scholarly journals Evaluating Hematologist/Oncologist Knowledge of Current and Emerging Treatments for Myeloproliferative Neoplasms

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-29
Author(s):  
Lauren Willis ◽  
Tristin Abair ◽  
Davecia R. Cameron
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Adverse Events ◽  
Risk Stratification ◽  
Scoring System ◽  
Myeloproliferative Neoplasms ◽  
Symptom Assessment ◽  
International Prognostic Scoring System ◽  
Clinical Practices ◽  
Emerging Therapies

Background: Myeloproliferative neoplasms (MPNs) are rare malignancies that include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia. The objective of this study is to assess current clinical practices of hematologist/oncologists (hem/oncs) related to current and emerging therapies for MPNs, in order to identify knowledge, competency, and practice gaps. Methods: A continuing medical education (CME)-certified clinical practice assessment consisting of 25 multiple-choice questions was developed to measure knowledge, skills, attitudes, and competence of hem/oncs regarding current and emerging MPN therapies. The self-assessment was available online to physicians without monetary compensation or charge. Respondent confidentiality was maintained, and responses were de-identified and aggregated for reporting. The activity launched on November 21, 2019 and responses collected through July 12, 2020 were analyzed and reported. Results: A total of 2,035 learners participated in the activity and 218 hem/oncs answered all questions in the assessment. Hem/onc demographics and patient load distributions are reported in Table 1. A majority (77%) of hem/oncs lack confidence treating adverse events of MPN therapies (Table 2). Baseline knowledge and competence of hem/oncs were grouped into themes: Knowledge/Competence with Risk Stratification, Prognostic Scoring, and Symptom Assessment: While 87% and 63%, demonstrated knowledge about variables included on the MPN Symptom Assessment Form Total Symptom Score and the Dynamic International Prognostic Scoring System (DIPSS), respectively, only 50% demonstrated knowledge about variables included in the mutation-enhanced International Prognostic Scoring System (MIPSS70). Additionally, only 27% demonstrated competence risk stratifying a patient with high-risk MF according to DIPSS. Knowledge of Available Therapies: While 62% demonstrated knowledge that the 5-year data from the COMFORT-1 trial found ruxolitinib demonstrated an overall survival benefit in patients with intermediate-2 (INT-2) and high-risk MF, only 57% demonstrated knowledge that in addition to reduction in spleen volume, ruxolitinib improved symptoms of patients with MF in the COMFORT trials. Additionally, only 56% demonstrated knowledge that in the RESPONSE trial ruxolitinib increased hematocrit control in patients with PV. A majority (77%) did not demonstrate knowledge that both ruxolitinib and fedratinib are approved for the first-line treatment of patients with high-risk MF. Knowledge of Emerging Therapies: Momelotinib: 72% did not demonstrate knowledge that in the SIMPLIFY-2 trial momelotinib increased symptom improvement compared to best available therapy (BAT) in patients with MF who were pretreated with ruxolitinib. Pacritinib: 47% did not demonstrate knowledge that in the PERSIST trial pacritinib did not demonstrate improved overall survival compared to BAT. Ropeginterferon: 80% did not demonstrate knowledge of the efficacy outcomes in patients with PV who received ropeginterferon in the PROUD-PV study. Knowledge and Competence Managing Adverse Events (AE): A majority (75%) demonstrated competence treating ruxolitinib-associated thrombocytopenia in a patient with INT-2 MF, however only 35% and 44%, respectively, demonstrated knowledge of the need to address thiamine deficiency before starting a patient on fedratinib (encephalopathy risk) and knowledge that diarrhea was the most common nonhematologic AE seen with ruxolitinib in patients on the COMFORT-II trial. Conclusions: This research identified several knowledge, competence, and confidence deficits for hem/oncs related to current and emerging MPN therapies in the areas of: (1) Risk stratification and use of prognostic scoring tools, (2) Clinical trial safety and efficacy data for currently available and emerging therapies, (3) Personalizing treatment selection for patients with MPNs, (4) Preventing and managing treatment-related AEs. Additional education is needed to address these gaps for hem/oncs who care for patients with MPNs, which is expected to translate into improved clinical performance and better patient outcomes. Acknowledgements: This CME activity was supported by an independent educational grant from Incyte Corporation. Reference: www.medscape.org/viewarticle/921334 Disclosures No relevant conflicts of interest to declare.

