scholarly journals The Prognostic Significance of Blast Aberrancies By Flow Cytometry in Low/Int Risk MDS

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5430-5430
Author(s):  
Kristen M Corrao ◽  
Alexandra M. Harrington ◽  
Steven H. Kroft ◽  
Laura C. Michaelis ◽  
Karen-Sue B. Carlson ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Median Time ◽  
Research Funding ◽  
Prognostic Significance ◽  
Red Blood Cell Transfusion ◽  
Rank Test ◽  
Intermediate Risk ◽  
Prognostic Information ◽  
Clin Pathol ◽  
Risk Patients

Background: The myelodysplastic syndromes (MDS) represent heterogeneous disorders with varied clinical courses. The major prognostic tool in MDS is the IPSS-R, which helps estimate survival outcome and estimate risk for AML transformation. In low or intermediate risk pts, the IPSS-R has shortcomings; in these pts, the development of transfusion dependent anemia is the major disease associated complication, and this is not addressed by IPSS-R stratification. Previous studies have indicated that aberrancies detected by flow cytometry can risk stratify pts with MDS. The purpose of this study was to determine whether detection of neoplastic-specific blast aberrancies in pts diagnosed with low or intermediate risk MDS can identify pts at higher risk for transfusion dependent anemia after MDS diagnosis. Methods: We performed a retrospective chart review on MDS patients initially diagnosed at our institution between 1/2010 and 12/31/2017. Patients with low/intermediate risk by IPSS-R were identified. Flow cytometry findings on initial diagnostic BM biopsies performed at our institution only were reviewed. Flow cytometry (4- and 8-color) was performed on bone marrow aspirates for the following antigens: CD3, CD7, CD11b, CD13, CD14, CD15, CD19, CD20, CD33, CD34, CD36, CD38, CD45, CD56, CD64, CD117, and HLA-DR using FACS Calibur or FACSCanto II flow cytometers. Myeloblasts were identified by cluster analysis, as previously described (Am J Clin Pathol. 2010 Nov; 134(5):749-61), and compared to 20 control cases. Blast aberrancies were defined as an immunophenotypic difference of > ¼ log compared to the blasts in the controls. Neoplasia-specific blast aberrancies were defined as: expression of CD7, CD11b, CD15, and/or CD56 and/or under expression of CD38 and CD45. We estimated probability of transfusion dependent anemia using Kaplan Meier product limit method and compared survival curves using log-rank test. Analyses were performed using Stata v12.0. Results: A total of 63 patients were identified, with median age of 68 years (range 31-89 years). Median hemoglobin (Hg) at diagnosis was 9.8 (range 5.2-15.3). Cytogenetic risk categories were very good, good, intermediate and poor in 3%, 71% 16%, and 10% respectively. IPSS-R category was very low or low in 70% (44 pts), and intermediate in 30% (19 pts). The presence of blast aberrancies was similar in proportion among low risk patients (61%, n=27) compared to intermediate risk patients (68%, n=13). Overall, the presence of only one blast aberrancy, whether neoplasia-specific or not, did not significantly segregate patients at greater risk for transfusion dependence. However, the presence of 2 or more aberrancies statistically defined two populations. Those possessing 0-1 blast aberrancy did not reach a median time to transfusion dependence, whereas those possessing 2+ aberrancies had a median time to transfusion dependence of 1.2 years (p=0.02). Additionally, when looking at neoplasia-specific blast aberrancies, pts with 0-1 aberrancy had a median time to transfusion of 4.7 years, compared to 2+ aberrancies, at 0.8 years (p=0.02). Figure 1 illustrates this finding. Conclusion: The determination of blast aberrancies by flow at time of MDS diagnosis may provide prognostic information in low/intermediate risk MDS patient and could help predict risk for early red blood cell transfusion dependence. Upfront risk stratification would be valuable information to plan follow-up for these patients, as well as treatment decision making including early initiation of ESAs. Disclosures Michaelis: Novartis: Consultancy; Celgene: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; JAZZ: Other: Data Safety Monitoring Board, uncompensated, Research Funding; BMS: Research Funding; Bioline: Research Funding; ASTEX: Research Funding; Janssen: Research Funding; Millenium: Research Funding; Macrogeneics: Research Funding; Pfizer: Equity Ownership, Research Funding; Incyte: Consultancy, Research Funding. Runaas:Agios: Honoraria; Blueprint Medicine: Honoraria. Atallah:Takeda: Consultancy, Research Funding; Pfizer: Consultancy; Jazz: Consultancy; Helsinn: Consultancy; Jazz: Consultancy; Novartis: Consultancy; Helsinn: Consultancy. Abedin:Actinium Pharmaceuticals: Research Funding; Pfizer Inc: Research Funding; Helsinn Healthcare: Research Funding; Agios: Honoraria; Jazz Pharmaceuticals: Honoraria.

Prognostic Impact of High Hematogones in Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1435-1435
Author(s):  
Dulcineia Pereira ◽  
Sergio Pereira Chacim ◽  
Edgar Mesquita ◽  
Ana Espirito-Santo ◽  
Ilidia Moreira ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Induction Chemotherapy ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
Cox Model ◽  
Disease Free Survival ◽  
Rank Test ◽  
Prognostic Impact ◽  
Intermediate Risk ◽  
Risk Patients

