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.     

World Health Organization classification in combination with cytogenetic markers improves the prognostic stratification of patients with de novo primary myelodysplastic syndromes

This study correlated chromosomal defects with French-American-British (FAB)/World Health Organization (WHO) classification subtypes, proposed a revised International Prognostic Scoring System (IPSS) cytogenetic grouping; and established which classification, when used with the IPSS cytogenetic categories, best predicted clinical outcome in the myelodysplastic syndromes (MDS). A higher prevalence of chromosomal defects and distinct defects were observed in patients with multi-lineage dysplasia and a blast cell percentage >10%. Abnormalities of the long arm of chromosome 3, del(7)(q31q35), trisomy 8, del(11)(q14q23), del(12p) and 20q- could be segregated from their respective IPSS cytogenetic categories and used to develop new cytogenetic subgroups. Clinical parameters, FAB/WHO classification, IPSS score and standard or revised cytogenetic categories were statistically relevant for overall survival (OS) and progression-free intervals (PFI) and were included within five distinct multivariate models compared by the Akaike Information Criterion. To predict OS, the best models included age, WHO classification and standard or revised IPSS cytogenetic categories; to predict PFI, the best model included the same variables and revised cytogenetic categories. In conclusion, (i) the WHO classification was associated with a more homogeneous cytogenetic pattern than the FAB classification, (ii) WHO classification and standard/revised IPSS cytogenetic categories were much more effective than IPSS for predicting MDS clinical outcome, (iii) revised cytogenetic subgroups predicted PFI more effectively than standard categories.     

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.     

International MDS risk analysis workshop (IMRAW)/IPSS reanalyzed: impact of cytopenias on clinical outcomes in myelodysplastic syndromes

The International Prognostic Scoring System (IPSS) was created for evaluating clinical outcomes of patients with myelodysplastic syndromes (MDS). We evaluated the depth of cytopenias to determine whether this parameter could further refine the prognostic ability of the IPSS. Correlation was determined between the depth of cytopenias in 816 patients from the International MDS Risk Analysis Workshop database and patients' clinical features. Univariate analyses of hemoglobin (Hb), absolute neutrophil count, and platelet depth levels were assessed relative to the IPSS risk groups, refined French-American-British categories, cytogenetic groups, bone marrow blast percentage (%), age groups, overall survival (OS), and time to evolution of acute myeloid leukemia (AML). Multivariate analysis of different cytopenic levels was performed to determine whether depth of cytopenias was prognostically additive to the IPSS. All cytopenic categories had statistically significant rank correlations with IPSS, bone marrow blast %, and refined French-American-British categories. In multivariate analysis, Hb levels had additive prognostic value to the IPSS for evaluation of OS, but not time to AML, with greatest prognostic value in Intermediate-1 and Intermediate-2 categories. In contrast, platelet or absolute neutrophil count levels alone or in combination lacked additive prognostic value to the IPSS regarding OS or time to AML evolution. The depth of Hb level per se at the time of diagnosis has additive predictive value to the IPSS for OS in the intermediate-risk groups. This information should prove useful for aiding therapeutic decision-making, prognostic classification, and designing clinical trials for patients with MDS.     

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.     

Revised international prognostic scoring system for myelodysplastic syndromes

The International Prognostic Scoring Sytem (IPSS) is an important standard for ssessing prognosis of primary untreated adult patients with myelodysplastic syndromes (MDS). To refine the IPSS, MDS patient databases from international institutions were coalesced to assemble a much larger combined database (Revised-IPSS [IPSS-R], n = 7012, IPSS, n = 816) for analysis. Multiple statistically weighted clinical features were used to generate a prognostic categorization model. Bone marrow cytogenetics, marrow blast percentage, and cytopenias remained the basis of the new system. Novel components of the current analysis included: 5 rather than 3 cytogenetic prognostic subgroups with specific and new classifications of a number of less common cytogenetic subsets, splitting the low marrow blast percentage value, and depth of cytopenias. This model defined 5 rather than the 4 major prognostic categories that are present in the IPSS. Patient age, performance status, serum ferritin, and lactate dehydrogenase were significant additive features for survival but not for acute myeloid leukemia transformation. This system comprehensively integrated the numerous known clinical features into a method analyzing MDS patient prognosis more precisely than the initial IPSS. As such, this IPSS-R should prove beneficial for predicting the clinical outcomes of untreated MDS patients and aiding design and analysis of clinical trials in this disease.     

