A Novel Machine Learning Algorithm Predicts Dementia With Lewy Bodies Versus Parkinson's Disease Dementia Based on Clinical and Neuropsychological Scores.

OBJECTIVE: Our aim was to develop a machine learning algorithm based only on non-invasively clinic collectable predictors, for the accurate diagnosis of these disorders. METHODS: This is an ongoing prospective cohort study (ClinicalTrials.gov identifier NCT number NCT04448340) of 78 PDD and 62 DLB subjects whose diagnostic follow-up is available for at least 3 years after the baseline assessment. We used predictors such as clinico-demographic characteristics, 6 neuropsychological tests (mini mental, PD Cognitive Rating Scale, Brief Visuospatial Memory test, Symbol digit written, Wechsler adult intelligence scale, trail making A and B). We investigated logistic regression, K-Nearest Neighbors (K-NNs) Support Vector Machine (SVM), Naïve Bayes classifier, and Ensemble Model for their ability to predict successfully PDD or DLB diagnosis. RESULTS: The K-NN classification model had an accuracy 91.2% of overall cases based on 15 best clinical and cognitive scores achieving 96.42% sensitivity and 81% specificity on discriminating between DLB and PDD. The binomial logistic regression classification model achieved an accuracy of 87.5% based on 15 best features, showing 93.93% sensitivity and 87% specificity. The SVM classification model had an accuracy 84.6% of overall cases based on 15 best features achieving 90.62% sensitivity and 78.58% specificity. A model created on Naïve Bayes classification had 82.05% accuracy, 93.10% sensitivity and 74.41% specificity. Finally, an Ensemble model, synthesized by the individual ones, achieved 89.74% accuracy, 93.75% sensitivity and 85.73% specificity. CONCLUSION: Machine learning method predicted with high accuracy, sensitivity and specificity PDD or DLB diagnosis based on non-invasively and easily in-the-clinic and neuropsychological tests.

The effect of 5-azacytidine treatment delays and dose reductions on the prognosis of patients with myelodysplastic syndrome: how to optimize treatment results and outcomes.

The regimen of 5-azacytidine for patients with myelodysplastic syndrome (MDS) has remained unchanged since its first approval. Although several modifications have since been made and delays and dose reductions are common especially during the first treatment cycles, there are minimal data on the prognostic effect of these modifications. In this study, based on data from 897 patients with MDS treated with 5-azacytidine recorded in a national registry, the effect of treatment delays and dose reductions on response, transformation to acute myeloid leukaemia, and survival (after 5-azacytidine initiation, OST ) were analysed. Delays during the first two cycles were noted in 150 patients (16·7%) and were found to adversely affect OST independently of the International Prognostic Scoring System score [hazard ratio (HR), 1·368; P = 0·033] or pre-existing neutropenia (HR, 1·42; P = 0·015). In patients achieving a response, delays before response achievement were correlated with its type (complete remission, 2·8 days/cycle; partial remission, 3·3 days/cycle; haematologic improvement, 5·6 days/cycle; P = 0·041), while delays after response achievement did not have any effect on retention of response or survival. Dose reductions were found to have no prognostic impact. Based on our results, treatment delays especially during the first cycles should be avoided, even in neutropenic patients. This strict strategy may be loosened after achieving a favourable response.

Estimated glomerular filtration rate independently predicts outcome of azacitidine therapy in higher-risk Myelodysplastic syndromes. Results from 536 patients of the Hellenic National Registry of Myelodysplastic and Hypoplastic syndromes.

