REVEAL: Characteristics of Patients with Polycythemia Vera Who Were Diagnosed within 6 Months of Enrollment

Background Polycythemia vera (PV), characterized by erythrocytosis and JAK2 mutations, is associated with increased morbidity and mortality. Patients (pts) are at risk for thrombotic events and experience symptoms (sxs) that may impact quality of life. Data describing the clinical characteristics of pts with PV at the time of diagnosis (dx) are limited. The Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (REVEAL) is a multicenter, prospective, observational study designed to collect data on disease burden, clinical management, and pt-reported outcomes (PROs) of adult pts (aged ≥18) with PV. This analysis describes pt demographic and clinical characteristics, treatment patterns, and sxs of newly dxed pts with PV. Methods Pts enrolled in REVEAL who were dxed ≤6 months prior to enrollment were included in this analysis. Descriptive statistics were used to summarize pt demographic and clinical characteristics, tests at dx, and management patterns at dx. Sxs were assessed with a validated PRO instrument: the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Mean and standard deviation for individual sx scores and total sx score (TSS) at enrollment are reported. Results Of the 2510 pts enrolled in REVEAL, 321 dxed within 6 months of enrollment were included in this analysis. Median age at enrollment was 67.0 (range, 23.0-94.0) years, 54.8% were male, and most (74.5%) had high-risk disease (aged ≥60 years and/or history of thrombosis). The most common physician-reported symptoms at the time of presentation included fatigue (24.6%), pruritus (17.1%), insomnia (10.3%), and muscle aches/bone pain (9.7%). Of those pts reported to have undergone mutation testing at dx (n=201), 99.5% were JAK2V617F positive. A history of thrombosis was reported for 15.9% of pts (arterial, 8.1%; venous, 8.7%), and the most common relevant comorbidities were hypertension (58.6%), obesity (19.6%), and diabetes mellitus (15.9%). Of 188 pts with lab values within 1 month before dx, 95.2% had elevated (≥45%) hematocrit and 59.6% had elevated (>10 × 109/L) white blood cell counts. Most high-risk and low-risk pts were reported to have received phlebotomies within 6 months after dx (71.7% and 78.4%, respectively). A higher proportion of pts with high-risk disease initiated a pharmacologic therapy for PV compared with those who had low-risk disease (60.5% vs 23.9%); hydroxyurea (HU) was the most common cytoreductive therapy (n=151 [93.2%]). Most of these pts (n=137 [90.7%]) were still receiving HU 2 years after dx. Of those who initiated HU within 6 months of dx, 5.3% (n=8) received an alternative cytoreductive therapy following HU. A total of 287 pts provided PRO data at enrollment (Table 1). The most common pt-reported sxs were fatigue (77.2%), early satiety (61.1%), and inactivity (58.0%); the mean (SD) MPN-SAF TSS was 18.5 (15.6). The sxs with the highest reported mean (SD) scores were fatigue (3.4 [2.7]), inactivity (2.6 [2.9]), and early satiety (2.5 [2.6]) and were largely similar between low-risk and high-risk pts. Conclusions Compared with all 2510 pts enrolled in REVEAL (Clin Lymphoma Myeloma Leuk 2018[18]12:788-95), this subgroup of 321 pts dxed within 6 months of enrollment was similar with respect to age and sex. However, in the newly dxed subgroup, a slightly lower proportion of pts (74.5%) had high-risk disease (77.3% of the full cohort). In the newly dxed subgroup, a higher proportion of pts (62.6%) underwent mutation testing (49.2% of all enrolled pts). The HU discontinuation rate early in the treatment course was approximately 9.3%, which is similar to the rate (6.3%) of HU discontinuation due to toxicity in patients with PV in a large, multicenter, MPN cohort (Am JHematol 2012[87]5:552-4). Sx burden in pts who completed the MPN-SAF TSS at enrollment was similar in the newly dxed pts (mean TSS, 18.5) and all pts enrolled in REVEAL (18.8; Clin Lymphoma Myeloma Leuk 2018[18]9:590-6); the most frequent pt-reported sxs (fatigue, early satiety, and inactivity) in this smaller pt subgroup were the same as those observed in the larger pt cohort. Overall, near the time of dx, a greater proportion of pts had low-risk disease. Despite this difference, the sx constellation and severity tends to be very similar to the larger cohort. It also appears that only a very small proportion of pts are unable to tolerate HU early on in the course of the disease. Disclosures Gerds: Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Incyte: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Pfizer: Consultancy; Celgene Corporation: Consultancy, Research Funding; Roche: Research Funding. Altomare:Novartis: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Speakers Bureau; Rigel: Consultancy. Colucci:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Burke:Roche/Genentech: Consultancy; Celgene: Consultancy; Gilead: Consultancy.

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A Novel Prognostic Model That Is Superior to FLIPI-1 and FLIPI-2 and Integrates Clinical and Treatment Factors to Predict Progression-Free Survival and Early Treatment Failure in Patients with Follicular Lymphoma in the GALLIUM Trial

Blood ◽

10.1182/blood-2018-99-114620 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2872-2872 ◽

Cited By ~ 2

Author(s):

Farheen Mir ◽

Andrew Grigg ◽

Michael Herold ◽

Wolfgang Hiddemann ◽

Robert Marcus ◽

...

Keyword(s):