scholarly journals Overall Survival in Patients with Myelofibrosis Who Have Discontinued Ruxolitinib: A Literature Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3457-3457
Author(s):  
Derek Tang ◽  
Ankush Taneja ◽  
Preety Rajora ◽  
Indeg Sly ◽  
Niall James Davison
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
High Risk ◽  
Literature Review ◽  
Survival Data ◽  
Scoring System ◽  
Janus Kinase ◽  
Cochrane Library ◽  
International Prognostic Scoring System ◽  
Independent Reviewer

Introduction: Myelofibrosis (MF) is a rare bone marrow cancer characterized by bone marrow fibrosis and abnormal cytokine expression, often leading to splenomegaly, constitutional symptoms, and cytopenia. Prognostic scoring systems (the International Prognostic Scoring System and the Dynamic International Prognostic Scoring System) classify patients into low-, intermediate-1-, intermediate-2-, or high-risk categories. Most patients with MF have either intermediate-2- or high-risk disease, indicating a poor overall prognosis and short survival time (5-year survival rate in Europe: 35%). Ruxolitinib is the first Janus kinase inhibitor (JAKi) treatment for MF approved by the US Food and Drug Administration and the European Medicines Agency. However, the rate of discontinuation of ruxolitinib in the first 2-3 years of treatment is high (> 50%) due to treatment resistance, disease recurrence, and worsening of anemia. This literature review aimed to assess overall survival (OS) in patients with MF who have discontinued ruxolitinib. Methods: A systematic literature review (SLR) was conducted in which Embase®, MEDLINE®, and the Cochrane Library were searched to identify published evidence from database inception until August 2018. Conference proceedings, health technology assessments, and bibliographies were also searched. Additionally, this SLR was updated in a targeted manner using Embase® until February 2019 to identify and update the OS evidence among patients with MF who have discontinued ruxolitinib. Retrieved studies were included if they were published in English and reported OS data in the targeted patient population of interest. Two independent reviewers assessed the studies against pre-defined eligibility criteria (Table 1) to include or exclude the studies, and any uncertainty was resolved by a third independent reviewer, in the case of the SLR, or by mutual agreement, in the case of the update. All extracted data were quality checked by a second independent reviewer. A descriptive, qualitative analysis was conducted to assess OS in patients with MF who have used and discontinued ruxolitinib. Results: Of the 4,011 publications retrieved, 11 studies were included (Table 2). Six were retrospective observational studies, 2 were randomized controlled trials (RCTs), and 3 were non-RCTs. Across all the included studies, 5 reported estimates of median OS. Across the 4 studies reporting median OS for standard of care or approved treatments, median OS ranged from 4.9-30 months (Kuykendall et al. 2017, Mehra et al. 2016, Newberry et al. 2017, Palandri et al. 2018). Patients receiving no treatment after ruxolitinib had a median OS of 4.9 months (Kuykendall et al., 2017). Median OS in patients who received treatment with salvage therapy or conventional agents (e.g. hydroxyurea, danazol, anagrelide) was typically around 14 months (14, 14, and 15 months in Mehra et al. 2016, Newberry et al. 2017, and Kuykendall et al. 2017, respectively). Estimated median OS following ruxolitinib discontinuation for early discontinuers and spleen responders in the COMFORT-II study was approximately 16.5 months (NICE, 2015). One study reported median OS for an investigational agent (Mascarenhas et al. 2018); median OS was 19.9 and 29.9 months for imetelstat 4.7 mg/kg and 9.4 mg/kg, respectively. Conclusions: This literature review revealed that patients with MF generally experience poor OS after discontinuing ruxolitinib, especially in patients who receive no further treatments. Line of therapy definitions were rarely reported across studies, which may contribute to variations across study findings. In addition, survival estimates after prior ruxolitinib therapy varied depending on the treatment received and the reason for discontinuation of ruxolitinib. Limited survival data for investigational therapies were available from early-stage trials and may be subject to substantial variations in large-scale registrational trials. Some of the studies included in this literature review may be ongoing as they are currently available in abstract form only, and new data may become available in the near future. Sustained efforts to develop more effective treatments for patients with MF who have discontinued ruxolitinib are imminently needed. Disclosures Tang: Celgene Corporation: Employment, Equity Ownership. Taneja:BresMed Health Solutions Ltd: Employment. Rajora:BresMed Health Solutions Ltd: Employment. Sly:BresMed Health Solutions Ltd: Employment. Davison:BresMed Health Solutions Ltd: Employment.