Abstract Abstract 1435 Introduction: The response to AML treatment is very heterogeneous and relapse risk is high. Hematogones (HG) are B lymphoid cell precursors present in all individuals. HG absolute count grows after chemotherapy, during medullar recovery and it seems to be related to prognosis. Objectives: Determination of HG number in AML patients with intermediate-risk karyotype, with complete response (CR). Determine prognostic value for HG number in these patients. Methods: Retrospective analysis of 148 patients with non promyelocytic AML, treated with “7+3” chemotherapy induction, followed in our centre, from 1998 to 2011. HG quantification was executed after induction chemotherapy, with flow cytometry pannel (4 colours - CD34, CD10, CD19, CD20 e CD45) in blood marrow samples in patients with CR, according to Cheson et al. (JCO 2003). The patients characteristics were compared with a X2test for binary variables and a Mann-Whitney test for continuous variables. Survival was plotted with Kaplan-Meier curves and the data for the various groups were compared with a log-rank test. Multivariate analysis was performed with a Cox model after the proportional hazard assumption was checked. A p value less than 0.1 was considered to be statistically significant. Results: There were 124 patients achieving CR after induction chemotherapy “7+3”, with a median follow up of 32 months ([0–141]), 46,8% (n=58) were male, median age of 50 years ([17–66]). There were 91,1% (n=113) patients with de novo AML and 63,9% (n=76) with intermediate-risk karyotype. In this study 16,3% (n=20) went on transplantation. Relapse occurred in 53,2% (n=66), with a disease free survival (DFS) of 15 months ([0–140]). HG quantification was possible in 33,1% (n=41) of the patients. Applying a cutoff of 0.01% (Chantepie S et al. Blood 2011) we can find 31,7% (n=13) with HG>0.01%. These patients had better DFS, when comparing to patients with HG≤0.01% (median 16 vs 9 months, p=0,05), to equal overall survival. According to multivariate Cox model, the HG>0,01% is a independent predictive value for DFS (IC 95% [0,8533-54.259], p<0,07), when comparing to HG≤0,01%, age, leucocytosys (>20000/μL), karyotype-risk groups and WHO classification of AML. We established a good prognosis associated to HG>0,01% group: patients with HG≤0,01% have a 6.8 hazard ratio (HR) or relapse comparing with HG>0,01% group. Considering this information and applying it to karyotype-intermediate risk patients, it was possible to obtain two different groups with prognostic impact on the DFS: low intermediate risk (HG>0,01%) and high intermediate risk (HG<0,01%).The 3 year-DFS is 83,3% for low intermediate risk group and 50% for high intermediate risk patients (p<0,094). Conclusion: Using flow cytometry is a simple and reproductively method for detecting HG. This quantification in AML patients with CR has clinically relevance, with prognostic impact in DFS (16 vs 9 months, p=0,05). For HG levels superior to 0,01% after induction chemotherapy the risk of relapse is decreased. The HR associated to HG value allowed the stratification of the intermediate-risk group in two subgroups of patients (low intermediate risk group and high intermediate risk patients) with different DFS (83.3% vs 50% 3-y EFS, p<0,094). This subdivision can have implications on clinical decision for therapeutic strategy, in the heterogeneous intermediate-risk karyotype group. This cohort needs to be enhanced in order to validate this approach. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Routine Use of Gemtuzumab Ozogamicin in 7+3-Based Inductions for All "Non-Adverse" Risk AML

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-37
Author(s):  
Gavin Hui ◽  
Abdullah Ladha ◽  
Edna Cheung ◽  
Caroline Berube ◽  
Steven Coutre ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Time ◽  
Research Funding ◽  
Gemtuzumab Ozogamicin ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
Myeloablative Conditioning ◽  
Advisory Committees ◽  
Monosomy 7

Introduction: The addition of gemtuzumab ozogamicin (GO) to 7+3 chemotherapy for newly diagnosed acute myeloid leukemia (AML) has been shown to significantly improve event-free survival (EFS) for cytogenetically favorable-risk AML, with marginal benefit for intermediate-risk AML, and no benefit for cytogenetically adverse-risk AML. Of note, with the exception of mutated FLT3-ITD, little is known about the impact of GO in ELN 2017-defined genotypically adverse-risk AML, and a recent randomized trial found no EFS benefit for 7+3+GO in patients (pts) with genotypically favorable-risk, NPM1-mutated AML. Since 2017, our institution incorporated GO into 7+3-based inductions for all "non-adverse" risk AML pts, as defined by wild-type FLT3 and no abnormalities on rapid FISH analysis for del(5q)/monosomy 5, del(7q)/monosomy 7, and del(20q). We report our experience treating all pts with "non-adverse" risk AML-as defined by this algorithm-with 7+3+GO. Methods: An institutional database was queried in order to identify all pts ≥18 years old who received 7+3-based chemotherapy for newly diagnosed AML between 2017 and 2020; pts who received the FDA-approved fractionated dose of GO were included in the analysis. Data collection included demographic variables, karyotype/FISH, targeted PCR analyses, and multigene NGS panels for AML-related mutations including, but not limited to, mutations in FLT3, NPM1, CEBPA, TP53, RUNX1, and ASXL1. Outcome data included response to induction, relapse, and death, as well as hematopoietic cell transplant (HCT) rates, conditioning regimens, and post-transplant complications. Results: Between January 2017 and July 2020, 96 pts received 7+3-based induction at our institution. Of these, 29 (30%) received 7+3 in combination with GO. Median age at diagnosis was 46 years (range 23-66), with 17 (59%) males. Sixteen (55%) pts had ELN favorable-risk AML (5 [31%] by cytogenetics and 11 [69%] by genotype), 6 (21%) pts had ELN intermediate-risk AML, and 7 (24%) pts had ELN adverse-risk AML (4 [57%] by cytogenetics and 3 [43%] by genotype). Median time from diagnosis to start of induction was 4 days (range 0-43). For cytogenetically adverse-risk pts, median time from diagnostic bone marrow biopsy to receipt of adverse karyotype results was 8 days (7-14). Median time from start of induction to receipt of multigene NGS results for all pts was 15 days (3-32). Overall, 22 (76%) pts achieved remission. All genotypically adverse-risk pts (1 with mutated TP53 and 2 with mutated RUNX1) were refractory to induction, while 3 of 4 (75%) cytogenetically adverse-risk pts (1 with t(6;9), 1 with monosomy 7, and 2 with 11q23 abnormalities) achieved remission. Eight of the 29 (28%) pts proceeded to HCT, including 4 adverse-risk pts. Of the adverse-risk pts, all received myeloablative conditioning prior to HCT and 3 (75%) developed veno-occlusive disease (VOD), with 2 (50%) requiring defibrotide therapy. In favorable/intermediate-risk pts, 4 (18%) proceeded to HCT (2 intermediate-risk pts in first remission and 2 favorable-risk pts in second remission). Of these, 2 (50%) received myeloablative conditioning and 1 (25%) developed VOD. At last follow-up, 23 of 29 pts (79%) remained alive, with a median overall survival not reached (range 1-29 months) and a median EFS of 20 months (9-31). The percentage of ELN favorable-, intermediate-, and adverse-risk pts who remained event-free at last follow-up was 75%, 33%, and 43%, respectively. Discussion: This single-center, retrospective cohort describes the outcomes of pts with "non-adverse" risk AML who received induction chemotherapy with 7+3+GO according to a pre-defined algorithm. Using this algorithm, 30% of all pts receiving 7+3-based inductions received GO. Of these, nearly 25% were ultimately found to have adverse-risk AML as defined by ELN 2017 criteria, largely driven by long turn-around times for karyotyping and NGS multigene panel results. No patient with genotypically adverse-risk AML by ELN criteria responded to induction chemotherapy, and 75% of cytogenetically adverse-risk pts who proceeded to HCT developed VOD. Routine use of 7+3+GO induction outside of the context of cytogenetically favorable-risk AML remains controversial, and further study is needed to define the role of GO, particularly for pts with ELN genotypically adverse-risk AML. Table Disclosures Gotlib: Blueprint Medicines Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Chair of the Response Adjudication Committee and Research Funding, Research Funding; Deciphera: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: co-chair of the Study Steering Committee and Research Funding. Liedtke:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; GSK: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Muffly:Adaptive: Research Funding; Amgen: Consultancy; Servier: Research Funding. Mannis:AbbVie, Agios, Bristol-Myers Squibb, Genentech: Consultancy; Glycomimetics, Forty Seven, Inc, Jazz Pharmaceuticals: Research Funding.

