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Objectives The purpose of this study was to assess the responsiveness of the newly developed Geriatric Assessment in Hematology (GAH) scale to clinical change in older patients diagnosed with hematologic malignancies. Methods A prospective observational study conducted in 164 patients aged ≥ 65 years and diagnosed with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), multiple myeloma (MM), or chronic lymphocytic leukemia (CLL). Responsiveness of the GAH scales was studied by means of the Eastern Cooperative Oncology Group (ECOG) score, the Karnofsky performance status (KPS) score, the visual analog scale (VAS), and the physician's subjective assessment, used as clinical anchors to identify whether patients had changed clinically (either improved or worsened) or not since the baseline visit. Responsiveness was evaluated on the basis of effect size (ES). Results 164 patients (men, 63.7%; median age, 77.0 (72.8–81.4) participated. Statistically significant correlations were obtained between the investigator's qualitative assessment and changes in ECOG, KPS, and VAS scores. Likewise, a statistically significant correlation was obtained between the investigator's qualitative assessment and changes in the GAH scale score. Responsiveness of the GAH scale to detect clinical change was satisfactory (ES 0.34). Conclusion Findings confirm that the GAH scale is responsive to clinical changes in patients' health status. Additionally, the GAH scale is a promising tool to improve clinical decision-making in older patients with hematological malignancies.

Introduction: Lenalidomide is a potent drug with pleiotropic effects in patients with myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 5 [del(5q)]. The clinical efficacy of lenalidomide in MDS patients has been extensively reviewed and although the mechanisms of action in del(5q) clone have been previously described, in vivo sequential studies of modulatory effect on T lymphocytes are lacking. Our study was conducted in patients included in the Sintra-REV Clinical Trial: Lenalidomide (Revlimid) phase III, multicenter, randomized, double-blind study versus placebo in patients with low-risk MDS (low and intermediate IPSS-1) with del(5q), with anemia (HB≤12gr/dl) and without transfusion needs. Aim: The aim of this study was to explore the effect of lenalidomide in T-lymphocytes in MDS patients with del(5q) and without transfusion dependence. Materials and Methods: Sequential study was carried out in 26 samples from 13 paired MDS patients with del (5q). Seven out 13 were treated with lenalidomide and achieved a major erythroid and cytogenetic response. Peripheral blood (PB) samples were collected before and one month after treatment in treated-patients and at the same time points for non-treated patients. CD3+ cells were collected from PB samples and total RNA was isolated. SureSelect Strand Specific RNA library (Agilent Technologies) was applied to study changes in RNA levels. Raw reads were aligned against the Human genome GRCh37 using the STAR aligner. Counts were assigned to Ensembl gene IDs through HTseq using its UNION version. Differential gene expression was determined with DESeq2, considering as statistically significant those genes with FDR < 0.05. Pathway over-representation analysis (ORA) was conducted in the Webgestalt suite. Results: 332 genes were differentially expressed in CD3+ lymphocytes one month after lenalidomide treatment in our cohort of patients; 199 of them were over-expressed after the administration of this drug (Fig 1a). Of note, none of them were observed in non-treated patients after one month. The ORA revealed significant differences in the gene expression profile of sixteen cytokines and enrichment of genes of the cell cycle pathway (35 genes). The most relevant up-regulated cytokines were: IL10, TNFSF10, IFNGand IL6. These data explain lenalidomide-induced activation of an antileukemic immune response and secretion of anti-inflammatory cytokines. Although lenalidomide has been reported to reduce the expression of IL6 secreted by myeloid cell derived from MDS clon, we have observed upregulation of this gene in T-lymphocytes. Moreover, our study showed a downregulation of MBP6 that may help to correct the anemia and also attenuate inflammation signaling in MDS patients with del(5q) (Fig 1b). In addition, the most represented up-regulated genes related to cell cycle pathway were: cyclines (CCNB1, CCNB2, CDK1), centromere genes (CENPE, CENPM, CENPU), kinesin family members (KIF18A, KIF23, KIF2C), BUB1 mitotic checkpoint genes (BUB1, BUB1B), and genes involved in cell division (CDC6, CDC7,CDC25A). It has been described that lenalidomide inhibits CDC25A selectively in the del(5q) clone resulting in G2/M arrest and apoptosis. By contrast, our study showed that this gene was upregulated in T-lymphocytes promoting cell cycle and proliferation of these cells (Fig 1b). Conclusions: The immunomodulatory properties of lenalidomide can be summarized in two: a) regulation of antileukemic and anti-inflammatory cytokines production, b) activation of cell cycle and proliferation in T cells. To our knowledge, this is the first report describing RNA expression profiles in PB CD3+ lymphocytes collected from lenalidomide-treated del(5q) patients, contributing to overall understanding of lenalidomide action. Disclosures Sanz: Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; LaHoffman Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Ltd.: Membership on an entity's Board of Directors or advisory committees; Helsinn: Membership on an entity's Board of Directors or advisory committees. Fenaux:Abbvie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Diez-Campelo:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. OffLabel Disclosure: Lenalidomide was administered in anemic but not transfusion-dependence patients with low-risk MDS and del(5q)

Background: Most IPSS low and int1 (lower) risk MDS patients with isolated del(5q) develop RBC TD or need treatment for symptomatic anemia early after diagnosis (median time to transfusion/treatment of 20 months, López Cadenas et al abstract 3180 ASH, 2016). Lenalidomide (LEN) is a reference treatment in MDS-del(5q) but approved in many countries only when RBC-TD occurs. LEN directly targets the del(5q) clone improving anemia and quality of life. Limited data also suggest a role of LEN in non-TD patients with del(5q) (Oliva et al Cancer Med 2015), but no randomized trial has assessed the efficacy and tolerance of early LEN treatment in this MDS subset. Material: The Sintra-Rev clinical trial is a phase III European multicenter study in low-risk MDS-del(5q) patients with anemia (Hb Results: Main clinical characteristics of the 61 patients (ITT population) included (Feb-2010 to Feb-2018) are summarized in Table 1: 82% females, median age 72 years (range 37-89), median time since diagnosis 3.6 months, median Hb at inclusion 9.8 g/dL (7.1 - 11.7) g/dL and 93% patients had isolated del(5q). Four patients were excluded due either to screening failure (1 pat) or failure to complete at least 12w of treatment (3 pat). Fifty-seven patients were included in the ITT evaluable population for efficacy and 59 for safety (2 patients did not receive any drug). Median time on treatment was 66 weeks (3-121), 95w in the LEN arm and 42w in the placebo arm (p=0.392). Forty-seven percent patients in the LEN arm successfully completed the study compared to 33% in the placebo arm. After a median follow up of 25.6 months (Q1 16-Q3 39), median OS was not achieved. Among the 57 patients evaluable for efficacy, median time to TD was 75.7 mo for the LEN patients and 25.9 mo for the placebo arm (HR 2.703, 95CI1.162-6.286, p=0.021, figure 1). HI-E response was observed in 72.5% of LEN patients compared to 0% in the placebo arm (p Fifty-eight patients developed at least one adverse event (AE) during the trial (no differences between the LEN and placebo arm), related to the drug 86.8% in the LEN and 33.3% in the placebo arm, respectively (p Conclusions: In this interim analysis we confirm that low dose LEN (5 mg) in anemic non-TD low risk MDS del(5q) patients prolongs the period of time to TD (75.7 mo vs 25.9 mo), improves Hb levels (72.5% of ER) and induces clonal responses (70% complete CyR), ie potentially more responses than in historical series of MDS del(5q) treated with LEN at time of TD, with a manageable safety profile, and no increased progression rate. Longer follow up will be required to assess the effect of early treatment with LEN, and particularly the effect of the early reduction of the del(5q) clone size, on long-term outcomes. Disclosures Hernandez-Rivas: Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Rovi: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees. Thepot:astellas: Honoraria; novartis: Honoraria; sanofi: Honoraria; celgene: Honoraria. Sanz:LaHoffman Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Ltd.: Membership on an entity's Board of Directors or advisory committees; Helsinn: Membership on an entity's Board of Directors or advisory committees. Giagounidis:AMGEN: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Platzbecker:BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Geron: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Götze:Celgene: Research Funding. Fenaux:BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Jazz: Honoraria, Research Funding. Diez-Campelo:Celgene-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. OffLabel Disclosure: LEN IN ANEMIC BUT NOT TD PATIENTS WITH LOW RISK MDS AND DEL(5Q)

