ALBERT

Description: Background: The accurate detection of cytogenetic abnormalities in Acute Myeloid Leukemias (AML) and Myelodysplastic Syndromes (MDS) play an important role in prognostic value and often assist in therapeutic choice. The most commonly used genetic test for the diagnostics of these conditions is karyotype (KT), which is able to detect frequent non-random chromosomal abnormalities. However, this technique requires metaphases and offers low resolution (5Mb), which may lead to the loss of clinically important smaller genomic rearrangements. Therefore, a complementary technique is sometimes needed. FISH, for example, is a highly reliable technique, it can be performed in interphases, has higher resolution, and can detect balanced translocations (important for prognosis mainly in AML), although it is very expensive. As an alternative method, MLPA is usually less costly, is able to evaluate more genomic regions at once and is performed with genomic DNA, which is convenient for biological material availability. On the other hand, it is not able to detect balanced translocations due to its semi-quantitative PCR-based method. The aim of this study was to evaluate MLPA as a complementary technique to KT, and to compare the outcomes of MLPA and FISH panels for the high resolution detection of common unbalanced genetic alterations in MDS and AML. Methods: A total of 23 samples from patients diagnosed with MDS (n=16)/AML(n=6) were tested for KT and MLPA. 20 metaphases were analyzed in G-banding KT. MLPA (Kits P144 and P145, MRC-Holland) was performed with genomic DNA extracted from bone marrows. A subset of 10 samples was tested for FISH MDS/AML panel (PML/RARA, CBFB/MYH11, RUNX1/RUNX1T1, MLL rearrangement, del5q, del7q, de17p and del20q, Cytocell), and the outcomes were compared to MLPA. Reagent costs were also compared between MLPA and FISH techniques. Results: Outcomes from KT and MLPA were mostly concordant: 91.3% of samples had either concordant or partially concordant results (considering "partially concordant" when MLPA could detect smaller genetic alterations not achieved by KT). Discordance between KT and MLPA occurred in two cases: (i) MLPA detected a deletion of RUNX1 gene (chr 21) in a previously normal KT, and (ii) MLPA showed different abnormalities than those in a complex KT case, with low mitotic index. When comparing regions that are notoriously related to MDS/AML (-5/del5q, -7/del7q, +8, del11q, del13q, del17p, del20q and del21q), all results were concordant between MLPA and KT. Comparison of MLPA and FISH was performed with 10 samples, of which 4 were negative for genetic alterations and 6 were positive. 90% of samples had concordant results, and 10% (one sample) showed extra genetic alterations in MLPA (del7q; del11q and del20q). This is expected since MLPA analyzes more genetic regions then FISH MDS/AML panel at once. Genomic regions accessed both by MLPA and FISH included -7, +8, del17p, del21q. Regarding financial expenses (cost of commercial MDS/AML panels and additional reagents), MLPA costs approximately U$280.00 (considering test sample plus internal controls), while FISH costs U$555.00 (values were converted from quotes provided by regional distributors and converted to dollars). Conclusions: MLPA results are equivalent to FISH for the detection of MDS/AML frequent unbalanced genetic alterations. Both techniques are reliable as complementary molecular biology tests for KT. Moreover, MLPA is a friendly and less expensive technique for the detection of high resolution genomic unbalanced abnormalities, frequently adding extra information to KT results. Nevertheless, it is important to notice that only FISH can detect balanced translocations with significant prognostic value in AML. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: The development of next-generation sequencing has made it feasible to interrogate the entire genome or exome (coding genome) in a single experiment. Accordingly, our knowledge of the somatic mutations that cause cancer has increased exponentially in the last years. MPNs and MDS/MPD are chronic myeloid neoplasms characterized by an increased proliferation of one or more hematopoietic cell lineages, and an increased risk of transformation to acute myeloid leukemia (AML). MPNs and MDS/MPDs are heterogenous disorders, both in clinical presentation and in prognosis. We sought to determine the genetic landscape of Ph-negative MPNs and MDS/MPD through next-generation sequencing. Methods: Paired DNA (sorted CD66b-granulocytes/skin biopsy) from 102 patients with MPNs or MDS/MPD was subjected to whole exome sequencing on a Illumina HiSeq 2000 platform using Agilent SureSelect kit. Diagnosis included primary myelofibrosis (MF; N=42), essential thrombocythemia (ET; N=28), polycythemia vera (PV; N=12), chronic myelomonocytic leukemia (CMML; N=10), systemic mastocytosis (MS; N=6), MDS/MPD-Unclassified (N=2) and post-MPN AML (N=2). Tumor coverage was 150x and germline coverage was 60x. Somatic variants calls were generated by combining the output of Somatic Sniper (Washington University), Mutect (Broad Institute) and Pindel (Washington University). The combined output of these 3 tools was further filtered by in-house criteria in order to reduce false-positive calls (minimum coverage at both tumor/germline ≥8 reads; fraction of reads supporting alternate allele ≥10% in tumor and ≤10% in germline; ratio of allele fraction tumor:germline 〉2; excluding mutations seen in SNP databases). All JAK2 and CALR mutations were validated through Sanger sequencing. Validation of other somatic mutations is currently underway. Analysis of driver mutations was made with the Intogen web-based software, using the Oncodrive-FM and Oncodrive-cluster algorithms (www.intogen.org). Significantly mutated genes were considered as those with a q-value of

Description: Introduction: Risk stratification in acute myeloid leukemia (AML) is continually being refined as we learn more about the molecular pathophysiology of this heterogeneous disease. European LeukemiaNet (ELN) 2017 used widely to stratify the 'genetic' risk of AML, but there are considerable challenges in its application, particularly in centres where molecular genetic testing either not available, or not sufficiently timely for clinical decision making. Up to a third of the study subjects cannot be stratified using a full cytogenetic-molecular model in real-time, real-life setting. There are few attempts to combine clinical features and genetic factors aiming to find a scoring system to improve AML survival prediction. There is only one to our knowledge (Sorror ML et al. 2017). This study has generated an Adapted Genetic Risk (AGR) assessment, and used it in combination with clinical risk parameters to create a novel scoring system which has now been validated using two independent cohorts. Methods: A training cohort from São Paulo (FMUSP, n = 167) of intensively treated AML patients (18-65 years) was assessed using ELN2017 genetic criteria. A comparative validation with our AGR which permits missing cytogenetic or molecular data (Figure 1) split these patients into favorable-risk (FR), intermediate-risk (IR), and adverse-risk (AR). This cohort was also used for Cox Proportional-Hazard Model (CPHM) univariate and multivariate analysis to find clinical parameters that would inform a novel Survival AML Score (SAMLS). Variables which are included in SAMLS had to be either significant in both CPHM models or significant in univariate and crucial for multivariate fitness as measured for the Akaike Information Criterion (AIC). We then applied the AGR strategy and SAMLS to 2 independent test cohorts of intensively treated adult AML patients : Riberao Preto (FMRP, n=145) and Oxford (OUH, n=157). The study was approved by the institutional review boards of the 3 participating centers. Informed consent was obtained from all patients according to the Declaration of Helsinki. Results: Table 1 shows the clinical characteristics for all the 3 cohorts. The median follow-up (FUP) was 72.3, 44.4, and 70.5 months for FMUSP, FMRP, and OUH, respectively. The median Overall Survival (OS) was 12.4, 12.5, and 56.4 months and the 5-year OS were 29.6%, 29.7%, and 49.7% respectively. Both ELN2017 and AGR correlated with significant differences in OS (p-value