Finding of Kinase Domain Mutations at Diagnosis IN PATIENTS with Chronic PHASE Chronic Myeloid Leukemia (CP-CML) MAY Identify Those at High RISK of Disease Progression.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4251-4251
Author(s):  
Angelo Michele Carella ◽  
Gabriella Cirmena ◽  
Gioacchino Catania ◽  
Gianmatteo Pica ◽  
Germana Beltrami ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Chronic Phase ◽  
Kinase Domain ◽  
Imatinib Treatment ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients ◽  
Kinase Domain Mutations

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

scholarly journals Mutations Highly Specific for Secondary AML Are Associated with Poor Outcomes in Patients with NPM1-Mutated ELN Favorable Risk AML

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 686-686
Author(s):  
Onyee Chan ◽  
Najla Al Ali ◽  
Hammad Tashkandi ◽  
Austin Ellis ◽  
Somedeb Ball ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cancer Center ◽  
Cell Transplant ◽  
Intermediate Risk ◽  
Advisory Committees ◽  
Secondary Aml ◽  
The Impact

Abstract Background: NPM1 is commonly mutated in acute myeloid leukemia (AML) and represents a distinct entity under the WHO 2016 classification. It is one of the few mutations that can potentially support favorable risk by European LeukemiaNet (ELN) 2017 criteria. Mutations that are highly specific for secondary AML including SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, and STAG2 (sMut) (Lindsley et al.) have been shown to confer poor prognosis. The impact of these mutations on NPM1-mutated AML warrants further investigation. Objective: In this study, we explore the outcomes in patients with NPM1-mutated AML. Methods: This was a retrospective study of NPM1-mutated AML patients who were diagnosed and treated at the Moffitt Cancer Center from 2013 to March 2021. Inclusion was restricted to NPM1-mutated patients with mutation analysis (NGS) performed at diagnosis (n=159). Kaplan-Meier, univariate, and multivariate analyses were performed. Results: Among 159 patients (78M/81F, median age 63 years at diagnosis), 80.5% had de novo AML. By ELN 2017 criteria, 63.5% (101/159) had favorable risk, 27.7% (44/159) had intermediate risk, and 8.2% (13/159) had adverse risk disease. Almost 90% had intermediate risk cytogenetics at the time of diagnosis. Common co-mutations included DNMT3A (47.2%), FLT3-ITD (35.8%), TET2 (26.4%), IDH1 (17.6%), FLT3-TKD (15.1%), and IDH2 (13.8%). sMut comprised 19.5% (31/159) of patients and 20.8% (21/101) of those with ELN favorable risk. In patients with treatment response data, those with sMut never achieved CR/CRi in 35.7% (10/28) compared to 17.2% (22/128) of patients without sMut (p=0.038). The overall survival (OS) was 43.7 months with a median follow up of 35.5 months. Patients with sMut had worse OS compared to those without sMut (14.7 months vs 57.6 months, p=0.011). Among patients with favorable risk disease, OS was 11.6 months compared to not reached for those with sMut and without sMut, respectively (p&lt;0.0001). Univariate analysis showed sMut and allogeneic hematopoietic cell transplant (HCT) significantly impacted OS (sMut: HR 3.48, 95% CI: 1.80-6.72, p&lt;0.001; HCT: HR 0.17, 95% CI: 0.07-0.44, p&lt;0.001). Multivariate regression using covariates including age, AML type, sMut, and HCT confirmed their prognostic significance on survival (sMut: HR 2.40, 95% CI: 1.17-4.93, p=0.017; HCT: HR 0.26, 95% CI: 0.08-0.56, p=0.002). Conclusions: Our findings suggest NPM1-mutated AML patients with sMut have significantly worse prognosis despite being classified primarily as favorable risk by ELN 2017 at diagnosis. This may have treatment implications altering the need for and/or timing of HCT. These findings should be assessed prospectively and validated in independent datasets. Figure 1 Figure 1. Disclosures Hussaini: Adaptive: Consultancy, Honoraria, Speakers Bureau; Stemline: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy; Celegene: Consultancy; Decibio: Consultancy; Guidepoint: Consultancy; Bluprint Medicine: Consultancy. Talati: AbbVie: Honoraria; Pfizer: Honoraria; Astellas: Speakers Bureau; BMS: Honoraria; Jazz: Speakers Bureau. Kuykendall: Incyte: Consultancy; Novartis: Honoraria, Speakers Bureau; Protagonist: Consultancy, Research Funding; Celgene/BMS: Honoraria; Abbvie: Honoraria; Blueprint: Honoraria; Pharmaessentia: Honoraria. Padron: Blueprint: Honoraria; Incyte: Research Funding; Kura: Research Funding; Stemline: Honoraria; Taiho: Honoraria; BMS: Research Funding. Sallman: Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Magenta: Consultancy; Takeda: Consultancy; Kite: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Aprea: Membership on an entity's Board of Directors or advisory committees, Research Funding. Sweet: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees. Komrokji: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy; BMSCelgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acceleron: Consultancy; AbbVie: Consultancy; Jazz: Consultancy, Speakers Bureau; Taiho Oncology: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees. Lancet: AbbVie: Consultancy; Celgene/BMS: Consultancy; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Millenium Pharma/Takeda: Consultancy; BerGenBio: Consultancy; Jazz: Consultancy; Agios: Consultancy; Astellas: Consultancy.