High Risk ◽

Board Of Directors ◽

Research Funding ◽

Prognostic Model ◽

Low Risk ◽

Prognostic Variables ◽

Advisory Committees ◽

High Risk Disease ◽

Risk Patients ◽

Equity Ownership

Abstract Introduction: Progression of disease within 24 months of initial therapy (POD24) is associated with poor survival in patients with follicular lymphoma (FL). Existing prognostic models, such as FLIPI-1 and FLIPI-2, show poor sensitivity for POD24, and are derived from cohorts lacking bendamustine-treated patients. More accurate predictive models based on current standard therapies are needed to identify patients with high-risk disease. The Phase III GALLIUM trial (NCT01332968) compared the safety and efficacy of standard chemotherapy regimens plus rituximab (R) or obinutuzumab (G) in patients with previously untreated FL. Using GALLIUM data, we developed a novel risk stratification model to predict both PFS and POD24 in FL patients after first-line immunochemotherapy. Methods: Enrolled patients were aged ≥18 years with previously untreated FL (grades 1-3a), Stage III/IV disease (or Stage II with bulk), and ECOG PS ≤2, and required treatment by GELF criteria. Patients were randomized to receive either G- or R-based immunochemotherapy, followed by maintenance with the same antibody in responders. The chemotherapy arm (CHOP, CVP, or bendamustine) was selected by each study center. POD24 was defined as progressive disease or death due to disease within 24 months of randomization (noPOD24 = no progression or lymphoma-related death in that period). The most strongly prognostic variables, based on PFS hazard ratios, were estimated using penalized multivariate Cox regression methodology via an Elastic Net model. Selected variables were given equal weights, and a clinical score was formed by summating the number of risk factors for each patient. Low- and high-risk categories were determined using a cut-off that provided the best balance between true- and false-positives for PFS. PFS correlation and sensitivity to predict POD24 were assessed. The data used are from an updated GALLIUM efficacy analysis (data cut-off: April 2018; median follow-up: 57 months). Results: 1202 FL patients were enrolled. Based on data availability and biological plausibility (i.e. could reasonably be linked with high-risk disease), 25 potential clinical and treatment-related prognostic variables were entered into the Elastic Net model (Table). A model containing 11 factors was retained by the methodology and chosen as the best model (Table). Patients were categorized as 'low risk' if they scored between 0 and 3 (n=521/1000 patients with complete data) and as 'high risk' if they scored between 4 and 11 (n=479/1000 patients). At 2 years, the PFS rate was 84.5% in the whole FL population. Using our model, 2-year PFS for high-risk patients was 77% compared with 79.9% for FLIPI-1 and FLIPI-2. In low-risk patients, 2-year PFS was 92% compared with 87.9% for FLIPI-1 and 87.6% for FLIPI-2 (low-intermediate-risk patients). Our model increased the inter-group difference in 2-year PFS rate from 8% (FLIPI-1) and 7.7% (FLIPI-2) to 15%. At 3 years, the inter-group difference increased from 6.9% (FLIPI-1) and 9% (FLIPI-2) to 17% (Figure). Sensitivity for a high-risk score to predict POD24 was 73% using our model compared with 55% for FLIPI-1 and 52% for FLIPI-2 (based on 127 POD24 and 873 noPOD24 patients with complete data). Excluding patients who received CVP, which is now rarely used, resulted in an inter-group difference in PFS of 15% at 2 years and 16.8% at 3 years. A sensitivity analysis showed that inclusion of the 9 clinical factors only (i.e. removal of CVP and R treatment as variables) formed a more basic scoring system (low-risk patients, 1-3; high-risk patients, 4-9); the inter-group difference in PFS was 16.5% at 2 years and 17.6% at 3 years. However, sensitivity for POD24 decreased to 56%. Conclusion: Our clinical prognostic model was more accurate at discriminating patients likely to have poor PFS than either FLIPI-1 or FLIPI-2, and its prognostic value was sustained over time. Our model also identified the FL population at risk of POD24 with greater sensitivity. Variables such as age and bone marrow involvement were not retained by our model, and thus may not have a major impact in the current era of therapy. Factors such as sum of the products of lesion diameters were included, as this captures tumor burden more accurately than presence of bulk disease. Future studies will aim to improve the accuracy of the model by considering gene expression-based prognostic markers and DNA sequencing to form a combined clinico-genomic model. Disclosures Mir: F. Hoffmann-La Roche: Employment. Hiddemann:F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding. Marcus:F. Hoffman-La Roche: Other: Travel support and lecture fees; Roche: Consultancy, Other: Travel support and lecture fees ; Gilead: Consultancy. Seymour:Genentech Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Consultancy; AbbVie: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bolen:Roche: Other: Ownership interests PLC*. Knapp:Roche: Employment. Launonen:Launonen: Other: Ownership interests none PLC; Travel, accommodation, expenses; Novartis: Consultancy, Equity Ownership, Other: Ownership interests none PLC; Travel. accommodation, expenses; Roche: Employment, Other: Travel, accommodation, expenses. Mattiello:Roche: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Oestergaard:Roche: Employment, Other: Ownership interests PLC. Wenger:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership, Other: Ownership interests PLC. Casulo:Gilead: Honoraria; Celgene: Research Funding.

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Outcome Of Patients (pts) With Low and Intermediate-1 Risk Myelodysplastic Syndrome (MDS) After Hypomethylating Agent (HMA) Failure

Blood ◽

10.1182/blood.v122.21.388.388 ◽

2013 ◽

Vol 122 (21) ◽

pp. 388-388 ◽

Cited By ~ 5

Author(s):

Elias Jabbour ◽

Guillermo Garcia-Manero ◽

Lianchun Xiao ◽

Al Ali Najla ◽

Asmita Mishra ◽

...

Keyword(s):