Azacitidine Use in MDS and AML Patients: Best Selection for Better Results

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5070-5070
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Stéphane Morisset ◽  
Carine Champigneulle ◽  
Florence Ranchon ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Scoring System ◽  
Refractory Anemia ◽  
International Prognostic Scoring System ◽  
First Line ◽  
Fab Classification ◽  
Group 2 ◽  
French American British ◽  
Group 1

Abstract Abstract 5070 In a recent phase III trial, azacitidine was demonstrated to significantly prolong OS compared with conventional care regimens in patients classified in intermediate-2 and high-risk myelodysplastic syndromes (MDS) according to the International Prognostic Scoring System (IPSS) (Fenaux et al. 2009). This study used the French- American-British (FAB) classification for MDS and included approximately one third of patients with refractory anemia with excess blasts in transformation (RAEB-t; 20% to 30% bone marrow blasts). WHO criteria now define AML as ≥20% BM blasts. Using those criteria, RAEB-t is now considered as AML. We conducted a retrospective analysis on patients who received azacitidine between August 2005 and November 2011 at our institution for MDS or AML. Patients were identified through the hospital database and individual charts were reviewed. The primary objective was to investigate the outcome of patients receiving azacitidine in a daily clinical practice in high risk MDS and AML patients and to evaluate its impact on overall survival (OS). Secondary objectives were hematological response rate and transfusion spare. Patients were included if they received at least one cycle of azacitidine. Disease status was defined by both the French American British (FAB) and the World Health Organization (WHO) classification systems, and risk was scored by the International Prognostic Scoring System (IPSS). All analyses were conducted using R statistical software. Descriptive statistics were used for baseline characteristics. Kaplan-Meier estimates were used to calculate overall survival (OS). There were 79 patients, 51 (65%) males and 28 (35%) females with a median age of 70 years (32–85). The indication of azacitidine was the first line treatment use for MDS, mainly refractory anemia with excess blasts, in 40 (51%) patients (group1) and treatment for patients who had AML and transformed, in 39 (49%) patients (group2). (post chemotherapy: n=16, first line: n=23). Patient characteristics, prognostic factors according to FAB classification, ISPP risk and cytogenetics for both groups are shown in table1. The median number of azacitidine cycles in groups 1 and 2 was 8 (1–30) and 3 (1–29) respectively. Evaluation after 6 cycles showed 55% of responders in group 1 and 31% in group 2; the rest of patients have progressed. The median OS for the group 1 was 24. 5 months (17. 8-NR) while in group2; it was 15. 5 months (11. 2-NR) for patients who received AZA in first line and 6 months (3. 9-NR) for patients with previous chemotherapy. In terms of transfusions number, we did not find any significant spare in terms of both RBC and platelets transfusion in group1 while there was a significant spare of 33% of red blood cells transfusions (p=0. 05) and 42% of platelets transfusions only in group 2 (p=0. 04). The multivariate analysis studying the impact of different variables on OS showed: a worse OS in AML patients with previous chemotherapy (HR= 9. 84 [ 3. 56 – 27. 19 ], p< 0. 001), a worse OS in patients with unfavorable caryotype (HR= 7. 30 [ 2. 13 – 24. 98 ], p< 0. 001), and a better OS in female patients (HR= 0. 31 [ 0. 14 – 0. 68 ], p= 0. 003). Our study confirmed results from previous prospective study in MDS patients while AML patients not receiving azacitidine in first line do not seem to benefit from this treatment. Cytogenetics remain a major factor impacting OS with no significant impact of IPSS. Disclosures: Nicolini: Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Prognosis and Outcomes in MDS-MPN Unclassifiable: Single Institution Experience of a Rare Disorder

