ALBERT

Description: Background. MDS may be characterized by hypocellular marrow, irrespective of their WHO classification or molecular characteristics. Their prognostic weight must still be completely evaluated. MDS with hypocellular marrow tend to be considered an aplastic anemia "overlap syndrome" or a pre-aplastic anemia stage. There are no strong specific therapy recommendations, and large studies analyzing the outcome of hypocellular MDS are lacking. While selective sensitivity to immunosuppressive therapy is suggested, evidence in this sense is controversial. Aims. We wanted to evaluate the clinical characteristics, outcome and choice of therapy of patients with hypocellular MDS and compare them with normocellular MDS. Methods. We analyzed 2559 MDS cases with complete clinical annotations and with evaluable bone trephine biopsy, enrolled in our Italian National Registry FISMonlus. In this cohort of patients, 438 had a bone marrow cellularity

Description: Background. A leukaemic evolution is evident in less than 50% of myelodysplastic patients. They can often die of age-related problems which are independent of myelodysplastic syndrome (MDS) itself, and the best therapy is difficult to define for this group of old patients, in which aggressive strategies are at high risk and supportive care can constitute the most useful option. A systematic analysis of causes of death is so far lacking. Aim of the work. To analyse the prognosis of a large group of myelodysplastic syndromes with particular reference to the causes of death. Patients and methods. From January 1999 to June 2005, data from 783 new cases of MDS were prospectively recorded into the Piedmont MDS register through our web site. Thirty two and 68 cases were excluded because RAEB-t and CMMoL respectively. The remaining 680 patients, who are the object of the present analysis, can be subdivided according to the WHO classification as follows: 99 RAEB-II; 160 RAEB-I; 104 RCMD; 317 MDS other than RAEB and RCMD. Data regarding co-morbidity and IPSS score are available for 457 and 404 patients respectively. At the moment of the analysis, 157 deaths were recorded and causes of death were registered for 153 patients. Results. Median age was 73 (range 27–95), with 151 patients (22%) older than 80. One or more co-morbidities were present at diagnosis in 399/457 (87%). The prognostic role of both IPSS scoring system and WHO classification were confirmed. The causes of death were subdivided as follows: complications due to cytopenia and/or leukaemic transformation in 57 patients (37%); infections in 20 patients (13%); other age or co-morbidity related causes in the remaining 76 patients (50%). No significant differences of causes of death were seen according to sex, while deaths from unrelated causes increased with increasing age from 29% under 60 years up to of 61% over 80 years (test for linear trend: p=0.02). Deaths due to cytopenia, and/or leukaemic transformations, and/or infections were more frequent in patients with no co-morbidities (75%), while no differences were seen according to the number of co-morbidities: 44%, 39% and 55% for patients with respectively one, two and three associated diseases. A significant relationship was evident between diagnostic subgroups and deaths from unrelated causes: 21% for RAEB-II; 51% for RAEB-I; 53% for RCMD; 76% for MDS other than RAEB and RCMD (p