High Risk ◽

Scoring System ◽

Lower Risk ◽

Research Funding ◽

Complete Response ◽

Low Risk ◽

International Prognostic Scoring System ◽

Cancer Center ◽

Primary Resistance ◽

High Risk Disease

Abstract Background HMA are standard of care in pts with high-risk MDS and commonly used in pts with lower risk. Pts with high-risk disease post HMA failure have a poor prognosis with a median survival of 4-6 months. The prognosis of pts with low and intermediate-1 risk MDS by the International Prognostic Scoring System (IPSS) after HMA failure is not known. Aims To assess outcome of pts with low and intermediate-1 risk disease post HMA failure that might benefit from specific strategies or investigational agents. Methods Data from 423 pts with low (n= 141, 33%) and intermediate-1 risk disease (n=282, 67%) by IPSS score treated with HMA at MD Anderson Cancer Center (MDACC; n=144) and Moffitt Cancer Center (MCC; n=279) between 2000 and 2011 were analyzed. Results Median age was 69 years. 294 (69%) pts had a diploid cytogenetic analysis. 63 (15%) pts had therapy-related MDS. 282 (67%) pts received azacitidine, 87 (21%) decitabine, and 54 (12%) both. Median number of cycles of HMA administered was 6 (range, 1-64) for a median duration of therapy of 7 months (range, 1- 74). Best response to HMA was complete response (CR) in 39 (9%) pts, partial response (PR) in 13 (3%), a bone marrow CR in 6 (1%), and hematologic improvement (HI) in 90 (21%) pts. Pts had discontinued HMA because of primary resistance in 198 (47%) pts, loss of response in 141 pts (33%), intolerance in 13 pts (3%) and other reasons in 71 pts (17%). At the time of HMA failure, 81 (19%) pts transformed into acute myeloid leukemia (AML). Of the 302 remaining pts evaluable by IPSS, 67 (22%) pts were of low-risk, 158 (53%) of intermediate-1 risk, 48 (16%) of intermediate-2 risk, and 29 (9%) of high-risk disease. By the revised IPSS (R-IPSS), the percentage of pts with low, very low, intermediate, high, and very high risk disease were 11%, 29%, 30%, 20%, and 10%, respectively. By the MDACC global prognostic scoring system (MDGPSS) 18%, 35%, 29%, and 18%, of the pts were of low-risk, intermediate-1, intermediate-2, and high-risk disease, respectively. After a median follow-up of 16 months from HMA failure, 117 (28%) pts remained alive. The median overall survival (OS) was 15 months (95% CI: 12-18) with estimated 1- and 3-year OS rates of 55% and 27%, respectively. Both, the R-IPSS and the MDGPSS were predictive of survival post HMA failure (Table 1 ). Conclusion In the largest cohort of lower risk MDS pts treated with HMA, the outcome after HMA failure is poor. Treatment of those patients remains an unmet medical need. OS is a reasonable primary endpoint for clinical studies targeting this population. Disclosures: Lancet: Celgene: Research Funding. Sekeres:Celgene: Consultancy; Amgen: Consultancy. List:Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau.

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Incidence and Prevalence of Patients with Myelodysplastic Syndromes (MDS) in Düsseldorf 1996-2005.

Blood ◽

10.1182/blood.v114.22.1774.1774 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1774-1774 ◽

Cited By ~ 1

Author(s):

Judith Neukirchen ◽

W. Marieke Schoonen ◽

Carlo Aul ◽

Rainer Haas ◽

Norbert Gattermann ◽

...

Keyword(s):

High Risk ◽

Myelodysplastic Syndromes ◽

Research Funding ◽

Population Based ◽

Low Risk ◽

High Risk Disease ◽

Population Counts ◽

Incident Cases ◽

The Town ◽

Age And Sex

Abstract Abstract 1774 Poster Board I-800 Background Population-based data on myelodysplastic syndromes (MDS) are scarce. Since its inception in 1982, the Düsseldorf MDS Registry has captured 3598 patients with MDS, of whom 21 % live in the town district of Düsseldorf. Between 1996-2005 we are confident that all MDS patients residing in the town district of Düsseldorf were entered and followed in the registry through regular follow-ups. As yearly age- and sex-specific population counts are also available for Düsseldorf, the Registry provides a unique opportunity to estimate MDS disease frequency. Here we aim to quantify the incidence and prevalence of MDS disease subtypes. Methods Patients were identified from the MDS Registry. Age- and sex-specific yearly population counts were obtained from the Statistical Office of North-Rhine Westphalia. The number of residents in Düsseldorf minimally increased during the study period from 1996 to 2005 (mean: 571,000 residents). The number of patients with a first-time MDS diagnosis in a given calendar year (incident cases) was divided by the total Düsseldorf population in that year to estimate incidence. Prevalence was estimated by dividing the number of existing plus incident MDS patients in a given year by the total population of Düsseldorf that year. Incidence (per 100,000 person-years (PY) and prevalence per 100,000 persons are presented with corresponding 95% confidence intervals (CI) calculated using the delta and Wilson methods, respectively. Low-risk MDS was defined as WHO subtypes RA, RCMD or MDS with del(5q). High-risk included subtypes RAEB-I and RAEB-II. Results 344 MDS patients were included in our analyses (279 incident patients). Incidence and prevalence of low-risk MDS was 2.87 (95%CI 2.46–3.35) per 100,000PY and 12.4 (95%CI 11.5–13.4) per 100,000 persons, respectively, with no difference between men and women (Table). High-risk disease was less common. The incidence of high-risk disease in men appeared to be higher (1.22 (95%CI 0.87–1.72) per 100,000PY) than in women (0.63 (95%CI 0.40–0.99) per 100,000PY). Prevalence of high-risk disease among men was statistically significantly higher in men compared to women (2.93 (95%CI 2.35 – 3.65) per 100,000 persons) and 1.56 (95%CI 1.17 – 2.08) per 100,000 persons), respectively (Table). Conclusion In this population-based study we found that MDS more common in men than in women. The majority of MDS cases had low-risk disease. Incidence and prevalence of high risk disease (but not low risk) is higher in men compared to women. Financial disclosures: This study was supported by Amgen Inc. Disclosures Neukirchen: Amgen Inc.: Research Funding. Schoonen:Amgen Inc.: Research Funding. Aul:Amgen Inc.: Research Funding. Haas:Amgen Inc.: Research Funding. Gattermann:Amgen Inc., Celgene, Novartis: Honoraria, Research Funding. Germing:Amgen Inc., Celgene, Novartis: Honoraria, Research Funding.

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Reduced TET2 expression in Patients with Myelodysplastic Syndromes and Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v120.21.2822.2822 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2822-2822

Author(s):

