The prognostic value of monosomal karyotype (MK) in higher‐risk patients with myelodysplastic syndromes treated with 5‐Azacitidine: A retrospective analysis of the Hellenic (Greek) Myelodysplastic syndromes Study Group

In this study, we investigated the incidence and prognostic impact of monosomal karyotype (MK) in 405 higher‐risk Myelodysplastic Syndromes (MDS) patients treated with 5‐AZA. The MK was present in 66 out of 405 (16.3%) patients, most of whom had complex karyotype (CK). MK was strongly associated with CK and the cytogenetic risk defined according to IPSS‐R, as well as with high‐risk disease, according to IPSS (P = .029), IPSS‐R (P < .001), and WPSS (P < .001) classification systems. The overall response rate (ORR) was not different between MK+ and MK– patients (46.6% vs. 46.2%). At 28 months median follow‐up, the median duration of response was 11 months in the entire cohort, 9.5 months in MK+ patients and 11 months in MK‐patients (P = .024). The estimated median time to transformation to acute myeloid leukemia for MK+ patients was 17 months vs. 23 months for MK– patients (P = .025). The estimated median OS for MK+ patients was 12 months vs. 18 months for MK– patients (P < .001). Multivariate Cox regression analysis revealed that performance status (P < .001), IPSS‐R (P < .001), and MK (P = .002) were independently associated with overall survival (OS). In a subgroup consisting of high and very‐high risk patients according to IPSS‐R, MK– patients showed better OS rates compared to MK+ patients (estimated median OS: 17 months vs. 12 months, P = .002). In conclusion, we found that MK is associated with reduced OS in patients with higher‐risk MDS treated with 5‐AZA. Furthermore, we showed that in MDS with high or very‐high IPSS‐R risk score, MK can further distinguish patients with worse outcome.     

Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population‐based setting: a report from the Swedish MDS register

The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population‐based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population‐based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS‐R) and the World Health Organization (WHO) Classification‐based Prognostic Scoring System (WPSS). We also present population‐based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy‐related MDS (t‐MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2·9 per 100 000 inhabitants. IPSS‐R had a significantly better prognostic power than IPSS (P < 0·001). There was a trend for better prognostic power of IPSS‐R compared to WPSS (P = 0·05) and for WPSS compared to IPSS (P = 0·07). IPSS‐R was superior to both IPSS and WPSS for patients aged ≤70 years. Patients with t‐MDS had a worse outcome compared to de novo MDS (d‐MDS), however, the validity of the prognostic scoring systems was comparable for d‐MDS and t‐MDS. In conclusion, population‐based studies are important to validate prognostic scores in a ‘real‐world’ setting. In our nationwide cohort, the IPSS‐R showed the best predictive power.     

Monosomal karyotype improves IPSS‐R stratification in MDS and AML patients treated with Azacitidine

IPSS‐R classifies cytogenetic abnormalities into five prognostic groups for survival. Monosomal karyotype (MK) is not a subgroup of IPSS‐R. Additional prognostic information from MK in poor and very poor karyotype has been recently shown. The aim of our study was to determine the prognostic value of IPSS‐R and MK for response and survival in AZA‐treated high‐risk MDS and AML with 20–30% of blasts patients. The study population included 154 patients who were classified according to IPSS‐R. IPSS‐R was not predictive of response (intermediate, 64%; poor, 44%; very poor, 56%; P = 0.28) or survival (intermediate, 25 months; poor, 12 months; very poor, 11 months; P = 0.14). Twenty‐one patients (15%) presented with MK and had a median OS of 9 months. Patients with a very high IPSS‐R score without MK had a median OS of 15 months, while patients with a high IPSS‐R score without MK had a median OS of 13 months (P = 0.18). We reclassified patients into the following three groups to include MK status: very high (MK only; OS median: 9 months), high (very high IPSS‐R without MK and high IPSS‐R without MK; OS median: 14 months) and intermediate (OS median: 25 months). As in recent publication including MK prognostic, we confirmed that this classification was predictive for survival in AZA treated patients (P = 0.008). IPSS‐R failed to discriminate between the prognostic subgroups. Stratification with MK has value in the prognosis of our cohort of AZA‐treated patients. Am. J. Hematol. 88:780–783, 2013. © 2013 Wiley Periodicals, Inc.     

Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy,adjusting for patient‐related factors and measuring from time of first red blood cell transfusion dependence: an MDS‐CAN analysis

Analyses suggest iron overload in red blood cell (RBC) transfusion‐dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient‐related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient‐related factors. TD International Prognostic Scoring System (IPSS) low and intermediate‐1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease‐modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non‐ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P < 0·0001). By multivariate analysis, not receiving ICT independently predicted inferior OS, (hazard ratio for death 2·0, P = 0·03). In matched pair analysis, OS remained superior for ICT patients (P = 0·02). In this prospective, non‐randomized analysis, receiving ICT was associated with superior OS in lower IPSS risk MDS, adjusting for age, frailty, comorbidity, disability, revised IPSS, TD severity, time to TD and receiving disease‐modifying agents. This provides additional evidence that ICT may confer clinical benefit.     

IPSS‐R in 555 Taiwanese patients with primary MDS: Integration of monosomal karyotype can better risk‐stratify the patients

The revised International Prognostic Scoring System (IPSS‐R) was recently developed to better assess the clinical outcome of adult patients with myelodysplastic syndrome (MDS). In this study, we aimed to investigate the prognostic impact of this new risk model on 555 MDS patients in Taiwan. Generally, the IPSS‐R could discriminate MDS patients regarding risk of leukemia evolution and overall survival in our cohort and it further refined prognostic stratification in all IPSS risk categories. However, we could not find the inter‐group difference between IPSS‐R very low and low risk subgroups in both leukemia‐free survival (LFS) and overall survival (OS). IPSS‐R couldn't distinguish the prognosis between very good and good and between good and intermediate risk cytogenetic categories in OS, and between very good and good and between intermediate and poor cytogenetic‐risk categories in LFS, either. On the other hand, incorporation of monosomal karyotype (MK) into IPSS‐R could further stratify MDS patients with higher‐risk IPSS‐R (intermediate, high and very high risk) into four groups, rather than three groups, with different OS (P < 0.001). Intriguingly, patients receiving allogeneic hematopoietic stem cell transplantation had longer survival than those without in the IPSS‐R high and very high, but not other risk groups. Similarly, patients treated with hypomethylating agents had better survival than those not in the IPSS‐R very high risk group. In conclusion, IPSS‐R can risk‐stratify MDS patients in Taiwan but with some limitations, especially in very low risk category, and MK has additional prognostic value in discriminating MDS patients with higher‐risk IPSS‐R. Am. J. Hematol. 89:E142–E149, 2014. © 2014 Wiley Periodicals, Inc.     

Patient‐related factors independently impact overall survival in patients with myelodysplastic syndromes: an MDS‐CAN prospective study

Little is known about the effects of frailty, disability and physical functioning on the clinical outcomes for myelodysplastic syndromes (MDS). We investigated the predictive value of these factors on overall survival (OS) in 445 consecutive patients with MDS and chronic monomyelocytic leukaemia (CMML) enrolled in a multi‐centre prospective national registry. Frailty, comorbidity, instrumental activities of daily living, disability, quality of life, fatigue and physical performance measures were evaluated at baseline and were added as covariates to conventional MDS‐related factors as predictors of OS in Cox proportional hazards models. The median age was 73 years, and 79% had revised International Prognostic Scoring System (IPSS‐R) risk scores of intermediate or lower. Frailty correlated only modestly with comorbidity. OS was significantly shorter for patients with higher frailty and comorbidity scores, any disability, impaired grip strength and timed chair stand tests. By multivariate analysis, the age‐adjusted IPSS‐R, frailty (Hazard ratio 2·7 (95% confidence interval [CI] 1·7–4·2), P < 0·0001) and Charlson comorbidity score (Hazard ratio 1·8 (95% CI 1·1–2·8), P = 0·01) were independently prognostic of OS. Incorporation of frailty and comorbidity scores improved risk stratification of the IPSS‐R by 30% and 5%, respectively. These data demonstrate for the first time, the importance of considering frailty in prognostic models and a potential target for therapeutic intervention in optimizing clinical outcomes in older MDS patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02537990.     

