom Comparisons Between HU, Anagrelide and Other Therapy Disclosures Kiladjian: Incyte Corporation: Consultancy; Novartis: Other: Travel grant; Research Funding paid to institution (Hôpital Saint-Louis et Université Paris Diderot); Novartis: Consultancy. Zweegman:Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Sanofi: Honoraria, Speakers Bureau; Shire: Speakers Bureau; Gilead: Honoraria; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Cervantes:Sanofi-Aventis: Consultancy; Novartis: Consultancy, Speakers Bureau; CTI-Baxter: Consultancy, Speakers Bureau. Barbui:Novartis: Speakers Bureau. Etienne:ARIAD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Congress Travel/Accomodations, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Roy:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding. te Boekhorst:Novartis: Consultancy; CTI Biopharma: Consultancy. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees. Mesa:Novartis. Research- incyte, Gilead, cti, Genentech, promedior, NS Pharma: Consultancy.

Symptom Burden and Health-Related Quality Of Life (HRQoL) In Patients With Myelofibrosis (MF) Treated With Fedratinib (SAR302503) In a Phase III Study (JAKARTA)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4061-4061 ◽  
Author(s):  
Ruben A. Mesa ◽  
Jorge E. Cortes ◽  
Francisco Cervantes ◽  
Donald Milligan ◽  
Tamás Masszi ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Symptom Burden ◽  
Phase Iii ◽  
Spleen Volume ◽  
Advisory Committees ◽  
Night Sweats ◽  
Symptom Response ◽  
Phase Iii Study ◽  
Ecog Ps

Abstract Introduction Fedratinib (SAR302503), a JAK2-selective inhibitor, has demonstrated clinical improvements in splenomegaly and constitutional symptoms in patients with MF in Phase I/II trials (J Clin Oncol 2011;29:789. Haematologica 2013;98:S1113). The aim of this primary analysis was to determine the effect of fedratinib on key MF symptom burden and global assessment of HRQoL in the JAKARTA trial (NCT01437787). Methods JAKARTA is a double-blind, placebo-controlled, international, 3-arm, Phase III study, in which patients ≥18 years of age with intermediate- or high-risk MF, platelet count ≥50 × 109/L, and splenomegaly were randomized (1:1:1) to receive placebo or fedratinib at a dose of 400 or 500 mg, orally, once daily, in consecutive 4-week cycles. Total symptom score (TSS), a key efficacy end point (TSS: averaged daily total score of 6 item measures over 1 week: night sweats, pruritus, abdominal discomfort, early satiety, pain under ribs on left side, and bone or muscle pain), was assessed through a daily electronic eDiary using the modified Myelofibrosis Symptom Assessment Form (MFSAF; Cancer 2011;117:4869. Blood 2011;118:401), with symptom response defined as a ≥50% reduction in TSS at the end of Cycle 6 (EOC6). HRQoL was assessed using the EuroQOL (EQ)-5D instrument that was completed at baseline and EOC6. Patient performance was assessed using the Eastern Cooperative Oncology Group Performance Scale (ECOG PS). Spleen volume was measured by MRI or CT at baseline and EOC6. Results In JAKARTA, a total of 289 patients were randomized: median age 65 years; 59% male; 63% primary MF; 48% high-risk MF; 67% JAK2V617F positive; 16% platelet count <100 × 109/L. The symptom evaluable population comprised 261 patients (placebo [n=82]; 400 mg [n=89]; 500 mg [n=90]). The mean (SD) baseline TSS was 14.6 (11.9), 17.6, (13.5), and 16.9 (11.9) in the placebo, 400 mg, and 500 mg groups, respectively. At Week 24 (EOC6), the proportion of patients with a symptom response was significantly higher (p<0.0001) in the 400 and 500 mg groups versus placebo (Table). Symptom responses with fedratinib were also higher than placebo in the subgroup of patients with baseline platelets <100 × 109/L (Table). For individual symptoms, the greatest improvements were seen for night sweats and early satiety (Table). Baseline HRQoL (EQ-5D, mean [SD]) was similar in the three groups (placebo: 62.5 [21.2]; 400 mg: 61.3 [22.2]; 500 mg: 60.1 [20.1]). Fedratinib treatment led to improvements in HRQoL from baseline to Week 24, whereas placebo treatment led to slight worsening of HRQoL (Table). At Week 24, the degree of improvement in TSS was greatest in patients with ≥35% reduction in spleen volume from baseline (Figure). Mean TSS improvement was correlated with improvement in HRQoL (TSS reductions were greater in EQ-5D improvers versus non-improvers), and ECOG PS (TSS reductions were greater in patients with ECOG PS 1 or 2 score improvement versus those with ECOG PS worsening). Conclusions Fedratinib treatment over 24 weeks led to significant improvements in MF symptoms versus placebo. Patients treated with fedratinib also experienced substantial improvements in HRQoL versus placebo. Symptom improvements were associated with spleen responses. This study was sponsored by Sanofi. Disclosures: Mesa: Incyte, Genentech, Lilly, MS Pharma, Gilead: Research Funding. Cortes:Incyte, Sanofi: Consultancy; Incyte, Sanofi: Research Funding. Cervantes:Novartis: Speakers Bureau; Novartis and Sanofi: Membership on an entity’s Board of Directors or advisory committees. Jourdan:Sanofi: Honoraria. Vannucchi:Novartis: Membership on an entity’s Board of Directors or advisory committees. Drummond:TargeGen, Novartis: Speakers Bureau; Sanofi, Novartis, Celgene: Honoraria; Sanofi, Novartis, Celgene: Consultancy. Passamonti:Novartis, Celgene, Incyte, Sanofi, Roche: Honoraria. Neumann:Sanofi: Employment. Joulain:Sanofi: Employment. Iqbal:Sanofi: Employment. Harrison:Novartis: Research Funding; Novartis, Sanofi, YM Bioscience, Celgene, SBio, Gilead: Honoraria; Novartis, Sanofi, Shire: Speakers Bureau; Novartis, Sanofi, YM Bioscience, SBio, Gilead: Membership on an entity’s Board of Directors or advisory committees.