scholarly journals Low Von Willebrand Factor: Cut-Off Value for Diagnosis and Risk Score to Predict Bleeding Incidence

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Ferdows Atiq ◽  
Esmee Wuijster ◽  
Moniek P.M. de Maat ◽  
Marieke J.H.A. Kruip ◽  
Marjon H. Cnossen ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Research Funding ◽  
Low Risk ◽  
Intermediate Risk ◽  
Spontaneous Bleeding ◽  
High Risk Patients ◽  
Risk Patients ◽  
Surgical Bleeding

Introduction Although large studies have recently provided valuable insights on the diagnosis, bleeding phenotype, and treatment outcomes of VWD patients, these aspects remain poorly understood in individuals with low VWF. Firstly, there is no clear evidence which cut-off value should be used to diagnose low VWF. Although 0.50 IU/mL is the most recommended cut-off value, some centers use the lower limit of normal (0.60 IU/mL). Secondly, the incidence of post-surgical bleeding, postpartum hemorrhage (PPH) and traumatic- or spontaneous bleeding after diagnosis of low VWF are still unknown. Lastly, it is hard to predict which individuals with low VWF have an increased bleeding risk. Therefore, we investigated the bleeding phenotype of individuals with historically lowest VWF levels of 0.31-0.50 IU/mL and 0.51-0.60 IU/mL, and the incidence of post-surgical bleeding, PPH and traumatic- and spontaneous bleeding after their initial diagnosis of "low VWF". Methods We performed a retrospective cohort study from January 2007 to November 2019 at the Erasmus MC, University Medical Center Rotterdam. All patients evaluated for the presence of a bleeding disorder with VWF antigen (VWF:Ag) and/or VWF activity (VWF:Act) and/or VWF collagen binding (VWF:CB) levels between 0.31-0.60 IU/mL, were included. Patients with VWF:Ag and/or VWF:Act and/or VWF:CB ≤0.30 IU/mL, acquired VWD and those with a concomitant bleeding disorder were excluded. For each individual we collected data from electronic patient files on baseline characteristics, reason for referral, family history of bleeding disorders, ISTH-BAT and laboratory measurements at diagnosis. Retrospective follow-up started from initial date of low VWF diagnosis through November 2019, during which we collected data on surgical procedures, pregnancies, and incidence of spontaneous- and traumatic bleeding. Results We included 439 patients; 269 patients with historically lowest VWF levels 0.31-0.50 IU/mL and 170 patients 0.51-0.60 IU/mL. Mean age at diagnosis was 28.8 ±17.7 years. Most patients were female (74.3%) and had blood group O (76.4%, Table 1). The bleeding score (BS) was similar in patients with historically lowest VWF levels of 0.31-0.50 IU/mL (3.7 ±3.0) and 0.51-0.60 IU/mL (4.0 ±2.9, p=0.209, Table 1). During the mean follow-up period of 6.3 ±3.7 years, 259 surgical procedures were performed in 146 patients, 81 deliveries in 56 women, and 109 spontaneous- or traumatic bleedings in 71 patients. The incidence of post-surgical bleeding was 7 (2.7%) during follow-up, whereas 8 deliveries (10%) were complicated by PPH. Overall, 65 out of 439 patients (14.8%) had a bleeding episode requiring treatment during follow-up, resulting in an incidence of bleeding requiring treatment of 0.5 ±1.9 per patient per decade. No difference was found in the incidence of bleeding requiring treatment between patients with historically lowest VWF levels of 0.31-0.50 IU/mL and 0.51-0.60 IU/mL (Figure 2A, p=0.154). We found that referral for a personal bleeding diathesis, a younger age at diagnosis and an abnormal BS at diagnosis were strong and independent risk factors for bleeding requiring treatment during follow-up, respectively HR=2.32 (95%CI: 1.16-4.63), HR=1.18 (95%CI: 1.01-1.38) and HR=1.77 (95%CI: 1.04-3.01). These risk factors were combined to develop a risk score to identify low VWF patients with an increased risk for bleeding requiring treatment (Figure 2B). The risk score performed excellent to differentiate in bleeding requiring treatment between low risk, intermediate risk and high risk patients (p&lt;0.001, Figure 2C). The number of patients with bleeding requiring treatment was 8/126 (6.3%) in patients with low risk, 18/143 (12.6%) in intermediate risk and 39/170 (22.9%) in high risk patients (p&lt;0.001). Likewise, the incidence of bleeding requiring treatment per patient per decade was 0.22 ±1.08 in low risk, 0.28 ±1.25 in intermediate risk and 0.87 ±2.61 in high risk patients (p=0.004, Figure 2D). Conclusion To conclude, there is no difference in the bleeding phenotype of individuals with historically lowest VWF levels of 0.31-0.50 IU/mL and 0.51-0.60 IU/mL. Therefore, the cut-off value to diagnose low VWF should be set at 0.60 IU/mL. Furthermore, the risk score developed in the current study may assist to identify low VWF patients with low, intermediate and high risk for future bleeding. Disclosures Atiq: SOBI: Other: travel grant; CSL Behring: Research Funding. Kruip:Boehringer Ingelheim: Research Funding; Pfizer: Research Funding; Bayer: Research Funding; Daiichi Sankyo: Research Funding; SOBI: Research Funding; Bayer: Speakers Bureau. Cnossen:Takeda: Research Funding; Shire: Research Funding; Baxter: Research Funding; Bayer: Research Funding; Sobi: Research Funding; CSL behring: Research Funding; Nordic Pharma: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding. Leebeek:CSL Behring: Research Funding; Shire/Takeda: Research Funding; Uniqure: Consultancy; Shire/Takeda: Consultancy; Novo Nordisk: Consultancy; SOBI: Other: Travel grant; Roche: Other: DSMB member for a study.

