Application of the International Prognostic Scoring System for myelodysplastic syndromes

Background: In march 1997 an international workshop introduced a new International Prognostic Scoring System (IPSS) for MDS. The goal of the present study was to apply the IPSS to a large group of MDS patients from one centre and to compare it to the FAB-classification.Patients: One hundred eighty-four MDS patients were included on the basis of similar criteria as used by the workshop but some of them (30) received AML-type therapy.Results: The IPSS separated our patients into distinctive prognostic subgroups (P = 0.0001). Median survival was respectively 6.5, 2.6, 1.3 and 0.75 years for the low-risk (22% of patients), the intermediate-1-risk (INT-1) (46%), the intermediate-2-risk (INT-2) (25%) and the high-risk group (7%). The IPSS also discriminated within each of the FAB-categories: RA patients (58 patients) were present in low-risk, INT-1-risk and INT-2-risk subgroups, RARS patients (23) were separated into low-risk and INT-1-risk subgroups. RAEB patients (53) were distributed predominantly between INT-1-risk and INT-2-risk groups, RAEB-t patients (23) between INT-2-risk and high-risk subgroups. CMML patients (27) were present in the low-risk, the INT-1-risk and the INT-2-risk group.Conclusions: Our results confirm the effectiveness of the IPSS in predicting clinical outcome in MDS patients and indicate that it is an improved method compared to the FAB-classification.     

Prognostic value of lactate dehydrogenase activity in myelodysplastic syndromes

Several prognostic factors for patients with myelodysplastic syndromes (MDS) have been defined in the past. One of these factors appears to be the serum lactate dehydrogenase (LDH) activity. However, the precise predictive value of an elevated LDH level with regard to AML transformation remains uncertain. In this study, the prognostic value of the LDH activity was examined in a cohort of 180 patients with de novo MDS (median age 71 years [27-93]; f/m-ratio 1:1.2; RA: n=53; RARS: n=37; RAEB: n=50; RAEBT: n=19; CMML: n=21). Significant differences in LDH activities were found among FAB groups (P<0.05), and especially among IPSS groups (HIGH: 411+/-574; INT-2: 221+/-90; INT-1: 254+/-145; LOW: 192+/-47 U/l; P<0.05). An LDH level of >/=300 U/l was found to be associated with a significantly shorter median survival (10.3 months) when compared to <300 U/l (33.7 months; P<0.01). Moreover, an LDH activity of >/=300 U/l indicated a reduced AML-free survival in our MDS patients (P<0.01). As assessed by Cox regression, the inclusion of LDH as additional variable into the IPSS system resulted in an improved prediction concerning survival, but not with regard to AML evolution. Together, our data show that a serum LDH activity of >/=300 U/l in MDS is associated with a significantly shorter survival and higher risk to transform to AML. The LDH activity should be considered as an important prognostic factor in MDS.     

Utility of 5-Methylcytosine Immunohistochemical Staining to Assess Global DNA Methylation and Its Prognostic Impact in MDS Patients

Background: DNA methylation plays a vital role in the pathogenesis of the myelodysplastic syndrome (MDS), a heterogeneous group of clonal hematopoietic stem cell (HSC) disorders. It is reported to be an independent prognostic factor affecting overall survival (OS). Our aim was to analyze the role of global DNA methylation using an anti-5-methylcytosine (5-MC) antibody by immunohistochemistry (IHC) of bone marrow biopsy (BM Bx) specimens in MDS patients, assessing correlations with various clinical and biological prognostic factors. Material and methods: A total of 59 MDS cases, classified as per the World Health Organization (WHO) 2008 guidelines, were evaluated over a period of 4 years. Clinical data were retrieved from departmental case records and anti-5-MC expression was analyzed with formalin fixed paraffin embedded sections of BM Bx specimens of MDS patients and controls. Results: The median age at diagnosis was 52 years (15-85years). Patients were categorized into low risk (59%) and high risk (41%) according to International Prognostic Scoring System (IPSS). The median follow-up time was 10 months (1 to 37 months). We generated a methylation score (M-score) using anti-5-MC and with the derived cut-off of 30.5 from the receiver operator curve (ROC), there was a significant difference between the two groups in the percentage of BM blasts (p=0.01), WHO sub-type (p=0.01), IPSS (p=0.004), progression to AML (p=0.04) on univariate analysis. Interestingly, patients showing a high M-score (M-score ≥ 30.5) demonstrated a significantly shorter OS and progression to AML. However, on multivariate analysis, only BM blasts (p=0.01) and IPSS (p=0.02) remained independent variables for progression to AML and OS respectively. Conclusion: Immunostaining with anti-5-MC antibody with BM Bx samples is a simple and cost effective technique to detect global methylation, a powerful tool to predict overall survival in patients with MDS.     

