A Global Delphi Consensus Initiative for Early Diagnosis of Gaucher Disease: Barriers, Their Resolution and the Impact on Patients

Abstract Background: Diagnosis of Gaucher disease (GD) can be difficult and diagnostic delays are common in both adult and paediatric patients. This may in part be attributable to the heterogeneous nature of early presenting signs and symptoms in GD, which may result in patients consulting various specialists before a diagnosis is reached. As part of this global Gaucher earlier diagnosis consensus (GED-C) initiative, a panel of expert physicians was asked to determine the most important barriers to diagnosis of GD. The panel was also asked about the impact of the initiative if its primary objective of facilitating earlier diagnosis was realized. Methods: In round 1 of an anonymous, multi-stage, iterative Delphi process, the panel provided free-text answers to a series of open questions, including: "In your experience, what are the greatest barriers to diagnosis in patients with early GD?" and "Assuming that this initiative achieves its goal, what difference could it make to clinical practice?" An independent facilitator grouped the responses to these questions by theme, and these were checked and consolidated as summary statements by the two non-voting co-chairs of the GED-C initiative. In round 2, panel members independently rated the importance of each statement using a 5-point Likert scale (1 = not important, 5 = extremely important). Statements awarded an importance score of at least 3 by more than 75% of respondents were reissued in round 3, in which panel members rated their level of agreement with each statement using a 5-point pivoted Likert scale (1 = strongly disagree; 3 = neither agree nor disagree; 5 = strongly agree). Consensus was defined as more than 67% of respondents agreeing or strongly agreeing (a score of ≥ 4) with a statement. Results: In total, 22 experts from 16 countries were recruited to the GED-C panel. Round 1 (100% response, n = 22) yielded 47 phrases relating to barriers to diagnosis, and 30 relating to the impact of the initiative on clinical practice, which were consolidated as 9 statements describing barriers to diagnosis, and 8 summarizing the initiative's impact. In round 2 (100% response, n = 22) and round 3 (100% response, n = 22), 6 barrier statements and all 8 impact statements met the stipulated importance criteria, and consensus was then reached for all 6 barrier statements and for 7 impact statements (Table). Discussion: This initiative highlights that, as well as the heterogeneous nature of GD, clinicians' lack of awareness of GD and poor knowledge of important presenting signs probably contribute to incorrect or delayed diagnoses. The GED-C initiative aims to resolve this by providing clinicians with simple guidance regarding important factors in GD, thereby improving disease awareness and facilitating early diagnosis. This may improve understanding of the natural history of GD, patient management, and potentially patients' long-term outcomes. Acknowledgment: Submitted on behalf of the GED-C panel members and the European Hematology Association Scientific Working Group 'Quality of Life and Symptoms'. Administration of the GED-C initiative was funded by an unrestricted educational grant from Shire. Table Table. Disclosures Kuter: Bristol-Myers Squibb: Research Funding; ONO: Consultancy; Protalex: Research Funding; Eisai: Consultancy; Shionogi: Consultancy; 3SBios: Consultancy; Syntimmune: Consultancy; MedImmune: Consultancy; CRICO: Other: Paid expert testimony; Amgen: Consultancy, Paid expert testimony; Pfizer: Consultancy; Rigel: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Shire: Consultancy; Genzyme: Consultancy. Salek:Novartis: Research Funding; Bristol-Myers Squibb: Research Funding; Shire: Consultancy; Servier: Consultancy; Sanofi: Research Funding; Agios: Consultancy. Mehta:Protalix/Pfizer: Honoraria, Other: travel grant, Research Funding; Genzyme: Honoraria, Other: travel grant, Research Funding; Actelion: Honoraria, Other: travel grant, Research Funding; Shire: Honoraria, Other: travel grant, Research Funding.

Download Full-text

Key Presenting Signs and Patient Co-Variables in Early Diagnosis of Type 3 Gaucher Disease: A Global Delphi Consensus Initiative

Blood ◽

10.1182/blood.v128.22.4886.4886 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4886-4886 ◽

Cited By ~ 1

Author(s):

David J Kuter ◽

Sam Salek ◽

Atul Mehta

Keyword(s):

