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

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 388-388 ◽  
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.

scholarly journals The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2657-2664 ◽  
Author(s):  
Bart L. Scott ◽  
Ted A. Gooley ◽  
Mohamed L. Sorror ◽  
Andrew R. Rezvani ◽  
Michael L. Linenberger ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Scoring System ◽  
Hematopoietic Cell Transplantation ◽  
Risk Groups ◽  
Hematopoietic Cell ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
High Risk Disease ◽  
Risk Patients

Abstract Studies by the International Working Group showed that the prognosis of myelofibrosis patients is predicted by the Dynamic International Prognostic Scoring System (DIPSS) risk categorization, which includes patient age, constitutional symptoms, hemoglobin, leukocyte count, and circulating blasts. We evaluated the prognostic usefulness of the DIPSS in 170 patients with myelofibrosis, 12 to 78 years of age (median, 51.5 years of age), who received hematopoietic cell transplantation (HCT) between 1990 and 2009 from related (n = 86) or unrelated donors (n = 84). By DIPSS, 21 patients had low-risk disease, 48 had intermediate-1, 50 had intermediate-2, and 51 had high-risk disease. Five-year incidence of relapse, relapse-free survival, overall survival, and nonrelapse mortality for all patients were 10%, 57%, 57%, and 34%, respectively. Among patients with DIPSS high-risk disease, the hazard ratio for post-HCT mortality was 4.11 (95% CI, 1.44-11.78; P = .008), and for nonrelapse mortality was 3.41 (95% CI, 1.15-10.09; P = .03) compared with low-risk patients. After a median follow-up of 5.9 years, the median survivals have not been reached for DIPSS risk groups low and intermediate-1, and were 7 and 2.5 years for intermediate-2 and high-risk patients, respectively. Thus, HCT was curative for a large proportion of patients with myelofibrosis, and post-HCT success was dependent on pre-HCT DIPSS classification.

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.

Clinical “MUTATOME” Of Myelodysplastic Syndrome; Comparison To Primary Acute Myelogenous Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 518-518 ◽  
Author(s):  
Hideki Makishima ◽  
Thomas LaFramboise ◽  
Bartlomiej P Przychodzen ◽  
Kenichi Yoshida ◽  
Matthew Ruffalo ◽  
...  
Keyword(s):  
High Risk ◽  
Lower Risk ◽  
Research Funding ◽  
Somatic Mutations ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
Clonal Architecture ◽  
Ras Family ◽  
Definition Of ◽  
The Impact

Abstract Chromosomal aberrations and somatic mutations constitute key elements of the pathogenesis of myelodysplastic syndromes (MDS), a clonal hematologic malignancy characterized by cytopenias, a dysplastic bone marrow and propensity to clonal evolution. Next generation sequencing (NGS) enables definition of somatic mutational patterns and clonal architecture as a discovery platform, and for clinical applications. We systematically applied NGS to 707 cases of MDS and MDS-related disorders. 