Description: BACKGROUND. The International Prognostic Scoring System (IPSS) of myelodysplastic syndromes (MDS) is based on bone marrow blast count, cytogenetic features and number of peripheral cytopenias. Transfusion requirement has been recently proposed as an important risk factor (Malcovati et al JCO23, 7594, 2005), and a new prognostic system (WPSS) has been suggested, based on WHO diagnostic subgroups, cytogenetic abnormalities and transfusion requirements (2005 ASH meeting abs.789). AIM OF THE WORK. To confirm the prognostic role of transfusion requirement and to compare the prognostic value of WPSS to that of IPSS. PATIENTS AND METHODS. The Piedmont MDS register is active since 1999. Clinical and laboratory data of patients were centrally recorded through our web site. Transfusion requirement data were retrospectively obtained from blood banks when possible. IPSS was calculated according to Greenberg et al. (Blood 89, 2079Blood 89, 1997). WPSS was calculated according to Malcovati et al. (2005 ASH meeting abst 789) by summing the score values of the following three variables: cytogenetic abnormalities scored according to the IPSS: 0 for good; 1 for intermediate; 2 for poor; transfusion requirement: 0 for absent; 1 for regular; WHO category: 0 for RA, RARS, 5q-, and unclassifiable; 1 for RCMD and RCMD-RS; 2 for RAEB-I; 3 for RAEB-II. WPSS score values were stratified into the proposed five risk groups: very low (score 0), low (1); intermediate (2); high (3–4); very high (5–6). RESULTS. From June 1999 to December 2004, 762 MDS patients were registered from 37 different institutions. Transfusion information was available for 376 patients. Data on both cytogenetics and transfusion requirements were available for 202 patients who are the object of the present analysis. 132 patients (65 %) needed regular transfusions, while the remaining 70 ones (35 %) did not. In univariate analyses all variables of both IPSS and WPSS scoring systems statistically influenced overall survival (OS). The time from diagnosis to the first transfusion was variable: less than six months in 97 cases (48 %); 6 to 12 months in 15 (7 %); more than 12 months in 20 (10 %). The OS of the 132 transfused patients was significantly worse than that of the 70 non-transfused ones, but the OS of patients who began to require transfusions more than 12 months after diagnosis was not significantly worse than that of not transfused patients. Only patients with an early transfusion requirement (within the first 12 month) had a poor outcome. When considering the prognosis of WHO subgroups the difference in OS between the subgroups 0 and 1 did not reach a significant level (p〉0.05). In stepwise multivariate analysis the best prognostic factors were blast count, peripheral cytopenias and cytogenetic abnormalities. When the IPSS variables were included into the Cox model, neither WHO subgroups nor transfusion requirement retained an independent prognostic value. CONCLUSIONS. The prognostic value of transfusion requirement was confirmed, but only patients requiring transfusion within the first 12 months since diagnosis showed a poor outcome. In our experience IPSS model fits prognosis better than WPSS.

Description: Abstract 3807 Background: The prognostic role of serum ferritin (SF) evaluation at baseline in patients (pts) affected by myelodysplastic syndrome (MDS) is still controversial. In fact, increased SF mainly due to transfusion requirement during disease history has a clear negative impact on overall survival (OS) (Malcovati et al., 2006) and also on leukemic evolution (LE) (Sanz, ASH 2008, de Swart ASH 2010) while contrasting data about its role at baseline on OS has been published. Park and colleagues (ASH 2010) failed to identify a negative prognostic impact of SF higher than 300 ng/mL in a cohort of low risk untransfused MDS patients while data from the European LeukemiaNet MDS registry identified SF as an independent prognostic factor for OS and progression-free survival in low- and int-1 MDS (de Swart, Edimburgh 2011). SF can be a marker of iron overload but also of inflammation and little is known about the impact on survival of other iron parameters such as transferrin saturation (TS) or inflammation such as C reactive protein (CRP) in MDS pts at diagnosis. Aim: Aim of our study was to evaluate the prognostic role of iron parameters and inflammation at diagnosis in MDS patients analyzing data collected in the MDS Piedmont Registry. Materials and methods: 1360 patients enrolled in the MDS Piedmont Registry (1999–2010) were