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p

Myelodysplastic syndromes (MDS) are the commonest hematologic malignancies in the elderly. Since many patients with MDS actually die from age-related ailments, the very disease burden of MDS remains largely unknown. This registry-based study was aimed at investigating the excess mortality attributable to MDS. We analyzed 7,408 adult patients diagnosed with primary MDS from 1980 to 2014. Excess mortality was estimated by comparing the patients' survival with that expected in the matched general population. Median age of patients was 74 years, 58% were males, and 65% belonged to the lower risk categories of the Revised International Prognostic Scoring System (IPSS-R). Excess mortality accounted for three-fourths of the all-cause mortality and was mainly driven by factors unrelated to leukemic transformation. Excess mortality increased with the IPSS-R risk category [Incidence rate ratio (IRR): 2.1, 95% CI: 1.9-2.3; P < .001]. Older age and male sex retained an independent association with higher excess mortality after discounting demographic effects. Excess mortality increased in the most recent periods just in the higher risk IPSS-R categories (IRR: 1.2; 95% CI: 1.1-1.3 when comparing periods 2007-14, 2000-06, and 1980-99). In conclusion, MDS carry a significant excess mortality, even in the lower risk categories, that is mainly driven by factors unrelated to leukemic transformation, and increases with older age, male sex, and poorer risk categories. Excess mortality has increased in recent years in the higher risk patients, which might be ascribed to a parallel increase in age-related comorbidities. Our results claim for more comprehensive treatment strategies for patients with MDS. Am. J. Hematol. 92:149-154, 2017. © 2016 Wiley Periodicals, Inc.

a b s t r a c t Patients with isolated del(5q) and MDS are considered to have good prognosis as compared to other MDS subtypes. Most patients suffered of anemia and 50% of them required transfusions at diagnosis. It is known that for patients with MDS and del(5q) in transfusion dependence(TD), Lenalidomide is the first choice treatment. However, there are no data regarding natural evolution of anemia in patients diagnosed in MDS and del(5q) without TD, factors that may impact on the development of TD or disease outcome. In the present study we have performed a retrospective multicenter analysis on 83 patients with low-int 1 MDS and del(5q) without TD. During the study 61 patients became TD at a median of 1.7 years and only the Hb level 9 g/dL was associated with poorer TFS (p = 0.007) in the multivariate analysis. Among these 61 TD patients, 49 received treatment (19 Lenalidomide). Median follow up was 48 months, estimated OS at 2 and 5 year was 92% and 50% respectively. In the multivariate analysis for OS, platelets

The natural course of chronic myelomonocytic leukemia (CMML) is highly variable but a widely accepted prognostic scoring system for patients with CMML is not available. The main aim of this study was to develop a new CMML-specific prognostic scoring system (CPSS) in a large series of 558 patients with CMML (training cohort, Spanish Group of Myelodysplastic Syndromes) and to validate it in an independent series of 274 patients (validation cohort, Heinrich Heine University Hospital, Dusseldorf, Germany, and San Matteo Hospital, Pavia, Italy). The most relevant variables for overall survival (OS) and evolution to acute myeloblastic leukemia (AML) were FAB and WHO CMML subtypes, CMML-specific cytogenetic risk classification, and red blood cell (RBC) transfusion dependency. CPSS was able to segregate patients into 4 clearly different risk groups for OS (P < .001) and risk of AML evolution (P < .001) and its predictive capability was confirmed in the validation cohort. An alternative CPSS with hemoglobin instead of RBC transfusion dependency offered almost identical prognostic capability. This study confirms the prognostic impact of FAB and WHO subtypes, recognizes the importance of RBC transfusion dependency and cytogenetics, and offers a simple and powerful CPSS for accurately assessing prognosis and planning therapy in patients with CMML.

Trisomy 8 is the most common chromosomal gain in myelodysplastic syndromes (MDS), however, little is known about the features of MDS with isolated trisomy 8 and the influence of additional cytogenetic aberrations. We determined the characteristics and prognostic factors of 72 patients with trisomy 8 as a single anomaly and analysed also the impact of other aberrations added to trisomy 8 in another 62 patients. According to our study, MDS with isolated trisomy 8 was more frequent in men, with more than one cytopenia in most patients (62%) and having about 4% bone marrow blasts. The multivariate analysis demonstrated that platelet count and percentage bone marrow blasts had the strongest impact on overall survival (OS). The median OS for isolated trisomy 8, trisomy 8 plus one aberration (tr8 + 1), plus two (tr8 + 2) and plus three or more aberrations (tr8 + ≥3) was 34·3, 40, 23·4 and 5·8 months, respectively (P < 0·001). Trisomy 8 confers a poorer prognosis than a normal karyotype in MDS patients with ≥5% bone marrow blasts. This study supports the view that MDS with isolated trisomy 8 should be included in the intermediate cytogenetic risk group. © 2012 Blackwell Publishing Ltd.

BACKGROUND: Red blood cell (RBC) alloimmunization is a major problem in chronically transfused patients because of the risk of hemolytic reactions and limited availability of compatible blood. This study was aimed at determining the characteristics of RBC alloimmunization in transfusion-dependent patients with myelodysplastic syndrome or chronic myelomonocytic leukemia (MDS/CMML). STUDY DESIGN AND METHODS: The transfusion and clinical records of all patients with MDS/CMML seen at our hospital from 1990 to 2009 were reviewed. The cumulative incidence of RBC alloimmunization was calculated by taking death as a competing risk. Incidence rates were compared by Poisson multivariate regression. RESULTS: A total of 272 patients were included. Median age was 74 years; 55% were men and had received a median of 33 (range, 4-421) RBC units. Forty-two (15%) patients formed 81 alloantibodies and seven autoantibodies. Three additional patients developed autoantibodies without alloantibodies. The incidence rate of RBC alloimmunization was 1 per 10.5 person-years and was independent of sex, age, and MDS diagnostic category. The cumulative incidence of alloimmunization increased with the number of RBC transfusions, reaching a plateau at 19.5% after 130 RBC units. The most common antibody specificities were Kell (26 cases), E (19), c (5), and Jka (5). In 26 (62%) of the 42 alloimmunized patients, only the Rh system and Kell were involved. CONCLUSION: RBC alloimmunization occurs in 15% of MDS/CMML patients on chronic transfusion support and mostly involves the Rh system and Kell. Transfusing these patients with extended antigen-matched blood, including Kell and CcEe antigens, would presumably reduce the RBC immunization rate.

BACKGROUND: Abnormalities involving chromosome 7 are frequent in myelodysplastic syndrome (MDS) and suggest a poor prognosis. METHODS: The authors examined the hypothesis that the clinical features and survival associated with isolated deletion (del) of part of the long arm of chromosome 7 (7q) in MDS are different from those associated with isolated monosomy 7 (complete loss of chromosome 7). In total, 133 patients with a diagnosis of de novo MDS (according to the World Health Organization [WHO] classification) and chromosome 7 abnormalities in the Spanish MDS Registry were evaluated retrospectively. Four karyotypic groups were identified: isolated del(7q) (n = 29), isolated monosomy 7 (n = 27), del(7q) with additional abnormalities (n = 24), and monosomy 7 with additional abnormalities (n = 53). RESULTS: Isolated del(7q) was more frequent in patients with less advanced MDS according to the WHO classification or the International Prognostic Scoring System. In addition, isolated del(7q) was associated with fewer blasts in bone marrow than other cytogenetics groups. Survival was significantly superior in patients with isolated del(7) than in those with isolated monosomy 7, del(7q) with additional abnormalities, or monosomy 7 with additional abnormalities. On multivariate analysis, age, the percentage of blasts in bone marrow, and other chromosome 7 abnormalities apart from isolated del(7q) were identified as independent risk factors for survival. CONCLUSIONS: The current results demonstrated that patients who had MDS with isolated del(7q) had some distinct clinical-pathologic characteristics as well as better survival than patients who had MDS with isolated monosomy 7. Cancer 2012;. © 2011 American Cancer Society.

BACKGROUND: Thrombocytopenia is very common in myelodysplastic syndrome (MDS); however, its clinical impact in low-risk patients remains controversial. METHODS: The authors analyzed the incidence and prognostic significance of thrombocytopenia at diagnosis in 2565 de novo MDS patients included in the Spanish MDS Registry. RESULTS: Thrombocytopenia (platelet count

Follicular lymphoma (FL), a typically nodal disease, can arise in extranodal sites in about 10% of cases. The present study aimed to analyse the main differential features of patients with primary extranodal FL. Thirty-nine patients with primary extranodal FL were identified from a series of 354 patients with FL diagnosed at a single institution and their main clinicobiological features were analysed. Twenty patients (5·6%) had a primary extranodal non-cutaneous FL, and 19 (5·4%) a cutaneous FL. BCL2(+) and CD10(+) expression and BCL2/IGHJ@ rearrangement were less frequently observed in cutaneous FL. Absence of 'B'-symptoms, early stage, absence of bone marrow involvement and low-risk Follicular Lymphoma International Prognostic Index (FLIPI) were more frequent in extranodal FL. Five-year overall survival (OS) was 100%, 83% and 78% for cutaneous, non-cutaneous and nodal FL, respectively. When stage I patients were analysed separately, no differences were seen in terms of OS. In multivariate analysis, FLIPI was the most important variable to predict outcome. In conclusion, extranodal FLs, particularly cutaneous, have particular clinico-biological features, which differentiate them from nodal cases. Nevertheless, primary site of the disease is not the main issue to predict outcome.