Renata Scopim-Ribeiro ◽

Joao Machado-Neto ◽

Paula de Melo Campos ◽

Patricia Favaro ◽

Adriana S. S. Duarte ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

High Risk ◽

Myeloid Leukemia ◽

Research Funding ◽

Erythroid Differentiation ◽

Low Risk ◽

High Risk Disease ◽

Cd34 Cells ◽

Acute Myeloid

Abstract Abstract 2822 Introduction: Acquired mutations in TET2 and DNMT3A have been found in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and may predict a worse survival in these diseases. TET2 mutations are considered to be a loss-of-function mutation and results in decreased 5-hydroxymethylcitosine (5-hmc) levels. In normal CD34+ cells, TET2 silencing skews progenitor differentiation towards the granulomonocytic lineage at the expense of lymphoid and erythroid lineages. Dnmt3a participates in the epigenetic silencing of hematopoietic stem cell regulatory genes, enabling efficient differentiation. Here, we attempted to evaluate the expression of TET2 and DNMT3A in total bone marrow cells from normal donors, patients with MDS and AML, and in CD34+ cells from MDS and normal controls during erythroid differentiation. Materials and Methods: The study included normal donors (n = 21), patients with MDS (n = 43) and AML (n = 42) at diagnosis. All normal donors and patients provided informed written consent and the study was approved by the ethics committee of the Institution. MDS patients were stratified into low and high-risk according to WHO classification (RCUD/RCMD/RARS=31 and RAEB1/RAEB2=12). TET2 and DNMT3A mRNA expression was assessed by quantitative PCR. CD34+ cells from normal donors (n = 9) and low-risk MDS patients (n = 7) were submitted to erythroid differentiation. Cells were collected and submitted to immunophenotyping for GPA and CD71 (days 6 and 12) and q-PCR for TET2 and DNMT3A expression (days 6, 8 and 12). Results of gene expression in normal donors and patients are presented as median, minimum-maximum, and were compared using Mann-Whitney test. Student t test was used for comparison of gene expression during CD34+ erythroid diferentiation. Overall survival was defined from the time of sampling to the date of death or last seen. Univariate analysis for overall survival was conducted with the Cox proportional hazards model. Results: TET2 expression was significantly reduced in both AML (0.62; 0.01–32.69) and MDS (1.46; 0.17–21.30) compared to normal donors (2.72; 0.43–31.49); P<0.0001 and P=0.01, respectively. TET2 expression was also significantly reduced in AML compared to MDS (P=0.0007). MDS patients were stratified into low and high-risk disease, and we still observed a significant reduction in TET2 expression in high-risk (0.73, 0.17–7.25) when compared to low-risk (1.58; 0.48–21.30; P=0.02) patients, but no difference was noted between normal donors vs. low-risk MDS, and high-risk MDS vs. AML. In MDS cohort, the median overall survival was 14 months (range 1–83), increased TET2 expression was associated with a longer survival (HR, 0.44; 95% CI, 0.21–0.91, P=0.03), and, as expected, WHO high-risk disease was associated with a shorter survival (HR, 10.16; 95% CI, 3.06–33.72, P<0.001), even though the confidence interval (CI) was large. TET2 expression did not impact survival in our cohort of AML patients. The erythroid differentiation was effective in cells from normal donors and MDS patients, as demonstrated by the flow cytometry analyses of GPA and CD71. TET2 expression was significantly increased on day 12 of erythroid differentiation, P<0.05. On the other hand, DNMT3A expression was similar between normal donors (0.74; 0.22–1.53), MDS (0.78; 0.26–3.46) and AML (0.95, 0.15–6.46), and during erythroid differentiation, with no impact on survival. Conclusion: These data suggest that decreased TET2 expression may participate in leukemogenesis, and supports the participation of TET2 in the erythroid differentiation of MDS. DNMT3A was not differentially expressed in AML and MDS, indicating that the presence of mutations in this gene may be the predominant mechanism of changes in protein function. We thus suggest that decreased TET2 expression may explain the reduced levels of 5-hmc found in TET2 wild type patients, and may become a predictive marker for outcomes in MDS and other myeloid diseases. Further studies would be necessary to better elucidate the clinical relevance and biologic significance of our findings, and whether the decreased TET2 expression results in hypermethylation in these diseases. Disclosures: Maciejewski: NIH: Research Funding; Aplastic Anemia&MDS International Foundation: Research Funding.

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Disease and Clinical Characteristics of Patients with Polycythemia Vera: An Early View of the Reveal Study

Blood ◽

10.1182/blood.v126.23.2813.2813 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2813-2813

Author(s):

Brady Stein ◽

Alison Moliterno ◽

Ralph V. Boccia ◽

Ahmad B. Naim ◽

Joseph A. Cordaro ◽

...

Keyword(s):