Detection of risk groups in myelodysplastic syndromes. A multicenter study.

BACKGROUND AND OBJECTIVES: Myelodysplastic syndromes (MDS) comprise a group of heterogeneous hematologic disorders with risk of leukemic evolution (LE). The French-American-British (FAB) co-operative group classifies them into five morphologic entities and the International Prognostic Scoring System (IPSS) proposes four groups of risk on the basis of clinical and cytogenetic variables. The aim of this study was to evaluate the application of the IPSS in our Argentine population, to test the prognostic value of its variables and to determine whether this score helps to associate prognostic subgroups of risk into FAB subtypes. DESIGN AND METHODS: Two hundred and thirty-four patients with primary MDS and a median follow-up of 28 months were evaluated using univariate analyses to determine median survival (SV) and the time to LE. The variables analyzed were FAB classification, IPSS, percentage of myeloblasts, cytogenetic groups of risk and number of cytopenias. RESULTS: Univariate analyses showed that all variables analyzed were predictive for SV and for LE in our MDS population. Application of the IPSS allowed discrimination into the 4 groups of risk and helped to identify prognostic subclasses among the FAB classification, associating 5%, 15% and 19% of cases with worse prognosis within the FAB classification of refractory anemia (RA), RA with ringed sideroblasts and RA with excess of blasts (RAEB), respectively. The IPSS was not informative for RAEB in transformation cases and would not be applied to patients with chronic myelomonocytic leukemia. INTERPRETATION AND CONCLUSIONS: This score could be applied to our MDS population, showing no geographic differences. Stratification of FAB patients according to IPSS would be helpful to develop risk-adapted therapeutic strategies.     

骨髓增生异常综合征99例临床分析

目的探讨骨髓增生异常综合征(MDS)患者WHO亚型分布、细胞遗传学特点及其与MDS诊断分型、疾病进展和预后的关系。方法回顾性分析2001年1月至2007年12月安徽医科大学附属安徽省立医院血液科收治的99例成人原发MDS患者的染色体核型、WHO分型及预后情况,随访观察并进行相关性研究。结果99例MDS患者难治性贫血(RA)型26例(26.26%);难治性贫血伴环形铁幼粒细胞增多(RAS)型6例(6.06%);难治性贫血伴多系发育异常(RCMD)型23例(23.23%);难治性贫血伴原始细胞增多(RAEB)型44例(44.44%)。按IPSS预后分组,中危Ⅱ和高危组的染色体核型异常检出率明显高于低危和中危Ⅰ组(χ2=17.88,P<0.01);中危Ⅱ和高危组患者进展为急性白血病的发生率明显高于低危和中危Ⅰ组(χ2=40.22,P<0.01)。按IPSS染色体核型分组,预后好、中、差的患者中位存活期分别为45(95%CI:39~51)、37(95%CI:25~49)和23(95%CI:13~31)个月,Log-rank检验三组总体生存(OS)率差异有统计学意义(P=0.010)。结论中国有别于西方国家MDS患者的WHO亚型分布,染色体核型分析是MDS诊断分型及预后评估的重要指标。     

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.     