Symptom Burden As Primary Driver for Therapy in Patients with Myelofibrosis: An Analysis By MPN International Quality of Life Study Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3117-3117 ◽  
Author(s):  
Robyn M. Scherber ◽  
Holly Geyer ◽  
Amylou Constance Dueck ◽  
Heidi E. Kosiorek ◽  
Jean-Jacques Kiladjian ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Symptom Score ◽  
Research Funding ◽  
Prognostic Score ◽  
Symptom Burden ◽  
Individual Item ◽  
Item Score ◽  
Advisory Committees ◽  
History Of ◽  
Symptom Criteria

Abstract BACKGROUND: The presence of constitutional symptoms has been associated with increased mortality risk in myelofibrosis (MF) (Blood 2010;115(9):1703-8). New therapies exist which alleviate the severe symptom burden profile observed in MF patients but are only approved for use in those with intermediate-2 or high risk disease (N Engl J Med 2012;366:787-798). However, it has been proposed that there are patients who may benefit from symptom based treatment regardless of prognostic score (Am Soc Hematol Educ Program 2014;2014:277-286). We have recently characterized symptom score cutoffs at which patients would statistically benefit from treatment based on symptom scores alone (Scherber et. al. EHA 2016: a2250). These treatment thresholds included aMyeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS or MPN-10) total score of greater than or equal to 20, a worst individual item score of greater than 5, or a combined criteria of those with both an MPN-10 total score of greater than or equal to 20 and a worst individual item score greater than 5. This abstract represents an additional analysis of our MF cohort to better characterize the profile of patients who meet criteria for symptom-based therapy. METHODS: Patient demographics, symptom burden via the MPN-10 score (JCO 2012;30(33)4098-103), and disease traits were collected from MF patients and their physicians at a single time point during therapy. Previously we identified MPN-10 cutoffs via AkaikeÕs Information Criterion (AIC) analysis (Ecology 2014;95: 631-6), which represented the optimal model among all models specified for the data at hand to determine which patients would most benefit from symptom-directed therapy. RESULTS: Demographics. 695 MF patients without previousruxolitinib therapy were included in this analysis. Overall, of 455 patients (65.4%) fit a cutoff of having a single worst symptom item of greater than 5/10. 401 patients (57.7%) had a MPN-10 score of equal to or greater than 20. A total of 381 (54.8%) patients fit both of these criteria. A distribution of worse MPN-10 individual scores is shown in Table 1. Mean TSS score was 26.4 (SD=17.7). Symptom Criteria Associations. Demographics and disease traits: Neither mean age or age greater than 60 was significantly associated with meeting any of the symptom score cutoff criteria. Females were significantly more likely to meet any of the symptom score cutoffs (for all criteria, p=0.0003 or less). Patients with splenomegaly, particularly spleen size of greater than 15cm below the LCM, were significantly more likely than those with a normal sized spleen to meet any of the three criteria (spleen enlargement of any size p=0.014 or less; spleen greater than 15cm p=0.0114 or less). Patients who met any of the three symptom criteria tended to have a longer MPN duration, although this trend did not meet significance. A prior history of thrombosis was not associated with achieving any cutoff criterions. Symptom burden: Individuals who met the any symptom criteria were significantly more likely to have higher DIPSS prognostic risk score (for all p=0.0002 or less). Laboratory values: For those meeting criteria for a worst symptom greater than 5, mean WBC was 11.7 vs 9.1 x 109/L (p=0.025) and platelet count was 238.7 versus 329.1 (p=0.023). For those meeting criteria for a TSS greater than or equal to 20, mean WBC was 11.8 vs 9.5 x 109/L (p=0.04). For individuals meeting both criteria, mean WBC was 11.9 vs 9.5 x 109/L (p=0.034). The presence of peripheral blasts were significantly more common in patients with an individual worst symptom score greater than 5 (p=0.0364). Hemoglobin level was not significantly associated with symptom criteria for any cutoffs. CONCLUSION: Our analysis indicates that patients who would be treated based on symptom criteria are similar to patients who would be treated based on high risk features such as high DIPSS prognostic score, concerning blood count abnormalities (i.e., leukocytosis, thrombocytopenia, presence of peripheral blasts), and splenomegaly (particularly massive splenomegaly). Thrombosis history and age were not associated with criterion cutoff assignment, and it is notable that elderly age nor history of thrombosis alone would likely alter treatment choice other than anticoagulation. This data supports that JAK2 inhibitor treatment be strongly considered in patients meeting symptom based criteria. Disclosures Dueck: Bayer: Honoraria. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zweegman:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Schouten:Sanofi: Consultancy; Novartis: Consultancy. Etienne:ARIAD: Speakers Bureau; Pfizer: Speakers Bureau; novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau. Harrison:Shire: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Incyte Corporation: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. Radia:Novartis: Honoraria; Pfizer: Honoraria. Cervantes:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan: Membership on an entity's Board of Directors or advisory committees. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mesa:Promedior: Research Funding; Celgene: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy.