205 cases (low-risk MDS: N=78, high-risk MDS: N=42, MDS/MPN: N=48 and sAML: N=37) were tested by whole exome sequencing (WES). For validation in an additional 502 patients (low-risk MDS: N=192, high-risk MDS: N=104, MDS/MPN: N=111 and sAML: N=95), targeted deep NGS was applied for 60 index genes which were most commonly affected in the cohort analyzed by WES. For NGS data analysis a statistical pipeline was developed to focus on: i) identification of the most relevant somatic mutations, and ii) minimization of false positive results. We studied serial samples from 21 exemplary informative patients. We also compared somatic mutational patterns to those seen in primary AML TCGA cohort (N=201). Given the size of the cohort, there was, for example, a 87% chance of seeing mutations at a frequency of 1% and a 98% of seeing those with a frequency of 2%. While focusing on the most common events, we observed 1117 somatic mutations in 199 genes. The 88 genes mutated mutated in >1% of cases with MDS carried 388 mutations in MDS+sAML (2.5/case), 128 in MDS/MPN (2.7/case) and 398 in pAML (2.0/case). The average number of mutations per case increased during progression (2.2 in lower-risk, 2.8 in higher-risk MDS, 3.4 in sAML). In MDS, the 30 most frequently affected genes were present at least once in 70% of patients. The 30 most frequently mutated genes in MDS/MPN were mutated in 82% of patients. Individual mutations were also sub-grouped according to their function. When we compared three MDS subcategories (lower-risk, higher-risk MDS and sAML) in a cross-sectional view, RTK family, RAS family, IDH family and cohesin family mutations were more frequently detected in the sAML group than in the MDS group. In contrast, the frequency of the DNMT family, TET2 and ASXL family gene mutations did not increase in frequency in the sAML cohort. In addition to better definition of mutational patterns of known genes, we have also defined new mutations, including in the RNA helicase family and the BRCC3pathway. Clonal architecture analysis indicates that mutations of TET2, DNMT3A, ASXL1, and U2AF1 most likely represent ancestral/originator events, while those of the IDH family, RTK family and cohesin family are typical secondary events. Establishment of mutational patterns may improve the precision of morphologically-based diagnosis. The comparison between MDS-related diseases (MDS+sAML) and pAML revealed a notably different mutational pattern suggestive of a distinct molecular derivation of these two disease groups. While RTK, IDH family and NPM1 mutations were more frequently observed in the pAML cohort, mutations of SF3B1 and SRSF2, were more common in MDS+sAML. With regard to the connections between individual mutation combinations, RTK mutations were strongly associated with DNMT, but not with RAS family mutations in the pAML cohort, while the mutual association between TET2 and PRC2 family, cohesin family and RUNX1were encountered in the MDS+sAML cohort. Individual mutations may have prognostic significance, including having an impact on survival, either within the entire cohort or within specific subgroups. In the combined MDS cohort, TP53 family mutations were associated with a poor prognosis (HR; 3.65, 95%CI; 1.90-7.01, P<.0001) by univariate analysis. Similar results were found for mutations in TCF4(HR; 7.98, 95%CI; 1.58-10.1, P<.0007). Such an individual approach does not allow for assessment of the impact of less common mutational events. In conclusion, our study continues to indicate the power of NGS in the molecular analysis of MDS. MDS and related disorders show a great deal of pathogenetic molecular overlap, consistent with their morphologic and clinical pictures, but also distinct molecular differences in mutational patterns. Some of the specific mutations are pathognomonic for specific subtypes while some may convey a prognostic rather than discriminatory value. Disclosures: Makishima: Scott Hamilton CARES grant: Research Funding; AA & MDS international foundation: Research Funding. Polprasert:MDS foundation: Research Funding.