Early Diagnosis ◽

Expert Testimony ◽

Gaucher Disease ◽

Research Funding ◽

Diagnostic Testing ◽

Early Type ◽

Travel Grant ◽

Major Factors ◽

Type 3

Abstract Background: Among the three phenotypes of Gaucher disease (GD), type 1 is the most prevalent in the Western hemisphere, but types 2 and 3 are increasingly seen, and occur with similar prevalence to type 1 in parts of Asia. There is a spectrum of signs and symptoms among these phenotypes, which range from fatal perinatal to asymptomatic adult disease, and this heterogeneity contributes to relatively high levels of misdiagnosis and delays in diagnosis of GD. As part of the global Gaucher earlier diagnosis consensus (GED-C) initiative, we report here the signs and patient co-variables that are regarded by expert physicians as most indicative of type 3 GD in its early stages. The overarching goal of the GED-C initiative was to generate a web-based point-scoring system for use across clinical specialties to facilitate identification of patients who may benefit from diagnostic testing for GD. Methods: In an anonymous, iterative Delphi process, a panel of expert physicians was asked to provide free-text answers to a series of open questions, including: "Which unexplained signs and co-variables may be important to consider in early type 3 GD?" An independent facilitator categorized responses from round 1 into themes, which were checked and consolidated by the two non-voting co-chairs of the initiative to generate a set of summary factors. In round 2, panel members independently rated the importance of each factor using a 5-point Likert scale (1 = not important, 5 = extremely important). Factors that were assigned an importance score of at least 3 by more than 75% of respondents were provisionally classified as major; other factors were classified as minor. In round 3, panel members rated their level of agreement with the provisional classification of factors as major using a 5-point pivoted Likert scale (1 = strongly disagree; 3 = neither agree nor disagree; 5 = strongly agree). Consensus was defined as more than 67% of respondents agreeing or strongly agreeing (a score of ≥ 4) with the classification; if consensus was not reached, factors were classified as minor. Results: In total, 19 physicians with expertise in type 3 GD were recruited to the GED-C panel from 14 countries. Round 1 (100% response, n = 19) yielded 70 phrases, which were grouped into 34 themes, then consolidated as 23 factors. In round 2 (100% response, n = 19), 16 factors were provisionally classified as major. In round 3 (100% response, n = 19), consensus was reached on 10 major factors in early type 3 GD, including 9 presenting signs and 1 patient co-variable. The mean importance scores (round 2) and agreement scores (round 3) awarded to these 10 major factors are given in Table 1. Minor factors included bleeding or bruising, cardiovascular calcification, cognitive deficit, growth retardation, hyperferritinaemia, aged 18 years or younger, Jewish ancestry and a family history of Parkinson disease. Discussion: Definitive diagnostic tests for GD have been available for several years, but patient referral for testing is impeded by several issues, including a lack of knowledge among clinicians of the signs and co-variables that should arouse suspicion of GD. In type 3 GD, the problem is exacerbated by the relative rarity of the phenotype. Presenting signs and patient co-variables identified by this multidisciplinary consensus initiative will help clinicians identify those patients who may benefit from diagnostic testing for GD. Several algorithms have been devised to facilitate GD diagnosis, but non-specialists may perceive these as complex. The GED-C initiative will use the factors identified here to create a point-scoring system that clinicians of any specialty can use to obtain clear direction regarding the need to test a patient for GD. Acknowledgment: Submitted on behalf of the GED-C panel members and the European Hematology Association Scientific Working Group 'Quality of Life and Symptoms'. Administration of the GED-C initiative was funded by an unrestricted educational grant from Shire. Table 1 Mean scores of importance and agreement for 10 major factors in early diagnosis of type 3 Gaucher disease. Table 1. Mean scores of importance and agreement for 10 major factors in early diagnosis of type 3 Gaucher disease. Disclosures Kuter: Eisai: Consultancy; Genzyme: Consultancy; MedImmune: Consultancy; Rigel: Consultancy, Research Funding; CRICO: Other: Paid expert testimony; Pfizer: Consultancy; Protalex: Research Funding; GlaxoSmithKline: Consultancy; Amgen: Consultancy, Paid expert testimony; Bristol-Myers Squibb: Research Funding; ONO: Consultancy; Shionogi: Consultancy; Shire: Consultancy; Syntimmune: Consultancy; 3SBios: Consultancy. Salek:Novartis: Research Funding; Bristol-Myers Squibb: Research Funding; Shire: Consultancy; Servier: Consultancy; Sanofi: Research Funding; Agios: Consultancy. Mehta:Protalix/Pfizer: Honoraria, Other: travel grant, Research Funding; Genzyme: Honoraria, Other: travel grant, Research Funding; Actelion: Honoraria, Other: travel grant, Research Funding; Shire: Honoraria, Other: travel grant, Research Funding.

Download Full-text

A Global Delphi Consensus Initiative for Early Diagnosis of Gaucher Disease: Key Presenting Signs and Patient Co-Variables in Type 1 Disease

Blood ◽

10.1182/blood.v128.22.3676.3676 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3676-3676

Author(s):

David J Kuter ◽

Sam Salek ◽

Atul Mehta

Keyword(s):

Scoring System ◽

Gaucher Disease ◽

Research Funding ◽

Diagnostic Testing ◽

Likert Scale ◽

Western Hemisphere ◽

Free Text ◽

Early Type ◽

Major Factors

Abstract Background: Gaucher disease (GD) is associated with a broad spectrum of signs and symptoms, with phenotypes ranging from fatal perinatal to asymptomatic adult forms. Given the heterogeneous presentation and rarity of the disease, misdiagnosis is common and diagnosis is often delayed, which can lead to avoidable morbidities and potentially irreversible tissue damage. Among the three phenotypes of GD, type 1 is the most prevalent in the Western hemisphere. As part of the global Gaucher earlier diagnosis consensus (GED-C) initiative, we report here the signs and patient co-variables that are regarded by expert physicians as most indicative of type 1 GD in its early stages. The overarching goal of the GED-C initiative is to generate a web-based point-scoring system that can be used by clinicians across specialties to facilitate identification of patients who may benefit from diagnostic testing for GD. Methods: In an anonymous iterative Delphi process, a panel of expert physicians was asked to provide free-text answers to a series of open questions, including: "Which unexplained signs and co-variables may be important to consider in early type 1 GD?" An independent facilitator categorized responses from round 1 into themes, which were checked and consolidated by the two non-voting co-chairs of the initiative to generate a set of summary factors. In round 2, panel members independently rated the importance of each factor using a 5-point Likert scale (1 = not important, 5 = extremely important). Factors assigned an importance score of at least 3 by more than 75% of respondents were provisionally classified as major; other factors were classified as minor. In round 3, panel members rated their level of agreement with the provisional classification of factors as major using a 5-point pivoted Likert scale (1 = strongly disagree; 3 = neither agree nor disagree; 5 = strongly agree). Consensus was defined as more than 67% of respondents agreeing or strongly agreeing (a score of ≥ 4) with the classification; if consensus was not reached, factors were classified as minor. Results: In total, 22 physicians with expertise in type 1 GD were recruited to the GED-C panel from 16 countries. Round 1 (100% response, n = 22) yielded 104 phrases, which were grouped into 38 themes, then consolidated as 21 factors. In round 2 (100% response, n = 22), 10 factors were provisionally classified as major. In round 3 (100% response, n = 22), consensus was reached on 9 major factors in early type 1 GD, including 7 presenting signs and 2 patient co-variables. The mean importance scores (round 2) and agreement scores (round 3) awarded to these 9 major factors are given in Table 1. Minor factors included asthenia, bleeding or bruising, dyslipidaemia, fatigue, gallstones, growth retardation, low bone mineral density and a family history of Parkinson disease. Table 1. Mean scores of importance and agreement for 9 major factors in rounds 2 and 3, respectively. Discussion: Definitive diagnostic tests for GD have been available for several years, but patient referral for testing is impeded by several issues, including a general lack of knowledge among clinicians of the signs and co-variables that should arouse a suspicion of GD. The presenting signs and patient co-variables identified by this multidisciplinary consensus initiative will help clinicians to identify those patients who may benefit from diagnostic testing for GD. Several algorithms have been devised with the aim of facilitating GD diagnosis, but these may be perceived as complex by the non-specialist. The next stage of the GED-C initiative will be to use the factors identified here to create a point-scoring system that clinicians of any specialty can use to obtain clear direction regarding the need to test a patient for GD. Acknowledgment: Submitted on behalf of the GED-C panel members and the European Hematology Association Scientific Working Group 'Quality of Life and Symptoms'. Administration of the GED-C initiative was funded by an unrestricted educational grant from Shire. Table 1. Table 1. Disclosures Kuter: Amgen: Consultancy; Eisai: Consultancy; Genzyme: Consultancy; GlaxoSmithKline: Consultancy; ONO: Consultancy; Pfizer: Consultancy; Shionogi: Consultancy; Shire: Consultancy; 3SBios: Consultancy; Bristol-Myers Squibb: Research Funding; Protalix: Research Funding; Rigel: Research Funding. Salek:Agios: Consultancy; Servier: Consultancy; Shire: Consultancy; Bristol-Myers Squibb: Research Funding; Novartis: Research Funding; Sanofi: Research Funding. Mehta:Actelion: Honoraria, Other: Travel grants, Research Funding; Genzyme: Honoraria, Other: Travel grants, Research Funding; Protalix/Pfizer: Honoraria, Other: Travel grants, Research Funding; Shire: Honoraria, Other: Travel grants, Research Funding.