Higher-risk Myelodysplastic syndromes (MDS) patients undergoing treatment with 5-azacytidine (AZA) are typically elderly with several comorbidities. However, the effect of comorbidities on the effectiveness and safety of AZA in real-world settings remains unclear. We analyzed data from 536 AZA-treated patients with higher-risk MDS, Myelodysplastic/Myeloproliferative neoplasms and low blast count Acute Myeloid Leukemia enrolled to the Hellenic National Registry of Myelodysplastic and Hypoplastic Syndromes. Multivariate analysis adjusted also for the International Prognostic Scoring System (IPSS), its revised version (IPSS-R) and the French Prognostic Scoring System (FPSS), demonstrated independent associations of overall and leukemia-free survival with estimated glomerular filtration rate (eGFR) <45 mL min-1 /1.73 m2 (P = .039, P = .023, respectively), ECOG performance status <2 (P = .015, P = .006), and presence of peripheral blood blasts (P = .008, P = .034), while secondary MDS also correlated with significantly shorter leukemia-free survival (P = .039). Addition of eGFR <45 mL min-1 /1.73 m2 , in IPSS-R and FPSS increased the predictive power of both models. Only FPSS ≤2 and eGFR <45 mL min-1 /1.73 m2 predicted worse response to AZA in multivariate analysis, whereas eGFR <45 mL min-1 /1.73 m2 correlated significantly with death from hemorrhage (P = .003) and cardiovascular complications (P = .006). In conclusion, in the second largest real-world series of AZA-treated MDS patients, we show that an eGFR <45 mL min-1 /1.73 m2 is an independent predictor of worse response and survival. This higher cut-off, instead of the commonly used serum creatinine >2 mg/dL, can be utilized as a more precise indicator of renal comorbidity during AZA therapy. Incorporation of eGFR in the prognostic assessment of AZA-treated MDS patients may prove useful not only in routine practice, but also for the appropriate patient stratification in clinical trials with AZA combinations.

Real-world data on incidence, clinical characteristics and outcome of patients with macrofocal multiple myeloma (MFMM) in the era of novel therapies: A study of the Greco-Israeli collaborative myeloma working group.

We investigated incidence, characteristics and outcome of patients with macrofocal multiple myeloma (MFMM) treated mainly with novel therapies. Based on definition (BMPCs <20% and lytic lesions/plasmacytomas, without anemia, renal insufficiency or hypercalcemia) we identified 140 patients with MFMM, among 4650 myeloma patients (3%). Twice the number of patients with typical myeloma were used as controls; 60% were <65 years and 70% had advanced bone disease. Plasmacytomas were more frequent in MFMM compared with standard myeloma (68% vs 15%, P < .05). Adverse prognostic parameters (high lactate dehydrogenase, advanced stage, high risk cytogenetics, immunoparesis) were less common in patients with MFMM compared with controls (P < .05); 90% received novel agents and 47% underwent autologous transplantation upfront; 90% achieved an objective response; 70% had at least very good partial response which was significantly higher compared with controls (P < .05). After a median follow-up of 52 months, 33 patients have died. Early death (<12 months) was infrequent in MFMM. Median progression-free survival and overall survival (OS) were 46 and 129 months respectively, both significantly longer compared with controls (P < .001). Proteasome inhibitor (PI)-based therapy was the only independent predictor for OS in the multivariate analysis (HR: 3.9; P < .001). In conclusion, MFMM is a distinct entity presented in young and elderly subjects, characterized by limited bone marrow infiltration, advanced bone disease and frequent presence of plasmacytomas; MFMM patients have less often adverse prognostic features and achieve excellent responses and prolonged OS especially when treated with PI-based therapies. Novel imaging will help in a more accurate classification of this entity.

The outcome of patients with high-risk MDS achieving stable disease after treatment with 5-azacytidine: A retrospective analysis of the Hellenic (Greek) MDS Study Group.

The demethylating factor 5-azacytidine (5-AZA) improves survival in intermediate-2 and high-risk myelodysplastic syndrome (MDS) patients [according to the International Prognostic Score System (IPSS)] responding to treatment. However, the outcome of patients achieving stable disease (SD) is unclear. This retrospective study of the Hellenic MDS Study Group included 353 intermediate-2 or high IPSS risk patients treated with 5-AZA. Forty-four out of 86 (51.6%) patients achieving SD and continuing treatment with 5-AZA showed a lower risk of transformation of MDS to acute myeloid leukemia (AML) and increased overall survival (OS), compared to SD patients who discontinued the treatment (estimated median AML-free survival = 38 months, 95% CI = 10.7-65.3 vs 15 months, 95% CI = 10.4-19.6, P < .001; estimated median OS = 20 months, 95% CI = 5.5-34.5 vs 11 months, 95% CI = 5.8-16.2, P < .001). Moreover, SD patients continuing treatment with 5-AZA had no differences in AML-free survival compared to patients showing response to 5-AZA (estimated median AML-free survival = 38 months, 95% CI = 10.7-65.3 vs 31 months, 95% CI = 23.6-38.4, P = .45; estimated median OS 20 months, 95% CI = 5.5-34.5 vs 25 months, 95% CI = 21.3-28.7, P = .50). In conclusion, MDS patients achieving SD in the first 6 months of treatment with 5-AZA as best response should continue receiving 5-AZA as they may benefit from prolonged treatment.

Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival.

We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death.

Correction to: Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival.

The original version of this article contained a mistake. The name of Eirini Katroditou should have been Eirini Katodritou. The original article has been corrected.

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.

"Real-world" data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who were treated according to the standard clinical practice: a study of the Greek Myeloma Study Group.

Lenalidomide and dexamethasone (RD) is a standard of care for relapsed/refractory multiple myeloma (RRMM), but there is limited published data on its efficacy and safety in the "real world" (RW), according to the International Society of Pharmacoeconomics and Outcomes Research definition. We studied 212 RRMM patients who received RD in RW. Objective response (≥PR (partial response)) rate was 77.4 % (complete response (CR), 20.2 %). Median time to first and best response was 2 and 5 months, respectively. Median time to CR when RD was given as 2nd or >2(nd)-line treatment at 4 and 11 months, respectively. Quality of response was independent of previous lines of therapies or previous exposure to thalidomide or bortezomib. Median duration of response was 34.4 months, and it was higher in patients who received RD until progression (not reached versus 19 months, p < 0.001). Improvement of humoral immunity occurred in 60 % of responders (p < 0.001) and in the majority of patients who achieved stable disease. Adverse events were reported in 68.9 % of patients (myelosuppression in 49.4 %) and 12.7 % of patients needed hospitalization. Peripheral neuropathy was observed only in 2.5 % of patients and deep vein thrombosis in 5.7 %. Dose reductions were needed in 31 % of patients and permanent discontinuation in 38.9 %. Median time to treatment discontinuation was 16.8 months. Performance status (PS) and initial lenalidomide dose predicted for treatment discontinuation. Extra-medullary relapses occurred in 3.8 % of patients. Our study confirms that RD is effective and safe in RRMM in the RW; it produces durable responses especially in patients who continue on treatment till progression and improves humoral immunity even in patients with stable disease.

Personalizing Deep Brain Stimulation Therapy for Parkinson's Disease With Whole-Brain MRI Radiomics and Machine Learning.

Background Deep brain stimulation (DBS) is a well-recognised treatment for advanced Parkinson's disease (PD) patients. Structural brain alterations of the white matter can correlate with disease progression and act as a biomarker for DBS therapy outcomes. This study aims to develop a machine learning-driven predictive model for DBS patient selection using whole-brain white matter radiomics and common clinical variables. Methodology A total of 120 PD patients underwent DBS of the subthalamic nucleus. Their therapy effect was assessed at the one-year follow-up with the Unified Parkinson's Disease Rating Scale-part III (UPDRSIII) motor component. Radiomics analysis of whole-brain white matter was performed with PyRadiomics. The following machine learning methods were used: logistic regression (LR), support vector machine, naïve Bayes, K-nearest neighbours, and random forest (RF) to allow prediction of clinically meaningful UPRDSIII motor response before and after. Clinical variables were also added to the model to improve accuracy. Results The RF model showed the best performance on the final whole dataset with an area under the curve (AUC) of 0.99, accuracy of 0.95, sensitivity of 0.93, and specificity of 0.97. At the same time, the LR model showed an AUC of 0.93, accuracy of 0.88, sensitivity of 0.84, and specificity of 0.91. Conclusions Machine learning models can be used in clinical decision support tools which can deliver true personalised therapy recommendations for PD patients. Clinicians and engineers should choose between best-performing, less interpretable models vs. most interpretable, lesser-performing models. Larger clinical trials would allow to build trust among clinicians and patients to widely use these AI tools in the future.

Paradigm shift in Parkinson's disease: using continuous telemonitoring to improve symptoms control. Results from a 2-years journey.

Introduction: Conventional care in Parkinson's disease (PD) faces limitations due to the significant time and location commitments needed for regular assessments, lacking quantitative measurements. Telemonitoring offers clinicians an opportunity to evaluate patient symptomatology throughout the day during activities of daily living. Methods: The progression of PD symptoms over a two-year period was investigated in patients undergoing traditional evaluation, supplemented by insights from ambulatory measurements. Physicians integrated a telemonitoring device, the PDMonitor®, into daily practice, using it for informed medication adjustments. Results: Statistical analyses examining intra-subject changes for 17 subjects revealed a significant relative decrease of -43.9% in the device-reported percentage of time spent in "OFF" state (from 36.2 to 20.3%). Following the 24-month period, the majority of the subjects improved or exhibited stable symptom manifestation. In addition to positively impacting motor symptom control, telemonitoring was found to enhance patient satisfaction about their condition, medication effectiveness, and communication with physicians. Discussion: Considering that motor function is significantly worsened over time in patients with PD, these findings suggest a positive impact of objective telemonitoring on symptoms control. Patient satisfaction regarding disease management through telemonitoring can potentially improve adherence to treatment plans. In conclusion, remote continuous monitoring paves the way for a paradigm shift in PD, focusing on actively managing and potentially improve symptoms control.