Therapy related‐chronic myelomonocytic leukemia (CMML): Molecular,cytogenetic, and clinical distinctions from de novo CMML

Therapy related myeloid neoplasms (t‐MN) including therapy related myelodysplastic syndromes (t‐MDS) and acute myeloid leukemia (t‐AML) are associated with aggressive disease biologies and poor outcomes. In this large (n = 497) and informative (inclusive of molecular and cytogenetic information) chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key biological insights and an independent prognostic impact for t‐CMML. T‐CMML was diagnosed in 9% of patients and occurred approximately 7 years after exposure to prior chemotherapy and/or radiation therapy. In comparison to de novo CMML, t‐CMML patients had higher LDH levels, higher frequency of karyotypic abnormalities and had higher risk cytogenetic stratification. There were no differences in the distribution of gene mutations and unlike t‐MDS/AML, balanced chromosomal translocations, abnormalities of chromosome 11q23 (1%) and Tp53 mutations (<2%) were uncommon. Molecularly integrated CMML prognostic models were not effective in risk stratifying t‐CMML patients and responses to hypomethylating agents were dismal with no complete responses. Median overall (OS) and leukemia free survival (LFS) was shorter for t‐CMML in comparison to d‐CMML (Median OS 10.9 vs 26 months and median LFS 50 vs 127 months) and t‐CMML independently and adversely impacted OS (P = .0001 HR 2.1 95% CI 1.4‐3.0). This prognostic impact was retained in the context of the Mayo Molecular Model (P = .001, HR 2.4, 95% CI 1.5‐3.7) and the GFM prognostic model (P < .0001, HR 2.15, 95% CI 1.5‐3.7). In summary, we highlight the unique genetics and independent prognostic impact of t‐CMML, warranting its inclusion as a separate entity in the classification schema for both CMML and t‐MN.     

Partial and total monosomal karyotypes in myelodysplastic syndromes: comparative prognostic relevance among 421 patients

Myelodysplastic syndromes (MDS) include a group of heterogeneous hematological disorders with a variable risk of leukemic evolution and short survival. Around 40-50% of patients show abnormal karyotypes that are mostly characterized by monosomies or deletions. Cytogenetic findings are an independent prognostic factor and the International prognostic scoring system (IPSS) differentiates three cytogenetic categories, despite the Intermediate one being heterogeneous. The aim of this study, including 421 Argentinean patients with primary MDS, is to characterize the cytogenetic profile, to test its prognostic value and to compare partial and monosomal karyotypes against other cytogenetic findings. An abnormal karyotype (median survival: 26 months) was observed in 176 patients. The presence of complex karyotypes, number of alterations, and the IPSS cytogenetic groups showed significant differences for predicting outcome. Behavior of patients with isolated deletions (median survival: 49 months) did not differ from those with normal karyotype (56 months, P = 0.654) or Good prognostic findings (43 months, P = 0.371). However, a worse prognosis was observed when another alteration was added (31 months, P = 0.043). Karyotypes with autosomal monosomies (median survival: 16 months) had a prognostic impact similar to other Poor cytogenetic findings (17 months, P = 0.626). In our population classified according to French-American-British (FAB) or World Health Organization (WHO), this new categorization of cytogenetic abnormalities, recognizing three different risk groups, showed an independent prognostic impact and a better discriminating power than the IPSS categories. It can be concluded that all isolate deletions (excluding 7q-) are good prognostic findings and all monosomies (excluding Y chromosome loss) are bad indicators.     

Dynamic assessment of RBC‐transfusion dependency improves the prognostic value of the revised‐IPSS in MDS patients

RBC‐transfusion dependency (RBC‐TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification‐based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS‐R) did not include RBC‐TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC‐TD. We aimed to test whether RBC‐TD adds prognostic value to the IPSS‐R. We analyzed MDS patients not treated with disease‐modifying therapy, and enrolled in SA‐MDS Registry (derivation cohort; n = 295) and Dusseldorf registry (Germany; validation cohort; n = 113) using time‐dependent Cox proportional regression and serial landmark analyses. In the derivation cohort, RBC‐TD patients had inferior OS compared to RBC transfusion‐independent (RBC‐TI) patients (P < 0.0001) at 6‐ (18 vs. 64 months), 12‐ (24 vs. 71 months), and 24‐months (40 vs. 87 months). In a Cox proportional regression analysis, RBC‐TD was an independent adverse prognostic marker in addition to age, sex, and IPSS‐R variables (P < 0.0001). A prognostic index (PI) was derived using these Cox‐proportional regression model variables. In the validation cohort, this PI classified patients into four prognostic groups with significantly different OS (P < 0.001) as in the derivation cohort. In conclusion, multivariate analysis by Cox proportional hazards regression and serial landmark analyses clearly demonstrates that development of RBC‐TD at any time during the course of MDS is associated with poor OS, independent of IPSS‐R. This study demonstrates that dynamic assessment of RBC‐TD provides additional prognostic value to IPSS‐R and should be included in treatment decision algorithms for MDS patients.     