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1698-1698 ◽  
Author(s):  
Ateefa Chaudhury ◽  
Rami S. Komrokji ◽  
Najla H. Al Ali ◽  
Ling Zhang ◽  
Pardis Vafaii ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Stratification ◽  
Scoring System ◽  
Lower Risk ◽  
Research Funding ◽  
Median Overall Survival ◽  
Scoring Systems ◽  
Rare Disorder ◽  
International Prognostic Scoring System ◽  
Cancer Center

Abstract Introduction: The 2008 World Health Organization (WHO) classification has recognized a unique overlap category that has features of proliferation found in myeloproliferative neoplasms (MPN) and also dysplasia found in myelodysplastic syndrome (MDS). The least well characterized of the 4 MDS/MPN overlap diseases is a rare entity known as MDS/MPN Unclassifiable (MDS/MPN-U), comprising <5% of myeloid disorders. Furthermore, given the rarity of this disorder, there is no validated risk stratification scoring system, although there are several commonly used prognostic models for MDS, including the International Prognostic Scoring System (IPSS), the Revised International Prognostic Scoring System (IPSS-R), and the M.D. Anderson Cancer Center model (MDAS). The objectives of this study were to evaluate the natural history of this very uncommon diagnosis and to determine which of the current scoring symptoms used for MDS best discriminates outcomes. Methods: The Moffitt Cancer Center database of over 3000 MDS patients was used to identify patients with MDS/MPN-U and to subsequently perform a comprehensive chart/pathology review. We then applied IPSS, IPSS-R, and the MDAS scores to each patient in order to compare differences in overall survival (OS) amongst different risk groups within each scoring system. Finally, we compared outcomes in the MDS/MPN-U group with a large number of matched MDS cases from within our database, using the MDAS. Descriptive statistical analyses were utilized. Chi square analysis and t- test were performed to compare categorical and continuous variables. Akaike information criteria (AIC) were used to assess the relative goodness of fit of the models. All data was analyzed using SPSS version 21.0 statistical software. Results: Forty three patients were identified with MDS/MPN-U and were pathologically confirmed to meet WHO criteria. Median age was 71 years (range 55 - 91) and the M:F = 26.17. Median baseline laboratory parameters: WBC 11.2 x 103/dL (range 0.9 - 84.8); Hb 9.7 g/dL (range 5.8-14.4); platelets 137 x 103/uL. Table 1 summarizes risk stratification per current validated MDS scoring systems. The majority of patients had lower risk disease by all the models. Forty of 42 (95%) patients evaluable for prognostic scoring were classified as low/Int-1 by IPSS. However, 11 out of the 40 pts (28%) classified as lower risk by IPSS were upgraded to Int-2 or high risk by MDAS. Twenty-two patients received hypomethylating agents (HMA) as first line treatment after supportive care. Per IWG 2006, 8 of 22, (36%) had complete response, partial remission, or hematologic improvement, 7 (32%) had stable disease, and 6 (27%) had progressive disease. The median OS for all MDS/MPN-U patients was 33 months (95% Confidence Interval 22 - 45). Within each MDS scoring system, statistically significant survival differences were detected between risk stages (table 1). The IPSS-R did not improve the IPSS prognostic value. Patients categorized as lower-risk (low/Int-1) by MDAS had superior survival compared to IPSS. Lastly, we compared outcomes between the 43 MDS/MPN-U patients and 1117 IPSS low/Int-1 matched controls within the MDS database. Median overall survival was inferior in MDS/MPN-U vs. MDS (33.4 mo vs. 57 mo, p = 0.005). In addition, using the MDAS, stage-by-stage, survival was significantly worse in the MDS/MPN-U group. Table 1. Risk Stratification Based on MDS Scoring Systems MDS/MPN-Un (%) Median Overall Survival (mo) P-value IPSS Low Int-1 Int-2 High 15 (35.7)25 (59.5)1 (2.4)1 (2.4) 33.433.312.86.0 < 0.001 IPSS-R Very Low Low Intermediate High Very High 6 (14.3)21 (50)10 (23.8)4 (9.5)1 (2.4) 18.2333.425.112.86.0 0.001 MDAS Low Int-1 Int-2 High 6 (14.3)20 (47.6)13 (31.0)3 (7.1) 52.433.425.16.0 < 0.001 Conclusions: MDS/MPN-U appears to have a variable disease course but with generally poor outcomes, even amongst lower-risk patients classified by MDS scoring systems, and despite a moderate rate of response to treatment. Matched comparisons indicate inferior outcomes compared with similarly staged MDS patients. The MDAS may offer increased discriminatory capacity for determining prognosis based on disease stage. Further work with a larger patient population and cross comparisons to other MDS/MPN diseases will assist further understanding of this rare disorder. Integration of somatic mutations data may compliment the clinical models. Disclosures Komrokji: Novartis: Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding; Pharmacylics: Speakers Bureau; Incyte: Consultancy. Lancet:Kalo-Bios: Consultancy; Celgene: Consultancy, Research Funding; Pfizer: Research Funding; Amgen: Consultancy; Seattle Genetics: Consultancy; Boehringer-Ingelheim: Consultancy.