Validation of the revised International Prognostic Scoring System in treated patients with myelodysplastic syndromes

The International Prognostic Scoring System (IPSS) was recently revised (IPSS‐R) under the auspices of the MDS Foundation as a collaborative international effort to refine its prognostic power. Our purpose was to externally validate this new risk model using a large single‐institution cohort, determine its prognostic power in patients receiving active treatment, and explore its utility in guiding therapeutic decisions. Data were collected retrospectively from our myelodysplastic syndrome (MDS) database and verified by chart review. Of the data available for 1,088 patients, 152 (14%), 353 (32%), 237 (22%), 190 (18%), and 156 (14%) patients were classified as very low, low, intermediate, high, and very high risk, respectively, with median overall survival (OS) of 90 (95%CI 71–109), 54 (95%CI 50–59), 34 (95%CI 26–43), 21 (95%CI 17–25), and 13 months (95%CI 11–15), respectively (P < 0.005). We found that the IPSS‐R further refined prognostic discrimination in all IPSS risk categories, particularly in the intermediate 1 and 2 groups. Among high and very high IPSS‐R patients receiving azacitidine, OS was significantly improved versus patients not receiving azacitidine, with corresponding median OS of 25 versus 18 months (P = 0.028) and 15 versus 9 months (P = 0.005), respectively. Similarly, patients with IPSS‐R high‐ and very high‐risk disease who underwent allogeneic hematopoietic stem cell transplantation had significantly improved OS versus nontransplant approaches (P < 0.005). High and very high IPSS‐R patients derived a survival advantage from disease‐modifying therapies. Our data validate the prognostic value of the proposed IPSS‐R and show that its refined IPSS prognostic discrimination can be applied to actively treated patients. Am. J. Hematol. 88:566–570, 2013. © 2013 Wiley Periodicals, Inc.     

Is International Prognostic Scoring System (IPSS) still standard in predicting prognosis in patients with myelodysplastic syndrome? External validation of the WHO Classification‐Based Prognostic Scoring System (WPSS) and comparison with IPSS

Background: This study was undertaken to evaluate the prognostic value of the WHO Classification‐Based Prognostic Scoring System (WPSS) and to compare it with that of the International Prognostic Scoring System (IPSS). Patients and methods: 149 patients de novo diagnosed as having myelodysplastic syndrome between December 1994 and February 2007, were evaluated retrospectively. Results: WPSS presented an excellent method for risk‐stratifying patients into five subgroups, with different risks of death and leukaemic evolution. On univariate analysis, three components of WPSS – cytogenetic risk, WHO category and transfusion dependency – had good correlations with overall survival (OS) and time to leukaemic evolution (TTL). However, one component of IPSS – number of peripheral cytopenias – did not correlate with OS or TTL. WPSS could distinguish the truly low‐risk patients (very low) who had an excellent long‐term survival with rare leukaemic evolution, while IPSS could not. These patients should be managed with clinical observation and delayed treatment strategies. Furthermore, on multivariate analysis for OS, WPSS was found to be an independent prognostic factor for survival along with age [P = 0.04; hazard ratio (HR) = 1.71; 95% confidence interval (CI) 1.02–2.85] and lactate dehydrogenase (LDH) (P = 0.002; HR = 2.47; 95% CI 1.41–4.31). On the other hand, the prognostic significance of IPSS was not confirmed. Conclusion: These results suggest that the WPSS might be a more powerful predictor of prognosis than IPSS and that independent validation of several other, larger data sets should be necessary.     