scholarly journals Redefining the Prognostic Significance of t(11;14) Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 43-43
Author(s):  
Susan Bal ◽  
Smith Giri ◽  
Kelly N. Godby ◽  
Luciano J. Costa
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Real World ◽  
Research Funding ◽  
Prognostic Significance ◽  
Rank Test ◽  
Prognostic Impact ◽  
The Impact ◽  
Standard Risk

Background In the era prior to introduction of novel agents, multiple myeloma (MM) harboring t(11;14) was characterized as standard risk. More recently, its unique biology, predictive ability and the prospect of targeted therapeutic agents have renewed interest in t(11;14) MM. Using a large, contemporary real-world database, we investigated the characteristics and outcomes of t(11;14) MM. Methods We used the Flatiron Health Electronic Health Record (EHR)-derived de-identified database to source patients (pts) with newly diagnosed MM from 1/2011 to 2/2020 with available Fluorescence in situ Hybridization (FISH) results documented within 90 days of diagnosis. We compared characteristics of t(11;14)+ patients [without additional high-risk FISH abnormalities: del(17p), Ch1 abnormality (Ch1a), t(4;14), t(14;16) or t(14;20)] vs. t(11;14)- patients (without additional high risk FISH) vs. del(17p) (irrespective of other abnormality) vs. Ch1a (Ch1a without additional high-risk FISH) vs. high-risk translocations [t(4;14), t(14;16) or t(14;20) without del(17p)]. We subsequently compared real-world progression-free survival (PFS) and overall survival (OS) across these five subsets. Additionally, we assessed the impact of t(11;14) as additional FISH abnormality in patients with del(17p) and in patients with Ch1a. We used Kaplan Meier methods with log-rank test and Cox proportional hazard regression model for survival analysis with date of diagnosis as the index date for follow-up. Results 6039 patients in the database met the inclusion criteria. Overall, 83.6% of patients received initial therapy with immunomodulatory agent (IMiD) and/or proteasome inhibitor (PI); of these 40.3% received combination of IMiD and PI. Overall, 27.1% received autologous hematopoietic cell transplantation. Median follow up was 2.1 years (IQR 0.8-4.0). There were 637 pts in t(11;14)+ group, 3173 in t(11;14)- group, 587 in del(17p), 1205 in Ch1a and 437 with high-risk translocations. The t(11;14)+ group had a higher proportion of men, IgM and light-chain isotype, as well as a higher proportion of patients with serum creatinine ³ 2mg/dl (Table). Patients in t(11;14)+ group had worse PFS (mPFS 3.1 vs. 3.3 years, p=0.02) and worse OS (mOS 5.9 vs. 6.5 years , p=0.04) compared to t(11;14)-, but better PFS and OS than the other three high-risk groups (Figure panels A and B). Worse PFS for t(11;14)+ was demonstrable even after adjustment for sex, age, race/ethnicity, immunoglobulin isotype, stage, comorbidities, and treatment received (adjusted HR=0.87, 95% C.I. 0.77-0.98, P=0.027). We subsequently analyzed the impact of presence of t(11;14) in MM with del(17p) or Ch1a.. The presence of t(11;14) in addition to del(17p) resulted in worse OS compared to del 17p without t(11;14) (mOS 2.8y vs. 3.7y; p=0.04). Indeed, the impact of t(11;14) on del(17p) was comparable to the impact of t(4;14) (Figure, Panel C). There was no difference in survival with concomitant presence of t(11;14) with Ch1a (Figure, Panel D). Conclusion MM with t(11;14) has distinct features at presentation and even when treated with modern therapy carries worse prognosis than otherwise standard-risk MM. The concomitant presence of t(11;14) portends a negative prognostic impact to MM with del(17p) but does not appear to impact MM with Ch1a. When present alongside del17p, t(11;14) behaves like a high-risk translocation and identifies a subset of MM in greatest need of newer therapies. Figure 1 Disclosures Costa: Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; AbbVie: Consultancy; Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Genentech: Consultancy.

scholarly journals Improving Risk Assessment of AML with a Precision Genomic Strategy to Assess Mutation Clearance

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5277-5277
Author(s):  
Meagan Jacoby ◽  
David H Spencer ◽  
Emma Hughes ◽  
Robert S Fulton ◽  
Michelle O'Laughlin ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Time Frame ◽  
Intermediate Risk ◽  
Advisory Committees ◽  
Free Survival ◽  
Post Induction ◽  
Flow Cytometric ◽  
Risk Patients