Description: Abstract 4841 Myelodysplastic syndromes (MDS) are a group of acquired clonal stem cell disorders that mainly affect the elderly population, characterized by ineffective hematopoiesis and high risk of leukemic transformation. MDS are heterogeneous in terms of morphology, clinical features and survival. An increasing body of work reveals that there might be differences in clinical features between Asian and Western cases. Japanese patients seem to be younger, have a lower frequency of refractory anemia (RA) with ringed sideroblast (RARS) and a higher frequency of RA, according to FAB classification, as well as different prognostic factors such as the frequency of cytogenetic abnormalities. Incidence rates for MDS in Brazil are unavailable. The purpose of the study was to obtain epidemiological data of MDS adult patients who presented from January 2003 to December 2007 in 10 Brazilian tertiary-care hematology centers from different regions of the country. Patient data collected by participating physicians were entered and stored with the use of an internet-based, data collection tool. Blood counts, bone marrow aspiration, trephine biopsy and chromosomal study were recorded. Survival was estimated through Kaplan-Meier method and the difference between survival curves was assessed by means of Log-Rank Test. Death incidence rates were estimated and compared. Statistical analyses of relevant variables were performed. Three hundred and forty three patients with diagnosis of MDS according to FAB/WHO classification were included in this retrospective analysis. The mean age at presentation was 68 years (range 17 to 98). Fifty percent of cases were male. Cigarette smoking, alcohol abuse and pesticide/herbicide exposure were reported in 33.5%, 13.4% and 14.3% respectively. Median hemoglobin was 8.7 g/dL, median neutrophils count was 1,575/mm3 and median platelets count was 97,000/mm3. There was no excess of blasts in 68.4% of cases. Bone marrow biopsy was performed in 78.5% of patients. Lymphoid nodules were seen in 11.3% and any degree of fibrosis in 28.6%. Cytogenetic analysis was performed in 67.8% of cases and showed chromosomal abnormalities in 50.5%. The del(5q) isolated or combined with other alterations were observed in 6.0%. Flow cytometry analysis for CD55 and CD59 was performed in 11,3% and was normal in 97,4%. Near 8% of cases were classified as secondary MDS. The distribution of disease subtypes according to FAB classification was: RA 42,3%, RARS 9,0%, RA with excess of blasts (RAEB) 20,7%, RAEB-t 4,2% and chronic myelomonocytic leukemia (CMML) 3,9%. According to IPSS patients were stratified as low-risk (low risk plus intermediate I) 55,9% and high risk (intermediate II and high risk) 13,1%. In 30,1% no stratification was possible. In 26,5% of cases iron overload was diagnosed although only 28,3% of cases had performed serum ferritin. The follow-up time ranged from 1 to 78 months (mean: 28 months). Thirty-six percent of patients died and the death was MDS-related in 68.3% of cases. The high and low risk survival curves were significantly different (p

Description: Objective Report immunophenotypic and genetic aspects and clinical course of a case of Splenic Diffuse Red Pulp Small B Cell Lymphoma with transformation to diffuse large cell. Introduction Until recently, only Hairy Cell Leukemia was recognized as B chronic lymphoproliferation with primary involvement of the splenic red pulp. The 2008 WHO classification included two new provisional entities: Splenic diffuse red pulp small-B cell lymphoma and Hairy Cell Leukemia variant. These entities are rare, encompassing less than 1% of B chronic lymphoproliferation, characteristically presenting as an indolent clinical course and good control with splenectomy. Case report Female, 29 years old, with non-replicative chronic hepatitis B, and splenomegaly detected 7 years before without evidence of portal hypertension or schistosomiasis. Two months before admission to our hospital, she developed increasing splenomegaly for 39cm, B symptoms and abdominal lymphadenopathy. CBC showed Hb: 8,1g/dl, platelet: 80.000/mm3, WBC: 12.000/mm3 with 85% of abnormal lymphoid cells with immunophenotyping CD45++/CD19+/CD20++/CD25+/CD23dim/CD200dim/FMC7+/CD11c-/CD103- and cykappa restriction. Complex karyotype in PB suggested lymphoproliferative disorder, with strutural abnormalities in 14q32, isocromosomes 8 and 17, deletions 6q and 7q and trisomy 18. FISH studies showed extra copy of MYC and p53 deletion. Bone marrow aspirate showed 7,6% of cells with same phenotype. CT and PET-CT showed splenomegaly of 39cm (SUV: 6.1), hepatomegaly (SUV: 3.2), abdominal lymph node conglomerate (SUV: 6.3), cervical and mediastinal lymphadenopathy with no increase in dimensions (SUV: 3,8). The patient was submitted to splenectomy and histological findings revelead mature lymphoid