analyzed. Patients with information on OS and LE and available baseline SF (n=670), TS (n=299), CRP (n=287) were included in the analysis. Survival analysis was performed using Kaplan-Meier method. Patients were stratified according to a cut off value of 800 ng/mL for SF, 40% for TS and values within or higher the normal range (0,8 mg/dL) for CRP. In order to compare survival curves, log-rank test was used. Cumulative incidence of LE, according to SF, TS and CRP levels, was calculated accounting for death from any causes as a competing event. Results: In the population with SF baseline values, 3-years OS in pts with SF 〈 800 ng/mL was 80.7 (95%CI: 75.8–84.8) and in pts with SF 〉800 ng/mL was 66.1 (95%CI: 46.7–79.8) (p= 0,006). The result seems to be confirmed in the low risk MDS subgroup in toto (n=226) and considering only the untransfused pts (136 cases) (p=0,0073 and p=0,0038 respectively) but no statistically significance in OS of high risk pts (n=108) has been observed. In subjects with available data on TS, 3-years OS for pts with TS lower than 40% was 75.0 (95% CI: 64.2–83.0) while in pts higher than 40% was 72.1 (95%CI: 59.5–81.4) (p=0,1). Finally, in pts with CRP values 3-years OS was 80.8 (95%CI: 69.7–88.2) for patients 〈 0,8 mg/dL and 47.2 (95%CI: 34.5–58.9) for pts 〉 0,8 mg/dL. Also 3-year cumulative incidence of LE was higher in pts with SF 〉 800 ng/mL [35.8 (95%CI: 20.3–51.2) vs 18.5 (95%CI: 14.4–22.5); p=0,002 ] and in those with CPR 〉 0,8 mg/dL [35.3 (95%CI: 23.9–46.7) vs 12.7 (95%CI: 5.7–19.7); p

Description: Abstract 611 Background: Improvements in hematologic parameters have been associated with iron chelation therapy (ICT) in transfusion-dependent patients with chronic anemia associated with hematologic malignancies. Data from a significant cohort of myelodysplastic syndromes (MDS) patients enrolled in the EPIC study and treated with deferasirox reported a percentage of 22.6% of erythroid responses. Several sporadic reports showed hematologic improvement in patients treated with deferoxamine or deferasirox in patients affected by myelofibrosis (PMF) and Aplastic Anemia (AA). The aim of this study was to retrospectively evaluate the hematologic response in the entire cohort of chronic anemias with iron overload receiving ICT with both deferasirox (DFX) or deferoxamine (DFO) in 6 hematological Italian centers from 1993 to 2011. Methods: 105 patients received ICT for at least 3 months. Sixteen were PMF, 8 AA, 75 MDS, 4 Chronic Myelomonocytic Leukemia (CMML), 2 Acute Myeloid Leukemia (AML). 30 patients received deferoxamine (6 PMF, 3 AA, 1 CMML, 2 AML, 18 MDS), and 68 deferasirox (9 PMF,5 AA, 3 CMML, 51 MDS), and 7 received deferasirox after a prior treatment with deferoxamine (1 PMF, 6 MDS). The median serum ferritin levels at the time of ICT was 1983 ng/ml and it was not significantly different between the two cohorts (p=0,8). Patients, at the time of ICT, had transfused a median of 30 Units of RBC (40 in the DFO cohort and 24.5 in DFX cohort, p=0.001). 25 out of 105 were receiving EPO therapy at the time of chelation, started at least 6 months before ICT, without a significant clinical improvement and three were receiving a JAK2 inhibitor started at least 1 year before ICT. Patients receiving any kind of therapy able to modify the erythroid response including azacitidine were excluded as well as patients receiving EPO started less than 6 months before ICT or JAK2 inhibitors or immunosuppressive therapy less than 12 months before. Hematological response (HR) was evaluated as follow: Achieving a RBC transfusion independency (complete HR) or Hematological improvement (HI-e) for patients showing a Hb increase of 1.5 g/dL or a reduction of 4 RBC transfusions/8 weeks (IWG 2006). Results: We retrospectively analyzed an unselected cohort of patients with transfusion dependent iron overload affected by different hematologic malignancies who received ICT outside clinical trials thus allowing the inclusion of high risk MDS/AML. 13 patients were not evaluable because they were receiving ICT for less than 3 months. 