Abstract The persistence of leukemic mutation(s) in AML patients who have achieved a morphologic complete remission (CR) after intensive induction chemotherapy is a strong predictor of early relapse and reduced overall survival (OS) (Klco JAMA, 2015; Morita, J Clin Oncol 2018; Jongen-Lavrencic, NEJM, 2018). There is no clinical consensus as to the optimal consolidation therapy for the ~50% of patients with intermediate-risk AML. The median relapse-free survival (RFS) for patients ≤60 years with ELN intermediate-risk disease is 0.8 years to 1.2 years, with a median OS of 1.2-2.1 years (Mrozek, J Clin Oncol, 2012). We have shown that intermediate-risk patients who clear all leukemia-associated mutations (LAMs) to a variant allele fraction (VAF) of <2.5% in first morphologic CR have a median event-free survival of 25.6 months, vs 8.8 months if they do not (HR 3.32). Median overall survival is 46.8 months if all LAMs are cleared, vs 19.3 months if they are not (HR 2.88). We hypothesized that improved post-remission risk stratification using LAM clearance can further refine risk assessment and optimize alloHCT decisions by identifying patients at lower risk of relapse, who might be expected to do well with standard chemotherapy. Here, we report the development of a pipeline to prospectively determine the persistence of LAMs after remission-induction, and return results in a clinically actionable time-frame. We perform enhanced exome sequencing (EES) of paired skin or buccal swab (normal tissue) and bone marrow DNA to comprehensively identify all LAMs at diagnosis (Day 0) and to assess their clearance post-induction (~Day 30). EES data are generated using a CLIA-compliant assay in the CLIA-licensed environment (CLE) lab at the McDonnell Genome Institute, and results are returned to the treating physician. Intermediate risk patients ≤60 years with clearance of all LAMs (VAFs <2.5%) are assigned to receive consolidation with high-dose cytarabine (HiDAC) (Cohort A). Patients with persistence of any mutation at a VAF ≥ 2.5% are assigned to the investigator's choice arm, and are treated with HiDAC and/or alloHCT at the discretion of the treating physician (Cohort B). This stratification is part of an ongoing clinical protocol (NCT02756962) whose primary objective is to determine whether the RFS of patients who have cleared all LAM(s) post-induction (VAFs <2.5%) and are treated with HiDAC alone (Cohort A) is significantly higher than expected from a historical intermediate risk group. Measurable residual disease testing by "difference from normal" flow cytometry (lower level of detection of 0.02%, Hematologics, Seattle WA) post-induction will be correlated with clearance or persistence of mutations and clinical outcomes. For the 23 patients sequenced to date, the mean turnaround time to issue sequencing results to the treating physician was 24 days from the time of the remission biopsy. All 23 patients had detectable LAMs at presentation (mean 28 per patient, range, 6 to 43) that could be used to track persistent disease in the day 30 remission sample. Eleven patients (48%) cleared all LAMs and received HiDAC only (Cohort A). There was no flow cytometric evidence of residual AML in Cohort A. Twelve patients (52%) had persistent LAMs (Cohort B, investigator's choice). The number of persistent leukemia-associated variants present in Cohort B ranged between 1 and 14. Surprisingly, 9 of the 12 patients with persistent LAMs by sequencing had no flow cytometric evidence of residual leukemia. Seven of 12 patients on the investigator's choice arm have received an alloHCT, and none have relapsed to date. The median follow-up for all subjects is 378 days (range, 59-683). Neither the median RFS (Fig. 1A) nor the median OS (Fig. 1B) has been reached for either cohort. While preliminary, these results suggest that patients who clear all LAMs to a VAF of <2.5% may have durable responses with HiDAC alone. The encouraging RFS seen in the investigator's choice arm (Cohort B) may reflect the decision to recommend transplant "upfront" in CR1 for patients who have molecular persistent disease. In summary, identifying persistent LAMs after induction chemotherapy is feasible in an actionable time-frame. Early data suggest that using LAM clearance post-induction may improve current risk-stratification for intermediate-risk AML. Accrual of patients and continued follow-up are ongoing. Disclosures Jacoby: NovoNordisk: Consultancy; Celgene: Speakers Bureau. Loken:Hematologics, Inc: Employment, Equity Ownership. Schroeder:Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Uy:GlycoMimetics: Consultancy; Curis: Consultancy. Vij:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kahl:Gilead: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy; CTI: Consultancy; ADC Therapeutics: Consultancy; Abbvie: Consultancy; Seattle Genetics: Consultancy; Acerta: Consultancy; Juno: Consultancy; Celgene: Consultancy.

scholarly journals Quantitative Multiplex Immunohistochemistry Identifies Immunosuppression in the AML Bone Marrow and NK-Cells As Prognostic Biomarker in Intermediate-Risk Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2774-2774
Author(s):  
Oscar Brück ◽  
Olli Dufva ◽  
Sami Blom ◽  
Riku Turkki ◽  
Mette Ilander ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Research Funding ◽  
Nk Cell ◽  
Cytotoxic T Cells ◽  
Helper T Cells ◽  
Intermediate Risk ◽  
Risk Patients ◽  
Immune Contexture ◽  
Cell Proportion