scholarly journals 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 ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2872-2872 ◽  
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.

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

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1774-1774 ◽  
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.

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

Blood ◽  
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.

scholarly journals 2149

2017 ◽  
Vol 1 (S1) ◽  
pp. 30-31
Author(s):  
Maureen Byrne ◽  
Renee Cowan ◽  
Jennifer Spross ◽  
Kara Long-Roche ◽  
Ginger Gardner
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Scoring System ◽  
Predictive Accuracy ◽  
Residual Disease ◽  
Low Risk ◽  
Stage Iiib ◽  
Cancer Center ◽  
Anatomical Location ◽  
Suboptimal Outcome

OBJECTIVES/SPECIFIC AIMS: To describe the use of primary debulking surgery and neoadjuvant chemotherapy in advanced-stage ovarian cancer patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) over the period of 1 year. Specifically, identify a subset of patients that are medically eligible to be considered for surgery. Examine the ultimate treatment designation for those patients, assessing the application of the MSKCC resectability algorithm and its utility in guiding treatment choice. METHODS/STUDY POPULATION: Using the prospectively maintained Ovarian Cancer Database at MSKCC, we queried patients who presented for initial management of ovarian cancer from July 1, 2015 to June 30, 2016. All patients with stage IIIB-IV disease who received their primary treatment at MSKCC were included in our study. Patients needed to have pathology-confirmed ovarian cancer and all histological subtypes were included. Data were collected and analyzed in Excel. RESULTS/ANTICIPATED RESULTS: There were a total of 173 patients treated for stage IIIB-IVB ovarian cancer at MSKCC during the study period. Of those 98 patients received PDS, whereas 75 were directed to NACT, making MSKCC’s overall NACT rate 43.4% for the year we studied. Of the patients who received NACT, 19 met full Aletti Criteria at diagnosis, precluding them from being considered for surgery. In addition, 21 patients had medical contraindications to surgery, meaning that a total of 40 patients who were given NACT were not able to be considered for PDS. If we then take into account only the patients who were medically eligible for PDS, the rate of NACT at MSKCC drops to 23.1%, almost half of the original value. These medically eligible patients are the population that should be receiving an MSKCC resectability score. Of the 98 patients who underwent PDS, 73.5% had a preoperative resectability score calculated. Based on the algorithm, 81.3% of those patients were deemed to be “low risk” and 15.2% were deemed to be “high risk” of a suboptimal debulking. The algorithm dictates that all “high risk” patients who go on to PDS should undergo a laparoscopy first to assess for resectability and potentially avoid an unnecessary open procedure. Hundered percent of the “high risk” cases that were taken to the OR had an initial laparoscopy before proceeding with PDS. Overall, 93.1% of patients that underwent PDS had an optimal cytoreduction, or ≤1 cm residual disease at the conclusion of surgery. Of the 6 patients throughout the year that had a suboptimal outcome, or >1 cm residual disease, 3 were initially scored as “low risk,” 1 was scored as “high risk,” and 2 did not receive an MSKCC resectability score prior to their procedure. Of note, 3 of the suboptimal cases had unresectable disease in an anatomical location not accounted for in the resectability algorithm. DISCUSSION/SIGNIFICANCE OF IMPACT: The rates of PDS Versus NACT vary widely between institutions, and it is not always clear how calculations are made. High-volume centers likely see a higher percentage of sicker patients with more advanced disease, which could increase their rates of NACT as many of these patients are not eligible for surgery. It is important to standardize the way our field quotes NACT rates, and to understand how treatment decisions are being made at a given institution. PDS has a demonstrated survival benefit, and while we would ideally use this modality for all of our patients, there will always be a baseline percentage of patients who cannot be considered for the surgery. Since we will never be able to offer those patients PDS, our objective should be to identify patients who can be considered for the procedure and to work toward optimizing their outcomes. In this study we identified the population of patients who are truly the PDS Versus NACT cohort as they were eligible for both modalities. We then examined the application and utility of the MSKCC resectability algorithm in an attempt to further optimize treatment allocation. This scoring system was implemented at our hospital over the past year with the goal that 100% patients going on to PDS would receive a preoperative score. Unfortunately, 26.5% of PDS patients were not scored prior to their procedure. This makes it more difficult to evaluate the efficacy of the scoring system, especially considering 1/3 of the suboptimal cases were not scored. Had these patients received a score, they might have been deemed “high risk” and could have avoided a lengthy operation with a significant chance of a suboptimal outcome. In addition, it is important to note that 3 of the suboptimal PDS outcomes were initially scored as “low risk,” and 3 of the suboptimal outcomes were due to disease locations not accounted for in the original resectability algorithm. We will continue logging disease locations of suboptimal cases, it is possible that a certain disease location not in the scoring system is responsible for a significant portion of suboptimal outcomes. The resectability score model had an overall predictive accuracy of 0.756 when it was initially published, and we must continue tracking scores and outcomes to determine its validity when applied prospectively in our population. In order to accurately do so however, an emphasis should be made to ensure 100% of patients being considered for PDS receive a score going forward.

scholarly journals Novel Prognostic Scoring System for Autologous Hematopoietic Cell Transplantation (AHCT) in Multiple Myeloma (MM)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 783-783 ◽  
Author(s):  
Binod Dhakal ◽  
Raphael Fraser ◽  
Zhubin Gahvari ◽  
Aric C. Hall ◽  
Natalie Scott Callander ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Scoring System ◽  
Research Funding ◽  
Validation Cohort ◽  
Progression Free Survival ◽  
Low Risk ◽  
Advisory Committees ◽  
Final Model ◽  
Free Survival