scholarly journals Unifying the Definition of High-Risk in Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2714-2714
Author(s):  
Ariel Siegel ◽  
Eileen M Boyle ◽  
Patrick Blaney ◽  
Yubao Wang ◽  
Hussein Ghamlouch ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Risk Scores ◽  
Individual Risk ◽  
Risk Models ◽  
Advisory Committees ◽  
High Risk Disease ◽  
Definition Of ◽  
Standard Risk

Abstract Introduction: There is considerable heterogeneity in the clinical outcome of newly diagnosed multiple-myeloma (NDMM) with some patients having a good prognosis while others fail to respond or relapse quickly after therapy progressing rapidly to death. Using risk scores based on clinical, biochemical and genetic features it is possible to predict some of this variation giving an ability to segment the disease into risk strata. Clinical studies have suggested that patients with standard-risk disease have benefited more from the recent advances in therapy compared to those with high-risk disease. The development of clinical trials specifically recruiting patients with high-risk disease features offers the potential to improve the outcome of a subgroup of patients with a very poor clinical outcome. To perform such studies is it important to have a unifying definition of high-risk including standard parameters, group size and outcome of individual risk strata so that clinical trial rigor can be achieved (e.g., common entry criteria, statistical power). In order to understand the size and feasibility of such studies we analyzed the Myeloma Genome Project (MGP) dataset to assess multiple risk factors and scores to determine and compare how they perform as risk stratifiers with each other. Methods: The MGP dataset is a large set of molecular and clinical data from 1273 patient with NDMM. Data were available on clinical variables (Albumin (Alb), B2-microglobulin (B2M), LDH, age), cytogenetic variables [t(4;14), t(14;16), t(14;20), 17p-, TP53 mutations, 1q+ and 1p-] and gene expression analysis (GEP70). A literature search was used to identify risk models used in clinical studies. Survival analysis was performed in R. The median follow-up at the time of analysis was 54.5 (53.2-56.5) months. Results: The median patient age was 66 years, with 641 (50.4%) patients over age 65. The sex ratio (M:F) was 1:0.66. African American, White, and Asian constituted 17%, 76%, and 2%, of cases respectively. 26.7% received a stem cell transplant. We determined the size of the strata and actual risk (measure by the hazard ratios, HR) compared to standard risk cases for both PFS and OS of the various clinical models available, data are summarized in Figure 1. When looking at individual risk scores, the HR for progression for t(4;14), TP53 inactivation (deletion and mutations), gain(1q), and del(1p) were 1.4, 1.1, 1.3, and 1.1 respectively. When considering overall survival these HR were 1.4, 1.7, 1.5, and 1.4 respectively. We went on to analyze the impact of these events in combination and show that combined, there is increased specificity, especially for OS (HR 2.3-5.1) but they identify small subsets making up &lt;10% of patients. We then analyzed the purely clinical scores (ISS) and combined clinical/genetic scores. We show again, that the more specific risk scores (double hit, Boyd IV, GEP70) identify between 7-13% of cases with HR (2-3.1) for OS. When we looked specifically at the younger patients (=&lt; 65), similar trends were seen with GEP70 by RNA-seq offering one of the most interesting means of identifying HR cases. Conclusion: In this large NDMM dataset, we demonstrate the clear variation in risk groups that occur dependent upon the approach used resulting in heterogeneous levels of risk, strata size, and performance. With the exception of GEP70, none of the single features are sensitive or specific enough to identify all cases. Risk models based on a combination of markers improve the ability to detect true high-risk disease but there remains variability. At a molecular level the inclusion of TP53 inactivation, and 1q+ improve the performance of the ISS. This analysis provides insights into standardizing the definition of high-risk and the generation of consensus definitions for clinical trial entry. Figure 1 Figure 1 Figure 1. Disclosures Braunstein: Jansen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Pawlyn: Celgene / BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cairns: Amgen: Research Funding; Merck Sharpe and Dohme: Research Funding; Takeda: Research Funding; Celgene / BMS: Other: travel support, Research Funding. Jackson: GSK: Consultancy, Honoraria, Speakers Bureau; takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; amgen: Consultancy, Honoraria, Speakers Bureau; celgene BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; J and J: Consultancy, Honoraria, Speakers Bureau; oncopeptides: Consultancy; Sanofi: Honoraria, Speakers Bureau. Morgan: BMS: Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees. Davies: Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Constellation: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Symptom Assessment in Patients with BCR-ABL-Negative Myeloproliferative Neoplasms at an Academic Medical Institution

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5859-5859
Author(s):  
Kelly L. Schoenbeck ◽  
Miguel Carlos Cerejo ◽  
Patricia A. Cornett ◽  
Lloyd E. Damon ◽  
Karin L. Gaensler ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Board Of Directors ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Symptom Burden ◽  
Symptom Assessment ◽  
Positive Symptoms ◽  
Problem List ◽  
Advisory Committees ◽  
Anxiety Depression