Circulating myeloid colony-forming cells predict survival in myelodysplastic syndromes

The growth characteristics and the prognostic value of cytokine-stimulated myeloid colony formation from peripheral blood mononuclear cells (PBMC) of patients with myelodysplastic syndromes (MDS) are largely unknown. In this study we have determined the number of myeloid colony-forming units (mCFUs) in semisolid medium from 112 MDS patients and correlated them with French-American-British (FAB) type, the international prognostic scoring system (IPSS), karyotype, peripheral blood (PB) and bone marrow (BM) blast cells, cytopenias, lactate dehydrogenase (LDH), and survival data. Concerning the FAB classification, lower median mCFUs were found in patients with refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) compared to refractory anemia with excess of blast cells (RAEB) and refractory anemia with excess of blasts cells in transformation (RAEB-T). In vitro growth in MDS clearly correlated with the cytogenetic risk groups defined by the IPSS (30.5/10(5) PBMCs with favorable karyotypes, 191 in the intermediate prognostic group, 677 with unfavorable cytogenetics, p=0.015 favorable vs unfavorable). BM blast cells >5% (60.5 vs 255 colonies, p=0.032) as well as LDH levels above the normal limit (64.5 vs 425 colonies, p=0.045) were also associated with higher colony formation. Patients were stratified according to the number of circulating mCFUs into a low growth, intermediate growth and high growth group. Median survival was 343 days in the high growth, 1119 days in the low growth, and 2341 days in the intermediate growth group ( p=0.0002). Multivariate analyses revealed colony growth ( p=0.0056), PB blast cells ( p=0.0069), cytogenetic risk group ( p=0.024), and platelet count ( p=0.018) to predict survival in our patients. After inclusion of the IPSS risk categories, mCFU levels remained a highly predictive parameter for survival ( p=0.0056) and acute myeloblastic leukemia (AML) transformation ( p=0.0003).     

Does cytogenetic evolution have any prognostic relevance in myelodysplastic syndromes? A study on 153 patients from a single institution

The present study was designed to establish the incidence of cytogenetic evolution (CE), defined as the acquisition of chromosomal defects during the course of MDS, in order to correlate it with the WHO classification and IPSS score, and to assess its impact on overall survival (OS) and risk of MDS/AML evolution (progression-free interval, PFI) by means of Cox models for time-dependent covariates. Adjustments for known risk factors were achieved by performing a bivariable analysis. The study was carried out in 153 MDS patients who were followed for a median period of 45.2 months. Disease progression occurred in 42.4% of patients after a 65.2-month median PFI, while CE occurred in 30.7% of patients. Our study shows that (1) CE was more common in advanced than in early MDS, and advanced MDS presented secondary chromosomal defects distinct from those of early MDS; (2) CE significantly affected OS and PFI independently of other prognostic variables; (3) del(7)(q31q34) was the only secondary chromosomal defect which significantly affected PFI; trisomy 8 had only a moderate influence.     

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.     

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.     