Background: Novel agent induction and AHCT remains the preferred initial therapeutic strategy for transplant-eligible MM patients. Current prognostic tools in MM focus solely on disease-specific factors at diagnosis to determine patient prognosis-International Staging System (ISS) and revised-ISS (R-ISS). A major limitation to both, the ISS and R-ISS, is that they are not specific for HCT-eligible patients and do not take into account other patient factors that may enter into a decision to pursue AHCT. The data used to generate these staging systems were from broad populations with varying upfront treatment strategies and included patients who were ineligible for intensive therapy. Additionally, there is considerable interest in identifying the population that relapses early despite modern induction/AHCT approaches who are candidates for novel approaches for maintenance/consolidation. To address these problems, we used data from the Center for Blood and Marrow Transplant Research (CIBMTR) registry to identify disease-, patient-, and transplantation-specific variables that are associated with progression-free survival (PFS) in patients undergoing upfront AHCT (within 12 months of diagnosis). Methods: We used the outcomes of 2528 MM patients undergoing upfront AHCT from 2008-2017 reported to the CIBMTR. Patients were divided into training and validation sets with a 50% random split. High risk cytogenetics was defined as the presence of one or more of the following: t(4;14), t (14;16), t (14;20), del 13q, del 17p, 1q gain, or 1p deletion. We used a Cox multivariable model to identify factors prognostic of progression free survival (PFS) in a training subset. The regression coefficients of the final model was transformed into a risk score with an appropriate transformation. A weighted score using these factors was assigned to the training cohort (n = 917) and validation cohort (n=897) using subset that had all values that entered the final model. Kaplan-Meier estimates of the individual scores were used to classify patients into risk groups for both cohorts. Results: Baseline characteristics of these patients are shown in Table 1. No cytogenetic abnormality, VRD induction, pre-AHCT bone marrow plasma cells (BMPCs) &lt;10% and 1 line of induction chemotherapy were assigned 0 points. Pre-AHCT BMPCs ≥10% (hazard ratio HR, 1.47; 95% CI, 1.19-1.83), use of ≥2 lines of induction chemotherapy prior to AHCT (HR 1.32; 95% CI 1.06-1.64), standard cytogenetic risk vs. no abnormality (HR 1.41; 95% CI 1.13-1.77) and induction regimens (non-VRD regimens vs. VRD) (HR 1.4, 95% CI 1.17-1.74) were associated with increased hazard of progression and assigned 1 point in the scoring system. Presence of high-risk cytogenetics vs. no abnormality (HR 1.87; 95% CI 1.45-2.42) was assigned 2 points, and the use of thalidomide and dexamethasone (TD) as an induction regimen (HR 2.19; 95% CI 1.48-3.2) was assigned 3 points. A two-category system was created based on the scoring: low risk (0-3) and high risk (4-6). The scoring system was prognostic for PFS when applied to both cohorts. High-risk group was found to have significantly higher risk of progression and/or death compared to low risk in training (HR 2.2; 95% CI 1.74-2.86; p&lt;0.0001) and validation cohort (HR 1.7, 95% CI 1.30-2.22; p=0.0001) respectively (Table 2). The 3-year PFS in the training cohort was 60% (95% CI 56%-64%) in low risk and 27% (95% CI 17%- 36%) in high risk while in the validation cohort was 51% (95% CI 47%-55%) in low risk and 28% (95% CI 16%- 39%) in high risk (Figure 1A and 1B). Conclusions: We describe a prognostic model specifically for patients undergoing upfront AHCT in MM which can identify patients at very high risk for early relapse/progression. These patients should be ideal candidates for studies of immunotherapy or other interventions after AHCT aimed at reducing relapse. Disclosures Dhakal: Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Shah:Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision biosciences GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Nkarta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teneobio: Consultancy, Membership on an entity's Board of Directors or advisory committees; University of California, San Francisco: Employment; Poseida: Research Funding; Indapta Therapeutics: Equity Ownership; Celgene, Janssen, Bluebird Bio, Sutro Biopharma: Research Funding. Qazilbash:Amgen: Consultancy, Other: Advisory Board; Autolus: Consultancy; Bioclinical: Consultancy; Genzyme: Other: Speaker. D'Souza:EDO-Mundapharma, Merck, Prothena, Sanofi, TeneoBio: Research Funding; Prothena: Consultancy; Pfizer, Imbrium, Akcea: Membership on an entity's Board of Directors or advisory committees. Hari:AbbVie: Consultancy, Honoraria; Cell Vault: Equity Ownership; Sanofi: Honoraria, Research Funding; Spectrum: Consultancy, Research Funding; Amgen: Research Funding; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation (allo HSCT) in Patients with IPSS Low or Intermediate-1 Myelodysplastic Syndrome (MDS): A Prospective Multicenter Phase II Study Based on Donor Availability By the GFM & SFGM-TC "MDS-ALLO-Risk"

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1842-1842
Author(s):  
Marie Sebert ◽  
Cendrine Chaffaut ◽  
Sylvain Thepot ◽  
Corentin Orvain ◽  
Thomas Cluzeau ◽  
...  
Keyword(s):  
High Risk ◽  
Lower Risk ◽  
Research Funding ◽  
Low Risk ◽  
Donor Group ◽  
Hematopoietic Stem ◽  
The Past ◽  
Group A ◽  
Group B