scholarly journals A Practical Guide for Using Myelofibrosis Prognostic Models in the Clinic

2020 ◽  
Vol 18 (9) ◽  
pp. 1271-1278
Author(s):  
Joan How ◽  
Gabriela S. Hobbs
Keyword(s):  
Risk Stratification ◽  
Scoring System ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Primary Myelofibrosis ◽  
Prognostic Models ◽  
International Prognostic Scoring System ◽  
Hematopoietic Stem ◽  
Clinical Presentations ◽  
Version 2.0

Primary myelofibrosis (PMF) has the least favorable prognosis of the Philadelphia chromosome–negative myeloproliferative neoplasms, which also include essential thrombocythemia (ET) and polycythemia vera (PV). However, clinical presentations and outcomes of PMF vary widely, with median overall survival ranging from years to decades. Given the heterogeneity of PMF, there has been considerable effort to develop discriminatory prognostic models to help with management decisions, particularly for the consideration of hematopoietic stem cell transplantation in patients at higher risk. Although earlier models incorporated only clinical features in risk stratification, contemporary models increasingly use molecular and cytogenetic features, leading to more comprehensive prognostication. This article reviews the most widely adopted prognostic models used for PMF, including the International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS)/DIPSS+, mutation-enhanced IPSS for transplant-age patients (MIPSS70)/MIPSS70+/MIPSS70+ version 2.0, genetically inspired prognostic scoring system, and Myelofibrosis Secondary to PV and ET-Prognostic Model in patients with post-ET/PV myelofibrosis. We also discuss newly emerging prognostic models and provide a practical approach to risk stratification in patients with PMF and post-ET/PV myelofibrosis.

scholarly journals Validated Risk Stratification System for Prediction of Adverse Events Following Open Reduction and Internal Fixation of the Ankle

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0016
Author(s):  
Daniel Bohl ◽  
George Holmes ◽  
Kamran Hamid ◽  
Johnny Lin ◽  
Simon Lee
Keyword(s):  
High Risk ◽  
Adverse Events ◽  
Risk Stratification ◽  
Scoring System ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Bundled Payments ◽  
Insulin Dependent ◽  
Stratification System ◽  
Risk Stratification System