Abstract BACKGROUND A complex interaction between blasts and surrounding cells in the acute myeloid leukemia (AML) bone marrow (BM) microenvironment sustains blast proliferation and confers chemoresistance. T- and NK-cells have been shown to be dysfunctional in AML, which might be associated with immune evasion and poor prognosis. Here, we present a comprehensive analysis of the immune contexture of the AML BM at diagnosis and study its interaction with clinicopathological variables. METHODS Diagnostic BM biopsies (n=69) were collected from AML patients treated in the Helsinki University Hospital during 2005-2017 and age and gender-matched controls (n=12) to construct tissue microarrays (TMA). Using 8-plex immunohistochemistry (mIHC) and computerized image analysis, we determined cell abundance and immunophenotypic states of millions of immune cells. Immunoprofiles were integrated with a total of 120 clinicopathological variables including cytogenetics and molecular genetics, ELN (European Leukemia Net) risk classification, disease burden parameters, and patient demographics. RESULTS Unsupervised hierarchical clustering of the immunologic contexture defined by mIHC analysis grouped AML patients distinctly from control subjects (Fig 1a). By extracting significant differences (Mann-Whitney U test, q<0.05) and annotating immunologic markers as either anti-cancer or immunosuppression drivers based on literature, we observed an interesting polarization of increased immunosuppression in AML compared to control BM (Fig 1b). In AML patients, lower fraction of granzyme B expressing (GrB+) cells was noted both in CD3+CD4+ helper T-cells (10.9% vs 24.3%, q=0.002, in AML vs control BM) and CD3+CD8+ cytotoxic T-cells (23.5% vs 33.5%, q=0.02). Moreover, we observed pronounced T-cell inhibition features, such as higher proportion of regulatory T-cells (1.5% vs 0.0% FOXP3+ of helper T-cells, q<0.001), and lower expression of class I HLA in BM cells (89.1% vs 100.0%, q<0.001). Putative exhausted PD1+ T-cells were also markedly enriched in the AML BM (15.7% vs 1.7% PD1+ of helper T-cells and 13.2% vs 2.0% PD1+ of cytotoxic T-cells, q<0.001). Among the high interpatient heterogeneity, we discovered two main immune profiles. Cluster 1 was characterized with higher proportion (Log2 fold change >0.5, q<0.05) of cytotoxic T-cells and expression of CD57, CD27, and CD25 in T-cells, as well as higher expression of PD-L1 in the BM. Moreover, lower expression (Log2 fold change <0.5, q<0.05) of OX40 and CD45RO in T-cells and proportion of CD11c+BDCA1+ (type 1 myeloid dendritic cells) were observed. Patients of Cluster 1 were associated with longer event-free survival (EFS; HR 1.9, p=0.049) as well as lower age (median 53.6 vs 64.4 years, p=0.001). No connection between immunologic clusters and FLT3 or NPM1 genotype, complex karyotype, ELN risk class, blast proportion or leukocyte count was found. To support clinical decision-making in ELN 2017 intermediate-risk patients, we developed a risk stratification model focusing on this particular subgroup (n=28) using L1-penalized Cox regression. Patient age over 60 years (HR 8.1, CI95% 2.5-26.6 p<0.001) and low proportion of CD45+CD2+CD3- NK-cells (HR 0.92, CI95% 0.85-0.99 p=0.03) predicted worse EFS. In intermediate-risk patients (n=68) of a separate validation cohort (n=145) analyzed with flow cytometry, low NK cell proportion and high age predicted worse EFS (HR 2.7 CI95% 1.6-4.6 p<0.001) and OS (HR 3.9 CI95% 2.1-7.3 p<0.001) after adjusting with induction therapy protocol. Lower NK-cell proportion was associated with FLT3-ITD genotype (0.45% vs 1.1% NK-cells/all cells in FLT3-ITD+ vs FLT3-ITD- AML patients, p=0.01), and higher than median PB leukocyte (WBC) count (0.50% vs 1.9% NK-cells/all cells in patients with PB WBC ≥7.8x10E9/L vs <7.8x10E9/L, p<0.001). CONCLUSIONS Using TMA cytometrics with mIHC and automated image analysis for detailed characterization of the immune contexture, we discovered pronounced immune exhaustion and suppression in AML BM. An aging-related immune profile was identified and was associated with poor prognosis. Furthermore, survival prediction of intermediate-risk patients might be enhanced by considering patient age and NK-cell proportion. Taken together, immunophenotyping of AML patients might improve risk stratification and identify a subgroup benefiting from immunomodulatory treatments. Disclosures Pallaud: Novartis: Employment. Marques Ramos:Novartis: Employment. Porkka:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Mustjoki:Ariad: Research Funding; Novartis: Honoraria, Research Funding; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding.

scholarly journals Single Cell Signaling Pharmacodynamics in a Phase 1b Trial of the Axl Inhibitor BGB324 in Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3995-3995 ◽  
Author(s):  
Monica Hellesøy ◽  
Stein-Erik Gullaksen ◽  
Benedicte Sjo Tislevoll ◽  
Oda Helen Eck Fagerholt ◽  
Hakon Reikvam ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Flow Cytometry ◽  
Single Cell ◽  
Peripheral Blood ◽  
Intracellular Signaling ◽  
Research Funding ◽  
Prognostic Information ◽  
Employment Equity ◽  
Phase 1B ◽  
Equity Ownership

Abstract Axl is a receptor tyrosine kinase that has been shown to have a strong oncogenic potential in many cancer types. Overexpression and activation of Axl is found in many cancers, and is linked to increased proliferation, migration/invasion and resistance to apoptosis. Axl overexpression has been shown to be a poor prognostic marker, and recently overexpression of Axl has also been linked to the acquired resistance to chemotherapy and other anticancer therapies in many malignancies, including AML. BGB324 (BerGenBio AS) is a first-in-class highly specific small molecule inhibitor of Axl. BGB324 has been shown to be safe and well tolerated in a clinical safety trial in healthy volunteers at doses up to 1500 mg/day with a predictable PK profile and long plasma half-life, and is currently in a phase 1b clinical trial in patients with refractory/relapsed AML and MDS (BGBC003, ClinicalTrials.gov Identifier:NCT02488408; Loges S et al. J Clin Oncol 34, 2016 suppl; abstr 2561). 20 AML and 4 MDS patients have been treated at the following dose levels (loading dose/continuation dose): 400/100mg, 600/200mg and 900/300mg. Objective responses were observed in 2/4 MDS patients and 2/20 AML patients including one CR (AML). Enrollment continues to define MTD. The effect of BGB324 on intracellular signaling and the immune profile of leukemic blasts in patients treated in the clinical study was investigated using phospho-flow cytometry. Blasts were identified using surface markers (CD45low, CD66b-, CD38-, and CD117+ and/or CD34+), and the following direct and indirect downstream targets of Axl were explored: phosphorylated (p)-Akt(S473 and T308), pErk(T202/Y204), pp38(T180/Y182), pPLCγ1(Y783), pNFκB(S529), pCREB(S113) and pSTAT1(Y701), 3(Y705), 5(Y694)and 6(Y641). Preliminary analyses of blood samples from six patients show very rapid responses in signaling pathways downstream of Axl (including Akt, Erk, NFκB and PLCγ1) within hours or days of ingestion of the first dose, although the response patterns varies from patient to patient (Figure 1A). Two distinct blast populations were identified: one CD117+/CD34- and one CD117+/CD34+. In most patients the CD117+/CD34- population displayed the most extensive signaling changes during treatment, and this population also decreased during treatment with BGB324. In contrast, the CD117+/CD34+ population expanded during the course of the treatment (Figure 1B). White cell differential counts of peripheral blood from two patients treated with BGB324 for a prolonged period of time (15 weeks or more) showed a decrease in peripheral blast count, and a corresponding increase in granulocyte and monocyte counts, suggesting that Axl inhibition may push the blasts towards differentiation. The clinical trial is ongoing, and the signaling profile of leukemic blasts in blood and bone marrow of treated patients will be further examined by conventional phosphoflow cytometry and mass cytometry searching for signaling profiles with prognostic information. In conclusion, BGB324 has unique pharmacodynamic properties and molecular responses to exposure can be observed in peripheral blood leukemic blasts by phospho-flow cytometry within hours of ingestion of the first treatment dose. Further studies may establish whether single cell signal profiling can discriminate responders from non-responders and provide information about dose-response in a clinically meaningful way. Disclosures Cortes: Astellas: Research Funding; Arog: Research Funding; Teva: Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Ambit: Research Funding. Heuser:Novartis: Consultancy, Research Funding; Tetralogic: Research Funding; BerGenBio: Research Funding; Karyopharm Therapeutics Inc: Research Funding; Bayer Pharma AG: Research Funding; Celgene: Honoraria; Pfizer: Research Funding. Lorens:BerGenBio AS: Employment, Equity Ownership, Research Funding. Gausdal:BerGenBio AS: Employment. Micklem:BerGenBio AS: Employment, Equity Ownership. Gjertsen:BerGenBio AS: Consultancy, Research Funding.