Comparisons of prognostic scoring systems for myelodysplastic syndromes: a Korean multicenter study.

We have conducted a multicenter collaborative retrospective analysis to evaluate clinical characteristics and to compare prognostic scoring systems of 149 Korean patients with myelodysplastic syndromes (MDS). The median age of the patients was 53 years (range 17-82 years) with high of the patients being younger than 40 years. Median survival was 22.6 months, and 25 patients (17%) progressed to acute myelogenous leukemia (AML) with a median interval of 6 months (range 1-45 months). Major independent variables assessed by multivariate analysis were FAB subtypes and bone marrow (BM) blast percentages for survival and BM blast percentages for AML transformation. To compare the various scoring systems in the prediction for survival and transformation to AML, FAB, Sanz and Bournemouth scoring systems were applied to all patients, while the international prognostic scoring system (IPSS), Lille and Toyama scoring systems were applied to 91 patients. The Sanz scoring system (P < 0.0001), FAB classification (P < 0.0001), IPSS (P < 0.001), and Toyama scoring system (P < 0.005) were highly predictive for survival showed greater discrimination than that of the other systems. For AML transformation, the IPSS (P < 0.0001), Toyama scoring system (P < 0.0001), FAB classification (P < 0.0001), and Lille scoring system (P < 0.005) successfully discriminated risk groups. Although the prognostic factors and the distribution of age were different from those in Western reports, the IPSS and Toyama scoring system were applicable for predicting survival and leukemic transformation in Korean patients with MDS.     

Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin.

Immunosuppressive therapy has been shown to induce sustained hematological responses in a subset of patients with myelodysplastic syndromes (MDS). In particular, antithymocyte globulin (ATG), a polyclonal immunoglobulin induces hematological responses in up to 60% of MDS patients. We report herein on the results of a retrospective multicenter study on the use of ATG in the treatment of 96 patients with MDS. Patients were evaluated for duration of response to ATG, as well as survival after administration of ATG. The median age of the cohort was 54.7 years (range: 19-75 years), with a median follow-up of 33.8 months (range: 0.8-133 months). A total of 40 patients (42%) achieved a hematological response, of which 30 patients (75%) had a durable hematological response lasting a median duration of 31.5 months (range: 6-92 months). On multivariate analysis, both low International Prognostic Scoring System (IPSS) and bone marrow (BM) hypocellularity were independent predictive factors for improved response to ATG (IPSS Int-2/high: odds ratio (OR) 0.08, P=0.018 and BM normo/hypercellularity: OR 0.49, P=0.012). In addition, IPSS was the sole predictor of overall survival, with Int-2/high risk patients having a significantly poorer survival outcome (OR 0.08, P<0.01). In conclusion, this study identifies BM hypocellularity and a low IPSS as important factors predicting response to ATG.     

