Additional Prognostic Value of Bone Marrow Histology in Patients Subclassified According to the International Prognostic Scoring System for Myelodysplastic Syndromes

2003 ◽  
Vol 21 (2) ◽  
pp. 273-282 ◽  
Author(s):  
E. Verburgh ◽  
R. Achten ◽  
B. Maes ◽  
A. Hagemeijer ◽  
M. Boogaerts ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
Prognostic Value ◽  
Predictive Power ◽  
Intensive Therapy ◽  
International Prognostic Scoring System ◽  
Prognostic System ◽  
Bone Marrow Histology

Purpose: The most recent and powerful prognostic instrument established for myelodysplastic syndromes (MDS) is the International Prognostic Scoring System (IPSS), which is primarily based on medullary blast cell count, number of cytopenias, and cytogenetics. Although this prognostic system has substantial predictive power in MDS, further refinement is necessary, especially as far as lower-risk patients are concerned. Histologic parameters, which have long proved to be associated with outcome, are promising candidates to improve the prognostic accuracy of the IPSS. Therefore, we assessed the additional predictive power of the presence of abnormally localized immature precursors (ALIPs) and CD34 immunoreactivity in bone marrow (BM) biopsies of MDS patients. Patients and Methods: Cytogenetic, morphologic, and clinical data of 184 MDS patients, all from a single institution, were collected, with special emphasis on the determinants of the IPSS score. BM biopsies of 173 patients were analyzed for the presence of ALIP, and CD34 immunoreactivity was assessable in 119 patients. Forty-nine patients received intensive therapy. Results: The presence of ALIP and CD34 immunoreactivity significantly improved the prognostic value of the IPSS, with respect to overall as well as leukemia-free survival, in particular within the lower-risk categories. In contrast to the IPSS, both histologic parameters also were predictive of outcome within the group of intensively treated MDS patients. Conclusion: Our data confirm the importance of histopathologic evaluation in MDS and indicate that determining the presence of ALIP and an increase in CD34 immunostaining in addition to the IPSS score could lead to an improved prognostic subcategorization of MDS patients.

Arsenic Trioxide in Patients With Myelodysplastic Syndromes: A Phase II Multicenter Study

2006 ◽  
Vol 24 (16) ◽  
pp. 2465-2471 ◽  
Author(s):  
Norbert Vey ◽  
Andre Bosly ◽  
Agnes Guerci ◽  
Walter Feremans ◽  
Herve Dombret ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
International Prognostic Scoring System ◽  
Risk Category ◽  
Moderate Activity ◽  
Loading Dose ◽  
Median Response ◽  
System Risk

Purpose Evaluation of the safety and efficacy of arsenic trioxide in patients with myelodysplastic syndromes (MDS). Patients and Methods MDS patients diagnosed according to standard French-American-British criteria received a loading dose of 0.3 mg/kg per day of arsenic trioxide for 5 days followed by a maintenance dose of 0.25 mg/kg arsenic trioxide twice weekly for 15 weeks. Patients were divided into two cohorts: lower-risk MDS (International Prognostic Scoring System risk category low or intermediate 1) and higher-risk MDS (International Prognostic Scoring System risk category intermediate 2 or high). Modified International Working Group criteria were used for response evaluation. Results Of 115 patients enrolled and treated in the study, 67% of patients were transfusion dependent at baseline; median age was 68 years. Most treatment-related adverse events were mild to moderate. The overall rate of hematologic improvement (intent-to-treat) was 24 (19%) of 115, including one complete and one partial response in the higher-risk cohort. The hematologic response rates were 13 (26%) of 50 and 11 (17%) of 64 in patients with lower-risk and higher-risk MDS, respectively. Major responses were observed in all three hematologic lineages; 16% of RBC transfusion-dependent patients and 29% of platelet transfusion-dependent patients became transfusion independent. At data cut off, the median response duration was 3.4 months, with responses ongoing in nine patients. Conclusion Arsenic trioxide treatment consisting of an initial loading dose followed by maintenance therapy has moderate activity in MDS, inducing hematologic responses in both lower- and higher-risk patients. This activity combined with a manageable adverse effect profile warrants the additional study of arsenic trioxide, particularly in combination therapy, for the treatment of patients with MDS.

scholarly journals Validation of Low Risk Prognostic Scoring System (LR-PSS) in Patients with Lower Risk IPSS-R Myelodysplastic Syndrome. Results from a Single Center