Abstract Background: Allo HSCT is a potentially curative treatment in MDS which, in higher risk (IPSS high and int 2) MDS demonstrated an overall survival (OS) advantage over conventional treatment (especially HMAs) in retrospective (Koreth et al., JCO 2013) and prospective (Robin et al. leukemia 2015) studies. Retrospective studies, on the other hand, suggested no OS advantage for allo HSCT in lower risk MDS (IPSS low and int 1), except possibly in the "poorest" lower risk MDS subsets, as classified by the WPSS (Alessandrino et al. AMJH 2013) However, about 25% of lower risk MDS patients are reclassified as higher risk by the R-IPSS and a proportion of other lower risk MDS can also harbor some higher risk features that compromise their outcome. MDS-ALLO-RISK trial (clinicaltrial.gov NCT02757989), was designed to assess outcome of lower risk MDS patients with some high-risk features after HLA-matched donor HSCT. Method: The primary objective of this study was to demonstrate an OS improvement in lower risk MDS patients with some high risk features with a donor compared with those without a donor (with a 3 year OS of 70% versus 40%, respectively) . Inclusion criteria were: IPSS low or int1 MDS with at least one of the following characteristics: 1) R-IPSS intermediate or higher 2) RBC transfusion dependent anemia and failure to two or more treatments (including EPO, Lenalidomide or HMA ); 3) platelets &lt; 20 G/L requiring transfusions 4) ANC &lt; 0.5 G/L with severe infection 5) no contra indication to allo HSCT 6) age &lt;70 years 7) HLA identical donor (sibling or 10/10 unrelated) 105 inclusions were planned: 62 in group with a donor (group A) and 43 in group without a donor (group B). Recruitment began in June 2016 and stopped in March 2021 due to futility on the interim analysis. Median follow-up was 20 months. Data cut off analysis was June 2021. Results: 79 patients were included, 64 in group A and 15 in group B. Median age was 62.4 (IQR: 58-65) years in group A and 66 (IQR: 60.5-68) years in group B. Patients in group A were more frequently males (73 vs 40%, p=0.029), WHO was CMML in 8 (10%), MDS-SLD in 5 (8%), MDS-MLD in 9 (11%), MDS-EB1 in 41 (52%), MDS-RS in 12 (15%), unclassified in 4 (6%) without significant differences between the two groups. IPSS /IPSS-R was similar in both groups: IPSS low in 10% (11% in group A and 7% in group B) and Int-1 in 90%. IPSS-R: very low risk (6% vs 0%); low risk (25% vs 27%); intermediate (50% vs 47%); high (19% vs 27%); no very high risk. Among the 64 patients with a donor, 58 (92%) received HSCT, 2 died before HSCT; 2 had progressive disease and 2 are planned for HSCT. Transplanted patients received reduced intensity conditioning regimen with busulfan 6.4mg/kg, fludarabine 150mg/m2 and ATG (rabbit antithymocyte globulin therapy, grafalon®) 30mg/kg and cyclosporine-mycophenolate mofetil as GVHD prophylaxis. In group A, 21/64 had died, including 13 died from a non-relapse cause. In group B, 4/15 patients had died, 3 from MDS progression and one from CNS bleeding. Three-year OS was 60% (95%CI: 46.9-76.8) in group A and 64.2% (41.3-99.6) in group B (p=NS). At the time of analysis, 20 and 5 patients had progressed/relapsed in group A and B respectively. with a cumulative incidence of relapse/progression (from inclusion) of 27.4% (IC95%: 15;39.8) in group A and 41.7% (IC95%:9.2;74.2) in group B (p=0.71). Among the 58 transplanted patients, 11 (19%) died without disease progression, including one death from a solid tumor. 3 years non-relapse mortality in transplanted patients was 23.4% (IC95%:9.7;37). 3 years Incidence of grade 2 to 4 acute GVHD was 40.8% and 3 years chronic GVHD was 24.9%. Conclusion: In this, to our knowledge, first prospective study in IPSS lower risk patients with some unfavorable clinical or biological features, HLA identical donor (sibling or 10/10 unrelated) HSCT yielded a 3-year OS of 60%. Non relapse mortality was however 23%, and OS somewhat lower than expected (70% at 3 years) and similar to that observed in patients without a donor. Long-term follow-up is needed to better define subgroups of IPSS lower risk MDS that may benefit from allo HSCT. Disclosures Sebert: Abbvie: Consultancy; BMS: Consultancy. Cluzeau: Pfizer: Other: travel, accommodations, expenses; Astellas: Speakers Bureau; Amgen: Speakers Bureau; Agios: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Speakers Bureau; Takeda: Other: travel, accommodations, expenses; Jazz Pharma: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria, Speakers Bureau. Loschi: AbbVie: Ended employment in the past 24 months, Honoraria; CELGENE/BMS: Honoraria; Gilead: Ended employment in the past 24 months, Honoraria; Novartis: Ended employment in the past 24 months, Honoraria; Servier: Ended employment in the past 24 months, Honoraria; MSD: Honoraria. Huynh: Jazz Pharmaceuticals: Honoraria. Ades: ABBVIE: Honoraria; NOVARTIS: Honoraria; CELGENE/BMS: Honoraria; CELGENE: Research Funding; JAZZ: Honoraria, Research Funding; TAKEDA: Honoraria. Fenaux: JAZZ: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria. Robin: NEOVII MEDAC NOVARTIS: Research Funding.

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

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3085-3085 ◽  
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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