Myelodysplastic syndromes in patients under 50 years old: a single institution experience

We report on our experience relating to 62 patients with myelodysplastic syndrome (MDS) aged less than 50 years, seen at our Institution and conservatively treated from July 1983 to December 2000. Patients demographics and clinical features at diagnosis were analysed for their prognostic value on survival and on risk of transformation to acute leukaemia. The median age at diagnosis was 43 years (range 21-50). According to FAB criteria there were 30 patients with refractory anaemia (RA), 3 with refractory anaemia with ringed sideroblasts (RARS), 18 with refractory anaemia with excess of blasts (RAEB), 6 with refractory anaemia with excess of blasts in transformation (RAEB-t) and 5 with chronic myelomonocytic leukaemia (CMML). Fifty patients had evaluable cytogenetic analysis: the most frequent karyotypic change was trisomy of chromosome 8 (10%), followed by monosomy 7 (6%); partial chromosome deletions and translocations were also common abnormalities, occurring on the whole in 16% of patients. At a median follow-up of 15 months 19 patients (31%) progressed to acute myeloid leukaemia (AML). From univariate analysis we identified some features, which appeared to be predictive of outcome and risk of transformation to AML. Age above 40 years (p = 0.002) and high risk according to IPSS score (p = 0.002) were found to be predictive for a shorter survival; FAB grouping (p = 0.0001), percentage > 5% of blasts in the bone marrow (p = 0.001) and high risk by IPSS score (p = 0.0003) were found to be predictive for a higher risk of transformation to AML. Presenting features in young MDS patients may identify subjects at higher risk of unfavourable outcome.     

Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS).

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.     

A four-parameter index of marrow dysplasia has predictive value for survival in myelodysplastic syndromes

Marrow dysplasia is a major characteristic of patients with myelodysplastic syndrome (MDS), along with marrow blastosis, cytopenia and cytogenetic anomalies. However, the impact of the degree of marrow dysplasia on survival has not been fully assessed. In this retrospective analysis of 111 patients selected according to the IPSS criteria of MDS diagnosis, the presence or absence of 21 dysplasia characteristics recognizable in bone marrow smears stained by the May-Grünwald-Giemsa method was correlated with patient survival. Using Cox proportional hazards regression analysis, megaloblastosis (MEGALO), neutrophil agranularity (AGRAN) and hypogranularity (HYPOGRAN) were highly significant predictors (p < 0.005), and Pelger-Hu?t anomaly (PELGHUET) a significant predictor (p = 0.05), of patient survival. The regression analysis yielded a dysplasia-based risk index (DI) where DI = 1.26 MEGALO + 0.82 AGRAN - 1.08 HYPOGRAN + 0.45 PELGHUET. The two subgroups of 60 and 47 patients with DI < or = 0 and > 0 showed highly significant differences in median survivals (2.6 vs 1.1 yrs; p <0.0001). Multivariate analysis further showed that DI offered additional predictive power that was independent of that provided by the IPSS (p=0.002 and 0.001 respectively). Analysis of survival curves stratified for IPSS and DI showed that the additional predictive power offered by inclusion of the DI essentially concerned the IPSS low/INT-1 risk categories. Further stratification for age did not improve survival prediction. The data indicate that a set of 4 dysplasia parameters can offer some prediction for survival of MDS patients in addition to that provided by the IPSS. Further multicenter studies should aim at including some form of evaluation of the degree of dysplasia in prognostic systems.     

Clinical Prognostic Factors for Survival and Risk of Progression to Acute Myeloid Leukemia in Patients With Myelodysplastic Syndromes With < 10% Marrow Blasts and Non-Unfavorable Cytogenetic Categories