Background: Patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs) have high symptom burdens that negatively impact quality of life, including risk for developing chronic pain and psychosocial complications. The NCCN guidelines recommended the use of the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) starting in 2017 to assess symptom burden. Our primary aim was to determine if the MPN-SAF TSS has been incorporated into patient care, and if not, how well BCR-ABL-negative MPN symptoms are captured by review of systems (ROS). Our secondary aim was to evaluate the prevalence of anxiety, depression, chronic pain, and opiate use in our patient population. Methods: We performed a single-center, cross-sectional study of all active BCR-ABL-negative MPN patients in the UCSF Hematology Clinic between January 2017 and March 2019. We reviewed all hematology visits for completion of the MPN-SAF TSS, and the most recent visit for the number symptoms from the MPN-SAF TSS explicitly captured in ROS or problem list and relevant medications. Descriptive statistics were used to summarize the data. Patients whose disease transformed into acute leukemia or were post-allogeneic stem cell transplantation were excluded. Results: Of 299 patients with BCR-ABL-negative MPN diagnoses, the median age was 66 (range 20-98) with an equal number of males (n=150) and females (n=149). Essential thrombocythemia (ET) was the most common diagnosis (n=109; 37%), followed by polycythemia vera (PV) (n=90; 30%), primary myelofibrosis (MF) (n=49; 16%), post-PV or post-ET MF (n=29; 10%), and MPN-Unclassifiable or overlap (n=22; 7%). Most were JAK2 V617F positive (n=213; 71%) and high-risk (n=148; 49.5%) by clinical criteria, IPSET-thrombosis, and DIPSS-plus. Nearly all were on active treatment (91%), with aspirin (n=205; 69%), hydroxyurea (n=130; 43.5%), phlebotomy (n=61; 20%), and ruxolitinib (n=37; 12%) being the most frequent treatments. Significant disease-related vascular complications were documented in 20.7% of patients. The 299 patients were evaluated by 22 hematology providers. The MPN-SAF TSS was formally documented in 1 patient (0.3%). Of the 10 symptoms in the MPN-SAF TSS, the median number documented as positive or negative on ROS was 3 (range 0-8), with 0 or 1 symptoms documented in 82 patients (27.4%). The mean number of positive symptoms was 0.7 (range 0-4) with at least 1 positive symptom reported by 44.7%. The most frequently charted symptoms were fever (n=182; 60.9%), unintentional weight loss (n=137; 45.8%), abdominal pain (n=137; 45.8%), and night sweats (n=130; 43.5%). More unique MPN symptoms were documented less frequently, including pruritis (n=89; 29.8%), early satiety (n=56; 18.7%), bone pain (n=28; 9.4%), and problems with concentration (n=3; 1%). The most common positive symptoms were fatigue (n=90; 73%), pruritis (n=30; 33.7%) and bone pain (n=9; 32%). Pain and psychological symptoms were infrequently charted in hematology clinic. Pain medications were used by 20.4% with nearly half (48%) on opiates, but chronic pain was on the provider problem list for only 5.7% of patients. Anxiety/depression medications were used by 20.4%, but anxiety/depression was on the provider problem list in only 4% of patients. Conclusions: To our knowledge, this is the first study to assess the implementation of the MPN-SAF TSS into clinical practice since the NCCN recommendations went into effect. The MPN-SAF TSS is not being utilized in regular practice at our site and a low number of disease-related symptoms are documented in clinic notes. Fatigue is the predominant symptom in our patients, which is similar to previously published studies. The discrepancy between medications taken and symptoms documented suggests that patients have a higher symptom burden than reported. Implementing a standardized way of consistently capturing patients' MPN-related symptoms in hematology practice will be explored in future quality improvement research. Disclosures Damon: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Logan:Incyte: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Research Funding; Kite: Research Funding; Kadmon: Research Funding; Pharmacyclics: Research Funding; Novartis: Consultancy; TeneoBio: Consultancy; Kiadis: Consultancy; Astellas: Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mannis:Jazz: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Abbvie/Genentech: Membership on an entity's Board of Directors or advisory committees; Forty Seven: Membership on an entity's Board of Directors or advisory committees; Curis: Membership on an entity's Board of Directors or advisory committees. Olin:Spectrum: Research Funding; Novartis: Research Funding; Mirati Therapeutics: Research Funding; MedImmune: Research Funding; Ignyta: Research Funding; Clovis: Research Funding; Daiichi Sankyo: Research Funding; Astellas: Research Funding; Genentech: Consultancy, Research Funding; Pfizer: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria; Revolution Medicine: Consultancy; AstraZeneca: Research Funding. Shah:Bristol-Myers Squibb: Research Funding. Atreya:Immunotherapeutics: Honoraria; Guardant Health: Research Funding; Novartis: Research Funding; Merck: Research Funding; Kura Oncology: Research Funding; Array Biopharma: Honoraria; Pionyr: Honoraria; Bristol-Meyers Squibb: Research Funding. Smith:Astellas Pharma: Research Funding; Abbvie: Research Funding; fujiFilm: Research Funding; Revolution Medicines: Research Funding.

scholarly journals SOCS1 Haploinsufficiency Presenting As Incidental Refractory Thrombocytopenia in a Pediatric Patient with Inflammatory Symptoms and History of Sars Cov-2 Infection

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4220-4220
Author(s):  
Jillian Lapinski ◽  
Sandra Hoang Ngo ◽  
Pui Y Lee ◽  
Kelly J. Walkovich ◽  
Mark Hannibal ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Next Generation Sequencing ◽  
Board Of Directors ◽  
Genetic Variants ◽  
Response To Therapy ◽  
Cytokine Signaling ◽  
Next Generation ◽  
Advisory Committees ◽  
History Of ◽  
Generation Sequencing