41 patients out of 92 (42.7%) evaluable patients achieved a hematologic response. In details: 18 (19,5%) became completely RBC transfusion independent. Six (1 AA, 3 RARS, 1 RCMD, 1 AML) were under DFO treatment and 12 (3 AA, 2 RA, 3 RARS, 1 RAEBII, 1 CMML, 2 PMF) under DFX. In addition, all 4 AA patients who achieved transfusion independency significantly increased the number of platelets ( median 17.000/mm3 before ICT and 35.000 and 55.000 after 6 and 12 months of ICT). Median time to response was 15 months for DFO and 3 months for DFX. 16 patients (17.3%) (6 RA, 4 RARS,1 RCMD, 1 RAEB, 4 PMF) obtained HI-e defined as a reduction of 4 U/8 weeks (5 in DFO and 11 in DFX cohorts) after a median of 6 months for both DFO and DFX. HI-e defined as an increased of 1.5 g/dL was observed in 7 patients (7.6%) ( 4 RA, 1 RARS, 1 RCMD, 1 PMF) after a median of 6 months for DFO and 3 for DFX. The hematologic improvement is not strictly related to an effective reduction of serum ferritin (p=0,4). Conclusions: Our data show a high rate of complete responses, mainly in AA and RARS but also in high risk MDS/AML representing 11% of those achieving complete transfusion independency. Notably 50% of AA achieved RBC and platelet transfusion independency. Despite the limitation due to the retrospective collection of data we suggest the ICT could result in hematologic improvement in a wide population including patients who are, at present, outside the published ICT guidelines. This study warrants further investigation on the mechanism of action of ICT in inducing erythroid response. Disclosures: Saglio: Novartis, Brystol Myers: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Description: Aim: to analyse the incidence and risk factors of cytomegalovirus (CMV) infection after ASTC. Methods: 129 pts who underwent ASCT in our Institution from June 1997 to June 2004 were analysed retrospectively ( 40 NHL, 66 MM, 8 HD, 8AML, 7CLL). Conditioning regimen consisted in MitoMel in NHL, Melphalan in MM (100–200/m2) and BEAM in AML and CLL. All patients were monitored with Ag pp65 twice weekly from conditioning therapy to hematological recovery. CMV prophylaxis consisted of acyclovir (400 mg p.o. twice daily) and the use of leucocyte-depleted blood products. Following the report of a positive CMV Ag all patients were treated with ganciclovir 5 mg/kg or foscarnet 90 mg/kg twice daily for 2 weeks or until the test was negative. Results: we observed 8 CMV Ag positive: 5 were MM in RP at the transplant and 2 out of 3 NHL were heavily pretreated. Six patients were older than 60 years. The number of CD34 infused was 3.8x106/kg (range 3.1–5.1 ). The mean time for PMN 〉 500/ul and platelets 〉 30.000/ul was respectively 11 and 21 days. CMV Ag occurred after a mean time of 21 days (4–45) following ASCT. All patients with a positive CMV Ag were febrile. CMV infection was considered the sole cause of fever in 4 pts; 2 had antibiotic-resistant fever, 1 acute enteritis and 1 pneumonia. The remaining 4 pts had concomitant sepsis: Klebsiella, Pseudomonas, Streptococcus Pneumoniae and Staphylococcus Epidermidis. Seven pts had CMV Ag levels 〉5/200000 cells and one pt 〉2/200000 at presentation. The resolution of fever and clearance of CMV Ag occurred after 5.6 days (3–9) from the start of antiviral treatment, but in 2 pts was delayed (respectively 14 and 18 days). Of note, these two pts had the highest CMV Ag levels observed (350 and 961) and one treated with foscarnet developed acute renal failure. Conclusion: 1) CMV infection is an infrequent complication of ASCT( 6,2%) 2) CMV Ag detection was unrelated to the number of CD34 infused and the duration of neutropenia. 3) Pts heavly pretreated, febrile or with sepsis had high rates of CMV reactivation and disease. This subset of pts require more frequent diagnostic evaluation and prompt antiviral therapy.