Download Full-text

Impact of Donor Chimerism-Guided Immunomodulation after Allogeneic Stem Cell Transplant on the Outcome of Patients with AML and MDS

Blood ◽

10.1182/blood-2018-99-116088 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2133-2133

Author(s):

Juliane Steinmann ◽

Sarah Lindner ◽

Zuzana Jedlickova ◽

Salem Ajib ◽

Saskia C. Gueller ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Small Molecules ◽

Research Funding ◽

Mixed Chimerism ◽

Cell Transplant ◽

Donor Chimerism ◽

Unrelated Donors ◽

Travel Grant ◽

The Impact

Abstract Introduction: After an allogeneic stem cell transplantation (SCT), analysis of donor chimerism (DC) is routinely used to monitor engraftment. In patients with myeloid malignancies, loss of a complete donor chimerism (CC) may indicate graft failure, but more often imminent leukemic relapse. Especially in patients without a valid marker for minimal residual disease (MRD), chimerism analysis may prompt reduction of immunosuppression or therapeutic interventions such as donor lymphocyte infusions (DLI) or hypomethylating agents (HMA). We retrospectively analyzed DC data and outcomes of 255 consecutive patients (pts) transplanted for an acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) at our center. Aims of our study were to evaluate the impact of (i) a falling DC, (ii) the first chimerism-guided intervention, and (iii) the application of DLI on survival and incidence of acute and chronic (a/c) GvHD. Patients and Methods: 255 pts that received a first SCT between 2005 and 2016 were monitored regularly (approx. every two weeks from day +14 to +100, then monthly) for DC using a validated, CE-labeled multiplex-STR PCR at a single laboratory (AgenDix GmbH, Dresden, Germany). CC was defined as ≥99% and mixed chimerism (MC) as <99% donor cells. Overall survival (OS), GVHD-free, relapse-free survival (GFRS) and the cumulative incidence (CI) of GVHD was analyzed for the whole cohort, OS and CI GVHD were analyzed for pts with MC and pts that received DLI with a prophylactic/preemptive (pDLI) vs. therapeutic (tDLI) indication. 245 pts (median age 53 years (range 19-73), 136 male) with AML (n=222) or MDS (n=23) achieved a CC within 60 days post SCT and were eligible for our analysis, 10 pts were excluded due to refractory disease (n=9) or early death (n=1). 101 out of 222 AML pts (45%) had intermediate (int)-2 or adverse cytogenetics according to ELN guidelines, and 10 out of 23 MDS pts (43%) had IPSS int-2 or high risk. 121 pts (49%) were transplanted in first complete remission (CR), 107 (44%) with active disease. For SCT, 96 pts (39%) had received myeloablative (MAC) and 149 (61%) reduced intensity conditioning regimens (RIC). Donors were HLA-matched siblings (MRD, n= 60) or unrelated donors (MUD, n=149), mismatched related (MMRD, n= 1) or unrelated donors (MMUD, n=27), or haploidentical family members (n=8). Results: A MC was detected in 95 pts (39%) at a median of 104 (range, 28-1764) days post SCT, of whom 18 pts (32%) had aGVHD G2-4. Pts with MC had received RIC significantly more often compared to pts with continued CC (69% vs 55%, p=0.046), the two groups did not differ regarding high risk cytogenetics/IPSS and remission status at SCT. MC prompted reduction of immunosuppressive therapy (IST, n=35), DLI (n=7), HMA (n=16), DLI+HMA (n=7), chemotherapy and/or 2ndSCT (n=7), small molecules (n=10) or best supportive care (BSC, n=13) as deemed appropriate by the treating physician. Median OS and GFRS were significantly better for pts with CC (OS not reached; GFRS 46 months (mths)) compared to pts with MC (OS 15.7 mths; Hazard ratio (HR) 0.25, 95%-CI 0.17-0.37, p<0.001, GFRS 3.7 mths; HR 0.39, 95%-CI 0.26-0.58, p<0.001, figures 1,2). 3-year survival was 75% for the CC group vs 31.7% for the MC group. For the 95 pts with MC, median OS was 27.4 and 35.8 mths following IST reduction or DLI+HMA, respectively, and 12, 8.8, 5.1 and 1.2 mths for pts treated with chemo/2ndHSCT, HMA, small molecules or BSC. Treatment of MC induced aGVHD G2-4 in only 2 additional pts (G3-4: n=1). CI of cGVHD requiring systemic IST was 27% at 1-year for all pts with MC compared to 13.9% for pts in the CC group. In the whole cohort, 46 pts (19%) received a median of 2 DLIs (median dose 0.5x106CD3+cells/kg). PDLIs were administered to 33 pts (72%) and tDLIs to 13 pts with relapsed disease (28%). The pDLI group had a 3-year survival of 82.9% and did not reach median OS, compared to 24.6% 3-year survival and 22 mths median OS in the tDLI group. Median GRFS was 91.4 vs 6.6 mths for the pDLI and tDLI group, respectively. No pt developed aGVHD G2-4 after DLI administration, 1 pt (8%) in the tDLI and 4 pts (12%) in the pDLI group developed cGVHD requiring systemic IST. Conclusion Occurrence of MC seems predictive of an inferior outcome, but early intervention such as careful reduction of IST if feasible or administration of DLI with or without HMA may effectively prolong OS and GRFS. Administration of pDLI after discontinuation of IST starting with low doses is safe and results in low rates of cGvHD. Disclosures Lang: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding. Toenges:Bayer: Research Funding. Schetelig:Sanofi: Consultancy, Research Funding; Roche: Honoraria; Abbvie: Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Serve:Bayer: Research Funding. Thiede:AgenDix: Other: Ownership; Novartis: Honoraria, Research Funding. Bug:Astellas Pharma: Other: Travel Grant; Novartis Pharma: Honoraria, Research Funding; Neovii: Other: Travel Grant; Jazz Pharmaceuticals: Other: Travel Grant; Janssen: Other: Travel Grant; Celgene: Honoraria; Amgen: Honoraria.