The incidence of myelodysplastic syndromes in Western Greece is increasing.

Descriptive epidemiology of the myelodysplastic syndromes (MDS) is always interesting and may reveal time-dependent and geographical variations, as well as occupational exposure. Epidemiological data in Greece are not available by now. We have collected and analyzed medical records of all patients with a documented diagnosis of MDS, performed by an expert hematologist and/or hematopathologist, in the geographical area of Western Greece, during the 20-year period, defined between 1990 and 2009. We have then calculated and described demographic and clinical features of the diagnosed MDS patient population, and assessed the incidence and prevalence rates of MDS in Western Greece, during the above-mentioned period. A total of 855 patients with newly diagnosed MDS have been identified. Refractory anemia was the most common subtype in both FAB and WHO classification systems and in both genders. Del-5q and RARS were more commonly encountered among females, and the dysplastic subtype of chronic myelomonocytic leukemia among males. Trisomy 8 was the most common single cytogenetic abnormality. The crude mean annual incidence rate of MDS was 6.0 per 100,000 inhabitants aged ≥15 years old (all subtypes according to FAB), and it was 4.8 per 100,000 when CMML and RAEB-T were excluded. Crude incidence rate was higher in rural than in urban areas, but this finding was not confirmed after age standardization. Age-standardized mean annual incidence rate in men was 7.9/100,000 and in women 3.4/100,000. A continuously increasing incidence rate of MDS has been observed throughout the study period.

New­onset non­motor symptoms in patients with Parkinson's disease and post­COVID­19 syndrome: A prospective cross­sectional study.

The clinical range of post-coronavirus disease 2019 (COVID-19) symptoms in patients with Parkinson's disease (PD) has not yet been thoroughly characterized, with the exception of a few small case studies. The aim of the present study was to investigate the motor and non-motor progression of patients with PD (PWP) and post-COVID-19 syndrome (PCS) at baseline and at 6 months after infection with COVID-19. A cross-sectional prospective study of 38 PWP+/PCS+ and 20 PWP+/PCS- matched for age, sex and disease duration was conducted. All patients were assessed at baseline and at 6 months using a structured clinicodemographic questionnaire, the Unified Parkinson's Disease Rating Scale Part III (the UPDRS III), the Montreal Cognitive Assessment, the Hoehn and Yahr scale, the Geriatric Depression Scale and the levodopa equivalent daily dose (LEDD). There was a statistically significant difference in the LEDD (P=0.039) and UPDRS III (P=0.001) at baseline and at 6 months after infection with COVID-19 between the PWP with PCS groups. The most common non-motor PCS symptoms were anosmia/hyposmia, sore throat, dysgeusia and skin rashes. There was no statistically significant difference in demographics or specific scores between the two groups, indicating that no prognostic factor for PCS in PWP could be identified. The novelty of the present study is that it suggests the new onset of non-motor PCS symptoms of PWP with a mild to moderate stage.

The Assessment of the Socioemotional Disorder in Neurodegenerative Diseases with the Revised Self-Monitoring Scale (RSMS).