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4270-4270
Author(s):  
Montserrat Arnan Sangerman ◽  
Helena Pomares ◽  
Esther Alonso ◽  
Mercedes Galiano ◽  
Maite Encuentra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Scoring System ◽  
Lower Risk ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Low Risk ◽  
Acute Myeloid

Background: Myelodysplastic syndrome (MDS) therapeutic decisions have been traditionally based on the International Prognostic Scoring System (IPSS) (Greenberg et al, Blood 1997) and IPSS-R (Greenberg et al, Blood 2012). Recently, next-generation sequencing genetics has been incorporated into management of MDS, however its use is limited in routine clinical practice. Current prognostic models do not allow the identification of patients with low risk disease (low or intermediate-1 IPSS) and poor prognosis, who could benefit from an early intervention. Garcia-Manero et al (Leukemia 2008) described a specific prognostic scoring system for this subgroup of patients (LR-PSS) based on age ≥60 years, hemoglobin <10g/dl, platelet count <50k/uL or 50-200k/uL, bone marrow blasts ≥4% and unfavorable cytogenetics (non-del(5q), non-diploid). This LR-PSS score system enables the stratification of low risk MDS patients into 3 different risk categories; interestingly, the third category identifies a subgroup of patients with a median overall survival (OS) similar to that of patients classified as intermediate-2 and high risk IPSS. Besides, the IPSS-R described by Greenberg et al (Blood 2012) has demonstrated a strong prognostic value for OS and LFS as compared to the IPSS when applied to different independent series of MDS patients. The prognostic impact of the LR-PSS has not been analyzed in MDS patients with very low-, low- and intermediate IPSS-R scores. Aim: To analyze the prognostic value of Low Risk Prognostic Scoring System(LR-PSS) in a population of lower risk MDS patients (very low, low and intermediate IPSS-R) analyzing as endpoints overall survival (OS) and leukemia free survival (LFS). Methods: A total of 890 consecutive patients with MDS (01/1992-7/2018) diagnosed at the Catalan Institute of Oncology in Barcelona were included in the study. 539 (60%) had available cytogenetics and therefore, IPSS-R could be assessed. 474 (88%) patients were classified as very low, low and intermediate IPSS-R and were included in the study. Results: 178 (37.6%) patients were classified as very low, 219 (46.2%) low and 77 (16.2%) intermediated IPSS-R risk MDS. Median age at diagnosis was 73 years (range 32-101). 332 (70%) were male. According to the 2008 WHO classification, 2.5% CRDU, 7.4% RA, 42.2% RCMD, 13.7% RAEB‐1, 3.6% RAEB‐2, 26.4% CMML and 4.2% MDS‐U with isolated 5q deletion. At diagnosis, median hemoglobin, platelet and bone marrow blast were 11.6 g/dL (5.5-17.1), 157 x109/L (1-1492) and 2 % (0-17), respectively. 84 (17.7%) patients had unfavorable LR-PSS cytogenetics at diagnosis. Median follow up time for survivors was 5.4 years (range 0.25-23.8). At the time of last follow up, 58.4 % (277) had died and 71 (15%) had progressed to acute myeloid leukemia. When the LR-PSS was applied to the very low, low and intermediate IPSS-R subgroups, three well-differentiated prognostic categories could be identified: 103 patients (21.7%) category 1 (scores 0-2); 330 (69.6%) patients category 2 (scores 3-4) and 41 (8.7%) patients category 3 (scores 5-7) with significant different OS and LFS. Median OS for categories 1, 2 and were 7.1 years (95% CI 4.9-9.2), 5.7 years (95% CI 4.7-6.7) and 2.8 years (95% CI 2.1-3.6), p<0.001 (Figure 1), respectively. Rate of progression to acute myeloid leukemia was 10% (10/99), 15% (48/323) and 27% (11/411) for categories 1, 2 and 3, respectively. Summary/Conclusion: When applied to a low risk (very low, low and intermediate) IPSS-R cohort of MDS population, LR-PSS identifies a subgroup of patients with a significantly worse prognosis who could benefit from an early treatment intervention. Disclosures Sureda: Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead: Consultancy; Roche: Honoraria; BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau.