Download Full-text

Semiautomatic VWF Multimer Densitometric Analysis: Validation of the Clinical Accuracy and Clinical Implications in Von Willebrand Disease

Blood ◽

10.1182/blood-2020-142287 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 15-16

Author(s):

Ferdows Atiq ◽

Johan Boender ◽

Marjon H. Cnossen ◽

Johanna G van der Bom ◽

Karin Fijnvandraat ◽

...

Keyword(s):

Clinical Practice ◽

Research Funding ◽

Von Willebrand Disease ◽

Densitometric Analysis ◽

Travel Grant ◽

Bleeding Score ◽

Type 3 ◽

Von Willebrand

Introduction Von Willebrand factor (VWF) multimer analysis is an essential tool in the diagnosis and classification of von Willebrand disease (VWD). Current visual VWF multimer analysis is observer dependent, time consuming and is inaccurate in detecting subtle changes in multimer patterns. Therefore, recent studies have investigated VWF multimer quantification using semiautomatic densitometric analysis. The accuracy of VWF multimer densitometric analysis in clinical practice needs further investigation before it can be widely used. The aim of the study was to validate the accuracy of VWF multimer densitometric analysis in clinical practice. Additionally, we aimed to identify patient characteristics associated with VWF multimer densitometry outcomes in type 1 and type 2 VWD patients, and we investigated whether subtle differences in VWF multimer pattern are associated with the bleeding phenotype of VWD patients. Methods We included patients from the nationwide Willebrand in the Netherlands (WiN) study. The inclusion criteria of the WiN study were a personal hemorrhagic diathesis or family history of VWD, and historically lowest VWF antigen (VWF:Ag), VWF activity (measured with the monoclonal antibody assay: VWF:Ab) or VWF collagen binding (VWF:CB) ≤0.30 IU/mL or FVIII activity (FVIII:C) ≤0.40 IU/mL in case of type 2N VWD. At inclusion in the WiN study, blood was drawn and patients filled in an extensive questionnaire containing a self-administered Tosetto bleeding score (BS). For multimer analysis, citrated blood samples were separated on 0.9% agarose gel and visualized by Western blotting. We used IMAGEJ for densitometric analysis. The five smallest bands on densitometric images were defined as small multimers, next five bands were defined as medium multimers and the remaining bands were defined as large multimers. Medium-large VWF multimer index was calculated by dividing the patient's multimer ratio (intensity of the medium and large multimers divided by the total intensity of all multimers) by the multimer ratio of a normal control in the same western blot. If no multimers could be detected, the multimer index was set as 0. Results We included 561 VWD patients: 328 type 1, 211 type 2 and 21 type 3 patients. The median age was 44 [IQR 29-58] and 351 patients (62.7%) were female (Table 1). Figure 1 illustrates typical densitometric outcomes of a type 1 VWD patient with normal VWF multimers (A) and a type 2A patient with reduced high-molecular-weight (HMW) VWF multimers (B). Medium-large VWF multimer index was 1.06 [0.99-1.12] in type 1 and 0.53 [0.29-0.89] in type 2 and 0.00 [0.00-0.00] in type 3 VWD. Medium-large VWF multimer index was in patients visually classified as normal, reduced and absent HMW VWF multimers, respectively 1.07 [1.02-1.12], 0.84 [0.71-0.91] and 0.31 [0.20-0.44] (p<0.001, Figure 2A). With visual examination as gold standard, medium-large VWF multimer index had a very good accuracy in distinguishing normal VWF multimers from reduced HMW VWF multimers (AUC: 0.96 (0.94-0.98) p<0.001, Figure 2B). It could also accurately distinguish reduced HMW VWF multimers from absence of HMW multimers, with an AUC of 0.95 (0.92-0.97, p<0.001), and type 2A and 2B from type 2M and 2N (AUC: 0.96 (0.94-0.99), p<0.001, Figure 2C and 2D). From VWF activity measurements, medium-large VWF multimer index was strongest correlated with VWF:CB (ρ=0.79, p<0.001). From the ratio of the various functional VWF measurements (divided by VWF:Ag), the strongest correlation was again found for VWF:CB/VWF:Ag ratio (ρ=0.80, p<0.001). In type 1 VWD, an increased clearance of VWF (defined as VWFpropeptide/VWF:Ag ratio ≥2.2) was independently associated with lower medium-large VWF multimer index (β=-0.10 (-0.14; -0.07), p<0.001). Also, type 1 VWD patients with a VWF gene variant had relatively lower medium-large VWF multimer index compared to type 1 patients without a VWF variant, respectively 1.03 [0.95-1.10] vs 1.08 [1.04-1.12] (p<0.001). In the total population, higher medium-large VWF multimer index was associated with a lower bleeding score: β=-4.6 (-7.2; -2.0), p=0.001, adjusted for age, sex, blood group and type of VWD. Conclusion Semiautomatic densitometric analysis of VWF multimers has an excellent accuracy in clinical practice, and may have an additional value in providing a better understanding of the clinical features such as the bleeding phenotype of VWD patients. Disclosures Atiq: CSL Behring: Research Funding; SOBI: Other: travel grant. Boender:SOBI: Current Employment; CSL Behring: Research Funding. Cnossen:Bayer: Research Funding; Novo Nordisk: Research Funding; Nordic Pharma: Research Funding; Sobi: Research Funding; Takeda: Research Funding; CSL behring: Research Funding; Pfizer: Research Funding; Shire: Research Funding; Baxter: Research Funding. van der Bom:Bayer: Speakers Bureau. Fijnvandraat:SOBI: Research Funding; NovoNordisk: Consultancy; Grifols: Consultancy; Takeda: Consultancy; Roche: Consultancy; CSL Behring: Research Funding; NovoNordisk: Research Funding. Van Galen:Bayer: Research Funding; Takeda: Speakers Bureau; CSL Behring: Research Funding. Laros-Van Gorkom:Baxter: Other: Educational grant; CSL Behring: Other: Educational grant. Meijer:Bayer: Research Funding; Sanquin: Research Funding; Pfizer: Research Funding; Bayer: Speakers Bureau; Sanquin: Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; BMS: Speakers Bureau; Aspen: Speakers Bureau; Uniqure: Consultancy. Eikenboom:CSL Behring: Research Funding; Roche: Other: Teacher on educational activities. Leebeek:Roche: Other: DSMB member for a study; SOBI: Other: Travel grant; Novo Nordisk: Consultancy; Shire/Takeda: Consultancy; Uniqure: Consultancy; Shire/Takeda: Research Funding; CSL Behring: Research Funding.