Description: Introduction Erythropoiesis stimulating agents (ESAs) have been demonstrated to reduce the transfusion requirements in International Prognostic Scoring System (IPSS) low/Int-1 risk MDS patients and response to ESAs is associated with an improved quality of life. Response to ESAs varies from 20 to 60% according to the different studies and an association between ESAs response and a better overall survival (OS), without any disease evolution to AML has been reported. Aim of our study is to analyze the real life use of ESAs in Italy and to assess which group of lower risk MDS patients can benefit more by this treatment. Methods From 1999 to 30 Jun 2013, 2487 patients affected by MDS were included in the Network of the Italian MDS Registries. Morphological MDS diagnosis was confirmed. Among them, 1411 IPSS low/int-1 patients with follow-up data available were selected. Furthermore we excluded the following cases: 87 patients who were treated at any time by azacytidine (n=61) or lenalidomide (n=26), 95 patients with WHO 2002 diagnosis of CMML and aCML, 96 patients with incomplete data, 84 patients unhomogeneously treated with ESAs other than EPO alpha. We obtained a final data base of 1049 cases. OS and leukemic evolution (LE) according to EPO treatment were analyzed using the Kaplan-Meier product-limit survival curve estimates and log-rank tests. Results Median age was 74 years, 59% of the patients were male and 41 % female. WHO 2002 classification was as follows: 296 (28 %) Refractory Anemia, 347 (33 %) refractory cytopenia with multilineage dysplasia, 94 (9%) refractory anemia with ringed sideroblasts, 46 (4 %) Del 5q, 188 (18 %) refractory anemia with excess of blasts and 78 (7 %) MDS unclassifiable. Median hemoglobin level at baseline was 10.0 g/dL. One hundred and twenty patients (11%) were previously transfused with a Hb baseline level less than 8.0 g/dL; 448 not yet transfused patients (43%) presented a mild anaemia with Hb ranging from 8 to 10 g/dL and 481 patients (46%) had a Hb level higher than 10 g/dL. Patients classification according to IPSS was as follows: low 55% (n=575); int-1 45% (n=474). 335 (32%) out of 1049 patients received EPO alpha treatment while the remaining 714 patients (68%) were supported without any ESAs treatment. The rate of erythroid response to EPO therapy was 61%. Median duration of response was 82 weeks. The response rate to EPO was significantly higher in non transfused than in transfused patients: 69% versus 14% respectively (p value 〈 0.001). Only 52 out of 1049 patients showed a LE and a higher incidence of LE in EPO treated patients was not observed. Considering the whole group of patients, the OS of EPO treated patients was not statistically different from untreated ones. However EPO responders patients showed a better OS in comparison to both the non responders and non-EPO treated patients (p value 〈 0.05). When we stratified patients according to the basal hemoglobin level (lower than 8 g/dL, from 8 to 10 g/dL and higher than 10 g/dL) in patients with Hb ranging from 8 to 10 g/dL we observed a significant improvement in OS following successful EPO treatment (median survival: EPO vs. non-EPO 64 vs. 43 months respectively; p 10 g/dL. Even if adverse events were not prospectively recorded in the Registry, no frequent thromboembolic events was reported in EPO group in comparison to non treated patients. Conclusions Our survey can suffer from selection bias due to the limits typical of a voluntary-based registry, but it can be considered a good real life picture of EPO alpha therapy in lower risk Italian MDS patients. Our data confirm that EPOa treatment is globally safe and that patients who can benefit more are the mild anemic untransfused subjects, with baseline Hb level ranging from 8 to 10 g/dL. Disclosures: Santini: Celgene: Honoraria; Novartis: Honoraria; GSK: Honoraria; Janssen: Honoraria.