Enumerating bone marrow blasts from nonerythroid cellularity improves outcome prediction in myelodysplastic syndromes and permits a better definition of the intermediate risk category of the Revised International Prognostic Scoring System (IPSS‐R)

The Revised International Prognostic Scoring System (IPSS‐R) has been recognized as the score with the best outcome prediction capability in MDS, but this brought new concerns about the accurate prognostication of patients classified into the intermediate risk category. The correct enumeration of blasts is essential in prognostication of MDS. Recent data evidenced that considering blasts from nonerythroid cellularity (NECs) improves outcome prediction in the context of IPSS and WHO classification. We assessed the percentage of blasts from total nucleated cells (TNCs) and NECs in 3924 MDS patients from the GESMD, 498 of whom were MDS with erythroid predominance (MDS‐E). We assessed if calculating IPSS‐R by enumerating blasts from NECs improves prognostication of MDS. Twenty‐four percent of patients classified into the intermediate category were reclassified into higher‐risk categories and showed shorter overall survival (OS) and time to AML evolution than those who remained into the intermediate one. Likewise, a better distribution of patients was observed, since lower‐risk patients showed longer survivals than previously whereas higher‐risk ones maintained the outcome expected in this poor prognostic group (median OS < 20 months). Furthermore, our approach was particularly useful for detecting patients at risk of dying with AML. Regarding MDS‐E, 51% patients classified into the intermediate category were reclassified into higher‐risk ones and showed shorter OS and time to AML. In this subgroup of MDS, IPSS‐R was capable of splitting our series in five groups with significant differences in OS only when blasts were assessed from NECs. In conclusion, our easy‐applicable approach improves prognostic assessment of MDS patients.     

Comparing the prognostic value of risk stratifying models for patients with lower‐risk myelodysplastic syndromes: Is one model better?

Some patients classified as having lower‐risk (LR)‐disease by the International Prognostic Scoring System (IPSS) fare more poorly than predicted. We examined the prognostic utility of IPSS, the MD Anderson LR‐Prognostic System (LR‐PSS), and the revised IPSS (IPSS‐R) in a large cohort of patients classified as having IPSS LR‐MDS in the MDS Clinical Research Consortium database. Actual overall survival (OS) was assessed in patients with IPSS LR‐MDS (i.e. low and intermediate‐1) using Kaplan–Meier methods. Harrell's c index (HCI) and Akaike information criteria (AIC) were used to compare the models. Median OS of 1,140 eligible patients was 47 months (95% CI, 44–52). Median follow‐up was 62 months. HCI values indicating the discriminatory power of the models (higher is better) were better for LR‐PSS (0.74, 95% CI, 0.70–0.78) than IPSS‐R (0.64, 95% CI, 0.60–0.67) and IPSS (0.64, 95% CI, 0.60–0.68). Similarly, AIC values indicating the goodness of the fit were better for LR‐PSS than IPSS‐R and IPSS (8,110, 8,147, and 8,150, respectively, lower is better). LR‐PSS assigned 25.1% and 37.4% of patients with IPSS LR‐MDS into LR‐PSS Category 3 and IPSS‐R Categories ≥Intermediate, respectively. Of 291 patients (25.5%) who survived ≤24 months from diagnosis, only 37.1% and 45% were classified as LR‐PSS category 3 and IPSS‐R categories ≥Intermediate, respectively (P = 0.06). While both LR‐PSS and IPSS‐R distinguish groups with varied survival outcome among patients with IPSS LR‐MDS, both tools fail to identify a significant subset with poor OS. Future studies should assess whether patients identified as at increased risk will benefit from earlier interventions with disease‐modifying therapies. Am. J. Hematol. 90:1036–1040, 2015. © 2015 Wiley Periodicals, Inc.     