Download Full-text

New Prognostic Factors in the Assessment of Bone Complications in Gaucher Disease. Report from the Argentinian Group for Diagnostic and Treatment for Gaucher Disease

Blood ◽

10.1182/blood.v124.21.4116.4116 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4116-4116

Author(s):

Guillermo I. Drelichman ◽

Nicolas Fernandez Escobar ◽

Nora F Basack ◽

Maria S Larroude ◽

Gabriel Aguilar ◽

...

Keyword(s):

Prognostic Factors ◽

High Risk ◽

Early Diagnosis ◽

Bone Disease ◽

Gaucher Disease ◽

Research Funding ◽

Disease Group ◽

Prognostic Groups ◽

Delay In Treatment

Abstract Objectives: the objectives of our study were to assess whether the current achievement of bone therapeutic goals (TG) correlate with the presence or absence of bone lesions (BL) and determine whether there are prognostic factors affecting response to enzyme replacement therapy (ERT) and the degree of bone involvement. Methods: 124 patients with Gaucher disease (GD) type 1 belonging to 45 centers in our country were studied. All studies were centralized in an imaging center and a central laboratory. Two points of evaluation were defined: 1) historical findings with data prior to diagnosis, diagnostic and data monitoring and 2) current findings with data obtained the day the following procedures were performed: total body resonance (TBR), volumetric resonance (VR), densitometry, complete blood count and chitotriosidase dosage. Five TG were evaluated according to the International Registration of Gaucher (ICGG). Results: with a median follow up of 15 years and a median treatment with ERT of 9.4, 105 patients (88%) achieved the five TG. Specifically bone TG were achieved by 90.3% of patients. However, this achievement was not correlated with the absence of BL as 87% of patients evaluated at day 0 showed different types of bone disease (BD) despite being in TRE. Reversible BL findings (infiltration and / or Erlenmeyer) and irreversible BL (infarcts and / or necrosis) increased from 71.8% at diagnosis versus 87% at study entry especially in relation to the appearance of acute BL (new) of osteonecrosis (24%). These discrepancies between the achievement of bone TG (90.3%), the presence of BD (87%) and the occurrence of acute BL (24%) show that the evaluation of the current bone TG is not accurate and it is necessary to evaluate more sensitive methods because it does not reflect the degree of bone involvement. We found four prognostic factors associated with the BD variable with statistical significance: ERT adherence, time between onset of symptoms and diagnosis, time between diagnosis and start of ERT and starting dose of ERT. Conclusions: these findings show that ERT "alone" can not maintain over time patients without chronic or acute BD or avoid the sequela. Several prognostic factors are associated with the likelihood that the patient is free of BD in the diagnosis and long-term monitoring. The findings at diagnosis of the following prognostic factors: late diagnosis (> 2 years) and a delay in treatment (> 2 years) were associated with a higher probability of irreversible BL. Findings in the monitoring of the following prognostic factors: good compliance to ERT, early initiation of ERT, early diagnosis and initial appropriate ERT dose at diagnosis according to risk level are associated with a greater likelihood of not presenting BD. According to this analysis we propose a new definition of bone TG and a new classification of prognostic groups (table 1). Table 1. New Prognostic Groups for BD in Gaucher Disease Prognostic Group Prognostic Factors Long - term consequences on Bone Group 1 (low risk of BD) ERT compliance > 90%Early diagnosis(< 2 years)Appropriate dose of ERT More likely not to present bone disease Group 2 (Intermediaterisk of BD) ERT compliance between > 80 and < 90%Delay in treatment(> 2 years) More likely to have reversible bone disease Group 3 (High risk of BD) ERT compliance between > 50 and < 80%More delay in treatment(> 2 years) More likely to have reversible and irreversible bone disease Group 4 (Very high Risk of BD) ERT compliance < 50%Low dose of ERT More likely to have reversible, irreversible and acute bone disease Disclosures Drelichman: Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Fernandez Escobar:Genzyme: Research Funding, Speakers Bureau. Larroude:Genzyme: Honoraria. Aguilar:Genzyme: Honoraria.

Download Full-text

TP53 Status As Well As Cytogenetic Complexity Significantly Impact on Prognosis in Myelodysplastic Syndromes with Complex (≥3 anomalies) Aberrant Karyotypes

Blood ◽

10.1182/blood-2019-126671 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3007-3007

Author(s):