BACKGROUND: Social cognition helps people to understand their own and others' behavior and to modulate the way of thinking and acting in different social situations. Rapid and accurate diagnoses of neurodegenerative diseases are essential, as social cognition is affected by these diseases. The Revised Self-Monitoring Scale (RSMS) is a scale that detects social-emotional cognition deficits. AIM: The aim of the current study is to examine how socioemotional parameters are affected by neurodegenerative diseases and whether the RSMS can discern these disorders based on the socioemotional parameters in the Greek population. METHODS/DESIGN: A total of 331 dementia subjects were included. Mini Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination (Revised, ACE-R) measurements were used in order to assess the cognitive deficits. The Neuropsychiatric Inventory (NPI) was used for the evaluation of the neuropsychiatric symptoms. The RSMS and its two subscales was used in order to detect the socioemotional deficits. RESULTS: The RSMS and its two subscales (RSMS_EX and RSMS_SP) can effectively detect neurodegenerative diseases. The RSMS can detect bvFTD in Alzheimer's Disease (AD), AD in a healthy cohort, behavioral variant Frontotemporal Dementia (bvFTD) in a healthy cohort, bvFTD in Parkinson's Disease (PD) and Frontotemporal Semantic Dementia (FTD/SD) in a healthy cohort. It is a useful tool in order to detect frontotemporal dementias. RSMS correlated negatively with the NPI questionnaire total and the subcategories of apathy, disinhibition and eating disorders. The RSMS results are associated with the ACE-R score (specifically verbal fluency). CONCLUSIONS: The RSMS is a helpful tool in order to identify socioemotional deficits in neurodegenerative dementias. It is also a useful scale that can discern bvFTD and svPPA in AD patients. A worse RSMS score correlates with a worse ACE-R and NPI. It seems to be a useful scale that can reliably measure social behavior in non-reversible neurodegenerative disorders, such as AD, FTD (bvFTD, svPPA), PDD and PD. The results also apply to the Greek population.

Clock-Drawing Tasks as Predictive Measurements for Disease Classification Among Patients With Parkinson's Disease and Essential Tremor.

Background Nonmotor cognitive symptoms are widely being recognized in both Parkinson's Disease (PD) and Essential Tremor (ET), the two most common movement disorders. Clock-drawing (CD) test seems to be impaired early in the process of cognitive (executive) decline in PD. However, the optimal measures for detecting cognitive changes in ET patients have not been established. Examining whether the CD test is a quick test could identify frontal and visuospatial deficits in patients with Parkinson's disease (PD) and essential tremor (ET). Methods Visuospatial performance was assessed in 58 consecutive patients with ET and 75 with PD and 22 healthy controls (HC) who visited two neurological clinics of Athens in Greece. The CD and copy (CC) items of the PD-Cognitive Rating Scale were used as a test of visuospatial function. Results Both CD and CC scores were lower for ET compared to PD patients and HC (p=<0.001 for both comparisons). A binomial logistic regression showed that both CD and CC items predict if participants had ET or PD with high sensitivity 94.7% and specificity 87.9% and an area under the curve (AUC) 0.980 (95% confidence interval, 0.962-0.997). The model explained 86.1% (Nagelkerke R2) of the variance in the disease variable (ET/PD) and correctly classified 91.7% of the cases. Conclusion Patients with ET have more visuospatial deficits compared to PD and HC. CD task may be an easy, useful tool to track cognitive changes in nondemented patients with ET in clinical practice.

Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World "POWERFUL" Study.

The "POWERFUL" multicenter, retrospective, and prospective study investigated the effectiveness of pomalidomide plus low-dose dexamethasone (POM/LoDex) therapy in relapsed/refractory multiple myeloma in routine care in Greece. Ninety-nine eligible adult patients treated with POM/LoDex according to the approved label after having received ≥2 prior therapies, including lenalidomide and bortezomib, were consecutively enrolled between 16 November 2017 and 21 February 2019 in 18 hematology departments. Fifty patients (50.5%) started POM/LoDex as third-line treatment. During the treatment period (median: 8.3 months; range: 0.3-47.6 months), the median POM dose was 4 mg/day, and 31.3% of the patients received additional antimyeloma agents. The overall response rate was 32.3%. During a median follow-up period of 13.8 months (Kaplan-Meier estimate), the median progression-free survival (PFS) was 10.5 months (95% CI: 7.4-14.4). The PFS was not significantly different between patients receiving POM/LoDex in the third versus later line of therapy, nor between patients receiving concomitant antimyeloma therapy versus POM/LoDEx doublet. During the prospective safety data collection period (median: 7.6 months) among patients with prospective follow-up (N = 75), POM-related adverse event incidence rate was 42.7% (serious: 18.7%; grade ≥ 3 hematological POM-related adverse events: 8.0%). Only neutropenia (13.3%) was reported at a frequency ≥10%. In conclusion, in this real-world study, POM/LoDex displayed a long PFS with no new safety signals emerging.

Serum ferritin and ECOG performance status predict the response and improve the prognostic value of IPSS or IPSS-R in patients with high-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia treated with 5-azacytidine: a retrospective analysis of the Hellenic national registry of myelodysplastic and hypoplastic syndromes.

