304 EPIDEMIOLOGICAL AND PROGNOSTIC FACTORS FROM THE ARGENTINEAN MDS REGISTRY

Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166

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Treatment consisted mostly of hydroxyurea (HU, 22/23). Other treatment options included mercaptopurine (4.3%), cytarabine (13%; either alone or in combination), and intensive chemotherapy (8.7%). 2 patients underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) after myeloablative conditioning from related donors. Both obtained complete remission. 1 died due to GvHD, the other isalive after 44 months after alloHSCT. Median overall survival was 14.3 months (95% CI 6.2-16.6). Neither sex, age, splenomegaly, platelet count (<100 G/l vs ≥100G/l), percentage of immature progenitors in peripheral blood, transfusion dependence did effect OS. There was however a trend for a shorter OS for more severely anemic patients (< 9 g/dl vs ≥ 9 g/dl; p=0.07, log rank). 4 patients (17.4%) transformed to AML. Conclusions: aCML is a rare disease of mostly elderly, male patients. Prognosisis poor, with short median OS and high risk of AML transformation. Fit patients may benefit from allogeneic hematopoietic stem cell transplantation, which may offer cure in at least part of them.

Results: Among the cohort of 23 patients 20 met the MDS with isolated del (5q) WHO criteria and 3 were classified as refractory anemia with excess blasts (RAEB). The median age of the cohort was 80 years (range 60-94) composed of 16 females and 7 males. The main morphological features are as follows: At diagnosis neutropenia was observed in 8 patients (34%) (0.68-1.8x109/l) and thrombocytopenia in 5 patients (21%) (70-145x109/l). During the follow-up (1-62 months, median 22.6) 4 patients developed thrombocytopenia and severe neutropenia 5 to 14 months after diagnosis, these patients presented with dysgranulopoiesis. Conclusion: In this series we observed in addition to the most consistent feature of abnormal megakaryocytes, variable dysplasia including dysgranulopoiesis. The del (5q) syndrome is a low risk MDS but dysgranulopoiesis and thrombocytopenia have been previously identified as negative pronostic factors, this finding is confirmed in our study. These results underline the importance of the careful evaluation of dysplasia at the time of diagnosis.

303 CLINICAL AND MORPHOLOGICAL CHARACTERISTICS OF 23 PATIENTS WITH MYELODYSPLASIC SYNDROME ASSOCIATED WITH ISOLATED DEL(5Q) A. Eischen1, A. Ittel2, A.C. Galoisy1, C. Mayeur-Rousse1, L. Monier1, S. Ame3, C. Gervais2, C. Helias2, L. Mauvieux1 1 Laboratoire d’Hématologie, Hôpital de Hautepierre CHU de Strasbourg, Strasbourg Cedex, France; 2Laboratoire de Cytogénétique, Hôpital de Hautepierre CHU de Strasbourg, Strasbourg Cedex, France; 3Service d’Hématologie Clinique, Hôpital de Hautepierre CHU de Strasbourg, Strasbourg Cedex, France

304 EPIDEMIOLOGICAL AND PROGNOSTIC FACTORS FROM THE ARGENTINEAN MDS REGISTRY J. Gonzalez1, M. Flores1, J. Arbelbide1, M. Iabstrebner1, E. Nucifora1, A. Enrico2, V. Prates2, M. Rosenhain1, L. Koremblitt1, R. Crisp3, G. Alfonso3, A. Basquieras4, C. Martín2, I. Santos1, V. Barcalá1, C. Belli1 1 Hematology, Argentinean MDS Registry, CABA, Argentina; 2 Hematology, Argentinean MDS Registry, La Plata, Argentina; 3 Hematology, Argentinean MDS Registry, Haedo, Argentina; 4 Hematology, Argentinean MDS Registry, Cordoba, Argentina

Introduction: Myelodysplasic syndrome (MDS) with isolated del(5q) has been initially characterized by macrocytic anemia, morphological abnormalities of megakaryocytes and an interstitial deletion involving the long arm of chromosome 5. The current WHO classification requires blast count of <5% in the bone marrow (BM), <1% in the peripheral blood (PB) and the absence of Auer rods, but does not specify the morphology. Purpose: The aim of our study was to investigate the morphological characteristics of PB and BM in patients with MDS syndrome associated with del (5q). Material and methods: Between 2009 and 2014 23 patients were identified in our institution with MDS and isolated del(5q). Morphological evaluation of PB and BM was performed according to standard evaluation protocol. Dysplasia was recorded if the dysplasic features within one cell line constitued more than 10% of the cells.

Argentinean MDS Registry was created in 2008 and is sponsored by The Argentinean Society of Hematology. The main objective was to collect MDS related data to describe epidemiological characteristics, prognostic factors and scoring risk stratifications.

Table 1.