Category: Ankle Introduction/Purpose: As orthopaedic surgery moves towards bundled payments, there is growing interest in identifying patients at high risk for postoperative adverse events. The purpose of this study is to develop and validate a risk stratification system for the occurrence of adverse events following open reduction and internal fixation (ORIF) of the ankle. Methods: Patients undergoing ORIF of closed ankle fractures as part of the National Surgical Quality Improvement Program (NSQIP) were identified. For patients undergoing surgery during 2006-2014, multivariate Cox proportional hazards modeling was used to identify factors that were independently associated with the occurrence of adverse events (including events such as surgical site infection, myocardial infarction, and pulmonary embolism). Based on these results, a nomogram was used to generate a point-scoring system for risk stratification. To evaluate the validity of the point-scoring system, the system was applied to patients undergoing ankle ORIF during 2015-2016. Results: Of the 6,140 patients undergoing surgery during 2006-2014, 5.8% developed an adverse event. Based on the Cox proportional hazards regression, patients were assigned points for each of the following statistically significant risk factors: anemia (+2 points), insulin-dependent diabetes (+2 points), age=65 (+1 point), dependent functional status (+1 point), chronic obstructive pulmonary disease (COPD; +1 point), and hypertension (+1 point; Figure 1A). 4,702 patients were identified in the 2015-2016 validation cohort. Among these patients, the risk-stratification system was found to strongly predict the risk for adverse events (p<0.001, Figure 1B). Conclusion: The occurrence of adverse events following ankle ORIF is associated with anemia, insulin-dependent diabetes, age=65, dependent functional status, COPD, and hypertension. We present and validate a simple point-scoring risk stratification system to predict the risk of adverse events. Future systems of bundled payments for ankle ORIF should exclude high-risk patients from the bundling systems, or make appropriate adjustments in reimbursement based on risk.

A Snapshot of Risk Stratification of Diabetic Patients Fasting during the Month of Ramadan

2021 ◽  
Vol 15 (12) ◽  
pp. 3427-3429
Author(s):  
Asim Hassan ◽  
Wedad Abullah Aldahasai ◽  
Shayma Abdulatif Alsalmi
Keyword(s):  
Diabetes Mellitus ◽  
High Risk ◽  
Risk Stratification ◽  
Armed Forces ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Clinical Practices ◽  
Oral Hypoglycemic Agents ◽  
Hyperosmolar Hyperglycemic State ◽  
Risk Patients

Objectives: To get a clinical snapshot of the diabetic patients who planned to fast during the month of Ramadan and to determine the ability of the RRR application to effectively risk-stratify patients. Study Design: Observational study. Place and Duration of Study: Department of Diabetes & Endocrinology, Armed Forces Hospital Al-Hada, Taif, Kingdom of Saudi Arabia from 1st April 2018 to 31st May 2018. Methodology: Ninety six patients over 15 years of age with diabetes mellitus were risk stratified using standardized risk criteria were enrolled. Detailed analysis of the information was performed to paint a clinical landscape of the patients who intended to fast. Results: Seventy four percent of the patients were type 2 diabetics, 11% GDM, 31% were between 60-70 years and 17 % had diabetes for more than 20 years. 17% of participants had serious complications during the last three months before Ramadan including hypoglycemia, Diabetic Ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). 59% had chronic diabetic complications. 28 % of patients were on both insulin and oral hypoglycemic agents (OHA) together and 16 % on high risk medications. 25% of patients had an HbA1C of more than 10%. Pertaining to the previous Ramadan experience 19% disclosed having serious complications in the past. 6 % were categorized as low risk individuals, 76% as moderate, 6% high and 12 % as very high risk. Conclusions: Astonishingly all the patients advised to refrain from fasting insisted on fasting. Considering the latest IDF numbers the above calculated percentages would translate into very huge numbers who are in serious jeopardy. In order to prevent serious consequences it is highly recommends that evidence based and validated risk stratification strategies are implemented in routine clinical practices. Keywords: Diabetes mellitus, Fast, Hypoglycemia, High risk patients

scholarly journals MIPSS70+ v2.0 predicts long-term survival in myelofibrosis after allogeneic HCT with the Flu/Mel conditioning regimen

2019 ◽  
Vol 3 (1) ◽  
pp. 83-95 ◽  
Author(s):  
Haris Ali ◽  
Ibrahim Aldoss ◽  
Dongyun Yang ◽  
Sally Mokhtari ◽  
Samer Khaled ◽  
...  
Keyword(s):  
Molecular Markers ◽  
High Risk ◽  
Scoring System ◽  
Conditioning Regimen ◽  
International Prognostic Scoring System ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients ◽  
Transplantation Outcomes ◽  
Very High

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

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