Validating the Lower-Risk MD Anderson Prognostic Scoring System (LR-PSS) and the Revised International Prognostic Scoring System (IPSS-R) for Patients with Myelodysplastic Syndromes

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1720-1720 ◽  
Author(s):  
Mikkael A. Sekeres ◽  
Paul Elson ◽  
Ramon V. Tiu ◽  
Yogen Saunthararajah ◽  
Anjali S. Advani ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
Goodness Of Fit ◽  
Cleveland Clinic ◽  
Information Criteria ◽  
Rank Test ◽  
International Prognostic Scoring System ◽  
Multivariable Analyses ◽  
Md Anderson

Abstract Abstract 1720 Background: The myelodysplastic syndromes are commonly divided into lower- and higher-risk subtypes depending on blast percentage and International Prognostic Scoring System (IPSS) score (0–1.0, low or Int-1, median overall survival (OS) 3.5–5.7 years). Because the IPSS is limited in its ability to identify poor prognosis lower-risk patients (pts), a prognostic scoring system specifically for lower-risk MDS pts (LR-PSS) was developed (Garcia-Manero Leukemia 2008) at MD Anderson (MDA), based on unfavorable (non-del(5q), non–diploid) cytogenetics, hemoglobin (hgb) <10g/dl, platelet count (plt) <50 k/uL or 50–200k/uL, bone marrow blast %≥4, and age ≥60 years. The IPSS-R (Greenberg Leuk Res 2011) improves upon the IPSS using novel cytogenetics classifications (Schanz EHA 2010) and a neutrophil cut-off of 800 k/uL. We validated the LR-PSS and the IPSS-R in a separate cohort of lower-risk MDS patients seen at Cleveland Clinic (CC) or at MDA not included in LR-PSS development. Methods: Of 1293 MDS patients identified at CC or MDA from 1991–2010, 664 had lower-risk disease and adequate data for analyses. OS was calculated from first date seen at either institution. The Kaplan–Meier method was used to estimate median OS. Univariable analyses were performed using the log-rank test; multivariable analyses used a Cox proportional hazards model stratified by treatment center. Harrell's c index and the Akaike information criteria (AIC) were used to assess the discriminatory power of the models and relative goodness of fit, respectively. Results: Comparing CC to MDA, baseline values were similar except median age: 70 vs. 67 years (p=.02); time since diagnosis: 2.7 vs. 1.1 months (p<.0001); hgb <10: 51% vs. 43% (p=.05); plt <50k/uL: 30 vs. 24% (p=.06); ANC <1.5 k/uL: 27% vs. 36% (p=.01); blasts <4%: 75% vs. 65% (p=.003); WHO classification RA/RARS/RCMD/CMML: 11/15/26/12% vs. 16/9/45/0% (p<.0001). Cytogenetics were diploid: 61% vs. 66%; del(5q): 9% vs. 2%; del(20q): 3% vs. 5%; -Y: 4% vs. 2%, respectively (p=.5). Median OS was 36.8 months (95% C.I. 33–45) and median follow-up of patients still alive was 13.9 months (range 0.01–155). LR-PSS and IPSS-R classifications for CC and MDA Pts and OS are in Table 1 and Figure 1. In univariable analyses, The IPSS, LR-PSS, and IPSS-R were all predictive of OS (p=.002, <.0001, and <.0001, respectively). Multivariable analyses confirmed the overall predictive abilities of the prognostic tools and of Hgb, plt, age, and IPSS/IPSS-R cytogenetics (all p≤.03). Compared to the IPSS-R, the LR-PSS had the higher (better) Harrell's c value (.64 vs.63) and lower (better) AIC (2518 vs. 2525). The LR-PSS upstaged 156 pts (25%) from IPSS low or Int-1 to LR-PSS Category 3, and downstaged 47 pts (12%) from Int-1 to Category 1. The IPSS-R upstaged 164 pts (27%) from IPSS low or Int-1 to IPSS-R Categories ≥Intermediate, and downstaged 5 pts (1%) from Int-1 to Very Good. Conclusions: The LR-PSS and IPSS-R are valid tools for distinguishing among pts previously thought to have lower-risk disease by the IPSS, and identifying those who have better and worse survival. This latter group of pts may benefit from earlier interventions with disease-modifying therapies, and should be considered in trials targeting higher-risk MDS pts. The LR-PSS appears to provide slightly better prognostic information. Disclosures: Sekeres: Celgene: Consultancy, Honoraria, Speakers Bureau. Maciejewski:Celgene: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Validation of a Prognostic Model and the Impact of Mutations in Patients With Lower-Risk Myelodysplastic Syndromes

2012 ◽  
Vol 30 (27) ◽  
pp. 3376-3382 ◽  
Author(s):  
Rafael Bejar ◽  
Kristen E. Stevenson ◽  
Bennett A. Caughey ◽  
Omar Abdel-Wahab ◽  
David P. Steensma ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
Prognostic Model ◽  
Prognostic Significance ◽  
International Prognostic Scoring System ◽  
Disease Modifying Therapy ◽  
Md Anderson ◽  
The Impact