Research Funding ◽

Clinical Characteristics ◽

Thromboembolic Event ◽

Employment Equity ◽

Advisory Committees ◽

Reveal Study ◽

Patient Reported ◽

The Us ◽

History Of ◽

Equity Ownership

Abstract Background: Patients with polycythemia vera (PV) have an increased symptom burden (eg, fatigue, pruritus, and splenomegaly-related symptoms) and an increased risk of mortality compared with the general population, often resulting from thrombotic events, disease transformation to myelofibrosis, or secondary malignancies. There are limited data regarding PV burden and treatment patterns in a contemporary, real-world US setting. REVEAL is an ongoing observational study being conducted to describe contemporary demographics, burden of disease, clinical management, patient-reported outcomes, and healthcare resource utilization among patients with PV in the US. The objective of this assessment is to describe the clinical characteristics at enrollment among patients currently enrolled in REVEAL (enrollment from July 22, 2014 to June 9, 2015). Methods: REVEAL is a multicenter, noninterventional, nonrandomized, prospective, observational study. Eligible patients are ≥18 years of age with a PV diagnosis and currently under active management by a physician in the US. Data regarding disease and clinical characteristics, patient-reported outcomes, and health resource utilization are being collected at usual-care visits over a planned 36-month observation period. Analyses of these preliminary data were descriptive. Results: At data cutoff, 865 patients were enrolled (total planned enrollment, n=2000) from 174 sites (academic, n=27; community, n=147). Median (range) age at enrollment was 67 (22-95) years, 55.5% were male, 89.5% were white, and 45.4% had a history of smoking. Most patients (99.4%) had health insurance, including Medicare (56.0%), PPO (24.3%), or HMO (11.6%). Fifty-two percent were retired, 29.6% were employed, and 4.5% were unable to work or disabled. A total of 40.2% of patients completed a college/graduate degree, 19.9% had some college, and 32.5% completed high school or the equivalent. Documented major World Health Organization diagnostic criteria included JAK2V617F mutation in 50.9% of patients, elevated hemoglobin in 52.3%, and red cell mass in 5.5%. A bone marrow biopsy was conducted in 24.0% of patients, approximately half of whom (52.4% of the 24.0%) had trilineage myeloproliferation. Erythropoietin levels were abnormal in 19.7% of patients. Approximately half (46.6%) of patients had physician-reported PV-related symptoms at diagnosis, most frequently fatigue (25.2%) and pruritus (14.0%). At enrollment, median disease duration was 52.6 months; 42.3% of patients were diagnosed ≥5 years before enrollment. The most common comorbidities were hypertension (51.3%), obesity (14.2%), dyspnea (13.4%), myalgia (11.2%), and diabetes mellitus (11.1%). Mean hematocrit was 44.9%, hemoglobin was 14.5 g/dL, white blood cell count was 11.4×109/L, platelet count was 363.7×109/L, and absolute neutrophil count was 363.7×109/L. Twenty-one percent of patients had a history of thrombotic events, with 13.1% and 8.6% of patients experiencing ≥1 venous or arterial thromboembolic event, respectively. Of the 261 reported thrombotic events, 43.7% occurred after diagnosis of PV. The most common PV symptoms recorded at enrollment (using the Myeloproliferative Neoplasm Symptom Assessment Form) were fatigue (37.1%), pruritus (24.0%), headache (18.6%), insomnia (17.0%), dizziness (13.2%), bone pain (10.5%), and blurred vision (7.9%); 19.7% of 518 evaluable patients had palpable splenomegaly. Fewer than half of patients were receiving aspirin at enrollment (47.7%). The most common PV treatments ± aspirin were phlebotomy (PBT; 63.5%), hydroxyurea (HU; 42.2%), watchful waiting (5.3%), and ruxolitinib (3.1%); 23.0% of patients received PBT + HU. Conclusion: The REVEAL study is unique in that it captures data from both academic and community centers, and therefore includes a broader segment of the PV population typically not described in the literature. REVEAL can provide novel insights into questions related to the contemporary demographics of PV, practice patterns regarding diagnosis and therapy, and the real-world burden of PV and its impact on patients' quality of life and work productivity. Preliminary descriptive data from this early subset of patients suggest that a high proportion of patients report having PV-related symptoms at diagnosis, fewer patients are treated with aspirin than expected, and that thromboembolic event rates remain high after diagnosis. Disclosures Stein: Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moliterno:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Boccia:Incyte Corporation: Honoraria. Naim:Incyte Corporation: Employment, Equity Ownership. Cordaro:Incyte Corporation: Employment, Equity Ownership. Peng:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Mesa:Promedior: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; NS Pharma: Research Funding; CTI Biopharma: Research Funding; Gilead: Research Funding; Pfizer: Research Funding; Incyte Corporation: Research Funding; Genentech: Research Funding.

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Disease Characteristics of Minority Patient Populations with Polycythemia Vera: An Analysis from the Reveal Study

Blood ◽

10.1182/blood-2018-99-112530 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4735-4735 ◽

Cited By ~ 1

Author(s):

Ivy Altomare ◽

Philomena Colucci ◽

Shreekant Parasuraman ◽

Dilan Chamikara Paranagama ◽

Anas Al-Janadi

Keyword(s):

United States ◽

High Risk ◽

The United States ◽

Low Risk ◽

Employment Equity ◽

Disease Characteristics ◽

Reveal Study ◽

High Risk Disease ◽

Caucasian Patients ◽

Equity Ownership

Abstract Introduction: Polycythemia vera (PV) is associated with increased blood cell counts, risk of thrombosis, and symptoms including fatigue and pruritus. Few studies have examined the presence or absence of racial/ethnic disparities among patients with PV. The objective of this analysis is to describe differences in disease characteristics, diagnosis, treatment, and quality of life (QOL) among Caucasian and non-Caucasian patients with PV in the United States enrolled in the prospective, observational REVEAL study. Methods: The ongoing REVEAL study (ClinicalTrials.gov ID, NCT02252159) is a prospective, multicenter, observational study of adult patients with PV in the United States. Patients were observed during a 36-month period, during which clinical data were collected from usual care visits. This analysis compared demographics, disease and clinical characteristics, disease management, comorbidities, and QOL between Caucasian and non-Caucasian patients with PV at enrollment. QOL was measured by the European Organisation for Research and Treatment of Cancer Questionnaire C30 (EORTC QLQ-C30) and Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Results are summarized with descriptive statistics. Results: Of the 2,510 patients enrolled in REVEAL, 2,237 were Caucasian (89.1%); 199 (7.9%) were non-Caucasian, comprised of African American (5.7%), Asian (1.5%), Native American Indian (0.2%), Pacific Islander (0.1%), and other patients (0.4%); no information was provided regarding race or ethnicity for 74 patients (2.9%). Baseline disease characteristics were similar for Caucasian and non-Caucasian groups with respect to gender and disease duration. There were no differences in method of diagnosis, laboratory values, or overall history of thrombosis between groups (Figure 1A). Mean age was higher among Caucasian patients compared to non-Caucasian patients (66.6 vs 63.8 years, respectively). The proportion of patients from rural areas was higher among Caucasian vs non-Caucasian patients (28.8% vs 12.6%); similarly, the proportion of patients from urban areas was lower among Caucasian vs non-Caucasian patients (23.1% vs 46.7%). The proportion of patients with some college or higher level of education was higher among Caucasian vs non-Caucasian patients (64.1% vs 50.3%). A higher proportion of Caucasian vs non-Caucasian patients were retired (52.0% vs 43.2%); a higher proportion of non-Caucasian patients reported being unable to work or were disabled (3.8% vs 10.1%). More Caucasian patients had high-risk disease (78.0%) compared with non-Caucasian patients (71.4%), and patients with high-risk disease were managed similarly between groups. However, Caucasian patients with low-risk disease received more phlebotomies (56.6%) than non-Caucasian patients with low-risk disease (40.4%), and over twice as many non-Caucasian patients received hydroxyurea (38.6%) than Caucasian patients (15.6%) (Figure 1B). MPN-SAF TSSs were higher for non-Caucasian patients compared with Caucasian patients, suggesting a worse symptom burden. Similarly, non-Caucasian patients reported lower functional and symptom outcomes on the EORTC QLQ-C30, including a disparity in financial difficulties, compared to Caucasian patients (Figure 1C). Conclusions: This analysis evaluated a cohort of racial/ethnic minority patients with PV treated in the United States. As in other cancer-related trials, there is a risk that racial and ethnic minorities may be underrepresented in REVEAL. With this limitation in mind, in this analysis, differences were not observed among Caucasian and non-Caucasian patients with respect to method of diagnosis, duration of disease, thrombosis rates, or management of high-risk disease. Non-Caucasian patients demonstrated higher rates of low-risk disease and cytoreductive therapy for low-risk disease yet had worse symptom burden, lower functional scores, and greater disability. This study underscores the importance of symptom assessment and ancillary resource availability for patients with PV Disclosures Altomare: Bayer: Consultancy; Genentech: Consultancy; Ipsen: Other: Advisory Board Member; Celgene: Other: Advisory Board Member; Incyte: Consultancy; Novartis: Consultancy; Amgen: Consultancy. Colucci:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership.