scholarly journals Distress and Perceived Impact on Well-Being for Low- or Intermediate-Risk and High-Risk Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5970-5970 ◽  
Author(s):  
Joanne S. Buzaglo ◽  
Melissa F. Miller ◽  
Clare Karten ◽  
Elisa S Weiss ◽  
Brian Tomlinson ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Well Being ◽  
Risk Groups ◽  
Intermediate Risk ◽  
Ability To Work ◽  
High Risk Patients ◽  
Risk Patients ◽  
Estimated Risk ◽  
Perceived Impact

Abstract Introduction: CLL treatment has changed considerably over the last several years, with significant improvement in overall survival and more effective treatment for genetically defined high-risk disease. The physical, intellectual, and emotional challenges of treatment, and living with CLL appear to impact patient quality of life (QOL). We aimed to describe patient distress and perceived impact of having a CLL diagnosis on their well-being using patient-reported CLL risk in a cross-sectional survey. Methods: From April 2014 to July 2016, the Cancer Support Community (CSC) registered 284 self-identified CLL patients to the Cancer Experience Registry: CLL, an ongoing, online initiative to study the psychosocial impact of CLL. The analysis was limited to US-based registrants diagnosed with CLL who completed survey questions about cancer-related distress (n=134) and perceived impact of CLL (n=99). Twenty-seven items from a validated distress screening tool (α=0.94) were summed for an overall distress score. Four items were summed for a depression score (α=0.85) that was also used to indicate risk for depression (low 0-4 vs. high 5 or greater). Participants were asked to evaluate the perceived impact of CLL on distinct aspects of well-being (QOL, ability to work, life expectancy, relationships, and finances): (1) retrospectively (When you were first diagnosed, how much did you think CLL would affect your well-being?); and (2) at the time of survey response (These days, how much would you say CLL affects your well-being?). CLL risk level (low, intermediate, or high) was captured through patient recall of the doctor's explanation of their estimated risk. We combined low and intermediate risk in analysis. Results: The sample was 53% male and 94% white with median age 62 y and time since CLL diagnosis 6 y. Over half (63%) reported low- or intermediate-risk disease, 17% indicated high-risk, and 20% didn't know their risk. Patients with high-risk CLL (n=20) had significantly higher levels of overall distress (mean=31, SD=23) than patients with low- or intermediate-risk CLL (n=76; mean=21, SD=16, p=0.029). High-risk CLL patients also were more likely to score at high risk for depression (55% vs. 30%; p=0.036). Though overall distress was higher among patients with high-risk CLL, we observed similar top concerns (% moderately to very seriously concerned) for both high- and low- or intermediate-risk groups, respectively: eating and nutrition (56%, 46%); exercising (55%, 34%); worry about the future (50%, 36%); financial worries (50%, 31%); and sleep problems (50%, 30%). Other top concerns among high-risk, but not low- or intermediate-risk patients included ability to think clearly (50%) and feelings of loneliness or isolation (50%). When asked how much CLL currently affects their lives (see Table), high-risk patients (n=15) reported a significantly greater impact on QOL (p<0.001), ability to work (p=0.002), relationships with friends and family (p=0.002), and finances (p=0.029) than low- or intermediate-risk patients (n=65). Interestingly, when asked to recall how much they thought CLL would affect their lives when first diagnosed, there was no difference in anticipated impact between those with low- or intermediate-risk and high-risk patients. And in both risk groups, 83% indicated they understood how lab test results reflected their risk. Conclusion: These initial data from our CLL registry suggest that most patients understand their estimated risk and that high-risk CLL patients experienced greater overall distress and depression risk at the time of survey response compared to patients with low- or intermediate-risk. Across disease risk categories, CLL patients anticipated considerable distress (see Table) when first diagnosed and reported similar top concerns. These findings can help clinicians shape discussions that are responsive to CLL patient and care partner concerns about diagnosis, treatment and survival. Disclosures Flowers: AbbVie: Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; NIH: Research Funding; Mayo Clinic: Research Funding; Roche: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Research Funding; Infinity: Research Funding; ECOG: Research Funding; Acerta: Research Funding; Genentech: Consultancy, Research Funding.

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