Christina Ganster ◽

Roxana Schaab ◽

Katayoon Shirneshan ◽

Lea Naomi Eder ◽

Anna Mies ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Genetic Profile ◽

Fish Analysis ◽

Advisory Committees ◽

Clone Size ◽

Increased Risk ◽

Travel Grant ◽

The Impact ◽

Tp53 Status

Introduction: Complex aberrant karyotypes (CK, ≥3 cytogenetic aberrations, CA) are associated with an unfavorable prognosis and an increased AML transformation rate in MDS. However, even MDS with CK (CK-MDS) are heterogeneous in terms of genetic profile and prognosis. Recently, we demonstrated that a high number of CA as well as mutations in TP53 (TP53mut) are associated with increased risk in CK-MDS (Haase et al, 2019). However, as there is a strong association between CK-MDS and TP53mut, it is still a matter of debate whether the karyotype and TP53mut are prognostically independent genetic markers. Furthermore, loss of heterozygosity (LOH) of 17p13 (TP53LOH), due to loss of genetic material or to copy number neutral LOH (CN-LOH), is also associated with a poor prognosis. We here aimed to characterize TP53mut andTP53LOH in CK-MDS and to elucidate the impact of cytogenetics, TP53mut and TP53LOH on the outcome of CK-MDS. Methods: We included 178 pts with MDS (N=138), CMML (N=5) and secondary AML after MDS (AML with myelodysplasia-related changes, N=35), all with CK. The median precentage of bone marrow (bm) blasts was 11% (range: 0-90%). The median age was 72 yrs (range: 30-95 yrs). The male:female ratio was 1.23:1. The number of CA was determined by banding analysis in all cases. The karyotype was confirmed by multicolor FISH in 134 cases. TP53LOH was verified by FISH analysis of the TP53 locus in 17p13 (146 analyses) and/or molecular karyotyping (MK, 41 analyses). In 144 cases further FISH probes in addition to TP53 were used. TP53mut was identified by NGS (54 cases) or Sanger sequencing (124 cases). Follow-up data for survival analyses were available for 127 pts with MDS and oligoblastic AML with less than 30% bm blasts. Results: The median number of CA was 7 (range: 3-46), 98/178 pts (55%) showed a TP53mut (median VAF: 34%, range: 8-93%) and 64/178 (36%) a TP53LOH (median FISH clone size: 65%, range: 6-99%), including 9 pts with a CN-LOH in 17p13. The CN-LOH was either identified by MK (5/41 pts (12%) where MK was available showed a CN-LOH, 4/5 with TP53mut) or by NGS (4/54 pts (7%) where NGS was available showed a VAF >70% and normal TP53-FISH). In total, a TP53mut and/or a TP53LOH was identified in 116/178 pts (65%). Overall survival (OS) did not significantly differ between CK-MDS with TP53mut only, TP53LOH only, and TP53mut+TP53LOH (Fig.1). Therefore, we merged TP53mut and TP53LOH to TP53altered in all further analyses. Regarding the cytogenetic characterization of pts with TP53altered, the number of CA was significantly higher in pts with TP53altered than in pts with normal TP53 (median 9 CA (range: 3-46) vs 5 CA (range: 3-24), P<0.001). Also notable was that the founder clone of pts with TP53altered included significantly more cases with del(5q) (determined by FISH, 69/92 cases, 75%) compared to pts with normal TP53 (22/52 cases, 42%, P<0.001). The number of CA as well as the TP53 status contributed significantly to OS (Fig.2). The presence of anemia (Hb <10 g/dl) at first diagnosis of the CK had the greatest impact on OS (HR: 3.95) in the multivariate model (Cox regression), followed by an altered TP53 gene (TP53mut and/or TP53LOH; HR: 3.53) and the presence of ≥5 CA (HR: 2.33). Based on these three parameters with the greatest impact on OS, we created a simple provisional prognostic system. One scoring point each was assigned to anemia (Hb <10 g/dl), TP53altered, and ≥5 CA. Regarding OS, the resulting four risk groups separated very well (Fig.4). Conclusions: The presence of ≥5 CA is associated with reduced OS in CK-MDS. A TP53mut as well as a TP53LOH both further segregate outcome. The impact of the clone size of TP53mut and TP53LOH on survival is currently being evaluated. Our data imply that the TP53 status (TP53mut and/or TP53LOH) and the complexity of the karyotype are independent prognostic markers. Based on the presence of anemia, the TP53 status (TP53mut and/or TP53LOH), and the number of CA, the individual risk of CK-MDS can be estimated more accurately. This will allow to better tailor treatment decisions for individual pts with CA. Funding (FS): 2017 SGR 288-GRC Disclosures Germing: Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria, Research Funding; Amgen: Honoraria; Celgene: Honoraria, Research Funding. Kaivers:Jazz Pharmaceuticals: Other: Travel Support. Kröger:Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding. Hertenstein:RS Media: Research Funding. Döhner:Daiichi: Honoraria; Jazz: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; CTI Biopharma: Consultancy, Honoraria. Bug:Hexal: Membership on an entity's Board of Directors or advisory committees; Celgene Neovii: Other: travel grant; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Sanofi: Other: travel grants; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; Jazz Pharmaceuticals: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees. Nickelsen:Roche Pharma AG: Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant; Janssen: Membership on an entity's Board of Directors or advisory committees. Platzbecker:Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

Download Full-text

Combined Ibrutinib and Venetoclax Changes Myeloid Phenotype and Improves Immune Function in CLL Patients

Blood ◽

10.1182/blood-2019-123410 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4289-4289 ◽

Cited By ~ 1

Author(s):

Rebecka Svanberg ◽

Sisse Rye Ostrowski ◽

Jakob Thaning Bay ◽

Lars Peter Ryder ◽

Hanne Vibeke Vibeke Marquart ◽

...

Keyword(s):

Immune Function ◽

Whole Blood ◽

Research Funding ◽

Rna Virus ◽

Cytokine Response ◽

Color Flow ◽

Hla Dr ◽

Tnf Α ◽

Travel Grant ◽

The Impact

Background: Monocytes and neutrophilic granulocytes are critical for innate immunity, through recognition and phagocytosis of pathogens, and mediation of acute inflammation through secretion of pro-inflammatory cytokines. Furthermore, monocytes constitute an important link between innate and adaptive immunity through antigen presentation to lymphocytes. Patients with chronic lymphocytic leukemia (CLL) have an increased risk of infection, despite often displaying normal neutrophil and monocyte counts. CLL-cells depend on interactions with the immune microenvironment (IME) for proliferation and survival, while inducing changes in surrounding immune cells. However, changes in myeloid cell function in patients with CLL remain sparsely documented. Since the btk-inhibitor ibrutinib impairs B-cell receptor signaling and disrupts CLL-IME interactions (Niemann et al, CCR, 2016), we investigated the impact of ibrutinib and venetoclax on monocyte- and neutrophil phenotype and function in CLL patients. Methods: Nine patients treated with ibrutinib 420 mg daily for 8 weeks followed by addition of venetoclax with an initial 5-week ramp up period were included. Blood samples were taken at baseline, after 8 weeks ibrutinib monotherapy, and after another 8 weeks of ibrutinib and venetoclax combination therapy. Immune phenotype was assessed in whole blood by an 8-tube, 10 color flow cytometry panel with custom designed lyophilized antibodies (Duraclone). Immune function was characterized using TruCulture, a whole blood-ligand stimulation assay applying the toll like receptor (TLR) ligands heat killed candida albicans (TLR 2,4,6), lipopolysaccharide (LPS; TLR4), resiquimod (single-stranded RNA-virus analog, TLR7,8), and Poly:IC (double-stranded RNA-virus analog, TLR3), after which the cytokine response was measured. Informed consent from patients and approval from the ethics committee was obtained. Results: Monocyte and neutrophil counts, as wells as distribution of mature and immature neutrophils, were within normal range at baseline (n=9) and remained unchanged throughout treatment. At baseline, expression of HLA-DR on monocytes was suppressed, but increased significantly upon combination treatment with ibrutinib and venetoclax (p=0.04). HLA-DR expression on neutrophils was high at baseline, remained unchanged upon ibrutinib treatment (n=8), but declined after addition of venetoclax (n=7) (p<0.01). LPS-stimulated TNF-α and IL-6 production was suppressed at baseline, IL-6 levels increased significantly upon ibrutinib monotherapy, and levels of both TNF-α and IL-6 almost normalized upon addition of venetoclax to ibrutinib (p=0.02 for TNF-α, p=0.009 for IL-6). Conclusion: Here we show for the first time that myeloid leukocytes in CLL patients exhibit an altered HLA-DR expression at baseline, which is paralleled by an impaired cytokine response to LPS stimulation. Following treatment with ibrutinib and venetoclax, HLA-DR expression increased on monocytes and decreased on neutrophils, both representing normalization. In parallel, LPS-induced TNF-α and IL-6 production improved, likely reflecting an improved monocytic function, as monocytes respond strongly to whole-blood LPS-stimulation. Increased monocyte HLA-DR expression has previously been linked to improved cytokine response (Belge et al, J Immunol, 2002). The contribution of neutrophils to the improved cytokine response is unclear, since the function of HLA-DR expressing neutrophils in CLL is largely unknown. We propose a model where ibrutinib and venetoclax eradicate CLL-cells, disrupt tumor-IME interactions, and maybe directly impact microenvironmental cell signaling, thereby restoring neutrophil and monocyte function and improving immune function. Further investigation of myeloid function in CLL at baseline and upon different treatment regimens is warranted to guide personalized treatment based on modulation of infection-risk. Disclosures Svanberg: Novo Nordisk Foundation: Research Funding; Abbvie: Other: Travel grant. Kater:Genentech: Research Funding; Roche: Other: Travel funding, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Niemann:Acerta: Consultancy, Research Funding; Roche: Other: Travel grant; Astra Zeneca: Consultancy, Research Funding; Novo Nordisk Foundation: Research Funding; CSL Behring: Consultancy; Janssen: Consultancy, Other: Travel grant, Research Funding; Gilead: Other: Travel grant; Sunesis: Consultancy; Abbvie: Consultancy, Other: Travel grant, Research Funding.