Purpose A subset of patients with myelodysplastic syndromes (MDS) who are predicted to have lower-risk disease as defined by the International Prognostic Scoring System (IPSS) demonstrate more aggressive disease and shorter overall survival than expected. The identification of patients with greater-than-predicted prognostic risk could influence the selection of therapy and improve the care of patients with lower-risk MDS. Patients and Methods We performed an independent validation of the MD Anderson Lower-Risk Prognostic Scoring System (LR-PSS) in a cohort of 288 patients with low- or intermediate-1 IPSS risk MDS and examined bone marrow samples from these patients for mutations in 22 genes, including SF3B1, SRSF2, U2AF1, and DNMT3A. Results The LR-PSS successfully stratified patients with lower-risk MDS into three risk categories with significant differences in overall survival (20% in category 1 with median of 5.19 years [95% CI, 3.01 to 10.34 years], 56% in category 2 with median of 2.65 years [95% CI, 2.18 to 3.30 years], and 25% in category 3 with median of 1.11 years [95% CI, 0.82 to 1.51 years]), thus validating this prognostic model. Mutations were identified in 71% of all samples, and mutations associated with a poor prognosis were enriched in the highest-risk LR-PSS category. Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS. Only EZH2 mutations retained prognostic significance in a multivariable model that included LR-PSS and other mutations (hazard ratio, 2.90; 95% CI, 1.85 to 4.52). Conclusion Combining the LR-PSS and EZH2 mutation status identifies 29% of patients with lower-risk MDS with a worse-than-expected prognosis. These patients may benefit from earlier initiation of disease-modifying therapy.

scholarly journals Eritropoietina Sérica como Marcador Prognóstico em Síndrome Mielodisplásica

2015 ◽  
Vol 28 (6) ◽  
pp. 720 ◽  
Author(s):  
Emília Cortesão ◽  
Rita Tenreiro ◽  
Sofia Ramos ◽  
Marta Pereira ◽  
Paula César ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Acute Leukaemia ◽  
Scoring System ◽  
De Novo ◽  
International Prognostic Scoring System ◽  
Lower Survival ◽  
Prognostic Indices ◽  
Serum Erythropoietin

<strong>Introduction:</strong> This myelodysplastic syndromes are a heterogeneous entity characterized by dysplasia, hypercellular bone marrow, cytopenias and risk of transformation to acute leukaemia. Prognostic factors, such as bone marrow fibrosis, lactate dehydrogenase and β2-microglobulin elevation have been described, but treatment is mainly based in the International Prognostic Scoring System.<br /><strong>Material and Methods:</strong> Our aim was to analyze serum´s erythropoietin at diagnosis in de novo myelodysplastic syndromes patients, through its impact in overall survival and possible implementation as prognostic marker. Clinical and laboratorial data from 102 patients with de novo myelodysplastic syndromes diagnosed between October/2009 and March/2014 were collected. Survival analysis was performed according to serum erythropoietin level stratification, using Kaplan-Meier methodology.<br /><strong>Results:</strong> Our 102 patients had a median age of 74 years, with a male:female ratio of 0.8. Mean erythropoietin was significantly lower in refractory cytopenia with unilineage dysplasia patients in contrast with the higher values observed in 5q- syndrome (p &lt; 0.05). Eleven patients progressed to acute leukaemia; these have higher mean erythropoietin values (p &lt; 0.05). In addition, elevated serum erythropoietin was associated with lower survival rates (p = 0.0336). Predictive value of serum erythropoietin was maintained after Cox regression adjustment. In multivariate analysis, serum erythropoietin is an independent survival predictor (p &lt; 0.001).<br /><strong>Discussion:</strong> Serum erythropoietin is a predictive factor for response to therapy with subcutaneous erythropoietin, and patients with myelodysplastic syndromes with higher values of erythropoietin have poorer response to administration of erythropoietin even at higher doses. Our sample shows that serum erythropoietin also has prognostic value, and in all myelodysplastic syndromes subtypes. Moreover, alone or in combination with other factors or prognostic indices, erythropoietin may enhance the prognostic indices such as the International Prognostic Scoring System, since high levels are associated with progression to acute leukemia and hence lower survival.<br /><strong>Conclusion:</strong> This study suggests that increased erythropoietin levels at diagnosis can by itself be a poor prognosis factor in<br />myelodysplastic syndromes patients, with higher values in patients with progression to acute leukaemia and decreased overall survival.