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Disease and Clinical Characteristics of Patients with Essential Thrombocythemia Enrolled in the MOST Study

Blood ◽

10.1182/blood-2018-99-112183 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4306-4306

Author(s):

Abdulraheem Yacoub ◽

Roger M. Lyons ◽

Srdan Verstovsek ◽

Ryan Shao ◽

David Tin Chu ◽

...

Keyword(s):

United States ◽

Observational Study ◽

Board Of Directors ◽

Essential Thrombocythemia ◽

Research Funding ◽

Clinical Characteristics ◽

The United States ◽

Advisory Committees ◽

History Of ◽

Equity Ownership

Abstract Introduction: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by clonal platelet production and an increased risk for thrombotic and hemorrhagic events. Limited real-world data exist regarding the clinical characteristics and treatment patterns of ET in the United States; most prior data have been generated outside the United States. The Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) is an ongoing observational study being conducted to describe contemporary demographics, burden of disease, clinical management, and patient-reported outcomes in patients with specific risk categories of myelofibrosis (MF) or ET in the United States. This analysis describes the clinical characteristics of patients with ET currently enrolled in MOST. Methods: MOST is a multicenter, noninterventional, prospective, observational study in patients with a clinical diagnosis of specific risk categories of MF or ET (NCT02953704). Eligible patients with ET included high-risk patients (≥ 60 years of age and/or a history of thromboembolic events [TEs]), or low-risk patients currently receiving ET-directed therapy. Key exclusion criteria included participation in blinded investigational drug studies, life expectancy ≤ 6 months, or diagnosis of other malignancy. Data regarding disease and clinical characteristics are collected at usual-care visits over a planned 36-month observation period. Patient demographics and clinical characteristics at enrollment were described with descriptive statistics. Results: At data cutoff (May 18, 2018), 793 eligible patients were enrolled from 85 sites since November 29, 2016. The median age at enrollment was 70 (range, 24-95) years, 66.5% were female, and 89.8% were Caucasian. The median time from ET diagnosis to enrollment was 4.2 (range, 0.0-42.1) years with a proportion of patients diagnosed within 1 year (19.5%), 1 to < 5 years (35.0%), 5 to < 10 years (21.7%), or ≥ 10 years (23.8%) of enrollment. Approximately 40% of patients were retired and 42.7% were working full- or part-time at enrollment. A total of 212 patients (26.7%) had a history of TE at the time of enrollment. The type of TE was available for 148 patients, the most common was arterial events (53.4%); 33.1% had venous, and 13.5% of patients had both arterial and venous events. Six hundred and eighty-eight patients (86.8%) were classified as high-risk. Assessments at the time of ET diagnosis, among evaluable patients, included bone marrow biopsy (51.4%; 393/765) and mutational testing (77.2%; 590/764). Three hundred and forty-nine patients had mutation test results reported at the time of diagnosis; of patients with JAK2 V617F test results reported at the time of diagnosis (n = 313), 78.6% were positive for JAK2 V617F (Table 1). Laboratory values and peripheral blood counts were reported for patients with available data (Table 2). The majority of patients (87.9%) had received at least 1 ET-directed therapy prior to enrollment, which in some cases was the same medication the patient was receiving at the time of enrollment. At the time of enrollment, 740 patients (93.3%) were receiving at least 1 current ET-directed therapy, including HU (71.6%; 530/740), anagrelide (13.1%; 97/740), ruxolitinib (4.7%; 35/740), interferon (3.0%; 22/740), and busulfan (0.3%; 2/740). Of 793 patients, the most frequently occurring relevant comorbid conditions were hypertension (52.7%), history of smoking (44.7%), and hyperlipidemia (24.1%). Among 761 patients with ET-related symptoms assessed at diagnosis, the most common symptoms documented by healthcare providers included constitutional (22.9%), vasomotor (16.0%), and spleen-associated symptoms (3.9%), and pruritus (2.6%). Conclusions: Prior real-world data in ET has predominately been generated outside of the United States or has been reported from single institutional experiences. The MOST study will provide a more complete picture of the patient characteristics and outcomes of patients receiving ET-directed therapy in the United States. Ultimately, these data will be important for determining ET treatment gaps and areas of unmet need. Disclosures Yacoub: Cara Therapeutics: Equity Ownership; Inycte: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Ardelyx, INC.: Equity Ownership; Seattle Genetics: Honoraria, Speakers Bureau; Dynavax: Equity Ownership. Verstovsek:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy. Shao:ASH: Membership on an entity's Board of Directors or advisory committees; ASCO: Membership on an entity's Board of Directors or advisory committees. Agrawal:Incyte: Speakers Bureau. Sivaraman:Incyte: Employment. Colucci:Incyte: Employment, Equity Ownership. Yao:Incyte: Employment. Mascarenhas:Celgene: Membership on an entity's Board of Directors or advisory committees; Promedior: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Merck: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Janssen: Research Funding.

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Low-Risk Polycythemia Vera Treated with Phlebotomies: Clinical Characteristics, Hematologic Control and Complications in 358 Patients from the Spanish Registry of Polycythemia Vera

Blood ◽

10.1182/blood-2021-145012 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3621-3621

Author(s):

Ana Triguero ◽

Alexandra Pedraza ◽

Manuel Pérez ◽

María Isabel Mata ◽

Beatriz Bellosillo ◽

...