BackgroundPrognosis of MDS and particularly in patients categorized as lower risk (< 10% blasts or low and intermediate-1 International Prognostic Scoring System [IPSS]) is very heterogeneous and includes patients with very different outcomes with current scoring systems. Recently, a new cytogenetic classification has been proposed for the revised IPSS in predicting the outcome for MDS.Patients and MethodsTo evaluate the prognostic significance of multiple variables for survival and risk of progression to acute myeloid leukemia, we analyzed baseline characteristics of 332 lower risk MDS patients within the lower risk cytogenetic categories by IPSS and the recent proposal for the new cytogenetic classification.ResultsIn multivariate analysis, severity of cytopenias, age > 60 years, bone marrow blasts (5%-9%) and transfusion dependency significantly influenced outcome. The combination of these variables allowed development of a model which categorizes patients in 3 different groups with median survival of 95, 44, and 13 months for groups 1, 2, and 3, respectively (P < .001). In addition, this score also stratified patients for their risk for leukemic progression, estimated at 2 years in 3.1%, 7.6%, and 21.3% for each group (P = .024).ConclusionAlthough karyotype remains the main prognostic factor in MDS, the current study identifies clinical parameters predicting outcome among patients with the better cytogenetic profile. Degree of cytopenias, blasts 5%-9% and transfusion dependence might identify a subset of patients within the nonadverse karyotype, in which early or more aggressive approaches could possibly be required to improve survival or prevent disease progression.     

Thrombocytosis in myelodysplastic and myelodysplastic/myeloproliferative syndromes

Thrombocytosis at diagnosis is uncommon in myelodysplastic (MDS) and myelodysplastic/myeloproliferative (MDS/MPD) syndromes. We conducted a retrospective analysis to determine the clinical and haematopathological features of such patients, and the effect of thrombocytosis on prognosis. Of the 388 patients diagnosed with MDS from 1980 - 2006, 31 presented with thrombocytosis. The majority (71%) had low risk features and a low incidence of spontaneous bleeding or thrombo-embolic events. Compared to a case-matched control group of MDS and MDS/MPD patients without thrombocytosis of similar ages and IPSS scores, patients with thrombocytosis had a slightly lower probability of progression to a higher grade of MDS (P = 0.03), equivalent risk of transformation to acute myeloid leukemia (AML), and a trend (P = 0.07) towards longer overall survival (median 35.4 months compared to 27.6 months for controls).     

Evaluation of epidemiological factors in survival of patients with de novo myelodysplastic syndromes

Myelodysplastic syndromes (MDS) prognosis is currently based solely on clinical parameters. The identification of additional factors associated with MDS outcome could be used to further improve the current scoring system such as the International Prognostic Scoring System (IPSS). The present study evaluates the role of epidemiological markers as predictors of survival for 365 adult de novo MDS patients. Multivariable Cox regression analysis was used to estimate overall survival. Median follow-up time was 22 months. At the time of last follow-up, 271 patients (74.3 %) had died. For all MDS patients, medium–high lifetime occupational agrochemical exposure (HR 1.85, CI 1.19–2.89) remained as an independent predictor of MDS survival. Stratified analysis by gender showed that ≥25 pack-years smoked (HR 1.44, CI 1.001–2.09) and medium–high lifetime occupational agrochemical exposure (HR 1.84, CI 1.15–2.97) were independent predictors of MDS survival in men, but not in women. For MDS patients stratified by IPSS categories, ≥25 pack-years smoked (HR 1.75, CI 1.005–3.06) was an independent predictor for intermediate 1 IPSS risk group only, and medium–high lifetime occupational agrochemical exposure was associated with increased mortality (HR 4.36, CI 1.20–15.8) in the high IPSS risk group. Smoking and lifetime occupational agrochemical exposure may play a role in MDS survival. Incorporating relevant epidemiological markers with known clinical predictors of outcome may help physician stratify patients and customize treatment strategies to improve the outcome of MDS.     