Transfusion-dependency is associated with poor prognosis in patients with MDS although the causal link for such association is disputed. This study tests thee hypotheses on the association between transfusion burden and prognosis in the MDS: (1) the cumulative transfusion burden is a confounder merely reflecting the time elapsed from diagnosis; (2) it is a surrogate for higher transfusion intensity, which would reflect a more severe disease; and (3) it is the total amount of transfused RBC units that influences on prognosis. We studied 191 transfusion-dependent patients with MDS or chronic myelomonocytic leukemia. Transfusion intensity was calculated at the time of each transfusion as the yearly-equivalent number of RBC units. The main outcome was acute leukemia-free survival from first transfusion. Median transfusion burden was 30 (range: 4-330) RBC units and 112 patients received ≥ 25 units after a median of 9 months from first transfusion. In nested Cox models, having received ≥ 25 RBC units had a significant effect on survival (P < 0.001) that was not abrogated by including follow-up ≥ 9 months as a time-dependent covariate. Including transfusion intensity in the model had a significant effect on leukemia-free survival (P < 0.001) and cancelled the prognostic value of having received ≥ 25 RBC units. In conclusion, transfusion intensity, instead of the cumulative transfusion burden, is the transfusion-related variable really influencing on the prognosis of patients with transfusion-dependent MDS.

The current classification system for Myelodysplastic Syndromes lumps all therapy-related (tMDS) into one subgroup assuming all tMDS had the same poor prognosis. We have put together a database including 2032 patients with a diagnosis of tMDS from several different IWG centers and the MDS clinical research consortium. With the idea of developing an individual scoring system for tMDS, we decided to start by optimizing the cytogenetic part of the IPSSR. First, we did an extensive review of karyotypes. Finally, 1245 patients had complete data and correct ISCN formula to be used for score development. We could show regarding karyotypes there are very limited differences between primary and tMDS. Mainly the distribution of risk groups differs with complex occurring more (37%) and normal karyotypes occurring less frequent, although still accounting for 30%. There are few exceptions that are relatively special for tMDS, like translocations including 11q23. A few karyotypes are less frequent; therefore, we could not evaluate the value of IPSS-R cytogenetics for all karyotypes. However, if we apply IPSS-R cytogenetics to our patient cohort, we can separate 5 different risk groups as in pMDS. We tested the performance of the score by using the Dxy. As main endpoint we chose transformation-free survival giving better information about the severity of the disease compared to the single endpoints survival and AML transformation that where calculated for completeness as well. The Dxy for the IPSS-R cytogenetic part is 0.31 for transformation-free survival. This indicates an effective prognostic performance although not as good as in pMDS. Several attempts were done to develop a tMDS specific cytogenetic score. The best draft scoring component achieves a Dxy of 0.33. Counting the number of aberrations achieves a score of 0.30. If normal clone present or not is added, the performance of this very simple model is improved with a Dxy of 0.32. As we could show, all these different approaches lead to a comparable performance. One can argue that still regarding a few karyotypes the prognostic impact is slightly different between p and tMDS (e.g. +8). On the other hand, the most practical approach seems to be to adopt the original cytogenetic part of the IPSS-R for further score development since clinicians do not need to use different scoring systems for different MDS subtypes. While the final analyses for the development of a tMDS specific risk score are currently under way, extensive calculations regarding the performance of different scores like WHO- (Dxy 0.24), FAB-classification (Dxy 0.19), WPSS-R (Dxy 0.35), IPSS-R (Dxy 0.37), and IPSS-R+age (Dxy 0.36), show all these systems can separate different risk groups within our cohort. However, these results also show an inferior performance of the scoring systems in t compared to pMDS. There are multiple possible reasons for this. The most important seem to be tMDS patients are often not cured from the primary disease and its disease specific risk of death should ideally be considered. Unfortunately, we don't have that data. And second, we included treated as well as untreated patients. It seems not to be feasible otherwise since the selection bias for old unfit patients would be unacceptable. We could show already in pMDS that the score performances are considerably worse if we analyze treated patients and the score performance in our cohort is better if limited to untreated patients. To conclude, we can say existing classification and scoring systems work in tMDS and can separate groups with clearly different risk for death and transformation. Although we could not develop a tMDS specific cytogenetic score this could be seen positively since it underlines tMDS do not seem to be much different regarding disease specific risk. This should initiate a discussion of a revision of the WHO-classification and encourage clinicians to use the existing tools for risk assessment and treatment decisions. A simple solution could be to use the WHO classification for pMDS and precede each subgroup with a t, like tMDS-SLD, and so on. Such an approach would be of importance for patients falsely classified as tMDS. After all this classification is done according to anamnestic information only and sporadic cases cannot be excluded. Until now, in the first analyzes performed with the final tMDS-database, we did not find any indication that risk factors established in pMDS would lose or change their meaning in tMDS. Figure. Figure. Disclosures Komrokji: Celgene: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. List:Celgene: Research Funding. Roboz:Orsenix: Consultancy; Eisai: Consultancy; Novartis: Consultancy; Celltrion: Consultancy; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Janssen Pharmaceuticals: Consultancy; Jazz Pharmaceuticals: Consultancy; Argenx: Consultancy; Janssen Pharmaceuticals: Consultancy; Pfizer: Consultancy; Cellectis: Research Funding; Daiichi Sankyo: Consultancy; Sandoz: Consultancy; Otsuka: Consultancy; Daiichi Sankyo: Consultancy; Eisai: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy; Novartis: Consultancy; Celltrion: Consultancy; Celgene Corporation: Consultancy; Cellectis: Research Funding; Orsenix: Consultancy; Aphivena Therapeutics: Consultancy; Otsuka: Consultancy; Jazz Pharmaceuticals: Consultancy; Sandoz: Consultancy; Roche/Genentech: Consultancy; Aphivena Therapeutics: Consultancy; AbbVie: Consultancy; Bayer: Consultancy; Bayer: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; AbbVie: Consultancy. Döhner:Jazz: Consultancy, Honoraria; Astex Pharmaceuticals: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AROG Pharmaceuticals: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria; AROG Pharmaceuticals: Research Funding; Pfizer: Research Funding; Sunesis: Consultancy, Honoraria, Research Funding; Celator: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Celator: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Bristol Myers Squibb: Research Funding; Astellas: Consultancy, Honoraria; Bristol Myers Squibb: Research Funding; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Jazz: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Valent:Pfizer: Honoraria; Novartis: Honoraria; Incyte: Honoraria. Platzbecker:Celgene: Research Funding. Lübbert:TEVA: Other: Study drug; Celgene: Other: Travel Support; Cheplapharm: Other: Study drug; Janssen: Honoraria, Research Funding. Díez-Campelo:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Stauder:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva: Research Funding. Germing:Janssen: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