scholarly journals Coalesced Multicentric Analysis of 2,351 Patients With Myelodysplastic Syndromes Indicates an Underestimation of Poor-Risk Cytogenetics of Myelodysplastic Syndromes in the International Prognostic Scoring System

2011 ◽  
Vol 29 (15) ◽  
pp. 1963-1970 ◽  
Author(s):  
Julie Schanz ◽  
Christian Steidl ◽  
Christa Fonatsch ◽  
Michael Pfeilstöcker ◽  
Thomas Nösslinger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
International Prognostic Scoring System ◽  
Prognostic Impact ◽  
Bone Marrow Blast ◽  
Poor Risk ◽  
Blast Count ◽  
The Impact

Purpose The International Prognostic Scoring System (IPSS) remains the most commonly used system for risk classification in myelodysplastic syndromes (MDSs). The IPSS gives more weight to blast count than to cytogenetics. However, previous publications suggested that cytogenetics are underweighted in the IPSS. Here we investigate the prognostic impact of cytogenetic subgroups compared with that of bone marrow blast count in a large, multicentric, international patient cohort. Patients and Methods In total, 2,351 patients with MDS who have records in the German-Austrian and the MD Anderson Cancer Center databases were included and analyzed in univariate and multivariate models regarding overall survival and risk of transformation to acute myeloid leukemia (AML). The data were analyzed separately for patients treated with supportive care without specific therapy, with AML-like chemotherapy, or with other therapy regimens (low-dose chemotherapy, demethylating agents, immune modulating agents, valproic acid, and cyclosporine). Results The prognostic impact of poor-risk cytogenetic findings (as defined by the IPSS classification) on overall survival was as unfavorable as an increased (> 20%) blast count. The hazard ratio (compared with an abnormal karyotype or a bone marrow blast count < 5%) was 3.3 for poor-risk cytogenetics, 4.8 for complex abnormalities harboring chromosomes 5 and/or 7, and 3.1 for a blast count of 21% to 30% (P < .01 for all categories). The predictive power of the IPSS cytogenetic subgroups was unaffected by type of therapy given. Conclusion The independent prognostic impact of poor-risk cytogenetics on overall survival is equivalent to the impact of high blast counts. This finding should be considered in the upcoming revision of the IPSS.

scholarly journals Mutation Status and Burden Can Improve Prognostic Prediction of Patients with Lower-Risk Myelodysplastic Syndromes

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3008-3008
Author(s):  
Lingxu Jiang ◽  
Yingwan Luo ◽  
Jie Jin ◽  
Hongyan Tong
Keyword(s):  
Myelodysplastic Syndromes ◽  
Scoring System ◽  
Lower Risk ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Prognostic Models ◽  
Molecular Profile ◽  
International Prognostic Scoring System ◽  
Mutation Status ◽  
Prognostic Prediction

Patients with lower-risk myelodysplastic syndromes (LR-MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter-individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS-relevant genes in 159 patients with LR-MDS using next-generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P=0.001), RUNX1 (P=0.031), EZH2 (P=0.049), TP53 (P=0.016), SRSF2 (P=0.046), JAK2 (P=0.040), and IDH2 (P=0.035). We also found significantly shorter OS in patients with a TET2 variant allele frequency (VAF) ≥18% versus those with either a TET2 VAF <18% or without TET2 mutations (median: 20.4 vs. 47.8 months; P=0.020; HR=2.183, 95%CI: 1.129-4.224). After adjustment for the IPSS, shorter OS was associated with mutation status of ASXL1 (P<0.001; HR=4.306, 95%CI: 2.144-8.650), TP53 (P=0.004; HR=4.863, 95%CI: 1.662-14.230) and JAK2 (P=0.002; HR=5.466, 95%CI: 1.848-16.169), as well as a TET2 VAF ≥18% (P=0.008; HR=2.492, 95%CI: 1.273-4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P<0.001). A novel prognostic scoring system based on the IPSS and the presence/absence of the 4 independent mutational factors further stratified LR-MDS patients into three prognostically different groups (P<0.001).The newly developed scoring system re-defined 10.1% (16/159) of patients as higher-risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of IPSS with mutation status/burden of certain MDS-relevant genes may improve the prognostication of patients with LR-MDSand could help identify those with worse-than-expected prognosis for more aggressive treatment. Figure Disclosures No relevant conflicts of interest to declare.

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