Improved risk stratification by the integration of the revised International Prognostic Scoring System with the Myelodysplastic Syndromes Comorbidity Index

Myelodysplastic syndromes (MDS) comprise bone marrow failure diseases with a diverse clinical outcome. For improved risk stratification, the International Prognostic Scoring System (IPSS) has recently been revised (IPSS-R). This single-centre study aimed to validate the IPSS-R and to evaluate prior prognostic scoring systems for MDS. We retrospectively analysed 363 patients diagnosed with MDS according to the FAB criteria between 2000 and 2012. The IPSS, MD Anderson Risk Model Score (MDAS), World Health Organisation (WHO)-classification based Prognostic Scoring System (WPSS), refined WPSS (WPSS-R), IPSS-R and MDS-Comorbidity Index (MDS-CI) were applied to 222 patients considered with primary MDS following the WHO criteria and their prognostic power was investigated. According to the IPSS-R, 18 (8%), 81 (37%), 50 (23%), 43 (19%) and 30 (13%) patients were classified as very low, low, intermediate, high and very high risk with, respectively, a median overall survival of 96 (95% Confidence interval (CI) not reached), 49 (95% CI 34–64), 22 (95% CI 0–49), 19 (95% CI 11–27) and 10 (95% CI 6–13) months (p < .000). The IPSS-R showed improved prognostic power as compared to the IPSS, MDAS, WPSS and WPSS-R. Furthermore, the MDS-CI refined the risk stratification of MDS patients stratified according to the IPSS-R. In conclusion, accounting for the disease status by means of the IPSS-R and comorbidity through the MDS-CI considerably improves the prognostic assessment in MDS patients.     

The clinical, haematological and morphological profile of patients with myelodysplastic syndromes: a single institution experience from Turkey

In a retrospective analysis of 113 patients with primary myelodysplastic syndromes (MDS) diagnosed according to French-American-British (FAB) classification, we evaluated the prognostic impact of FAB and World Health Organisation (WHO) classifications, International Prognostic Scoring System (IPSS), and other clinical and laboratory variables. The median age was 69. IPSS could be applied to 75 patients classified according to the FAB criteria and to 50 patients reclassified according to the WHO criteria. At a median follow-up of 24 months, 22 patients (19.5 %) transformed to acute myelogenous leukaemia (AML). Overall survival (OS) of patients differed significantly between the FAB and WHO subgroups (p < 0.0001). In WHO classification, significant differences were observed in both OS and leukaemia free survival (LFS) between patients with RA/RARS and refractory cytopenia with multi-lineage dysplasia/refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts (RCMD/RS-RCMD) (p = 0.0001). High-risk according to IPSS score and blood transfusion need were significantly predictive for a shorter survival and higher risk of transformation. Hemoglobin <10 g/dl, neutrophil count <0.5 x 10(9)/L, platelet count <50 x 10(9)/L had an unfavourable prognostic impact on survival in multi-variate analysis. Our conclusions support the previous findings on the value of WHO classification for prediction of prognosis in MDS.     

Incidence and prognostic significance of karyotype abnormalities in de novo primary myelodysplastic syndromes: a study on 331 patients from a single institution.

The impact of clinical parameters, International Prognostic Scoring System (IPSS) scores/cytogenetic categories, and some single cytogenetic defects on overall survival (OS) and time to myelodysplastic syndromes (MDS)/AML progression (progression-free interval (PFI)) was evaluated in 331 MDS patients. Statistical analysis demonstrated that OS and PFI were significantly affected by all these parameters. Since single 7q- showed a better survival than the poor IPSS cytogenetic category (P=0.009), it was considered as a new prognostic entity ('modified IPSS categories'). In multivariate analysis OS was significantly influenced by age, marrow blast cell percentage, number of cytopenias and either modified or standard IPSS cytogenetic categories; hazard ratios for MDS/AML progression were influenced by all the former, except for age and cytopenias. Multivariate analysis of del(7)(q31q35) confirmed the results of univariate analysis, but the Akaike Information Criterion showed no difference in evaluating OS and PFI between the modified and standard IPSS cytogenetic grouping. In conclusion, (i) chromosome defects as grouped by IPSS and blast cell percentage are the most relevant parameters for predicting OS and PFI; (ii) the prognostic power of the IPSS cytogenetic grouping is not ameliorated by the introduction of del(7)(q31q35) as a new entity; (iii) complex karyotypes have a prognostic value independent of blast cell percentage.     