Impact of lenalidomide use among non‐transfusion dependent patients with myelodysplastic syndromes

Chemotherapies approved for defined subgroups promise personalized oncologic care, but their off‐label impact is unclear. Lenalidomide is approved for lower‐risk, transfusion‐dependent (TD) myelodysplastic syndromes (MDS) with del(5q), but frequently used in MDS outside this indication. We characterized lenalidomide use and outcomes among non‐TD patients with MDS. Patients 65 or older diagnosed with MDS between 2007 and 2013 were identified using SEER; linked Medicare claims were evaluated for transfusions, lenalidomide use, and incident toxicities. TD was ≥2 transfusion episodes within an 8‐week period; responses were transfusion independence (TI) and ≥50% transfusion reduction (minor response). We compared overall survival for non‐TD patients receiving lenalidomide versus those not receiving lenalidomide, matched on disease and patient characteristics. We identified 676 patients who had received lenalidomide, including 275 (40.7%) TD and 401 (59.3%) non‐TD; 18.5% (125/676) had zero claims for RBC transfusion prior to receiving lenalidomide. Incident toxicities among patients prescribed lenalidomide were similar in TD and non‐TD groups, except incident thromboembolic events were higher among non‐TD patients (10.8% vs. 6.0%, P = .04). Comparing 191 non‐TD patients receiving lenalidomide within 6 months of MDS diagnosis to risk‐matched MDS controls, lenalidomide was not associated with improved OS (P = .78). Among TD patients (n = 275), 31% achieved TI, and 30% achieved minor hematologic response, with a median time to TI of 4.1 weeks. In conclusion, we confirmed the benefit of lenalidomide among TD patients with MDS; however, many non‐TD patients also received lenalidomide. These patients experienced accompanying toxicity without evidence of benefit in terms of transfusion needs or overall survival.     

Acquisition of cytogenetic abnormalities in patients with IPSS defined lower‐risk myelodysplastic syndrome is associated with poor prognosis and transformation to acute myelogenous leukemia

We hypothesized that the dynamic acquisition of cytogenetic abnormalities (ACA) during the follow up of myelodysplastic syndromes (MDS) could be associated with poor prognosis. We conducted a retrospective analysis of 365 patients with IPSS low or intermediate‐1 risk MDS who had at least two consecutive cytogenetic analyses during the follow up. Acquisition of cytogenetic abnormalities was detected in 107 patients (29%). The most frequent alteration involved chromosome 7 in 21% of ACA cases. Median transformation‐free and overall survival for patients with and without ACA were 13 vs. 52 months (P = 0.01) and 17 vs. 62 months (P = 0.01), respectively. By fitting ACA as a time‐dependent covariate, multivariate Cox regression analysis showed that patients with ACA had increased risk of transformation (HR = 1.40; P = 0.03) or death (HR = 1.45; P = 0.02). Notably, female patients with therapy‐related MDS (t‐MDS) had an increased risk of developing ACA (OR = 5.26; P < 0.0001), although subgroup analysis showed that prognostic impact of ACA was not evident in t‐MDS. In conclusion, ACA occurs in close to one third of patients with IPSS defined lower risk MDS, more common among patients with t‐MDS, but has a significant prognostic impact on de novo MDS. Am. J. Hematol. 88:831–837, 2013. © 2013 Wiley Periodicals, Inc.     

Hypoalbuminemia is an independent prognostic factor for overall survival in myelodysplastic syndromes

We hypothesized that hypoalbuminemia is an independent prognostic factor in patients with myelodysplastic syndromes (MDS). We analyzed records of 767 patients treated at Moffitt Cancer Center between January 2001 and December 2009 to evaluate the relationship between serum albumin (SA) at the time of presentation and overall survival (OS). Patients (median age of 69 years) were stratified into three groups based on SA concentration (≤3.5, 3.6–4.0, and >4.0 g/dL). Two‐thirds of the patients had low or intermediate‐1 International Prognostic Scoring System (IPSS)‐based risk for MDS. Median OS by SA concentration of ≤3.5, 3.6–4.0, and >4.0 g/dL was 11, 23, and 34 months, respectively (P < 0.005), whereas rate of acute myeloid leukemia progression was highest in patients with low SA (≤3.5 g/dL). The SA level offered prognostic discrimination for outcomes within the lower and higher IPSS risk groups, as well as with the MD Anderson risk model. In multivariable analysis, SA was a significant independent co‐variate for OS after adjustment for IPSS, age, serum ferritin, and transfusion dependence (hazard ratio = 0.8; 95% CI 0.6–0.9; P = 0.004). Our findings indicate that hypoalbuminemia is an independent prognostic biomarker that may serve as a surrogate representative of disease biology or comorbidities in patients with MDS. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.     