Keyword(s):

Polycythemia Vera ◽

Research Funding ◽

Clinical Characteristics ◽

Treatment Strategies ◽

Myeloproliferative Disorders ◽

Primary Prophylaxis ◽

Low Risk ◽

Major Hemorrhage ◽

Risk Patients

Abstract Introduction: Current recommendations for patients with low-risk polycythemia vera (PV) include hematocrit (Htc) control with phlebotomies and primary prophylaxis of thrombosis with low-dose aspirin. There is scarce information regarding the hematological control, the incidence of complications and the need for cytoreduction in PV patients treated with phlebotomies only. Methods: A total of 358 patients with low-risk PV (<60 years old and without history of thrombosis) from the Spanish Registry of Polycythemia Vera were included in the present study. PV-related symptoms and blood counts were collected at 6, 12, 18, 24, 36, 48 and 60 months from diagnosis while the patients were treated with phlebotomies only. The duration of the treatment with phlebotomies, the indication of starting cytoreduction and the incidence of thromboembolic and hemorrhagic events during the cytoreduction-free period was also analyzed. Results: Baseline characteristics at the time of diagnosis are described in Table 1. Table 2 summarizes the main hematological and clinical characteristics under treatment with phlebotomies. Inadequate control of the Htc (> 45%) was reported in 61-70% of the patients, leukocytosis >15x10 9/l in 10% and thrombocytosis >1000x10 9/l in 5%. In addition, about 20% of the patients had pruritus and 10% had microvascular symptoms. Of the 358 patients included, 275 (77%) required cytoreduction, 261 (73%) with hydroxyurea and 14 (4%) with IFN. The main indication of cytoreduction was thrombocytosis (20%), followed by age >60 years old (15%) and microvascular symptoms (13%). Median duration of cytoreduction abstention was 4.7 (0.1-30.4) years being significantly longer in patients younger than 50 years (6 and 2 years for patients younger and older than 50 years, respectively, p<0.0001). With a follow-up of 1659 person-years under phlebotomy only treatment, 14 thrombosis were observed (arterial n=9, venous n= 5), 12 hemorrhages (major n=4, minor n=8) and 4 solid tumors (1 melanoma and 3 non-cutaneous carcinomas). The incidence of complications during the cytoreduction-free period by person-years was: 0.8% for thrombosis, 0.2% for major hemorrhage and 0.2% for second neoplasia. The median follow-up until last visit including the time after starting cytoreductive therapy was 8.4 (0.2-39) years. Of 14 deaths observed, none occurred during the phlebotomy period. Half of the patients died from PV related reasons but the other 50% were not related. The median survival estimation by K-M was 36.5 years. Disease progression was documented in 27 (7.5%) patients, 26 of them to myelofibrosis, 1 to myelodysplastic syndrome and none to acute leukemia. Progression to myelofibrosis occurred during the cytoreduction-free period in 5 patients (1.4%) after a median of 5.8 years (Range: 4.9-8.9). Conclusions The incidence of thrombotic and hemorrhagic complications was very low in this series of low-risk patients treated with phlebotomies, even though only 30-40% of patients maintained the Htc <45%. The data from the present study show that low-risk patients have different therapeutic needs than other PV patients and support the development of new treatment strategies. Representing the Spanish Group of Myeloproliferative Disorders. GEMFIN Figure 1 Figure 1. Disclosures Bellosillo: Qiagen: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding; Thermofisher Scientific: Consultancy, Speakers Bureau. Ferrer Marin: Cty: Research Funding; Incyte: Consultancy, Research Funding; Novartis: Speakers Bureau. Garcia Gutierrez: Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding.

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Characteristics Associated with Hydroxyurea Treatment Change in Patients with Polycythemia Vera: An Analysis from the Reveal Study

Blood ◽

10.1182/blood-2018-99-111986 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1770-1770

Author(s):

Anas Al-Janadi ◽

Ruben A. Mesa ◽

Philomena Colucci ◽

Shreekant Parasuraman ◽

Dilan Chamikara Paranagama ◽

...

Keyword(s):