Income and outcome in myelodysplastic syndrome: The prognostic impact of SES in a single-payer system

We examined the prognostic impact of SES, estimated by census median household income, in 312 adult MDS patients. Age, progression to AML, use of recombinant erythropoietin, WHO diagnosis and IPSS risk category were independent predictors of survival but there was no association between SES and survival. Unexpectedly, progression to AML was more prevalent in the highest income quartile (HR 3.96 for highest vs. lowest; p = 0.0032). The previously demonstrated association of low SES with poor outcome MDS in the United States may have been driven primarily by reduced access to care rather than other SES-linked factors such as co-morbidity.     

Clinical Outcomes of Decitabine Treatment for Patients With Lower-Risk Myelodysplastic Syndrome on the Basis of the International Prognostic Scoring System

IntroductionDecitabine has shown clinical benefits in patients with intermediate (INT)-2 or high-risk myelodysplastic syndrome (MDS), determined according to the International Prognostic Scoring System (IPSS), but the benefits have not been well demonstrated in patients with lower-risk (IPSS low or INT-1) disease. Recently, it was proposed that the prognosis for patients with IPSS lower-risk disease is heterogeneous, with a substantial proportion of these patients having poor survival.Patients and MethodsThis study included patients with IPSS lower-risk MDS from the DRAMA (An Observational Study for Dacogen Long-Term Treatment in Patients With Myelodysplastic Syndrome; NCT01400633) and DIVA (A Study for Dacogen Treatment in Patients With Myelodysplastic Syndrome; NCT01041846) studies, which were prospective observational studies on the efficacy and safety of decitabine treatment in patients with MDS. Using the Lower-Risk Prognostic Scoring System [LR-PSS], we classified IPSS lower-risk MDS. Patients in each LR-PSS category were divided according to overall response (OR) to decitabine treatment, and survival outcomes were compared.ResultsOne hundred sixteen patients were enrolled: LR-PSS category 1 (n = 12; 10.3%), category 2 (n = 56; 48.3%), and category 3 (n = 48; 41.4%). Survival outcomes differed among the 3 categories (P = .046). The overall survival according to OR showed a significant difference in total patients (P = .008) and category 3 patients (P = .003). We analyzed predictive factors for OR, but no variable was found to significantly affect OR.ConclusionDecitabine treatment showed a survival benefit in the higher-risk group of IPSS lower-risk MDS patients who responded to treatment, and classification using the LR-PSS category was helpful for this subgroup, indicating that decitabine treatment might alter the natural course of disease in these patients.     

Influence of Acute Myeloid Leukemia Progression on the Prognosis of 831 Patients With Myelodysplastic Syndromes From the Argentine Database

BackgroundA large group of patients with myelodysplastic syndromes (MDS) will die of causes intrinsic to bone marrow failure. One third of patients will develop acute myeloid leukemia (AML), which is associated with an extremely poor outcome and a short survival. Our objectives were to analyze the prognostic variables and scoring systems in the attempt to determine the influence of progression on the overall survival of MDS patients.Patients and MethodsWe performed a retrospective analysis of 831 MDS patients, including those from the Argentine Registry.ResultsOf the 831 MDS patients, 158 (19.0%) experienced transformation, with a median overall survival of 17.9 months from diagnosis and 3.5 months after progression. The survival of patients with adverse karyotypes or greater risk, according to the International Prognostic Scoring System-revised (IPSS-R) or World Health Organization-based Prognostic Scoring System (WPSS) was not affected when stratified by patients with and without evolution to AML (P > .05). In contrast, the survival of lower risk patients was significantly reduced for those patients with progression to AML (P < .001) and those younger (P = .024) than those who died of non–AML-related causes. The intermediate-risk patients were heterogeneously distributed; however, an upgrade from a lower IPSS-R to a higher WPSS-hemoglobin risk category was associated with a worse outcome, not affected by progression (P = .420), with a median event-free survival of 16 months.ConclusionThe use of the IPSS-R and WPSS systems simultaneously might help in identifying those patients who require more aggressive treatment. Nevertheless, more efforts are needed to improve the identification of those lower risk patients whose survival is significantly reduced by progression to AML.     