Background: Lenalidomide (LEN) is a reference treatment in IPSS low and in1 (lower) risk MDS patients with isolated de(5q) (MDS-del(5q)) and RBC - TD. Most low risk MDS-del(5q) patients with anemia and independent of transfusions develop TD or need of treatment for symptomatic anemia very early after diagnosis (median time to transfusion/treatment of 20 months, López Cadenas et al abstract 3180 ASH, 2016). LEN directly targets the del(5q) clone improving anemia, quality of life and survival in this subset of patients. Limited data also suggest a role of LEN in non-TD patients with del(5q) (Oliva et al Cancer Med 2015). However no prospective randomized study of LEN has been performed in this group of patients. Material: The Sintra-Rev clinical trial is a phase III European multicenter study, in low-risk MDS-del(5q) patients, with anemia (Hb Results: Main clinical characteristics of the 58 patients included are summarized in Table 1: 81% were females, median age was 72 years (37-89), median Hb at inclusion 9.8 g/dL(7.1 - 11.7) g/dL and most patients (86%) had isolated del(5q) cytogenetic abnormality. Three patients were excluded due to screening failures and 58 were finally included in the trial. Seven patients discontinued before 12 weeks: Three developed disease progression (defined as TD), two withdrew consent, one due to changes in patient's status and it was not specified in the remaining patient. Therefore, fifty-four patients were finally evaluable for efficacy and 58 for safety at w12. HI-E was observed in 20/54 patients (37%), minor HI-ER in 6/54 (11%), stable disease in 25/54 (46%) and TD (transfusion dependency) in 3 (6%). In the 26 patients achieving HI-E or minor HI-E, the median Hb level rise was 2.2 g/dL (range 1-4.4) and median Hb level was 12.5 g/dL (9.8-14.2). Cytogenetic response (CyR) was available in 41/54 patients: complete in 16 (30%), partial in 9 (17%), no CyR in 16 (30%) and no available in 13 (23%) patients. 54 patients developed adverse events (AE) in the first 12w, most of them hematological and probably related to the treatment. Hematological toxicity occurred in 74% of patients (neutropenia or thrombocytopenia) and only one third was grade 3/4 (neutropenia 35% or thrombocytopenia 3%). Non-hematological adverse events potentially related to the investigational drug were described in 19 patients (35%) but only 2/19 (11%) were grade 3. Nine serious AE were reported in 7 patients: congestive heart failure (2), vestibular neuritis, polyarthritis, arterial hypertensive crisis, carpal arthritis, respiratory infection, chronic obstructive pulmonary disease exacerbation and blurred vision. Only the last one (blurred vision) was potentially related with the study drug Conclusions: In this preliminary and blinded analysis we confirm a high rate of erythroid and cytogenetic responses early (w12) after study treatment with an adequate safety profile. Unblinded data will be presented at the meeting. Disclosures Platzbecker: Celgene: Research Funding. Götze:JAZZ Pharmaceuticals: Honoraria; Takeda: Honoraria, Other: Travel aid ASH 2017; Novartis: Honoraria; Celgene: Honoraria, Research Funding. Díez-Campelo:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Purpose WHO classification of myeloid malignancies is based mainly on the percentage of bone marrow (BM) blasts. This is considered from total nucleated cells (TNCs), unless there is erythroid-hyperplasia (erythroblasts ≥ 50%), calculated from nonerythroid cells (NECs). In these instances, when BM blasts are ≥ 20%, the disorder is classified as erythroleukemia, and when BM blasts are < 20%, as myelodysplastic syndrome (MDS). In the latter, the percentage of blasts is considered from TNCs. Patients and Methods We assessed the percentage of BM blasts from TNCs and NECs in 3,692 patients with MDS from the Grupo Español de Síndromes Mielodisplásicos, 465 patients with erythroid hyperplasia (MDS-E) and 3,227 patients without erythroid hyperplasia. We evaluated the relevance of both quantifications on classification and prognostication. Results By enumerating blasts systematically from NECs, 22% of patients with MDS-E and 12% with MDS from the whole series diagnosed within WHO categories with < 5% BM blasts, were reclassified into higher-risk categories and showed a poorer overall survival than did those who remained in initial categories (P = .006 and P = .001, respectively). Following WHO recommendations, refractory anemia with excess blasts (RAEB)-2 diagnosis is not possible in MDS-E, as patients with 10% to < 20% BM blasts from TNCs fulfill erythroleukemia criteria; however, by considering blasts from NECs, 72 patients were recoded as RAEB-2 and showed an inferior overall survival than did patients with RAEB-1 without erythroid hyperplasia. Recalculating the International Prognostic Scoring System by enumerating blasts from NECs in MDS-E and in the overall MDS population reclassified approximately 9% of lower-risk patients into higher-risk categories, which indicated the survival expected for higher-risk patients. Conclusion Regardless of the presence of erythroid hyperplasia, calculating the percentage of BM blasts from NECs improves prognostic assessment of MDS. This fact should be considered in future WHO classification reviews.

The benefit of azacitidine treatment in survival of high risk myelodysplastic syndromes (MDS) patients compared to conventional care treatment (CCT) has not been established outside clinical trials. To assess its effectiveness, we compared overall survival between azacitidine and conventional treatment (CCT) in high-risk MDS patients, excluding those undergoing stem cell transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several Cox regression and competing risk models, considering azacitidine as a time-dependent covariate, were used to assess survival and AML progression. Among 821 patients included, 251 received azacitidine. Median survival was 13.4 (11.8–16) months for azacitidine-treated patients and 12.2 (11–14.1) for patients under CCT (P=0.41). In a multivariate model, age, IPSS and LDH were predictors of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence interval 0.86–1.35, P=0.49). However, in patients with chromosome 7 abnormalities, a trend towards a better survival was observed in azacitidine-treated patients (median survival 13.3 [11–18] months) compared to CCT (median survival 8.6 [5–10.4] months, P=0.08). In conclusion, our data show that, in spite of a widespread use of azacitidine, there is a lack of improvement in survival over the years. Identification of predicting factors of response and survival is mandatory., Bernal, T., Martínez-Camblor, P., Sánchez-García, J., De Paz, R., Luño, E., Nomdedeu, B., Ardanaz, M.T., Pedro, C., Amigo, M.L., Xicoy, B., Del Cañizo, C., Tormo, M., Bargay, J., Valcárcel, D., Brunet, S., Benlloch, L., Sanz, G., On behalf of The Spanish Group on Myelodysplastic Syndromes and PETHEMA Foundation, Spanish Society of Hematology

Although specific prognostic models for chronic myelomonocytic leukemia (CMML) exist, few are based on large series of patients. MD Anderson prognostic score (MDAPS) has been the most useful for CMML risk assessment. Due to recent emergence of CMML-specific prognostic scoring system (CPSS) and Mayo prognostic model, we compared the three scores. One hundred forty-six CMML patients diagnosed between 1998 and 2014 were retrospectively analyzed. Univariate analysis was performed to assess prognostic impact on overall survival (OS) and leukemia-free survival (LFS) of the variables composing the scores and all items showed prognostic value on OS with the exception of the presence of circulating immature myeloid cells. Regarding LFS, only CPSS variables, bone marrow blast ≥10% and an absolute monocyte count >10×109/L had an impact. When the scores were applied, all showed an impact on OS and retained their significance in multivariate analysis. By using ROC curves and C-index, CPSS showed a slightly better predictive value for mortality and leukemia transformation. Variables composing the three indexes were compared in multivariate analysis and only CPSS parameters and platelets

BACKGROUND. Anemia occurs as a comorbidity in from 80% to 85% of patients with myelodysplastic syndromes (MDS): It causes fatigue, increases transfusion needs, and reduces quality of life. Darbepoetin α (DA) is an erythropoiesis-stimulating protein (ESP) that is more highly glycosylated and has a longer half-life relative to recombinant human erythropoietin (rHuEPO), thus, allowing less frequent administration, increased convenience, and better compliance. METHODS. This retrospective analysis included 81 patients with MDS who were enrolled at 9 Spanish centers and who received once-weekly, subcutaneous DA (75–300 μg) for 16 weeks. RESULTS. Fifty-five percent of all patients (38 of 69 evaluable patients) achieved responses; 30.4% of were major responses, and 24.6% were minor responses; 64.7% of rHuEPO-naive patients and 45.7% rHuEPO-treated patients responded; and 43.2% had received previous rHuEPO. Most responses (65.8%) occurred at or before Week 8. The median age at diagnosis was 70 years (range, 38–87 years), the median age at the initiation of DA treatment was 75 years (range, 39–91 years), and 56.8% of patients were women. The median time from last ESP dose to DA initiation was 16.8 weeks (range, 0.0–159.0 weeks

Background: Different prognostic scores have been proposed to predict the outcome of follicular lymphoma (FL) patients at diagnosis. A new prognostic index specifically addressing FL patients, the Follicular Lymphoma International Prognostic Index (FLIPI), has recently been developed, which might also be useful in patients with progression. Patients and methods: One hundred and three patients (55 male, 48 female; median age 59 years) with FL in first relapse/progression after an initial response to therapy (50 complete responders/ 53 partial responders) were included in the study. Results: Five-year survival from progression (SFP) was 55% (95% confidence interval 44%-66%). The distribution according to the FLIPI at relapse was 39% good prognosis, 24% intermediate prognosis and 37% poor prognosis. Five-year SFP for these groups were 85%, 79% and 28%, respectively (P