Download Full-text

Is this the ‘new normal’? A mixed method investigation of young person, parent and clinician experience of online eating disorder treatment during the COVID-19 pandemic

Journal of Eating Disorders ◽

10.1186/s40337-021-00429-1 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Catherine Stewart ◽

Anna Konstantellou ◽

Fatema Kassamali ◽

Natalie McLaughlin ◽

Darren Cutinha ◽

...

Keyword(s):

Eating Disorders ◽

Eating Disorder ◽

Young People ◽

Thematic Analysis ◽

Mixed Method ◽

Likert Scale ◽

Free Text ◽

Virtual Care ◽

The Future ◽

The Impact

Abstract Introduction Prior to the COVID-19 pandemic, research in virtual care for young people with eating disorders was preliminary and implementation rare. This study explored the experience of young people, parents and clinicians when therapy was transitioned to virtual provision as a result of the UK lockdown in March 2020. Methods A mixed-method approach was used in this study. Online questionnaires that included a mixture of rating (Likert scale) and free-text response questions were completed by 53 young people with any eating disorder, 75 parents and 23 clinicians. Questions focused on the experience of online treatment as well as the impact on engagement, perceived treatment efficacy and preferences around treatment mode in the future. Likert scale questions were analysed using a summary approach. Free-text responses were analysed qualitatively using reflexive thematic analysis. Results Responses to rating scale questions indicate satisfaction with treatment, good engagement and ability to manage technology. Young people who had transitioned care, rather than started care virtually in lockdown, rated therapy as less effective. However, individual accounts of experience were more varied. Reflexive thematic analysis of free-text responses identified key themes of 1) Making it work, 2) Home as a therapeutic space, and 3) Disrupted connection and 4) Into the future. Conclusions These results have implications for ongoing care during the pandemic and for future implementation of virtual care in the treatment of young people with eating disorders. Particular issues arising are the trade-off between accessibility and therapeutic engagement and depth and need for consideration of equal access to treatment in socially unequal societies.

Download Full-text

Improved Clinical Outcomes and Replacement FVIII Consumption in Patients with Hemophilia a after Prophylaxis Adjustment Using a FVIII Pharmacokinetics Estimation Based on Bayesian Models

Blood ◽

10.1182/blood.v128.22.3780.3780 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3780-3780

Author(s):

Maria Eva Mingot-Castellano ◽

Rafael Parra ◽

Ramiro Nuñez ◽

Marta Martorell ◽

Ana Isabel Heiniger Mazo

Keyword(s):

Clinical Practice ◽

Research Funding ◽

Hemophilia A ◽

Bayesian Models ◽

Severe Bleeding ◽

Bleeding Rate ◽

Two Samples ◽

Before And After ◽

The Impact ◽

Trough Levels

Abstract INTRODUCTION Current guidelines recommend that subjects with severe hemophilia A (HA) receive prophylaxis in order to prevent severe bleeding and recurrent hemarthrosis that lead to the development of arthropathy, an extremely painful and disabling condition. Success of this approach greatly depends on treatment individualization, and the pharmacokinetics (PK) of factor VIII (FVIII) replacement therapy in a given patient is a crucial consideration. Standard PK studies require extraction of 6 to 10 samples, a procedure that takes several hours and causes adult patients and the parents of pediatric patients to miss work and children to miss school. This represents a significant barrier for routine performance of PK tests, and more rapid methods are needed in order to universalize PK-based adjustment in clinical practice. Björkman et al. developed a method to estimate PK parameters of factor FVIII using Bayesian models (Haemophilia 2010, 16(4):597-605). This approach requires only 2-3 blood extractions between 4 and 48 h after infusion, and may help introduce PK-based tailoring in hemophilia clinics. Based on this methodology, an online tool was developed to perform PK estimates in patients using the FVIII product Advate® (myPKFiT®, www.mypkfit.com; Baxter Healthcare Corporation; Haemophilia 2014, 20 (Suppl.2):15). This report describes the impact of using this tool to adjust prophylaxis regimens in clinical practice, in terms of clinical bleeding and joint bleeding rates and FVIII consumption, in subjects with HA receiving prophylaxis. METHODS This is an observational case series of 3 Spanish centers. Thirty-four patients were evaluated (30 severe and 4 moderate HA) aged 7-52 years (median 22 years). All were receiving prophylaxis, and all received Advate® as replacement factor. myPKFiT® was used for estimations in 2014-2015. FVIII trough levels were adjusted between 1% and 2%. We evaluated the annual bleeding rate (ABR), the annual joint bleeding rate (AJBR) and annual FVIII use before and after PK adjustment of prophylaxis using the study tool. RESULTS Of the 34 patients,16 had not previously undergone a PK study (NPAP group), while 18 had already had their therapy previously adjusted by trough FVIII levels determination (PAP group). Most patients (n = 23) were following an M/W/F infusion schedule before myPKFiT® study. Median weight was 60 kg (interquartile range [IQR] = 32-78). Two samples were used for determinations in 27 patients, 3 in 5, and 4 in 2. Median FVIII half-life calculated with the study tool was 11.95 h (IQR = 10.13-14.33); median clearance was 0.035 dl/h/kg (IQR = 0.027-0.042), and median time until FVIII level 1% was 59.5 (IQR = 50.8-72.0). FVIII use, ABR and ABJR before and after adjustment with the parameters provided by myPKFiT® are summarized in Table 1. Adjustment had an impact in the individual factor consumption of most patients: in 14 cases, the annual amount was reduced (mean −34824 ± 49925 IU/year), and in 16 it was increased (mean +60605 ± 43517 IU/year). However, this did not have a significant impact in the mean amount used in the whole series compared to that used the year prior to myPKFiT-adjusted prophylaxis (p = 0.196). Regarding clinical outcome, ABR and AJBR were both significantly reduced in the NPAP group, where 68.7% and 62.5% of patients reduced their ABR (p = 0.008) and AJBR (p = 0.008), respectively, after adjustment. These rates were generally maintained after myPKFiT-based personalization in the PAP group. CONCLUSIONS Clinical experience in this series suggests that PK-adjusted prophylaxis by means of a tool such as myPKFiT® may have a favorable impact on the prophylaxis regimens of HA patients. Clinical benefit can be achieved in patients whose therapy has not previously been adjusted using PK-based methods, and this personalized approach can reduce bleeding rates without significantly increasing the overall cost of FVIII therapy. Furthermore, the maintenance of bleeding rates in patients with prophylaxis previously adjusted by determination of trough levels suggests that outcomes with this method might be comparable. Disclosures Mingot-Castellano: Amgen: Consultancy; Pfizer: Consultancy; Novo Nordisk: Consultancy, Research Funding; Baxalta: Consultancy, Research Funding; Novartis: Consultancy; Bayer: Consultancy, Research Funding. Parra:Baxalta: Consultancy.