Description: Abstract 943 Introduction: Arsenic trioxide (ATO) inhibits angiogenesis, induces apoptosis and differentiation in variety of malignant cells. Two multicenter phase II studies have documented that ATO has as a moderate activity both in low and high risk myelodysplasia with 19-21% haematological improvement. Ascorbic acid in “vitro” increases in tumor cells the activity of ATO by depleting GSH and inhibiting NF-kb. High EVI-1 levels have been reported to predicted the response to arsenic trioxide and thalidomide combination therapy. We report the results of a multicenter phase II study with combination of arsenic trioxide and acid ascorbic in myelodysplastic patients. Patient eligibility included:a) pts with 3q26 rearrangement or high EVI-1 levels; b) non-RAEB pts at low-intermediate/1 risk who failed a previous therapy; c) RAEB or high-intermediate-2 risk patients not elegible to chemotherapy and/or bone marrow transplant. Study design: Arsenic trioxide was administrated intravenously over 1 hour at the loading dose of 0.30 mg/kg/day for 5 consecutive days, followed by 0.25 mg/kg/day twice weekly for 15 weeks. Ascorbic acid 1000 mg was given IV within 30 minutes after each arsenic trioxide infusion. Response evaluation was scheduled after two and four months of treatment according to the IWG criteria (Cheson 2000) Patients: 44 pts were enrolled .Median age was 71 years (range 47–80). WHO categories were non-RAEB (15 pts), RAEB-1 (12 pts), RAEB-2 (17 pts). 23 patients had a low/intermediate-1 IPSS score; 18 had a high/intermediate-2 risk. Risk category, could not be assessed in 3 pts lacking of cytogenetic data. Before starting therapy EVI-1 was highly expressed in 13 out of 34 evaluated pts (38%); high WT-1 levels was documented in 25 out of 35 pts (71%). 31 pts (57%) were transfusion dependent at baseline. Results: Ten out of 44 evaluable patients obtained a response (23%). They included 1 complete remission, 2 major erythroid hematologic improvement (HI-E major), 3 minor HI-E, 2 major neutrophil improvemet (HI-N) and 2 major trilineage responses. Response rate was 35% in lower risk IPSS patients and 6% in higher risk pts (p 0.05).Only 3 pts with high EVI-1 expression achieved a response. In 8 out of ten responders, the response was evident within the first 8 weeks of treatment. Twenty three (52%) patients discontinued treatment because disease progression (11%), severe adverse events (32%), drug unrelated adverse events (5%), withdrawal of consent (5%). Severe neutropenia and thrombocytopenia were observed respectively in 45% and 23% pts. The other G3-4 adverse events observed were: ATRA-like syndrome (9%), cardiotoxicity (11%) infection (11%), hepatotoxicity (9%). No toxic death was observed. Summary and Conclusions: The combination of ATO and ascorbic acid is tolerable and it is active in about 25% of MDS patients. The addition of ascorbic acid to ATO does not increase neither the toxicity nor the response rate to ATO. The tolerability of this regimen is reduced in elderly and high risk patients. In our study high EVI-1 transcript levels were not confirmed to predict the response to ATO. Disclosures: Off Label Use: Arsenic trioxide is yet approved for the treatment of MDS, even if its efficacy has been shown in other phase II studies.

Description: Abstract 4028 BACKGROUND. The corner stone of the WHO classification and prognostic scores of myelodysplastic syndromes (MDS) is the blast count in bone marrow. The standard cytology evaluation of at least 500 bone marrow cells is easy to perform, but some concerns arise about reproducibility of this method. Nowadays bone marrow trephine biopsy and flow cytometry are frequently considered for the diagnosis of MDS. However there is so far paucity of data comparing cytology, histology and flow cytometry in quantifying bone marrow blasts in order to differentiate non RAEB from BAEB-I and RAEB-II cases. AIM OF THE WORK. The Aim of the work was to analyse the differences and the prognostic impact of cytology, histology and flow cytometry in differentiating non RAEB from BAEB-I and RAEB-II. PATIENTS AND METHODS. Since 1999, clinical and laboratory data from 1256 new cases of MDS were prospectively recorded into the Piemonte MDS Registry. Blast count could be performed with the three different methods: BMC (bone marrow cytology) has been performed in 844 cases, BMH (bone marrow histology) in 874 cases, and BMF (bone marrow flow cytometry) in 636. In order to quantify blasts, immune-histochemistry evaluation of CD34+ cells was used in BMH, while both CD34+ and CD117+ cells were considered in BMF. Out of the total of the 636 patients analysed by BMF only 420 had an accurate and complete registration of CD34 and CD117 