Background: Survival of patients with primary central nervous system lymphoma (PCNSL) has improved with methotrexate-based combination regimens and radiotherapy (RT). However, the prognosis of patients who fail or relapse after initial response is poor. Very little data is available on salvage treatment at recurrence. Patients and methods: Sixteen immunocompetent patients (13 males/three females, median age 54 yr) with refractory (one patient) or recurrent (15 patients) PCNSL, homogeneously treated at diagnosis with the cyclophorphamide, doxorubicin, Vimcritime, dexamethasome/carmuntime, Uimcritime, cytarabine and methotrexate (CHOD/BVAM) and RT regimen, received etoposide (VP-16), ifosfamide and cytarabine (Ara-C) (VIA) chemotherapy as a salvage treatment. VIA included etoposide 100 mg/m2/d days 1–3, ifosfamide 1000 mg/m2/d days 1–5, and cytarabine 2000 mg/m2/12 h day 1. The therapy was repeated every 28 d for a total of planned six cycles. Results: Median time between first complete response (CR) and relapse was 19 months (range: 6–46 months). Thirteen patients (81%) had a performance status ≤2, six had multifocal PCNSL and six (of eight tested) positive cerebrospinal fluid cytology. The median number of courses per patient was four (range: 1–6). Five patients completed the whole VIA therapy. Six patients (37%) achieved CR. After a median follow-up of 15 months for surviving patients, two have relapsed, with a median failure-free survival of 5 months. Twelve patients have died from progression of PCNSL, with a 12-month overall survival of 41% [95% confidence interval (CI): 16–66]. The major toxicity was World Health Organization grade 2–4 neutropenia (69% of patients) and thrombocytopenia (50%). Five patients had grade 3–4 infectious complications. Finally, one patient developed a severe but reversible ifosfamide encephalopathy. Conclusion: The data presented show that the chemotherapy VIA is an effective salvage regimen for patients with recurrent PCNSL.

epartment of Hematology, Hospital Clinic de Barcelona, Villarroel 170, 08036 Barcelona, SpainHematopathology Unit, Pathology Department, Hospital Clinic de Barcelona, Villarroel 70, 08036 Barcelona, SpainDepartment of Hematology, Hospital Clinic de Barcelona, Villarroel 170, 08036 Barcelona, SpainHematopathology Unit, Pathology Department, Hospital linic de Barcelona, Villarroel 170, 08036 Barcelona, SpainDepartment of Hematology, Hospital Clinic de Barcelona, Villarroel 170, 08036 Barcelona, Spain

T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-resistant malignancy with a median survival of 7.5 months. Preliminary results indicated a high remission induction rate with the human CD52 antibody, CAMPATH-1H. This study reports results in 39 patients with T-PLL treated with CAMPATH-1H between March 1993 and May 2000. All but 2 patients had received prior therapy with a variety of agents, including 30 with pentostatin; none achieved complete remission (CR). CAMPATH-1H (30 mg) was administered intravenously 3 times weekly until maximal response. The overall response rate was 76% with 60% CR and 16% partial remission (PR). These responses were durable with a median disease-free interval of 7 months (range, 4-45 months). Survival was significantly prolonged in patients achieving CR compared to PR or no response (NR), including one patient who survived 54 months. Nine patients remain alive up to 29 months after completing therapy. Seven patients received high-dose therapy with autologous stem cell support, 3 of whom remain alive in CR 5, 7, and 15 months after autograft. Stem cell harvests in these patients were uncontaminated with T-PLL cells as demonstrated by dual-color flow cytometry and polymerase chain reaction. Four patients had allogeneic stem cell transplants, 3 from siblings and 1 from a matched unrelated donor. Two had nonmyeloablative conditioning. Three are alive in CR up to 24 months after allograft. The conclusion is that CAMPATH-1H is an effective therapy in T-PLL, producing remissions in more than two thirds of patients. The use of stem cell transplantation to consolidate responses merits further study.

Summary The impact of lenalidomide treatment on long-term outcomes of patients with lower risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)) is unclear. This study used time-dependent multivariate methodology to analyse the influence of lenalidomide therapy on overall survival (OS) and acute myeloblastic leukaemia (AML) progression in 215 patients with International Prognostic Scoring System (IPSS) low or intermediate-1 risk and del(5q). There were significant differences in several relevant characteristics at presentation between patients receiving (n = 86) or not receiving lenalidomide (n = 129). The 5-year time-dependent probabilities of OS and progression to AML were 62% and 31% for patients receiving lenalidomide and 42% and 25% for patients not receiving lenalidomide; differences were not statistically significant in multivariate analysis that included all variables independently associated with those outcomes (OS, P = 0·45; risk of AML, P = 0·31, respectively). Achievement of RBC transfusion independency (P = 0·069) or cytogenetic response (P = 0·021) after lenalidomide was associated with longer OS in multivariate analysis. These data clearly show that response to lenalidomide results in a substantial clinical benefit in lower risk MDS patients with del(5q). Lenalidomide treatment does not appear to increase AML risk in this population of patients.

Purpose Complex karyotype (CK) is the poorest risk factor in patients with myelodysplastic syndrome (MDS). It has recently been reported that monosomal karyotype (MK) worsens the prognosis of patients with CK. Patients and Methods We analyzed 1,054 adult patients with MDS with an abnormal karyotype from the Spanish Registry of MDS. The aim of the study was to describe the incidence, characteristics, and prognosis of MK; the main end points were overall survival (OS) and leukemia-free survival. Results MK was identified in 172 patients (16%), most of whom (88%) presented with CK. Variables significantly associated with OS were age (hazard ratio [HR], 1.90; P < .001), bone marrow (BM) blast percentage (HR, 1.05; P < .001), hemoglobin level (HR, 1.71; P < .001), platelet count (HR, 1.41; P < .001), karyotype complexity (CK [three abnormalities]: HR, 1.81; P = .003; very CK [> three abnormalities]: HR, 2; P < .001), and abnormalities of chromosome 5 and/or 7 (HR, 1.89; P < .001). Variables significantly related to the risk of transformation to acute myeloid leukemia (AML) were higher BM blast percentage (HR, 1.12; P < .001) and karyotype complexity (CK: HR, 2.53; P = .002; very CK: HR, 2.77; P < .001). Conclusion After accounting for karyotype complexity, MK was not associated with OS or evolution to AML. In conclusion, these results demonstrate that the prognostic value of MK in MDS is not independent and is mainly the result of its strong association with number of chromosomal abnormalities.

To develop a prognostic scoring system tailored for therapy-related myelodysplastic syndromes (tMDS), we put together a database containing 1933 patients (pts) with tMDS from Spanish, German, Swiss, Austrian, US, Italian, and Dutch centers diagnosed between 1975-2015. Complete data to calculate the IPSS and IPSS-R were available in 1603 pts. Examining different scoring systems, we found that IPSS and IPSS-R do not risk stratify tMDS as well as they do primary MDS (pMDS), thereby supporting the need for a tMDS-specific score (Kuendgen et al., ASH 2015). The current analysis focuses on cytogenetic information as a potential component of a refined tMDS score, based on this large, unique patient cohort. Of the 1933 pts, 477 had normal karyotype (KT), 197 had missing cytogenetics, while 467 had a karyotype not readily interpretable. Incomplete karyotype descriptions will be reedited for the final evaluation. Of the remaining 1269 pts the most frequent cytogenetic abnormalities (abn) were: -7, del(5q), +mar, +8, del(7q), -5, del(20q), -17, -18, -Y, del(12p), -20, and +1 with >30 cases each. Frequencies are shown in Table 1. Some abn were observed mostly or solely within complex KTs, such as monosomies, except -7. Others, like del(20q) or -Y, are mainly seen as single or double abn, while del(5q), -7, or del(7q) are seen in complex as well as non-complex KTs. The cytogenetic profile overlapped with that of pMDS (most frequent abn: del(5q), -7/del(7q), +8, -18/del(18q), del(20q), -5, -Y, -17/del(17p), +21, and inv(3)/t(3q) (Schanz et al, JCO 2011)), with notable differences including overrepresentation of complete monosomies, a higher frequency of -7 or t(11q23), and a more frequent occurrence of cytogenetic subtypes in complex KTs, which was especially evident in del(5q) occurring as a single abn in 16%, compared to 70% within a complex KT. IPSS-R cytogenetic groups were distributed as follows: Very Good (2%), Good (35%), Int (17%), Poor (15%), Very Poor (32%). Regarding the number of abn (including incomplete KT descriptions) roughly 30% had a normal KT, 20% 1, 10% 2, and 40% ≥3 abn, compared to pMDS: 55% normal KT, 29% 1, 10% 2, and 6% ≥3 abn. To be evaluable for prognostic information, abn should occur in a minimum of 10 pts. As a single aberration this was the case for -7, +8, del(5q), del(20q), del(7q), -Y, and t(11;varia) (q23;varia). Of particular interest, there was no apparent prognostic difference between -7 and del(7q); del(5q) as a single abn was associated with a relatively good survival, while the prognosis was poor with the first additional abn; t(11q23) occurred primarily as a single abn and was associated with an extremely poor prognosis, and prognosis of pts with ≥4 abn was dismal independent of composition (Table 1). To develop a more biologically meaningful scoring system containing homogeneous and prognostically stable groups, we will further combine subgroups with different abn leading to the same cytogenetic consequences. For example, deletions, unbalanced translocations, derivative chromosomes, dicentric chromosomes of 17p, and possibly -17 all lead to a loss of genetic material at the short arm of this respective chromosome affecting TP53. Further information might be derived from analyses of the minimal common deleted regions. For some abn, like del(11q), del(3p), and del(9q), this can be refined to one chromosome band only (table 1). Conclusion: Development of a robust scoring system for all subtypes of tMDS is challenging using existing variables. This focused analysis on the cytogenetic score component shows that favorable KTs are evident in a substantial proportion of pts, in contrast to historic data describing unfavorable cytogenetics in the majority of pts. Although complex and monosomal KTs are overrepresented, this suggests the existence of distinct tMDS-subtypes, although some of these cases might not be truly therapy-induced despite a history of cytotoxic treatment. The next steps will be to analyze the prognosis of the different groups, develop a tMDS cytogenetic score, and examine minimal deleted regions to identify candidate genes for development of tMDS, as well as to describe the possible influence of different primary diseases and treatments (radio- vs chemotherapy, different drugs) on induction of cytogenetic subtypes. Our detailed analysis of tMDS cytogenetics should reveal important prognostic information and is likely to help understand mechanisms of MDS development. Disclosures Komrokji: Novartis: Consultancy, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Sole:Celgene: Membership on an entity's Board of Directors or advisory committees. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees. Roboz:Cellectis: Research Funding; Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy. Steensma:Amgen: Consultancy; Genoptix: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Millenium/Takeda: Consultancy; Ariad: Equity Ownership. Schlenk:Pfizer: Honoraria, Research Funding; Amgen: Research Funding. Valent:Amgen: Honoraria; Deciphera Pharmaceuticals: Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Ariad: Honoraria, Research Funding; Deciphera Pharmaceuticals: Research Funding. Giagounidis:Celgene Corporation: Consultancy. Giagounidis:Celgene Corporation: Consultancy. Platzbecker:Celgene Corporation: Honoraria, Research Funding; TEVA Pharmaceutical Industries: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen-Cilag: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Lübbert:Janssen-Cilag: Other: Travel Funding, Research Funding; Celgene: Other: Travel Funding; Ratiopharm: Other: Study drug valproic acid.