High Risk ◽

Polycythemia Vera ◽

Alternative Treatment ◽

Research Funding ◽

Index Date ◽

Symptom Burden ◽

Treatment Change ◽

Employment Equity ◽

Risk Patients ◽

Equity Ownership

Abstract Introduction: Polycythemia vera (PV) is associated with increased blood cell counts, risk of thrombosis, and symptoms. Guidelines support the use of hydroxyurea (HU) in high-risk patients, or low-risk patients with an indication for cytoreductive therapy. However, a proportion of patients become resistant or intolerant to HU over time. The objective of this analysis is to describe patients with PV enrolled in REVEAL who changed from HU to an alternative treatment. Methods: REVEAL (NCT02252159) is a prospective, observational study of adult patients with PV in the US. Patients were observed over a 36-month period and clinical data were collected from usual care visits. In this analysis, an index date of 6 months prior to enrollment was determined for each patient. Patients who received other PV-related treatments prior to initiating HU, who never received HU prior to data cutoff, or who discontinued HU within 3 months of the data cutoff were excluded. Patients who initiated HU prior to their index date and continued through the index date and patients who initiated HU after the index date were included. This patient cohort was subdivided into 3 subgroups: patients who discontinued HU and did not initiate an alternative; patients who were still receiving HU at the time of data cutoff; and patients who started an alternative treatment after HU. For patients who initiated an alternative treatment, laboratory values (maximum values within the reporting period), number of phlebotomies, and symptoms were evaluated within 3 months prior to the treatment change. For patients who discontinued and for those who continued HU, data were evaluated within 3 months prior to discontinuation or data cutoff, respectively (time of evaluation). Symptom burden was assessed using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). All data were analyzed with descriptive statistics. Results: Of the 2,510 patients enrolled in REVEAL, 1,239 met the criteria for this analysis. Of these patients, 56 (4.5%) discontinued HU without initiating an alternative therapy, 1,059 (85.5%) continued HU, and 124 (10.0%) started an alternative cytoreductive treatment after HU. Patients who discontinued HU treatment were older, with a median age (range) of 74.0 (28.0-91.0) years compared with patients who continued HU or who started an alternative treatment (Table). A similar proportion of patients who discontinued HU had high-risk disease (89.3%) compared to those who continued HU (87.2%) or initiated an alternative treatment (83.1%). Among those who started an alternative treatment, ruxolitinib was the most common (102 patients, 82.3%), followed by anagrelide (17 patients, 13.7%), interferon (4 patients, 3.2%), and chlorambucil (1 patient, 0.8%). Patients who initiated an alternative treatment for PV had higher mean blood counts and more frequent phlebotomy procedures compared with those who discontinued HU and with those who continued (Table). Patients who initiated an alternative treatment had higher mean HU dose at the time of treatment change (968.6 mg/d) compared with those who discontinued HU (707.1 mg/d at the time of discontinuation) or those who continued (811.2 mg/d at the time of data cutoff). Similarly, the maximum HU dose received since index was higher for those who initiated an alternative treatment compared with those who discontinued HU or continued HU (1072.9, 803.6, and 891.9 mg/d, respectively). Patients who initiated an alternative treatment following HU had a higher mean TSS, both at the time of treatment change and at enrollment (29.8 and 25.9) compared with those who discontinued HU (at the time of discontinuation, 22.5 and 20.4) and those who continued HU (at the time of data cutoff, 20.8 and 16.8). A higher proportion of patients who discontinued HU had a history of nonhematological adverse events (12.5%) compared with those who started another alternative treatment (8.1%) or those who continued HU (5.9%). Conclusion: Patients with PV who received HU demonstrated variation with respect to HU management. Patients who started alternative treatments after HU were younger, had higher counts, more frequent phlebotomies, and higher symptom burden before changing treatment. These data support current criteria for HU resistance/intolerance. Disclosures Mesa: Promedior: Research Funding; Novartis: Consultancy; UT Health San Antonio - Mays Cancer Center: Employment; Pfizer: Research Funding; NS Pharma: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Incyte Corporation: Research Funding; Gilead: Research Funding; CTI Biopharma: Research Funding. Colucci:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Grunwald:Celgene: Consultancy; Pfizer: Consultancy; Agios: Consultancy; Merck: Consultancy; Janssen: Research Funding; Forma Therapeutics: Research Funding; Genentech: Research Funding; Cardinal Health: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Research Funding.

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International Working Group Scores Predict Post-Transplant Outcomes In Patients with Myelofibrosis

Blood ◽

10.1182/blood.v116.21.3085.3085 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3085-3085 ◽

Cited By ~ 1

Author(s):

Bart Lee Scott ◽

Ted A. Gooley ◽

Michael L. Linenberger ◽

Brenda M. Sandmaier ◽

David Myerson ◽

...

Keyword(s):

High Risk ◽

Working Group ◽

Scoring System ◽

Prognostic Model ◽

Low Risk ◽

Post Transplant ◽

International Working Group ◽

High Risk Disease ◽

Risk Patients ◽

History Of

Abstract Abstract 3085 The International Working Group (IWG) has determined that prognosis in myelofibrosis is predicted by a scoring system that includes the following parameters: age > 65 years, constitutional symptoms, hemoglobin < 10 g/dL, leukocyte count > 25 × 109/L and circulating peripheral blasts ≥ 1%. Based on these factors patients may be placed into 4 separate categories: low, intermediate-1, intermediate-2 or high risk. The median survivals of these 4 groups are 135, 95, 48 and 27 months, respectively. The IWG scoring system has been validated in a dynamic prognostic model. However, there have been no publications evaluating the use of the IWG prognostic model in patients with myelofibrosis who receive hematopoietic cell transplantation (HCT). We performed a retrospective review of 181 patients with a diagnosis of myelofibrosis who underwent HCT at the Fred Hutchinson Cancer Research Center between March, 1990 and November 2009. Twelve patients received an autologous transplant and 169 patients underwent an allogeneic transplant using an HLA-matched related (78), syngeneic (3), HLA-mismatched related (4), HLA-matched unrelated (66) or HLA-mismatched unrelated (18) donor. The median age at time of HCT was 51 (range: 12–78) years. Among the 169 patients who received allogeneic transplants, conditioning regimens consisted of oral busulfan, 16 mg/kg (136); oral busulfan, 7 mg/kg with TBI 12 Gy (9); TBI 12–13 Gy (4); Melphalan, 140 mg/kg (3); Fludarabine, 90 mg/m2 with TBI 2–4 Gy (16); and Treosulfan, 42 gm/m2 with Fludarabine, 150 mg/m2 (1). GVHD prophylaxis consisted of cyclosporin/methotrexate (99), tacrolimus/methotrexate (49), cyclosporin/mycophenolate (14) or tacrolimus/mycophenolate (4). We were able to obtain the full set of parameters involved in calculating the IWG score in all 181 patients. Historical records pre-transplant and arrival records prior to transplant were reviewed. Patients were assigned to the highest possible IWG score based on age at time of HCT, history of constitutional symptoms, hemoglobin < 10 g/dL or transfusion dependence at time of transplant, history of leukocyte counts > 25 × 109/L, and history of peripheral blasts ≥ 1%. Based upon these parameters, there were 21 patients with low risk, 48 patients with intermediate-1, 54 patients with intermediate-2, and 58 patients with high risk disease. The IWG score was highly predictive of survival in the post-transplant setting with a hazard ratio (HR) of 4.4 (95% CI 1.6–12.5, p=0.005) for mortality in high risk patients compared to low risk patients. Patients in the low risk category had a significantly lower risk of relapse HR=0 (95% CI 0, p=0.046) in comparison to patients with high risk disease. In addition, patients with high risk disease had a significantly greater risk of transplant related mortality HR=3.7 (95% CI 1.3–11, p=0.016) in comparison to patients with low risk disease. This is the first examination of post-transplant outcomes by the pre-transplant IWG score. This analysis suggests that patient and disease characteristics considered in the IWG score and shown to be of prognostic significance at diagnosis also predict post-transplant survival. These findings, with a follow-up extending to two decades, indicate that while transplantation was curative for a proportion of patients, it could not completely overcome the risk conveyed by pre-transplant risk factors. It is our hope that future studies will use this information to address the optimal timing of appropriate interventions including HCT. Disclosures: No relevant conflicts of interest to declare.

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