neoplasm, ranging from small to intermediate cells with few large cells, primary from spleen red pulp and diffusely infiltrating the sinusoidal spaces and secondly the white pulp (CD20+, DBA44+, CD5-, CD10-, CD23-, CD3-, cyclin D1- and Ki67: 40%). The cytogenetic analysis of the spleen showed similar complex karyotype as seen in PB. With the diagnosis of Splenic Diffuse Red Pulp Small B Cell Lymphoma with aggressive transformation to diffuse large cell, she was submitted to 8 cycles of R-CHOEP and is in complete remission, waiting for consolidation with high-dose chemotheraphy followed with peripheral stem cells rescue. Discussion Splenic Diffuse Red Pulp Small B-cell Lymphoma was included as a provisional entity in WHO 2008 classification. The few cases reported show an indolent course with good response to splenectomy. In this case the diagnosis was suspect with clinical course, cytogenetic and flow cytometry PB studies and confirmed after splenectomy when the clinical course of disease changed with B symptoms, spread to peripheral blood with atypical cells and increased proliferative markers, such as LDH. This fact highlights the difficulty in establishing the diagnosis of this entity during the course of prolonged and indolent disease, manifested by splenomegaly oligosymptomatic often neglected by physicians and by the patients themselves. Disclosures: No relevant conflicts of interest to declare.

Description: Eosinophilia is a rare recurrent finding in Acute Myeloid Leukemia (AML). The classical cases being: Core Binding Factor AMLs with chromosome 16 abnormalities, and AMLs with rearrangements of PDGFRA, PDGFRB and FGFR1. According to the 2008 WHO Classification, acute myeloid leukemia with t(6;9)(p23;q24) is a rare entity (0,7-1,8% of all AMLs) characterized by multilineage dysplasia, basophilia and unfavorable prognosis. The translocation leads to the development of the hybrid protein DEK-CAN. This cytogenetic alteration usually presents as a single abnormality, but can also be associated with complex karyotype. There are no descriptions of eosinophilia associated with DEK-CAN+ AML. We report the case of a 16-year old male patient that presented with generalized cutaneous pruritus and fever associated with peripheral blood eosinophilia (absolute count: 7.830/mm3) on August of 2010. We ruled out the most common causes of secondary eosinophilia, and then submitted the patient to a bone marrow aspiration that showed erythroid hyperplasia (58,8%), with dyserythropoiesis, eosinophilia (16,4%), dysgranulopoiesis, and 9,6% of blast cells, compatible with the diagnosis of AML-M6 according to the FAB classification. Cytogenetic study showed the presence of t(6;9) (p23;q34), FISH was negative for inv (16) and molecular studies showed FLT3 and NPM1 to be wild type. PDGFRb rearrangement was negative. The patient was treated with 2 cycles of cytarabin based chemotherapy, achieving hematological remission, but with sustained peripheral eosinophilia (absolute count: 920/mm3). Since the presence of t(6;9) is associated with dismal prognosis, the patient received a peripheral blood HLA matched related allogeneic stem cell transplantation (ASCT) in first remission. Four months after the ASCT, he presented with symptoms of sinusopathy and worsening of the peripheral blood eosinophilia (absolute count: 10.655/mm3). Bone marrow aspirate revealed blast count 〈 5% with 50,8% of eosinophils, and decreasing donor chimerism. Cytogenetic study revealed persistence of t(6;9) (p23;q24) associated to other abnormalities (including monosomy 5), revealing a complex karyotype. He was then submitted to a therapeutic trial with imatinib without response. Afterwards he received one cycle of cytarabine plus azacytidine with donor lymphocyte infusion during post chemotherapy aplasia. The patient recovered counts with 100% donor chimerism and shortly developed signs of chronic graft versus host disease (cGVHD) affecting eyes, skin and liver. Bone marrow evaluation revealed complete morphological and cytogenetic remission with normal eosinophil counts and 100% donor chimerism. He was then treated with prednisone and tacrolimus with good control of GVHD. Eleven months later, during tacolimus taper, the patients developed eosinophilia again. Bone marrow evaluation revealed morphologic and cytogenetic complete remission with 100% donor chimerism. Since eosinophilia had been a marker of