Clinical and prognostic studies were carried out in a series of 143 patients with low-grade (small-lymphocytic, follicular small cleaved cell, follicular mixed small- and large-cell) lymphoma. After treatment with alkylating agents (21.5% cases), combination chemotherapy (73.3%) or other therapies (5.2%), complete response (CR) was obtained in 40.7% of cases and partial response (PR) in 43.7%. The stage of the disease was the most important factor for response. With a median follow-up of 6.5 years, 48.0% (95% Cl: 37.5-58.5) of patients were alive 10 years after diagnosis. Among the initial parameters, advanced stage. B-symptoms, poor performance status, nodal involvement3 sites, extranodal involvementor = 2 sites, WBC countor = 10 x 10(9)/L, leukemic expression, high serum LDH levels, and bone marrow infiltration were all related to survival; treatment modality, however, had no influence on survival. In the multivariate analysis, stage (p = 0.008) and age (p = 0.053) were the most important prognostic factors. When considering response to therapy, both CR (p0.001) and PR (p = 0.003) emerged as the most important predictive variables, with only the absence of B-symptoms retaining its prognostic significance (p = 0.014) among the other parameters. In addition, in CR patients the duration of the response (or = 1 year vs.1 year) was the most significant parameter for survival (p0.001). Finally, the initial stage (p = 0.011) and the histologic subtype (those patients with follicular mixed lymphoma relapsing less frequently than the others) (p = 0.052) were the only significant factors for relapse.

This article describes two patients with localized Castleman's disease (CD) of the mixed hyaline vascular and plasma cell type located at the mesentery of the small bowel, associated with systemic symptoms, anemia, an increased plasma level of acute phase reactants, and systemic amyloidosis. There were amyloid deposits on the vascular walls of the liver, spleen, and mesenteric lymphoid mass. On immunohistochemical studies, amyloid was shown to be of the AA type in both cases. After surgical resection of the mesenteric mass, clinical and laboratory manifestations improved, and the amyloidosis showed no progression in these patients 23 years and 1 year later. The authors' review of the literature shows a striking similarity of CD cases associated with amyloidosis in terms of the abdominal localization of the lymphoid mass, secondary pattern (AA type) of amyloidosis, and improvement of clinical manifestations after removal of the tumor, without progression of amyloid deposition.

Thalidomide is active in patients with refractory myeloma. Seventeen patients (nine men/eight women, median age 73 years) with multiple myeloma (MM) were treated with thalidomide. Fifteen patients had refractory disease and two untested relapse. The median dose of thalidomide was 500 mg (range, 200-800 mg). Nine of the 17 patients (53%) responded. The response rate was significantly higher in patients with no extramedullary disease than in those with soft tissue masses (75% CI: 43-95% versus 0%; P = 0.01)). Of note, no decrease in the size of soft tissue plasmacytomas was observed in all the five patients who had extramedullary involvement. This data suggests that the mechanism of action and effectiveness of thalidomide might depend on the site of the tumour cells.

Background High-dose chemotherapy (HDT) followed by autologous stem-cell transplantation (ASCT) is considered the gold standard in the treatment of patients with relapsed or refractory Hodgkin’s lymphoma (HL). However, the optimal salvage regimen has not yet been established. Patients and methods We retrospectively analyzed the efficacy and toxicity of MINE (mesna, ifosfamide, mitoxantrone, and etoposide) alternated with ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in the treatment of 61 relapsed or refractory HL patients after ABVD-based chemotherapy. Results Overall, 25 patients (41%) achieved a complete response (CR), 23 (38%) a partial response (PR), 4 (7%) a stable disease, and 8 (13%) progressed for an overall response rate of 79%. Response to first-line chemotherapy was the most important prognostic factor for response to MINE–ESHAP (P = 0.041). No grade 4 extrahematologic toxic effects or toxic deaths were observed. Adequate peripheral blood stem-cell collection was achieved in 56 of 59 (95%) mobilized patients. Overall survival and event-free survival after HDT and ASCT were significantly higher for patients achieving CR/PR in comparison with those refractory to MINE–ESHAP (46% and 35% versus 74% and 69%, respectively). Conclusion MINE–ESHAP results in a high response rate with acceptable toxicity in patients with HL having failed ABVD-based treatment.

Many patients who receive co-treatment with GnRH agonists (GnRH-a) during chemotherapy treatment preserve their ovarian function and are at risk of unintended pregnancies. Therefore, it is important to offer them effective contraception. Also, pregnancies occurring after cancer therapy in women who received GnRH-a are not associated with adverse neonatal outcomes.

Multiple herpes virus co-infection is a very rare complication in patients with chronic lymphocytic leukemia (CLL). We describe a patient with a CLL who developed an herpes virus lymphadenitis. Inmunohistochemical study was positive for HSV-1, HSV-2, and Epstein-Barr Virus (EBV). The coinfection of EBV with a profile of expresion of viral latent genes type III, is usually seen in inmunodepressed patients. To the best of our knowledge, this is the first reported case of a multiple human herpes virus infection mimicking Richter syndrome.

Wiskott-Aldrich syndrome is a primary immunodeficiency characterized by infections, thrombocytopenia, and eczema. We present a 33-year-old man with this syndrome who underwent a one-stage ascending aorta, aortic arch and descending aortic aneurysm repair under moderate hypothermia and continuous visceral and cerebral perfusion. Histologic examination showed the presence of an aortitis with granulomatous inflammatory response and multinucleated cells.

Several non-randomized studies suggest a possible survival advantage for chronic myelogenous leukaemia (CML) patients treated with an autologous stem-cell transplantation. Due to the possible contribution of residual leukaemic cells present in the inoculum in post-transplant relapse, several methods are being evaluated to eliminate neoplastic cells or to select 'normal' (Ph 1 negative progenitor cells for autografting. Recently, several studies have shown that Ph 1 negative blood progenitor cells can be mobilized by rHuG-CSF alone in patients who have a cytogenetic response to alpha-interferon (IFN). We describe the first case, as far as we are aware, of a CML patient responding to IFN autografted by using blood progenitor cells collected by rHuG-CSF alone.