SCORE

n

Survival (months)

Time to AML (months)

Low Int-1 Int-2 High

157 148 48 23

105 44 17 13

116 31 9 4

Very-Low Low Intermediate High Very-High

110 151 41 40 31

105 NA 69 17 12

116 NA 12 10 9

Very-Low Low Intermediate High Very-High

25 142 74 63 22

105 NA 35 18 15

116 NA 32 12 6

Low Int-1 Int-2 High

103 175 84 80

NA 105 30 12

NA 116 11 9

0 1 2 3 ≥4

262 114 82 45 25

77 47 34 23 24

Risk Group

IPSS n:377

IPSS-R n:384

WPSS-R n:326

Laboratory and pathological features

Entire cohort n=23

RAEBI n=3

Hemoglobin (g per 100 ml) median and range

9.4 (7.4-11.8)

9.7 (8.0-10.8)

MCV (fl)

103 (92-129)

114 (101-123)

2.34 (0.68-3.96)

1.57 (1.37-1.80)

237 (71-435)

311 (210-435)

BM dyserythopoiesis number (%)

14 (60%)

3 (100%)

BM dysgranulopoiesis number (%)

11 (47%)

3 (100%)

BM dysmegakaryopoiesis (nonlobulated nuclei) number (%)

22 (96%)

3 (100%)

Trilineage dysplasia number (%)

9 (39%)

3 (100%)

Ring sideroblasts (>15%) number (%)

5 (21%)

0

1 RAEBII (5 months) 1 LAM (14 months)

1 RAEBII

Absolute neutrophil (count x 109/l) Platelets (count x 109/l)

Desease transformation (time in months from diagnosis)

Table 1.

MD Anderson Score n: 442

Charlson’s Comorbidities Index n: 528

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Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166

After 7 years, 14 institutions from Argentine, have been reporting data from 532 patients (89% with de novo MDS) diagnosed mostly since 2007. Median age was 72 (17-95) years with a gender ratio (M/F) of 1.3. During follow-up (mean: 18 months, range: 1-129 m), 104 (19.5%) evolved to AML and 211 (39.7%) died. Age, sex, bone marrow blast percentage, hemoglobin level, platelet and neutrophil counts, karyotype, LDH level, ferritin levels, myelofibrosis and red blood cell transfusion requirement were significant predictive variables for prognosis (Kaplan-Meier and Long-Rank test, p<0.05). FAB and WHO classifications and scoring systems (IPSS, IPSS-R, WPSS-R, MDA score, and Charlson’s Comorbidities Index) allowed to differentiate groups with different outcomes (p<0.001) (Table). Concerning causes of death of de novo MDS, 68 (38%) were related to AML, other 68 (38%) included bleeding, infection, post-HSCT, 31 (18%) comorbidities (cardiovascular complications and other neoplasia), and 7% unknown causes. Cross-tabulation of patients causes of death and IPSS showed that LMA related death increased from 22% to 50%, while other related causes decreased from 47% to 36%, in Low and High risk, respectively; while the impact of comorbidities was more evident in lower risk groups (22-25% vs 0-7%). Descriptive studies are necessary not only to establish epidemiological features useful for public health strategies but also to define prognosis factors and generate suitable therapeutic schemes.

305 IPSS AND IPSS-R ROUTINELY USED IN VERY OLD PEOPLE SUFFERING FROM MDS? PRELIMINARY RESULTS FROM A FRENCH CARE NETWORK M.P. Gourin1, E. Guerin2, A. Penot1, C. Kennel1, S. Lefort3, J.B. Simeone1, Z. Boutalbi1, F. Trimoreau2, D. Bordessoule1 1 Hematologie Clinique et Therapie Cellulaire, Centre Hospitalier Dupuytren, Limoges, France; 2Laboratoire d’Hématologie, Centre Hospitalier Dupuytren, Limoges, France; 3Oncologie Hématologie, Centre Hospitalier, Brive, France Introduction: MDS guidelines with validate prognostic scores like IPSS and IPSS-R are available for physicians to adjust management according risk assessment. For the oldest patients (Pt), some comorbidities, dependence, disability, placement in institution and distance from referral centers are additional difficulties for the management, from diagnosis to therapeutic decision. The objective of this study is to assess how these two prognostic scores used in real world in this population. Patients and methods: We performed a retrospective analysis of a cohort of MDS Pt, ≥80 years, managed in a French hematology care network coordinated by a university hospital. Inclusion criteria is a cytological diagnosis on bone marrow sample. We collected data to determine WHO classification, IPSS and IPSS-R. Statistical analysis was performed with Statview Software. Results: Preliminary results were obtained from 331 P, sex ratio 1.38, median age 84 yrs [80;99]. Diagnosis was performed since 1993 and from consecutive Pt 2002-2014. Anemia has been observed in 47.1% (n=156), neutropenia 27.7% (n=91) and thrombopenia 28.1% (n=92). One or more cytopenia was observed in 73% (n=237). Bone marrow blasts (BMB) were <5% in 52.1% (n=170) (with respectively ≤2% BMB for 21% (n=36), >2-<5% BMB 28% (n=47)), 5-10% in 26.7% (n=87) and 10-20% in 21.2% (n=69). OMS classification distributed in del 5q 2.4% (n=8), RA 12.4% (n=41), RCMD 7.9% (n=26), RARS 20.5%(n=68), RCMD-RS 0.9% (n=3), RAEB1 22.1%(n=73), RAEB2 18.1% (n=60), CMML1 10% (n=33), CMML2 2.7%(n=9), MDS-U 3% (n=10). Cytogenetic (CTG) was performed in 52.1% (n=174), normal in 60.5% (n=103), -Y 12% (n=21), del(5q) 6.9% (n=12), complex 5.7% (n=10), failure 2.3% (n=4), del(20q) 2.4% (n=6), 7 abnormality 2.3%