Myelodysplastic syndromes according to FAB and WHO classification. Single center experience

The results of clinical and laboratory observations of 119 MDS patients divided acc. to FAB, and - after excluding RAEB-t and CMML groups -- of 95 patients divided accordingly to WHO classification are presented. The diagnosis of MDS was based on medical interview, physical examination, blood biochemistry, peripheral blood (PB) and bone marrow (BM) cytomorphology and cytochemistry, trephine biopsy and cytogenetic examination. All hematologic examinations were done according to routine methods. Cytogenetic analyses were carried out on BM cells from 24-48 h cultures in standard conditions. At least 15-20 GTG-banded metaphases were analyzed in every patient. The survival time (ST) of patients differed significantly between the FAB or WHO groups, with p=0.0004 for FAB and p=0.02 for WHO. The progression to AML was more common in less favorable groups, with p=0.0001 for FAB and p=0.00016 for WHO. The distribution of IPSS prognostic index among the groups showed statistically significant difference (p=0.0004 for FAB, and p=0.0001 for WHO), whereas the distribution of karyotypic abnormalities did not. However, in univariate analysis statistically significant influence on ST showed, beside the both classification systems: cytogenetics, the presence of blasts in PB, age and IPSS index. In multivariate analysis the sole independent prognostic factors were: PB blasts and cytogenetics. The authors conclude that the WHO classification offers a good prognostic tool for MDS patients. However, the karyotype and the presence of blasts in PB should always be taken into account.     

Evaluating the prognosis of patients with myelodysplastic syndromes

One of the hallmarks of myelodysplastic syndromes (MDS) is their prognostic heterogeneity which complicates decision making regarding treatment for individual patients. The French-American-British (FAB) classification provides significant prognostic information, but carries the disadvantage of arbitrary demarcation of subgroups and overemphasis of morphological findings. In addition, there is considerable variation in survival and risk of acute myeloblastic leukemia (AML) development even within defined FAB subgroups, particularly in patients with refractory anemia with ring sideroblasts (RARS) and chronic myelomonocytic leukemia (CMML). Over the last 2 decades, several research groups have tried to identify additional clinical, hematological, and cell biological parameters in order to more accurately predict the natural course of MDS. These investigations have clarified that the number and extent of peripheral blood cytopenias, the bone marrow blast count, and the cytogenetic pattern are the most powerful prognostic indicators in MDS. Recent efforts have been directed at constructing prognostic scoring systems. These scoring systems try to enhance the predictive power by combining several features of the disease, which have proved their independent prognostic weight on multivariate analysis. The International MDS Risk Analysis Workshop substantially advanced the prognostic categorization of MDS patients by proposing a new scoring system (International Prognosis Scoring System, IPSS) that can be successfully applied to risk assessment of newly diagnosed patients and will likely prove useful for the design and analysis of therapeutic trials in MDS.     

WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

We evaluated the impact of World Health Organization (WHO) classification and WHO classification-based Prognostic Scoring System (WPSS) on the outcome of patients with myelodysplastic syndrome (MDS) who underwent allogeneic stem cell transplantation (allo-SCT) between 1990 and 2006. Five-year overall survival (OS) was 80% in refractory anemias, 57% in refractory cytopenias, 51% in refractory anemia with excess blasts 1 (RAEB-1), 28% in RAEB-2, and 25% in acute leukemia from MDS (P = .001). Five-year probability of relapse was 9%, 22%, 24%, 56%, and 53%, respectively (P < .001). Five-year transplant-related mortality (TRM) was 14%, 39%, 38%, 34%, and 44%, respectively (P = .24). In multivariate analysis, WHO classification showed a significant effect on OS (P = .017) and probability of relapse (P = .01); transfusion dependency was associated with a reduced OS (P = .01) and increased TRM (P = .037), whereas WPSS showed a prognostic significance on both OS (P = .001) and probability of relapse (P < .001). In patients without excess blasts, multilineage dysplasia and transfusion dependency affected OS (P = .001 and P = .009, respectively), and were associated with an increased TRM (P = .013 and P = .031, respectively). In these patients, WPSS identified 2 groups with different OS and TRM. These data suggest that WHO classification and WPSS have a relevant prognostic value in posttransplantation outcome of MDS patients.     

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.