Multidimensional assessment of patient condition and mutational analysis in peripheral blood,as tools to improve outcome prediction in myelodysplastic syndromes: A prospective study of the Spanish MDS group

The International Prognostic Scoring System and its revised form (IPSS‐R) are the most widely used indices for prognostic assessment of patients with myelodysplastic syndromes (MDS), but can only partially account for the observed variation in patient outcomes. This study aimed to evaluate the relative contribution of patient condition and mutational status in peripheral blood when added to the IPSS‐R, for estimating overall survival and the risk of leukemic transformation in patients with MDS. A prospective cohort (2006–2015) of 200 consecutive patients with MDS were included in the study series and categorized according to the IPSS‐R. Patients were further stratified according to patient condition (assessed using the multidimensional Lee index for older adults) and genetic mutations (peripheral blood samples screened using next‐generation sequencing). The change in likelihood‐ratio was tested in Cox models after adding individual covariates. The addition of the Lee index to the IPSS‐R significantly improved prediction of overall survival [hazard ratio (HR) 3.02, 95% confidence interval (CI) 1.96–4.66, P < 0.001), and mutational analysis significantly improved prediction of leukemic evolution (HR 2.64, 1.56–4.46, P < 0.001). Non‐leukemic death was strongly linked to patient condition (HR 2.71, 1.72–4.25, P < 0.001), but not to IPSS‐R score (P = 0.35) or mutational status (P = 0.75). Adjustment for exposure to disease‐modifying therapy, evaluated as a time‐dependent covariate, had no effect on the proposed model's predictive ability. In conclusion, patient condition, assessed by the multidimensional Lee index and patient mutational status can improve the prediction of clinical outcomes of patients with MDS already stratified by IPSS‐R.     

High flow cytometric scores identify adverse prognostic subgroups within the revised international prognostic scoring system for myelodysplastic syndromes

The estimation of survival of myelodysplastic syndromes (MDS) and risk of progression into acute myeloid leukaemia is challenging due to the heterogeneous clinical course. The most widely used prognostic scoring system (International Prognostic Scoring System [IPSS]) was recently revised (IPSS‐R). The aim of this study was to investigate the prognostic relevance of flow cytometry (FC) in the context of the IPSS‐R. Bone marrow aspirates were analysed by FC in 159 patients with MDS. A flow score was calculated by applying the flow cytometric scoring system (FCSS). Patients were assigned to IPSS and IPSS‐R risk groups. The FCSS correlated with the World Health Organization classification, IPSS and IPSS‐R risk groups. Mild flow cytometric abnormalities were associated with significantly better overall survival (OS) and lower risk of disease evolution. The presence of aberrant myeloid progenitors was associated with transfusion dependency and disease progression. Most importantly, the FCSS identified prognostic subgroups within the IPSS‐R cytogenetic good risk and low risk group. Flow cytometric analysis in patients with MDS provides additional prognostic information and is complementary to the IPSS‐R. The addition of a flow cytometric score next to the clinical parameters within the IPSS‐R is a further refinement of prognostication of patients with MDS.     