INTRODUCTION: Although specific prognostic models for Chronic Myelomonocytic Leukemia (CMML) exist, few are based on large series of patients. Since its publication in 2002, the MD Anderson prognostic score (MDAPS) has been the most powerful prognostic tool for CMML. Due to the recent emergence of the CMML-specific prognostic scoring system (CPSS) and the Mayo prognostic model, we compared the three scores to assess their usefulness in our series. These three indexes, and not those based on clinical and molecular variables (Mayo Molecular Model and GFM prognostic score), were selected as the most easy-to-apply in normal clinical practice. AIM: 1) To assess the prognostic impact on overall survival (OS) and leukemia-free survival (LFS) of the variables composing the scores: MDAPS, CPSS and Mayo prognostic model; 2) To test the capability of the scores to detect the high-risk CMML patients; 3) To detect the index with the best predictive value for mortality and leukemia transformation, and 4) To implement a new score after selecting the best variables of the three indexes in terms of OS prognostic information. PATIENTS AND METHODS: From January 1997 to August 2013 a retrospective analysis including 146 patients diagnosed with CMML was performed in Hospital Clínic of Barcelona (n=134) and Hospital Germans Trias i Pujol (n=12). The median age was 76 years (range 27-96 years) and 63% were males. One-hundred and twenty-nine (88%) had a CMML-1, 17 (12%) a CMML-2, 102 (70%) a CMML-MD and 44 (30%) a CMML-MP. The median follow-up for surviving patients was 24.5 months and the median OS was 20 months (range 0-159 months). The prognostic impact in terms of OS and LFS of each of the variables that compose the indexes were studied by a univariate survival analysis (Kaplan-Meier; Log-Rank). A multivariate analysis (Cox model) was performed to assess the independent impact of the variables that showed significance in the univariate analysis in order to select the ones with the best prognostic information. The global prognostic scores were analyzed by univariate and multivariate analyses. In addition, ROC curves and the concordance index (C-index) were implemented to select the score with the best predictive power for mortality or leukemia transformation. RESULTS: All the variables that compose the MDAPS (hemoglobin level < 12 g/dl, absolute lymphocyte count > 2.5 x 109/L, presence of circulating immature myeloid cells (IMCs) and BM blasts ≥ 10%), the CPSS (CMML-MD vs. CMML-MP, CMML-1 vs. CMML-2, RBC transfusion dependency and the Spanish cytogenetic risk classification) and the Mayo prognostic model (absolute monocyte count > 10x109/L, presence of IMCs, hemoglobin < 10 g/dl and platelet count < 100 x 109/L) showed prognostic value on OS with the exception of circulating IMCs. Regarding LFS, only CPSS variables, BM blast ≥ 10% and an absolute monocyte count > 10x109/L had an impact. When the scores were applied, all showed an impact on OS and retained their significance in multivariate analysis. By using ROC curves and C-index, CPSS (ROC area: 0.80, CI 95%: 0.72-0.88; C-index: 0.73) showed a slightly better predictive value for mortality. Variables composing the three indexes were compared in a multivariate analysis and only CPSS parameters and platelets < 100 x 109/L retained their significance. Based on these findings, by adding platelet count information to CPSS, a new score was implemented (CPSS-P) showing the best risk stratification in our series (Figure 1). CONCLUSIONS: The present study reinforces the validity of CPSS, the MDAPS and the Mayo prognostic model for the assessment of CMML patients. Moreover, by including the platelet count information to the CPSS improved the prediction capacity for OS and LFS in our series. It is of importance to remark that platelet count information could help to better stratify CMML patients, being of special value in the subset of patients with normal karyotype. Figure 1. Associations Between Genetic Mutations and Clinical or Demographic Parameters Figure 1. Associations Between Genetic Mutations and Clinical or Demographic Parameters Disclosures No relevant conflicts of interest to declare.

Background Therapy-related Myelodysplastic Syndromes (t-MDS) are those MDS occurring after cytotoxic and/or radiation therapy administered for a prior neoplastic or non-neoplastic disorder. Their prognosis is generally very poor. The commonly used risk prognostic models for MDS (IPSS and IPSS-R) are not validated in this entity as they were developed after the exclusion of therapy-related cases (Greenberg et al. Blood 1997; Greenberg et al. Blood 2012). Aims The main aims of this study are: a) to report clinical findings and overall survival on 233 patients with t-MDS, and to compare them with a large series of de novo cases; b) to test if IPSS-R is applicable to t-MDS patients. Patients and methods The study is based on the Spanish Registry for MDS, a retrospective database that includes more than 10000 cases. The investigators were asked to fill in a questionnaire regarding prior disease (PD) and prior therapy in those cases reported to be t-MDS. Herein are described the clinical features and overall survival of the first 233 cases with the required information, and compared with patients with de novo MDS from a single center series (n=725). Log Rank test was applied to asses IPSS-R in t-MDS group. Results The 233 reported patients were diagnosed between January 1993 and February 2014. The series includes 104 women (44,6%) and 129 men (55,4%). One hundred and two patients (43.9%) had a primary hematologic malignancy, 119 (51%) had a solid tumor, and 12 (5.1%) received cytotoxic therapy for autoimmune disorders. Ninety eight patients (42.6%) received only chemotherapy (CT), 45 (19.6%) received only radiotherapy (RT), 44 (19.1%) received combined modality treatment (CMT), and 43 (18.6%) received an autologous stem cell transplantation (ASCT). The median time of latency between PD and diagnosis in t-MDS group was 4.56 years (range: 0.03-29.63) in patients previously treated with CT or CMT, significantly lower than the observed after RT (8.54; range 0.83-23.02) or ASCT (8.64; range 2.87-28.32) groups (p=0.023 and p Conclusions In conclusion, our data supports the notion that t-MDS may contain entities with heterogeneous prognosis due to a diverse biological basis. The capacity of the IPSS-R for separating good prognostic from bad prognostic cases shown in this study could be very useful in the clinical setting in order to offer risk-adapted treatments to patients, although the development of a specific prognostic score for these entities would be needed. Disclosures No relevant conflicts of interest to declare.

BACKGROUND, Combination chemotherapy, including hybrid regimens, is the standard treatment for patients with advanced Hodgkin disease (IID). Although a prolonged complete response (CR) is achieved in up to 70-80% of patients, long term complications, such as secondary leukemia, are of concern. Cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (C-MOPP/ABV) is a hybrid chemotherapy in which cyclophosphamide is substituted for mechlorethamine, an agent that has been implicated as the cause of secondary malignancies. METHODS. Seventy-three patients (37 males and 36 females; median age, 35 years) diagnosed with Stage III or IV HD or Stage II with bulky disease, B-symptoms, elevated erythrocyte sedimentation rate, or hilar adenopathy were treated with 8 courses of C-MOPP/ABV at a single institution during a 6-year period. Radiotherapy (RT) was administered when bulky disease or residual masses were present. Endpoints of the study were response to therapy, failure free survival (FFS), overall survival (OS), and toxicity. RESULTS. Sixty-five patients (90%) received the 8 planned courses, with 49 of them (70%) receiving the full prescribed doses. After chemotherapy, 57 patients (78%) reached CR. Seven additional patients who achieved partial response (PR) reached CR after complementary radiotherapy, with an overall CR rate of 88%. The median follow-up was 31 months. Twelve patients relapsed; the 4-year FFS was 66% (95% CI, 54-78%). Two patients died during treatment because of sepsis and four due to disease progression. The 4-year OS was 92% (95% CI, 86-98%). Age > 60 years and bone marrow involvement were related to severe infectious complications. No late toxicity was reported. CONCLUSIONS, C-MOPP/ABV induces CR with acceptable toxicity in a high proportion of advanced HD patients. (C) 2000 American Cancer Society.

Patients with diffuse large-cell lymphoma (DLCL) achieve a complete response (CR) in most cases, but at least one-third of them eventually relapse. Such an event occurs most frequently within 2 yr from CR achievement. The aim of the present study was to analyse the risk and pattern of relapse of patients with DLCL in CR. One hundred and three patients with DLCL (53 male/50 female; median age: 55 yr) in CR after doxorubicin-containing first-line treatments were included in the study. Main clinicobiological characteristics at diagnosis and at relapse were analysed. Uni- and multivariate studies were performed. Forty-one patients (40%) eventually relapsed, in 27 cases within 2 yr from CR and 14 thereafter. Histological subtype was the same at diagnosis and at relapse in all the early relapsing patients and in 8 of 10 late relapsing patients with available biopsy. The most important variables at diagnosis for predicting relapse were advanced stage (p < 0.01) and bone marrow infiltration (p = 0.05), with stage (I–II vs. III–IV) (p = 0.009; relative risk = 2.28) being the only predictive variable in the multivariate analysis. No differences were found according to the treatment given. The second CR rate obtained in the late relapsing patients after salvage therapies was higher that in early relapsing (50% vs. 37%). Median survival from relapse was 1.4 yr for patients early relapsing and it was not achieved for those with late relapses (p = 0.09). Late relapse is a quite common event in DLCL lymphomas, with those patients achieving more frequently a second CR and having better survival than early relapsed patients.