Abstract BACKGROUND: Immune thrombocytopenia purpura (ITP) has a complex pathogenesis and may be a primary diagnosis or secondary to an underlying condition 1. Evaluation for underlying diagnoses in patients presenting with atypical features of classic ITP is key, as this can impact treatment decisions, therapy response, and prognosis. Genetic variants that predispose patients to ITP are especially important to investigate as patients may be at risk for additional autoimmune phenomenon or malignancy. The SARS CoV-2 pandemic has added further complexity as reports suggest the infection can lead to autoimmunity in those with genetic predispositions 2,3. Loss of the suppressor of cytokine signaling 1 (SOCS1) function has been described to manifest with autoinflammatory syndrome, with or without immunodeficiency 4,5. Reports of autoimmunity developing in patients with SOCS1 haploinsufficiency after SARS CoV-2 infection are documented, including multi-system inflammatory syndrome (MIS-C) 2. A proposed mechanism of this virus-triggered autoimmunity includes a transient innate and adaptive immunodeficiency 3. This raises the question whether patients harboring genetic variants with risk of autoimmunity are placed at an even higher risk for ITP in the wake of SARS-CoV2 infection. CASE PRESENTATION: We present a 6-year-old female with isolated thrombocytopenia of 4,000/uL identified during evaluation for severe arthralgias unresponsive to corticosteroid treatment (maximum dose 1mg/kg/day) over a 6-month period. Laboratory results at presentation were consistent with ITP, including presence of platelet autoantibodies. Evaluation revealed hypocellularity for age (~50%) on bone marrow evaluation as well as elevated IgE (2080 kU/L), with IgA, IgM, and IgG levels within reference range. She had a remote history of SARS CoV-2-like illness and SARS CoV-2 antibodies were found present in serologic assay, without a history of vaccination. Genetic testing, including chromosomal microarray from peripheral blood and marrow, was included in the diagnostic workup given concern for a history of developmental delays with macrocephaly and necessity to rule-out malignancy with the patient noted to have a 5 mega-base deletion at 16p13.2p13.11, which includes the SOCS1 gene. Comprehensive next generation sequencing for additional immune dysregulation/primary immunodeficiency associated variants was unremarkable. Functional studies of surface expression of interferon-inducible genes (CD169 (SIGLEC-1)) and STAT1 phosphorylation via analysis of CD14+ monocytes revealed excess interferon signaling previously described in patients with SOCS1 haploinsufficiency (Figure 1). Measurements of B-cell-activating factor were also found to be extremely elevated at 6432 pg/mL. The patient's ITP course was complicated by hematuria, melena and refractory platelet response to first line therapy consisting of intravenous immunoglobulin 1 g/kg x2 doses and 2 mg/kg/day prednisolone. She required escalation to high dose methylprednisolone (30mg/kg), rituximab 375 mg/m 2/weekly x4 doses, and concurrent romiplostim (2 doses) for control of thrombocytopenia and bleeding manifestations. Her rheumatologic symptoms subsided with initiation of corticosteroids, and she has subsequently completed a prolonged corticosteroid taper. She currently has a normal platelet count with non-steroidal anti-inflammatory therapy utilized for arthralgia management with plan to transition to JAK inhibition for maintenance therapy. CONCLUSION: This case highlights the potential impact of investigating for susceptibility genes for ITP with consideration for broader testing including targeted next generation sequencing panels or microarray analysis in patients with atypical ITP presentations or response to therapy, as knowledge of this patient's underlying genetics led to earlier treatment and use of alternative agents. Additionally, the case adds the novel finding of bone marrow hypocellularity to the clinical phenotype of SOCS1 haploinsufficiency, as this has not yet been reported and contributes to the literature on the relationship of autoimmunity and SARS CoV-2 infections in patients with predisposing genetic variants. Figure 1 Figure 1. Disclosures Walkovich: Horizon Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharming: Honoraria, Membership on an entity's Board of Directors or advisory committees; Swedish Orphan Biovitrum AB (Sobi): Consultancy, Honoraria; X4 Pharmaceuticals: Other: Local PI for clinical trial involving mavorixafor and patients with neutropenia.

scholarly journals Impact of Myeloproliferative Neoplasms (MPNs) on Patients’ Overall Health and Productivity: Results from the MPN LANDMARK SURVEY in the United States

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3183-3183 ◽  
Author(s):  
Ruben Mesa ◽  
Carole B Miller ◽  
Maureen Thyne ◽  
James Mangan ◽  
Sara Goldberger ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Risk Score ◽  
Sexual Desire ◽  
Burden Of Disease ◽  
Research Funding ◽  
Symptom Burden ◽  
Risk Scores ◽  
Advisory Committees ◽  
Significant Burden ◽  
Equity Ownership