BACKGROUND: 5-azacytidine (5-AZA) improves survival of patients with higher-risk myelodysplastic syndromes (MDSs) and oligoblastic acute myeloid leukemia (AML); however, predictive factors for response and outcome have not been consistently studied. METHODS: This study of the Hellenic MDS Study Group included 687 consecutive patients with higher-risk MDS and oligoblastic AML treated with 5-AZA. RESULTS: The International Prognostic Scoring System (IPSS) revised version (IPSS-R), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 or 1 versus ⩾2) and baseline serum ferritin (SF) levels > 520 ng/ml were shown to independently predict response to 5-AZA. In the survival analysis, the IPSS and IPSS-R risk classification systems along with the ECOG PS and SF levels > 520 ng/ml proved to be independent prognosticators for overall survival (OS), as well as for leukemia-free survival (LFS). Next, we built new multivariate models for OS and LFS, incorporating only ECOG PS and SF levels besides IPSS or IPSS-R risk classification systems. Thereby, the new modified IPSS and IPSS-R risk classification systems (H-PSS, H-PSS-R) could each discriminate a low, an intermediate and a high-risk patient group regarding OS and LFS. The H-PSS and H-PSS-R proved to be better predictors of OS than their previous counterparts as well as the French prognostic score, while the most powerful OS predictor was the new, H-PSS-R system. CONCLUSIONS: ECOG PS and SF levels > 520 ng/ml independently predict response to 5-AZA, OS and LFS. Their incorporation in the IPSS and IPSS-R scores enhances these scores' predictive power in 5-AZA-treated higher-risk MDS and oligoblastic AML patients.

Characteristics of Long-Term Survival in Patients With Myelodysplastic Syndrome Treated With 5-Azacyditine: Results From the Hellenic 5-Azacytidine Registry.

BACKGROUND: Hypomethylating agents have altered the prognosis of myelodysplastic syndrome (MDS) so that long-term survival is now a feasible treatment goal. PATIENTS AND METHODS: We analyzed data from patients with MDS treated with 5-azacytidine recorded in the Hellenic 5-azacytidine registry. We divided patients, on the basis of their survival after 5-azacytidine initiation (OST), in groups of long-term survivors (Q3 and P90 group with OST above the third quartile and the 90th percentile of the whole group, respectively) and short-term survivors comprising the remaining patients, and compared the characteristics between the groups. The study included 626 patients, 157 in the Q3 group and 63 in the P90 group. RESULTS: Categorization per the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), and World Health Organization-based prognostic scoring system (WPSS) was found to predict long-term survival, while multivariate analysis revealed that response to 5-azacytidine was the strongest predictor of long-term survival. Nevertheless, patients with hematologic improvement (HI) and stable disease (SD) were equally distributed in the groups of short- and long-term survival. CONCLUSION: SD should not be considered a poor treatment response and should not be grouped with failure, while HI offers similar prognosis to SD and thus should not be grouped with complete and partial remission. Patients with SD should continue treatment with 5-azacytidine.

The prognostic significance of chromosome 17 abnormalities in patients with myelodysplastic syndrome treated with 5-azacytidine: Results from the Hellenic 5-azacytidine registry.

In patients with myelodysplastic syndrome (MDS), the prognostic significance of chromosome 17 abnormalities has not yet been fully elucidated, except for isochromosome 17q that has been characterized as an intermediate risk abnormality in the Revised International Prognostic Scoring System (IPSS-R). To further characterize the prognostic significance of chromosome 17 abnormalities we analyzed the hematologic and prognostic characteristics of 548 adult patients with MDS treated with 5-azacytidine through the Hellenic 5-azacytidine registry and found 32 patients with a chromosome 17 abnormality (6 with i[17q], 15 with -17, 3 with add[17p] and the rest with other rarer abnormalities, mostly translocations). The presence of a chromosome 17 abnormality was correlated with poor prognostic features (high IPSS, IPSS-R, and WPSS scores) and a low overall survival rate (15.7 vs 36.4 months for patients without chromosome 17 abnormalities, Kaplan-Meier, Log Rank P < 0.00001), but these results were confounded by the fact that most (92.3%) of the cases with a chromosome 17 abnormality (with the exception of i(17q) that was found in all cases as an isolated abnormality) were found in the context of a complex karyotype. Nevertheless, one should not ignore the contribution of chromosome 17 abnormalities to the prognostic significance of a complex karyotype since 33.8% of complex karyotypes encompassed a chromosome 17 abnormality.