(n=4), trisomy 8 2.3% (n=4), others and double clone 5.6% (n=10). IPSS is calculated for 49.5%(n=164) split into low 70.1% (low and Int-1) and high 29.9% (Int-2 and high). IPSS-R is calculated for 35.6% (n=118) split into very low 11% (n=13), low 28.8% (n=34), intermediate 28.8% (n=34), high 27.9% (n=33) and very high 3.4% (n=4). Geriatric assessment (GA) and survival data will be present. Conclusion: In real world, it has been possible to assess IPSS (49.5%) and in lower percentage IPSS-R (35.6%) in MDS older than 80 yrs. The main difficulty is the lack of CTG due to many reasons: physician or family reluctance, comorbidities, lack of therapeutic goal due to frailty detect by GA. The difference between the two scores is due to difficulties to precised retrospectively lower BMB count between ≤2% and >2-<5%. The weight of GA in the prognostic score should be revised in this oldest group of MDS Pt, in relation with the access of innovative therapeutics.

306 COMPARISON OF A RESTRICTIVE VERSUS LIBERAL RED BLOOD CELL TRANSFUSION POLICY IN MYELODYSPLASTIC SYNDROMES AND OTHER BONE MARROW FAILURE DISORDERS – A SYSTEMATIC REVIEW Y. Gu1, L. Estcourt2, C. Doree3, M. Trivella4, S. Hopewell4, P. Vyas5 1 Department of Haematology, NHS/University of Oxford, Oxford, United Kingdom; 2Haematology/Transfusion Medicine, NHS Blood and Transplant, Oxford, United Kingdom; 3Systematic Review Initiative, NHS Blood and Transplant, Oxford, United Kingdom; 4Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom; 5MRC Molecular Haematology Unit and Department of Haematology, University of Oxford and Oxford University Hospitals NHS Trust, Oxford, United Kingdom Background: Myelodysplastic syndromes (MDS) are predominantly a disease of the elderly. Due to the ageing populations in many Western countries, the incidence of MDS is rising. Patients who are not fit for curative therapy often require regular red blood cell (RBC) transfusions to treat their anemia. Despite transfusions playing a central role in the supportive management of such patients, the optimal RBC transfusion strategy (restrictive versus liberal) is currently unclear. Aim: This systematic review aimed to assess the safety and efficacy of a liberal versus restrictive RBC transfusion program for patients with chronic bone marrow failure disorders who are not receiving potentially curative treatment. Methods: We searched eleven electronic databases (including CENTRAL, Embase, CINAHL) and two ongoing trial databases for randomized controlled trials (RCTs) up to 13/08/2014 that compared a restrictive versus liberal RBC transfusion policy in patients with chronic bone marrow failure disorders. We used the standard methodological procedures expected by The Cochrane Collaboration. Results: 952 studies were initially identified, 931 studies were excluded on the basis of the abstract. Twenty-one full-text articles were reviewed from which, four RCTs were eligible (one completed study (TEMPLE), and three ongoing trials (ISRCTN26088319, NTR2684, NCT02099669). All four studies assess RBC transfusion strategies in patients with MDS. The TEMPLE Study randomized 13 patients to a restrictive [haemoglobin (Hb) transfusion trigger <72g/l, 8 patients] or liberal [Hb trigger <96g/l, 5 patients] transfusion policy. The study showed a 55% reduction in RBC usage in the restrictive group. There were no anemia-related complications (cardiac failure) and no effect on activity levels, however the study was small and follow-up was shorter than planned (mean 6.2-7.4 months versus 15 months). The three trials in progress plan to randomize between 30 and 100 patients. Trial NTR2684 (100 participants-Netherlands) is