Abstract Background: Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET), are chronic MPNs associated with a broad array of symptoms that may negatively impact patients’ quality of life (QoL). To enhance patient care, it is important to have a current and clear understanding of how MPNs affect the overall health and daily lives of patients. The MPN LANDMARK SURVEY was developed to examine patients’ perceptions of these MPNs related to disease burden, QoL, productivity, and activities of daily living (ADLs). Methods: Eligible patients diagnosed with an MPN were recruited to participate in an online survey conducted from May–July 2014in the US. Patients were asked about the overall burden of disease and impact of symptoms on their QoL, productivity, and ADLs. Descriptive analyses were conducted to assess these outcomes and examined by calculated (not reported) prognostic risk score (MF - DIPSS: Passamonti, Blood 2010; PV: Tefferi, Leuk 2013; ET - IPSET: Passamonti, Blood 2012) and symptom severity quartiles, which were determined using the MPN Symptom Assessment Form (MPN-SAF) total symptom scores. Results: 813 patients (MF=207; PV=380; ET=226) responded to the survey. A majority of patients were female (MF, 54%; PV, 62%; ET, 72%), approximately half were aged 60–74 years (MF, 55%; PV, 51%; ET, 46%), and most were covered by health insurance (>98%). Nearly half (48%) were diagnosed within the last 5 years and average time to diagnosis from first symptoms was >2 years. A high proportion of patients had intermediate to high prognostic risk scores (MF, 94%; PV, 87%; ET, 44%). The majority of patients reported feeling anxious or worried about their MPN (MF, 91%; PV, 78%; ET, 74%). Among all groups, fatigue was the most severe symptom reported (mean MPN-SAF score=6.0–6.4 on a scale of 0–10). A subset of patients in each group described their symptoms as very severe (severity score ≥7 on a scale of 0–10; MF: fatigue [59%], problems with sexual desire [49%], inactivity [46%]; PV: inactivity [48%], fatigue [49%], problems with sexual desire [49%]; and ET: problems with sexual desire [49%], fatigue [50%], headaches [40%]). The majority of patients reported that MPN-related symptoms reduced their QoL (MF, 81%; PV, 66%; ET, 57%); this was reported in all risk groups but more frequently by patients with a high risk score vs a low risk score in MF and ET (MF, 89% vs 69%; PV, 63% vs 65%; ET, 71% vs 59%). A more substantial QoL impact was reported by patients in high vs low symptom quartiles (MF, 95% vs 51%; PV, 94% vs 33%; ET, 93% vs 15%). Similarly, MPNs also had a marked negative impact on reduced work hours, sick days, voluntary job termination, receipt of medical disability, early retirement, and ADLs (Table 1). For example, among patients employed, approximately one fourth reported missing ≥1 day of work (MF, 29%; PV, 19%; ET, 23%) in the last 30 days before the survey. Even patients with low prognostic risk scores often reported missing ≥1 day of work (MF, 33%; PV, 23%; ET, 22%) or cancelling ≥1 day of planned activities (MF, 46%; PV, 35%; ET, 34%). Patients in the high vs low symptom quartiles were more likely to call in sick to work (MF, 48% vs 0%; PV, 52% vs 4%; ET, 38% vs 0%) or cancel ≥1 day of planned activities (MF, 77% vs 5%; PV, 56% vs 7%; ET, 67% vs 3%). Conclusion: The findings from this large, first-of-its-kind survey demonstrate a marked burden of disease across all 3 MPNs that is not limited to symptoms but extends to QoL, productivity, and ADLs. Although high prognostic risk scores have long been associated with a significant burden of disease, in this study, patients with a low risk score also reported significant burden. The symptom burden reported is consistent with previous studies, thus validating the present dataset. MPN treatment considerations should include reducing the symptom burden and improving QoL and productivity to enhance the overall health and lives of MPN patients. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Miller:Incyte Corporation: Honoraria, Research Funding. Thyne:Incyte Corporation: Speakers Bureau. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Goldberger:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Fazal:Incyte Corporation: Consultancy, Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau. Ma:Incyte Corporation: Consultancy. Wilson:Incyte Corporation: Honoraria. Dubinski:Incyte Corporation: Employment, Equity Ownership. Boyle:ICF International: Employment, Equity Ownership. Mascarenhas:Incyte Corporation: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Research Funding.

Symptom Severity and Clinical Variables of Polycythemia Vera Patients with Splenomegaly, Phlebotomy Requirements and/or Hydroxyurea Use: a Retrospective Evaluation of 1334 Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1848-1848 ◽  
Author(s):  
Holly Lynn Geyer ◽  
Robyn M Scherber ◽  
Amylou Constance Dueck ◽  
Jean-Jacques Kiladjian ◽  
Zhijian Xiao ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Board Of Directors ◽  
Research Funding ◽  
Unmet Needs ◽  
Symptom Burden ◽  
Risk Scores ◽  
Control Group ◽  
Advisory Committees ◽  
Specific Symptom ◽  
Symptom Profile