The prognostic value of circulating myeloblasts in patients with myelodysplastic syndromes

The prognostic value of peripheral blasts (PB) is not well-studied in patients with myelodysplastic syndromes (MDS). We evaluated the impact of PB on overall survival (OS) and transformation to acute myeloid leukemia (AML) in a large cohort. The MDS database at the Moffitt Cancer Center was retrospectively reviewed to identify patients with ≥?1% PB (PB-MDS) and those without PB (BM-MDS). We also assessed the correlation between PB and gene mutations. One thousand seven hundred fifty-eight patients were identified, among whom 13% had PB near the time of diagnosis. PB-MDS patients were more likely to be younger with trilineage cytopenia, complex karyotype, higher-risk disease, transfusion dependence, and therapy-related MDS. The rate of AML transformation was 49 vs. 26% (p?<?0.005) and median OS was 16.5 vs. 45.8 months (p?<?0.005) in the PB-MDS and BM-MDS groups, respectively. In Cox regression analysis, the presence of PB was an independent prognostic covariate for OS, HR 1.57 (95% CI 1.2–2). Among 51 patients with an available gene panel, the rate of ≥?1 gene mutation in the PB-MDS group (n?=?4) was 100% compared to 81% in the BM-MDS group (n?=?47). The presence of PB in MDS is an adverse independent prognostic variable that refines prognostic discrimination.     

Validation of the revised international prognostic scoring system (IPSS‐R) in patients with lower‐risk myelodysplastic syndromes: a report from the prospective European LeukaemiaNet MDS (EUMDS) registry

Baseline characteristics, disease‐management and outcome of 1000 lower‐risk myelodysplastic syndrome (MDS) patients within the European LeukaemiaNet MDS (EUMDS) Registry are described in conjunction with the validation of the revised International Prognostic Scoring System (IPSS‐R). The EUMDS registry confirmed established prognostic factors, such as age, gender and World Health Organization 2001 classification. Low quality of life (EQ‐5D visual analogue scale score) was significantly associated with reduced survival. A high co‐morbidity index predicted poor outcome in univariate analyses. The IPSS‐R identified a large group of 247 patients with Low (43%) and Very low (23%) risk score within the IPSS intermediate‐1 patients. The IPSS‐R also identified 32 High or Very high risk patients within the IPSS intermediate‐1 patients. IPSS‐R was superior to the IPSS for predicting both disease progression and survival. Seventy percent of patients received MDS‐specific treatment or supportive care, including red blood cell transfusions (51%), haematopoietic growth factors (58%) and iron chelation therapy (8%), within 2 years of diagnosis; while 30% of the patients only required active monitoring. The IPSS‐R proved its utility as a more refined risk stratification tool for the identification of patients with a very good or poor prognosis and in this lower‐risk MDS population.     

Comparison of five prognostic scoring systems, the French–American–British (FAB) and World Health Organization (WHO) classifications in patients with myelodysplastic syndromes: results of a single-center analysis

We retrospectively studied 89 consecutive patients diagnosed with primary myelodysplastic syndrome (MDS) over a period of 10 years to (1) identify prognostic factors for overall survival (OS) and leukemia-free survival (LFS); (2) to assess and compare the Bournemouth-, Spanish-, Düsseldorf-, Lille-, and the International prognostic scoring systems (IPSS); and to (3) compare the French–American–British (FAB) and World Health Organization (WHO) classifications. The median age of patients was 63 years (range, 26–85). Karyotype analyses were done in 85 patients (96%). Median OS was 3 years; 67 patients (75%) have died, and 28 (31%) had progression to acute myeloid leukemia (AML). Major independent prognostic variables for both OS and LFS (multivariate analysis) were percentage of bone marrow (BM) blasts (P<0.0001), and in patients with cytogenetic data available, cytogenetic risk groups by Lille-score (OS, P=0.031/LFS, P=0.002) and IPSS (OS, P=0.024). All five prognostic scoring systems successfully discriminated risk groups as regards OS and LFS, but in patients with cytogenetic data available, the major independent prognostic score for OS (P<0.0001) and LFS (P=0.006) was the IPSS. The FAB and WHO classifications also successfully discriminated between risk groups. The new WHO subgroups [refractory cytopenia with multilineage dysplasia (RCMD), with (RCMD-RS) or without ringed sideroblasts] showed a significantly (P=0.0454) different prognosis for OS, but not for LFS (P=0.0839), in comparison to the subgroups having erythroid dysplasia only (RA/RARS). Risk stratification into refractory anemia with excess blast-I (RAEB-I) and RAEB-II tended to yield different prognoses for OS and LFS. The 5q-minus syndrome strongly predicted for a good prognosis. In patients treated with the demethylating agent decitabine (n=24), IPSS “poor risk” cytogenetics were unable to predict for the expected worse prognosis when compared to “intermediate-risk” cytogenetics. In conclusion, we confirm in a single-center patient cohort that the use of the WHO classification improves the predictive value of the FAB classification and that, in patients with cytogenetic data available, the IPSS can be used for clinical decision-making.     