positivity and were considered for the present analysis. In two hundred and thirty six cases all three evaluations were contemporary available. The concordance of each diagnostic method with the others and their prognostic value were evaluated in both univariate and multivariate analyses. A comparison between BMC and BMH was available in 571 cases, between BMC and BMF in 228 cases, and between BMH and BMF in 279 cases. RESULTS. The disagreement in classifying patients as non-RAEB or RAEB-I or RAEB-II between BMC and BMH was 156/571 (27%), with BMH over-evaluating blasts in 114/571 cases (20%) and under-evaluating blasts in 42/571 cases (7%). The disagreement between BMC and BMF was 80/228 (35%), with BMF over-evaluating and under-evaluating blast percentage in comparison to BMC in 53/228 (23%) and in 27/228 (12%) cases respectively. The disagreement between BMH and BMF was present in 113/279 (41%), with BMF over-evaluating and under-evaluating blast percentage in comparison to BMH in 44/279 (16%) and in 69/279 (25%) cases respectively. In univariate analysis all three methods of quantifing blasts and differentiating non-RAEB from RAEB-I and RAEB-II retained an important prognostic value for both leukemic evolution and survival. However when the three models were tested in multivariate analysis in order to define the best predictor of leukemic evolution, BMC retained the best predictive value. CONCLUSIONS. When BMH or BMF are used instead of BMC in order differentiate non-RAEB from RAEB-I and RAEB-II, the shift to a different WHO category is evident in at least 30% of patients and BMH and BMF do not play the same role as BMC. BMC still remain the standard method to quantify blasts for classification and prognostic evaluation of MDS. Disclosures: Off Label Use: Lenalidomide in Mantle Cell Lymphoma. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Saglio:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Description: Abstract 1729 Background: Management of neoplastic patients is strongly influenced by comorbidities, especially in more advanced ages. Due to that, comorbidities evaluation is a critical issue in the global assessment of patients (pts) affected by myelodysplastic syndromes (MDS). Until now, there is no agreement on which comorbidity index (CI) is more suitable in this setting and different CI has been proposed. Recently a new MDS-specific score (MDS-CI) has been published by Della Porta et al., while the majority of CI in use has been developed in geriatric oncology setting. One of the most useful is Cumulative Illness Rating Scale of Geriatrics (CIRS-G). Aim of our study: Aim of our study was to test the usefulness of the conventional and easy to apply CIRS-G score among a cohort of MDS pts enrolled in the MDS Piedmont Registry from 1999 to 2010 in predicting OS and leukemic progression. Materials and methods: 788 patients from the MDS Piedmont Registry with CIRS-G evaluation at diagnosis were included in our statistical analysis. 78% of the patients were low and Int-1 IPSS risk, the remaining 22% were Int-2-high risk. The majority of patients (69%) carried an histological diagnosis of non RAEB MDS according to WHO classification, the remaining 31% were RAEB I-II. Age stratification was as follows: 10% up to 60, 23% from 61 to 70, 43% from 71 to 80, 24% over 80 years. Comorbidities with score up to 2 were considered mild while the ones with values higher than 2 were considered severe. We evaluated the global impairment of each patient creating two comorbidity scores based on the number of mild comorbidities (mild comorbidities score, MCS) and severe comorbidities (severe comorbidities score, SCS). Results: The majority of our patients showed only mild comorbidities and the comorbidities with the greater number of patients carrying severe grade of impairment are the cardiac (25%), hypertensive (30%) and endocrinological (20%) ones. COX analysis did not show an impact of comorbidities on leukemic progression risk while there is a statistically significant impact on overall survival of respiratory, renal, urological and osteo-muscular comorbidities (HR respectively of 1,18; 1,3; 1,3; 1,16). There is a trend of increased risk of non MDS related death in patients with severe grade of each comorbidity. Then we set up a Fine and Gray regression model in order to evaluate the global impact of comorbidities on leukemic progression and overall survival according to SCS and MCS. Neither SCS nor MCS showed an impact on the leukemic progression risk. Considering overall survival (OS), MCS showed a HR of 1,12 (p= 0,009) and moreover SCS has a strong impact on the risk of death (HR 1,59; p= 0,000). MCS remains statistically significant in low IPSS risk patients (p