Download Full-text

Analysis of Free-Text Responses in an International Myeloproliferative Neoplasms Patient Survey to Assess Impact of the COVID-19 Pandemic on Clinical Care

Blood ◽

10.1182/blood-2020-143172 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 11-12

Author(s):

Blake T. Langlais ◽

Carolyn Mead-Harvey ◽

Heidi E. Kosiorek ◽

Gina L. Mazza ◽

Ruben Mesa ◽

...

Keyword(s):

Research Funding ◽

Negative Impact ◽

Myeloproliferative Neoplasms ◽

Clinical Care ◽

Healthcare Delivery ◽

Lead Author ◽

Free Text ◽

Increased Risk ◽

The Impact ◽

Positive Impacts

Background The COVID-19 pandemic continues to challenge effective treatment delivery to hematologically-compromised patients, including those with myeloproliferative neoplasms (MPNs). MPNs are characterized by clonal proliferation of hematopoietic cell lines in bone marrow. As such, increasing reports of COVID-19 related thrombotic events highlight how MPN patients are at an increased risk in navigating potential complications during this pandemic. Mitigation strategies to lesson MPN patient exposure to COVID-19 are vital. Though, such efforts come at an inherent cost to effective healthcare delivery. Restriction of regular in-clinic treatments and reported shortages of MPN pharmacotherapies present these patients with diminishing continued care. To understand how MPN patient care has been impacted by COVID-19, an internet-based questionnaire was deployed surveying a variety of disease and pandemic related items (reported elsewhere; Palmer J et al, ASH 2020 submitted). A single free-text response item instructed respondents to: "Please tell us anything else (bad or good) about how the COVID-19 outbreak has impacted your MPN care." This qualitative analysis evaluated first-hand comments directly from patients in order to form a richer understanding of how those with MPNs have been managing disease-related care amidst this pandemic. Methods This COVID-19 survey was hosted via Mayo Clinic's secured REDCap system for online surveys and posted on MPN organizational partner websites. Surveys were completely anonymous. The free-text responses describing impacts to MPN care were each independently reviewed by 2 individuals for overall sentiment (positive, negative, both, or neutral [no impact]) and categorized for themes. The 2 reviewers were assessed for agreement. Conflicting reviews were evaluated then adjudicated by an algorithm for cases meeting selected conditions or by lead author review for all remaining cases. Descriptive statistics are reported. Results Of the 1217 consenting adult patients participating in the overall COVID-19 study, 824 provided free-text responses. Of these, respondent MPN diagnoses included, essential thrombocythemia (n=324, 39%), polycythemia vera (n=251, 30%), myelofibrosis (n=153, 19%), and other/undisclosed (96, 12%); 69% (n=567) were female; median age was 63 (range 21-93); 38% (n=313) were from the US, 38% (n=313) UK, and 24% (n=198) other/unknown. There was 89% (n=734) sentiment agreement between reviewers. Free-text responses about the impact of COVID-19 on MPN care were 49% (n=400) negative, 21% (n=177) positive, 8% (n=65) both positive and negative, and 22% (n=182) neutral/no impact. Table 1 shows a selection of MPN patient free-text responses reflecting common negative and positive sentiment themes. Negative impact (n=400): The most common negative impact involved delays or cancellations of visits or perceived inaccessibility to regular providers (n=261, 65%). Primarily this sentiment was driven by lack of clinic availability and restrictions at treatment centers or by providers. However, some respondents reported delaying or canceling visits themselves due to fear of COVID-19 exposure. Perceived health consequences from this delay were also expressed. There were 129 (32%) respondents with concern regarding changes or access to medications, including explicit drug supply shortages. Some patients resorted to self-adjusting medications and reusing single-use supplies. General anxiety, stress, and isolation were also reported (n=98, 25%). Positive impact (n=177): Availability of telemedicine comprised the majority of positive impacts of the pandemic (n=95, 54%), with many noting the reduced travel time to visits. Routine local testing coupled with follow-up telemedicine was favorable. Despite general positivity towards telemedicine, some reported preferences for in-person visits; commenting that telemedicine was impersonal, difficult to schedule or receive virtual communication, and expressed concern for lack of spleen examinations during virtual visits. Conclusion Positive and negative aspects were reported including MPN-specific issues. Healthcare systems should use such data to emerge from the COVID-19 pandemic and retain the positive impacts such as telemedicine, while developing education materials and other resources to address the reported negative impacts where possible. Disclosures Mesa: CTI BioPharma: Research Funding; Promedior: Research Funding; Novartis: Consultancy; Sierra Oncology: Consultancy; Samus Therapeutics: Research Funding; Genentech: Research Funding; AbbVie: Research Funding; Incyte: Research Funding; LaJolla Pharmaceutical Company: Consultancy; Bristol Myers Squibb: Research Funding.

Download Full-text