Background Older patients are increasingly prevalent in oncological practice. However, the evidence suggests that this group of patients is undertreated, mainly because of their advanced age, regardless of whether they are highly functional patients, do not present comorbidities, or could benefit from oncological therapies. The US National Comprehensive Cancer Network and the International Society of Geriatric Oncology have recommended that some form of geriatric assessment should be conducted to help Hematologists and Oncologists in order to identify current health problems and to guide interventions to reduce adverse outcomes and optimize the functional status Currently, the main tool for assessing older patients is a comprehensive geriatric assessment, although its complexity and duration may hinder its regular use in daily practice as a tool for clinical decision making. Several attempts have been made to assess comorbidities in the specific field of mielodysplasia, but mainly focused on organic damage rather than global assessment. Aim We are in the process of developing and validating a comprehensive health status assessment scale (Geriatric Assessment in Hematology, GAH Scale) with eight dimensions in patients ≥ 65 years with: Myelodysplastic syndromes (MDS), acute myeloblastic leukemia (AML) and multiple myeloma (MM). Methods After item-pool generation, stakeholder consultation and content validation, a brief scale of 8 dimensions with selected items has been created. Feasibility was confirmed in 83 patients. Afterwards, a multicenter, observational, prospective study has been carried out in 20 hospitals in Spain, enrolling 189 elderly naïve to treatment patients with newly diagnosed MDS, AML or MM. The scale validation process integrates the analysis of criterion and concept validity, internal consistency (Cronbach's alpha), test-retest reliability, as well as the evaluation of intraclass correlation coefficient (ICC) and factor analysis. After psychometric validation phase, further studies will be carried out in order to evaluate its clinical use for prognosis and clinical decision making. Results 189 patients fulfilling inclusion criteria have been enrolled in the study, 54% women. Median age at diagnosis was 73.3 ± 6.64 years. According to diagnosis, 103 patients (54.5%) had MDS or AML and 86 (45.5%) had MM. Regarding feasibility, mean time for filling in the questionnaire was 12.1 ± 4.5 min. 83.6% of patients answered 100% of questions of the scale. Mean percentage of unanswered questions per patient was 1%. Test-retest was completed by 112 patients. GAH Scale showed satisfactory test-retest reliability. ICC was statistically significant for each dimension, being greater than 0.65 for 6 of the 8 dimensions (p Internal consistency, content validity and factor analysis are being carried out and results will be presented in the forthcoming congress. Conclusion This new GAH Scale is a valid, reliable and consistent tool, simple enough to assess health status in older patients with haematological malignancies. Further studies will have to stablish if it may be a tool to improve decision making in such patients. Disclosures: Bonanad: Celgene: Consultancy. Gonzalez:Celgene: Consultancy. Durán:Celgene: Employment. Marcos:Celgene: Employment. López:Celgene: Employment. Cruz-Jentoft:Celgene: Research Funding.

Myelodysplastic syndrome with 5q- (MDS 5q-) is the only cytogenetically defined MDS category recognized by the world Health Organization (WHO) in 2001 and 2008 and is defined as a MDS with isolated deletion on the long arm of chromosome 5 and less than 5% of blast cells in bone marrow (BM). It is well known that for patients with MDS 5q- and transfusion dependence (TD), Lenalidomide is the first choice treatment. However, as far as we know there are no data regarding factors that may impact on the development of TD in these patients or the disease evolution in patients diagnosed without TD. In the present study a retrospective multicenter analysis on patients with low-int 1 MDS 5q- without TD at diagnosis has been performed in order to answer these questions. Patients and methods Data from eighty-four low-Int 1 risk MDS 5q- patients diagnosed between 1980 and 2012 were retrospectively analyzed. Ninety percent of patients had a single 5q deletion and according to IPSS-R 99% were in low and very low risk. Statistical analysis The event of TD was defined as the development of TD according to the IWG criteria (2006) and/or the beginning of a treatment which could modify disease course (Lenalidomide or ESA). Patients follow up was updated on March 30, 2013, and all follow up data were censored at that point. Transfusion free survival (TFS), Overall survival (OS) and AML were analyzed using the Kaplan – Meier method. TFS, OS, and Leukemia free survival (LFS) were measured from diagnosis to TD or to last follow up if transfusion free (TFS), death from any cause or last follow up (OS) and evolution to AML or last follow up (LFS). Multivariate analysis was performed using Cox’s proportional hazards regression model. Incidence of progression to AML was analyzed with cumulative incidence competing risk method. For comparison of Kaplan Meier curves the long rank test was used, with statistical significance with p Results During the study 61 (73%) became TD at a median of 1.7 years from diagnosis. The unique factor associated with poorer TFS was Hb level Disclosures: Díez-Campelo: Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen-Cilag: Research Funding. Off Label Use: In the present study we describe Lenalidomide treatment among patients with MDS and del(5q-) receiving this drug, not approval for this use in Europe, patients with anemia and transfusional requirements. Solé:Celgene: Consultancy, Honoraria; Celgene: Consultancy. Consuelo:Celgene Jansen-Cilag Arry Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Background Specific scoring systems developed for patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) (Garc'a-Manero G et al. Leukemia 2008; Falantes J et al. Clin Lymphoma Myeloma Leuk 2013) are able to identify a significant fraction of pts with a poorer (median OS, 13 months) than expected outcome (Greenberg P et al. Blood 1997). Retrospective data of azacitidine (AZA) in LR-MDS showed hematological improvement and survival when compared to non-responder pts (Lyons R et al. J Clin Oncol 2009; Musto P et al. Cancer 2010). However, the impact of AZA treatment in the group of LR-MDS with poor prognosis by a LR-specific score (LR-S) is uncertain. Aim To evaluate the impact of AZA treatment in LR-MDS pts with more adverse LR-S by multivariable time-dependent analysis. Patients Eighty-eight LR-MDS pts (IPSS Low/Int-1 or Results Median age was 71 years (range, 48-86). Patients in the AZA cohort were older and included more RAEB-1, transfusion dependent and elevated LR-S pts. Baseline characteristics and differences between cohorts are shown in Table 1. Median time from diagnosis to AZA therapy was 4 months (range, 0.5-21). At last follow-up, 72 pts (81%) had died (Non-AZA cohort: 55/61; 90% and 17/27; 63% in the AZA group). Median OS for the overall series was 18 months. The actuarial probabilities of OS at 1 and 2 years were 62.4% and 45% for AZA and 25.4% and 11% for Non-AZA cohort (P=10-4). In a multivariable analysis including blast % (0.5x10e9/L), thrombocytopenia (50x10e9/L) and AZA treatment as time-dependent covariate, the later did not significantly influenced OS (HR, 1.502; 95% CI, 0.258-3; P=0.258) and only severe thrombocytopenia ( Conclusion Azacitidine appeared to increase survival in LR-MDS pts within the most adverse LR-S although differences in OS were not statistically significant in a multivariable time-dependent analysis. Larger number of pts and prospective randomized trials are needed to better address this issue. Thrombocytopenia ( Disclosures: Off Label Use: 5 azacitidine. Treatment for lower-risk MDS in Europe.

Introduction Despite the existence of specific prognostic scoring systems, the International Prognostic Scoring System (IPSS) has been the most used for the evaluation of Chronic Myelomonocytic Leukemia (CMML) although it is not applicable for proliferative variants. Since its publication in 2002, the MD Anderson Prognostic Score (MDAPS) has been the most specific and powerful prognostic tool for CMML. Due to the recent emergence of CMML-specific Prognostic Scoring System (CPSS), we sought to determine its usefulness in our series and it was compared with the MDAPS to identify the index with the best capability to discriminate between high and low risk patients. Aim 1) To assess the prognostic impact of each of the variables composing the prognostic scoring systems: MDAPS and CPSS and 2) to evaluate the discriminative ability of both scores to detect the highest risk patients. Patients and Methods One hundred and twenty-two patients (74M/48F; median age: 76 years, 27-96 years; median follow-up: 1.88 years, 0-11.4 years) diagnosed with CMML (108 CMML-I; 14 CMML-II; 92 dysplastic CMML; 30 proliferative CMML) between 1998 and 2013 from the Hospital Clínic de Barcelona (n=110) and the Hospital Universitari Germans Trias i Pujol (n=12). The prognostic impact in terms of overall survival (OS) and leukemia free survival (LFS) of each of the variables that compose the score systems and both scores were studied by an univariate survival analysis (Kaplan-Meier; Log-Rank). The two prognostic indices were faced in a multivariate analysis (Cox Regression) to assess the discriminative power of each one to detect the highest risk patients. Finally, Receiver Operating Characteristics (ROC) curves were plotted and the area under the ROC curve was calculated as an index for the predictive value of the model. Results All the variables that compose the CPSS (CMML-I vs. II, transfusion requirement, dysplastic vs. proliferative variant and CPSS cytogenetics) had prognostic impact in terms of OS (p 2500/mm3, presence of circulating immature cells and bone marrow blasts ≥ 10%) only the Hb Conclusions In our series, CPSS seems to be a better tool than MDAPS for the prediction of OS and LFS in CMML. These data reinforce the validity of the CPSS and could serve as an additional validation cohort. Disclosures: No relevant conflicts of interest to declare.