Abstract Background Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by erythrocytosis, splenomegaly and a frequently burdensome symptom profile. Despite current guidelines of aspirin, phlebotomy, and selective cytoreduction, many patients have inadequately controlled PV-related symptoms and/or disease features. We performed a comparison of PV symptom burden/disease feature phenotypes to understand unmet needs in current medical management. Methods Data was collected prospectively amongst an international cohort of PV patients including symptom burden, demographics, and disease features. Subgroups were identified who had previously failed hydroxyurea (PV-HU), required ongoing phlebotomy (PV-P), had palpable splenomegaly (PV-S), or had all 3 features (PV-HUPS). Control groups were derived from the remaining PV patients lacking the specified subgroup trait; patients in whom the trait status was unknown were excluded from each respective control group. All participants completed the MPN specific symptom burden questionnaire (MPN-SAF TSS (MPN-10 – Table 1)) and had no prior history of splenectomy. Surveyed symptoms on the MPN-10 included the patient's perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. PV risk scores were calculated using the 2013 criteria (Leukemia 2013). Comparison of symptoms between groups employed t-tests. Results Patient Demographics and Disease Features Between Phenotypic Groups A total of 1334 PV patients completed the MPN-10, and were assigned to categories of PV-HU (499 [37%]), PV-P (646 [48%]), PV-S (369, [28%]), and PV-HUPS (148 [12%]). The demographics between these groups were similar (comparable age (median range 60-63), PV risk scores (mean risk range: Low 16.4-23.7%; Intermediate 31.4%-36.6%; High 42.8%-47%). Mean hemoglobin was similar among PV subgroups (range 14.4-14.9); PV-HUPS had a higher mean WBC count (20.3 g/dL vs. 8.8-11.8 g/dL) and platelet count (703.5 x 10(9)/L vs. 327.5-462.8 x 10(9)/L), and disease duration (11.5 years vs. 6.4-8.8 years). Prior thrombosis was most common in PV-S patients (28.5% vs. 21.8-25.2%) and prior hemorrhage was most common in PV-HUPS patients (23.8% vs. 13.7-15.8%). Symptom Burden The MPN-10 scores of each problematic PV phenotype (HU, P, S, HUPS) were compared to the remainder of the PV cohort lacking the trait (PV-control; Table 1). Both individual symptom scores and TSS were highest for PV-HUPS patients (mean TSS 32.5 vs. 27.7-29.2). All problematic PV subgroups demonstrated significant differences for individual symptoms and TSS compared to PV-control. Comparing "problematic" subgroup responses, PV-HU patients described more inactivity whereas PV-S patients described more early satiety and pruritus. No statistical differences were noted in PV-HU, PV-P and PV-HUPS patient responses to MPN-10 items of "fever" and "weight loss". Discussion PV patients who have either failed HU, are undergoing phlebotomy and/or have splenomegaly exhibit moderate to severe symptomatology and demonstrate unmet medical need for management. As evidenced in this study, considerable overlap in symptomatology exists in PV-HU, PV-P, PV-S and PV-HUPS. Current randomized trials of JAK inhibitors have demonstrated benefits in a PV-HUPS phenotype. This data suggests that PV patients with any evidence of inadequate control (PV-HU, P, or S) have similarly unmet needs and may be candidates for clinical trials, intensification of medical therapy or perhaps JAK inhibitor therapy. Disclosures Kiladjian: Shire Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zweegman:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Research Funding. Besses:Shire Pharmaceuticals: honoraria for educational lectures Other. Birgegard:Shire Pharmaceuticals: Consultancy, Honoraria, Research Funding. Etienne:Novartis, BMS, Pfizer, Ariad: Honoraria. Roy:Merck: Peg-Interferon provided for academic clinical trial in CML Other. te Boekhorst:Novartis: Consultancy. Griesshammer:Novartis: Honoraria; Shire: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Roche: Honoraria. Mesa:Incyte Corporation, CTI, NPS Pharma, Inc., Gilead Science Inc., Celgene: Research Funding.

Prognostic Factors for Developing Thrombosis in Polycytemia Vera: A Retrospective Analysis of 331 Patients with Long-Term Follow-up Highlights the Importance of White Blood Cells Levels

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-49
Author(s):  
Samantha Ferrari ◽  
Chiara Pagani ◽  
Mariella D'Adda ◽  
Nicola Bianchetti ◽  
Annamaria Pelizzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
High Risk ◽  
Board Of Directors ◽  
Advisory Board ◽  
Advisory Committees ◽  
Risk Status ◽  
History Of ◽  
Wbc Count

Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis, constitutively active mutations in JAK2 and an increased susceptibility to thrombotic events (TEs). There is still controversy about the role of increased hematocrit and of other variables including elevated white blood cell count as risk factors for the occurrence of TEs. A better definition of the relative prognostic importance of hematologic parameters would help us to better tailor the therapeutic approach to PV patients (pts), which is currently mainly based on the use of acetilsalycilic acid (ASA), venesection and hydroxyurea . The aim of our study was to analyze if any clinical or laboratory variables were significantly associated to the occurrence of TEs both at PV diagnosis and during the course of the disease in a large series of PV pts uniformly followed at a single Center over a period of 29.5 years from January 1986 to June 2019. Clinical and laboratory data were obtained from the time of diagnosis until death, progression to acute leukemia or last follow-up. Hematocrit (Hct), hemoglobin (Hb), white blood cell (WBC) and platelet (PLT) levels were recorded for each patient at least every 6 months. Among a total of 331 pts, the median age was 65 years (range 30-92 years), and 56% were male. "High risk" features (age ≥ 60 years and/or history of prior thrombosis) were present in 221 pts (66.7%). The incidence of cardiovascular risk factors was: hypertension 64%, diabetes 15%, hyperlipidemia 28%, history of active or remote smoking 41%. Patients on ASA were 279 (84%), 19 (6%) were on oral anticoagulation, while 27 (8%) were on ASA+oral anticoagulant. At PV diagnosis 54 pts (16%) presented with thrombosis, arterial in 32 (59%) and venous in 22 (41%). A previous TE was recorded in 57 pts (17%): in 43 (75%) arterial, in 12 (22%) venous and in 2 (3%) mixed (arterial+venous). Previous thrombosis was the only variable significantly associated with the presence of a TE at PV diagnosis (P=0.02). After PV diagnosis, with a median follow-up of 81 months (range 1-374 months), 63 pts (19%) experienced a TE and 11 of them a further episode, for a total of 74 TEs. The incidence rate (pts/year) of TEs was 2.7%. Forty-two events were arterial (57%), 31 were venous (42%) and 1 (1%) was mixed. It was the first TE for 37 pts. Cerebrovascular accidents and deep-venous thrombosis were the most frequent arterial and venous TEs both at PV diagnosis and throughout the disease course, with a relative incidence of 50% and 32% respectively. The table compares the characteristics of patients who did or did not develop a TE after PV diagnosis. At univariate analysis, PV high risk status, a previous TE and hyperlipidemia at PV diagnosis were significantly associated with a subsequent TE. Among hematologic variables an elevated WBC count at the time of thrombosis, but not Hct or PLT levels, was highly significantly associated with the development of a TE. At multivariate analysis, WBC count ≥10.4 x 10^9/L and hyperlipidemia maintained their independent prognostic value, while high risk status and a previous TE lost their prognostic significance. Both at univariate and multivariate analysis, hyperlipidemia at diagnosis (P=0.009 and P=0.002) and high WBC count at thrombosis (P=0.001 and P=&lt;0.0001) predicted for arterial thromboses, while only a history of prior thrombosis (P=0.03) predicted for venous ones. In conclusion, our analysis confirms that elevated WBC count at the moment of the event more than increased hematocrit is associated to the development of thrombosis in PV pts. We also found that hyperlipidemia was an independent risk factor for arterial thrombosis, calling for an accurate management of increased lipid levels. Whether a reduction of the WBC count during the course of PV may reduce the frequency of TE remains to be demonstrated by prospective studies. Table Disclosures D'Adda: Novartis: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Other: Advisory board. Rossi:Daiichi Sankyo: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Identifying Factors That Predict for Unplanned Readmissions for Acute Myeloid Leukemia Patients Receiving Consolidation Cytarabine Based Therapies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3433-3433
Author(s):  
Caitlin Siebenaller ◽  
Madeline Waldron ◽  
Kelly Gaffney ◽  
Brian P. Hobbs ◽  
Ran Zhao ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Smoking Status ◽  
Consolidation Therapy ◽  
Peripheral Vascular ◽  
Consolidation Chemotherapy ◽  
Advisory Committees ◽  
History Of ◽  
Acute Myeloid