Bone marrow blasts level predicts prognosis in patients with refractory cytopenia with multilineage dysplasia

Objectives: Current prognostic models for myelodysplastic syndrome (MDS) do not consider the prognostic value of a bone marrow blast level that is <5%. Exploring the prognostic value of the International Prognostic Scoring System (IPSS) and a marrow blast level that is <5% may lead to better risk‐adapted therapeutic strategies. Methods: According to the World Health Organization classification, most of our patients (65.5%) fell into the new category ‘refractory cytopenia with multilineage dysplasia’ (RCMD). We evaluated the prognostic value of the IPSS in 435 adult patients with de novo MDS and in the 285 of them that had RCMD in a Chinese population. We also analyzed the prognostic value of bone marrow blast levels in patients with RCMD and in different IPSS risk groups. Results: We found a significant difference in survival times between RCMD patients with a marrow blast level of 3.5% or higher vs. those with a blast level of <3.5%, with median survival times of 23.7 and 40.8 months, respectively. In addition, application of a marrow blast level cutoff of 3.5% in patients with RCMD could identify patients with a lower IPSS risk but with a potentially worse prognosis. Multivariate analysis showed marrow blast level (using 3.5% as the cutoff) to be an independent factor that impacted survival times of patients with RCMD. Furthermore, we also found that IPSS had strong prognostic value in Chinese RCMD population. Conclusion: In patients with RCMD, a higher percentage of marrow blasts was associated with a worse prognosis.     

Prognostic value of trisomy 8 in primary myelodysplastic syndrome

Background: According to the International Prognostic Scoring System (IPSS), sole +8 is categorized as intermediate cytogenetic subgroup. But as some myelodysplastic syndrome (MDS) patients with +8 perhaps progress quickly to acute leukaemia and have shorter survival, some reports have suggested that +8 should be categorized into poor risk cytogenetic group. The aim of this study was to clarify the prognostic role of +8 in MDS patients by comparing patients with normal karyotype, 20q‐ and ‐7/7q‐. Methods: The consecutive samples of 435 MDS patients in Shanghai were collected by prospective methods and diagnosed according to World Health Organization classification. Cytogenetic analysis was performed using conventional G‐banding karyotyping and fluorescence in situ hybridization techniques. Prognosis was estimated by univariate Log‐rank method and multivariate Cox proportional hazard models. Results: Of 424 cases completing the cytogenetic analysis, 71 (16.7%) had +8, including 38 patients with sole +8 (9.0%). No significant difference in median survival was observed between patients with sole +8 and that with +8 and one of other abnormalities. The +8 clone size was not linked to survival. The median survival of patients with +8, normal karyotype and complex karyotype was 25 months, 38.1 months and 5.9 months respectively. However, no significant difference was observed between patients with 20q‐ (21.4 months) and ‐7/7q‐ (25.8 months). Trisomy 8 was an independent prognostic factor by Cox regression model. Conclusion: There is no significant difference in prognosis between patients with +8 and patients with 20q‐ or ‐7/7q‐. Trisomy 8, 20q‐ and ‐7/7q‐ are categorized as intermediate cytogenetic risk according to our primary study.