Hypocellularity in myelodysplastic syndrome is an independent factor which predicts a favorable outcome

Hypocellular myelodysplastic syndrome (MDS) represents only a small portion of MDS, of which, the clinical significance has not been well-defined. By using currently accepted age-adjusted criteria to define hypocellularity as <30% in patients <70 years old, and <20% in >70 years old, we identified 163 (15.5%) hypocelluar MDS from 1049 consecutive adult MDS patients over an 11-year period (1995-2006). Compared to normal/hypercellular MDS, hypocellular MDS patients were younger (p<0.01), less anemic (p=0.02), but more neutropenic (p<0.001) and thrombocytopenic (p=0.05), and had a comparable cytogenetic risk group distribution (p=0.09) and international prognostic scores (IPSS, p=0.13). With a median follow-up of 52 months, hypocellular MDS showed a favorable overall survival (56 months versus 28 months, log-rank p<0.0001) over normal/hypocellular MDS, and this survival preference was also demonstrated in all IPSS groups and cytogenetic risk groups, and was independent of all other risk factors (Cox regression test, p=0.01). In conclusion, our study demonstrated that hypocellular MDS has characteristic clinicopathologic features, and bone marrow hypocellularity in MDS is an independent factor which predicts a favorable outcome.     

A prospective,multicenter, observational study of long-term decitabine treatment in patients with myelodysplastic syndrome

This prospective observational study evaluated the efficacy and safety of long-term decitabine treatment in patients with myelodysplastic syndrome (MDS). Decitabine 20 mg/m²/day was administered intravenously for 5 consecutive days every 4 weeks to MDS patients in intermediate-1 or higher International Prognostic Scoring System (IPSS) risk categories. Active antimicrobial prophylaxis was given to prevent infectious complications. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to response were evaluated, as were adverse events. The final analysis included 132 patients. IPSS risk was intermediate-2/high in 34.9% patients. The patients received a median of 5 cycles, with responders receiving a median of 8 cycles (range, 2-30). ORR was 62.9% (complete response [CR], 36; partial response [PR], 3; marrow complete response [mCR], 19; and hematologic improvement, 25). Among responders, 39% showed first response at cycle 3 or later. OS at 2 years was 60.9%, with 17% progressing to acute myeloid leukemia. PFS at 2 years was 51.0%. Patients achieving mCR showed comparable survival outcomes to those with CR/PR. With active antibiotic prophylaxis, febrile neutropenia events occurred in 61 of 1,033 (6%) cycles. Long-term decitabine treatment with antibiotic prophylaxis showed favorable outcomes in MDS patients, and mCR predicted favorable survival outcomes.     

Reduced expression of FLIP SHORT in bone marrow of low risk myelodysplastic syndrome

Apoptosis is dysregulated in patients with myelodysplastic syndrome (MDS) and acute myelogenous leukaemia (AML). FLIP (FLICE (FAS-associated death-domain-like IL-1 beta-converting enzyme)-inhibitory protein) has been described as an anti-apoptotic protein. Here, we characterize the expression level of FLIP(LONG) and FLIP(SHORT) mRNA in bone marrow aspirates from 61 patients diagnosed with MDS or AML. FLIP(SHORT) mRNA expression was significantly lower in low risk MDS, compared to high risk MDS, according to FAB classification (RA/RARS versus RAEB/RAEBt, P=0.0127) and IPSS (low risk/intermediate-1 versus intermediate-2/high risk, P=0.0345). Furthermore, FLIP(SHORT) mRNA expression was significantly lower in low risk MDS, compared to MDS-AML/AML de novo (P=0.0006), according to FAB classification. FLIP(LONG) expression did not differ between these groups. Increased levels of FLIP(SHORT) in RAEB and AML may be related to apoptosis resistance in these diseases and to MDS progression.