Background: Younger patients (pts) with acute myeloid leukemia (AML) who enter a remission after intensive induction chemotherapy routinely receive at least one cycle of consolidation therapy with high dose cytarabine (HiDAC). This is commonly administered over a five-day inpatient stay, after which pts are discharged home as their blood counts nadir. It is thus a natural consequence of therapy that readmission for febrile neutropenia (FN) occurs, which can impact measures of quality and value in this population. Precise descriptions of incidence, type, and severity of infection, if identified, are lacking, and thus it is unknown to what standard cancer centers should be held for anticipated readmission. We measured these rates, and attempted to identify predictive factors for readmission. Methods: Adult AML pts ≥ 18 years of age who received at least one cycle of HiDAC consolidation (1000-3000 mg/m2 for six doses) in 2009-2019 were included. Our primary aim was to identify predictive factors for readmission after the first cycle of consolidation chemotherapy. The following pt characteristics and co-morbid conditions were analyzed: age, gender, body mass index (BMI), smoking status, AML cytogenetic risk status, history of diabetes, peripheral vascular disease, cardiovascular disease, chronic pulmonary disease, hepatic impairment, and other cancers. Secondary aims included: estimating rates of all-cause readmissions among all HiDAC cycles, defining the rate of FN readmissions, estimating rates of intensive care unit (ICU) admissions, clinical (e.g., probable pneumonia per imaging) and microbiologically-documented infections, prophylactic (ppx) medications used, and mortality. Statistical analyses interrogated potential risk factors for evidence of association with hospital readmission after the first cycle of consolidation chemotherapy. Results: We identified 182 AML pts who fit inclusion criteria. The median age was 50 years (range 19-73); 55% were female and 45% were male. Statistical analyses revealed no association with readmission after cycle 1 for cytogenetic risk (p=0.85), history of heart failure (p= 0.67), chronic pulmonary disease (p=1), connective tissue disease (p=0.53), cerebrovascular accident (p=0.63), diabetes (p=0.63), gender (p=0.07), history of lymphoma (p=0.53), other solid tumors (p=0.53), liver disease (p=1), myocardial infarction (p=0.71), peripheral vascular disease (p=1), or smoking status (p= 0.52). For 480 HiDAC cycles analyzed (88% at 3000 mg/m2), the overall readmission rate was 50% (242/480), of which 85% (205/242) were for FN. Those readmissions which were not FN were for cardiac complications (chest pain, EKG changes), non-neutropenic fevers or infections, neurotoxicity, bleeding or clotting events, or other symptoms associated with chemotherapy (nausea/vomiting, pain, etc.). Median time to FN hospital admission was 18 days (range 6-27) from the start of HiDAC. Of the 205 FN readmissions, 57% had documented infections. Of these infections, 41% were bacteremia, 23% fungal, 16% sepsis, 12% other bacterial, and 8% viral. Of 480 HiDAC cycles, ppx medications prescribed included: 92% fluoroquinolone (442/480), 81% anti-viral (389/480), 30 % anti-fungal (142/480), and 3% colony stimulating factor (14/480). Only 7% (14/205) of FN readmissions resulted in an ICU admission, and 1% (3/205) resulted in death. Conclusions: Approximately half of patients treated with consolidation therapy following intensive induction therapy can be expected to be readmitted to the hospital. The majority of FN readmissions were associated with clinical or microbiologically documented infections and are not avoidable, however ICU admission and death associated with these complications are rare. Readmission of AML pts following HiDAC is expected, and therefore, should be excluded from measures of value and quality. Disclosures Waldron: Amgen: Consultancy. Hobbs:Amgen: Research Funding; SimulStat Inc.: Consultancy. Advani:Macrogenics: Research Funding; Abbvie: Research Funding; Kite Pharmaceuticals: Consultancy; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Research Funding. Nazha:Incyte: Speakers Bureau; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmacutical: Research Funding; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee; Tolero, Karyopharma: Honoraria. Gerds:Imago Biosciences: Research Funding; Roche: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees.

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