AML activity in this patient, it became crucial to define whether this represented an impending relapse. We then performed eosinophil enrichment of peripheral blood eosinophils with Easysep (CD66b) beads, reaching a final sample with 80% of eosinophils (CD45high/CD16negative/CD13positive), and performed chimerism analysis in this sample. The results were compatible with 100% eosinophil donor chimerism, what ruled out the possibility of recipient neoplastic eosinophils. Tacrolimus tapering was stopped and two weeks later the patient developed worsening of cGVHD symptoms with sustained eosinophilia. Upon increasing the dose of tacrolimus, the eosinophilia resolved and we interpreted it to be secondary to cGVHD activity. Afterwards we designed a PCR reaction specific for DEK-CAN rearrangement and tested retrospectively all bone marrow samples RNA we had stored. While the test was positive in all previous episodes of eosinophilia, the testing of the last sample was negative, in agreement with the eosinophil chimerism finding. The patient is now in complete molecular remission 24 months after DLI with good cGVHD control. In conclusion, we have described a case of AML with DEK-CAN rearrangement secondary to t(6;9)(p23;q24) with eosinophilia. Additionally we have demonstrated how the study of eosinophil chimerism can be essential in the differential diagnosis between “neoplastic” and reactional eosinophilia. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4960 Introduction: Transfusion dependent anemia and iron overload are associated with reduced survival in patients with MDS. Increased iron absorption at the gastrointestinal tract may also contribute to iron overload. Serum ferritin is the most common method of assessing body iron content, but it can be elevated in patients with inflammatory conditions, and may not correlate with iron overload in specific organs such as the heart. T2* MRI is a non-invasive method for detecting iron overload in patients with transfusion-dependent anemia, and its efficacy has been validated in patients with thalassemia major. There are few studies reporting on the efficacy of T2* MRI for detection of iron overload in patients with MDS. Objective: To evaluate the efficacy of T2* MRI in detection of iron overload in patients with MDS, the prevalence of iron overload in this disease and correlate MRI findings with iron indexes (ferritin, transferrin and non-transferrin bound iron [NTBI]). Methods: Patients with MDS or chronic myelomonocytic leukemia (CMML), independent of transfusion requirements, were recruited into a prospective, single center trial to assess the efficacy of T2* MRI for detection of iron overload in this scenario. Patients receiving iron chelation therapy were excluded. Iron indexes were measured at the time of T2* MRI evaluation. Hepatic iron overload was considered in patients with a hepatic iron concentration (HIC) ≥ 2 g/mg. Cardiac iron overload was considered in patients with a T2* value 〈 20 milliseconds. Mann-Whitney and Fischer exact tests were used to compare baseline continuous and categorical variables among patients with and without iron overload as assessed by HIC. Correlation between HIC and iron indexes was assessed with Spearman correlation. Results: A total of 37 patients with MDS and one patient with CMML were recruited. Three patients were not evaluated by MRI due to claustrophoby, so 35 patients remain for the analysis. Median age was 68 years (range 18–84). MDS subtypes by the WHO classification include refractory anemia (N=3), refractory anemia with ring sideroblasts (N=5), 5q- syndrome (N=3), refractory cytopenias with multilineage dysplasia (N=13), refractory anemia with excess blasts-I (N=6) and –II (N=3) and unclassifiable MDS (N=1). Information about transfusion requirement was available for 28 patients, and 14 (50%) were transfusion dependent. Twenty-two patients could be classified by the WHO Prognostic Score System (WPSS) and were categorized as very low-risk (N=6), low-risk (N=3), intermediate risk (N=6) and high risk (N=7). Median ferritin, transferrin saturation and NTBI values were 1079.6 ng/mL (range 21.8–12738 ng/mL), 63% (range 6–100%) and 0.34 microM (range 0–12.93 microM), respectively. Median cardiac T2* value was 45.3 ms (range 19.7–70.1 ms), and only one patient had a T2* value indicative of cardiac iron overload. Median HIC value was 3.31 g/mg (range 0.2–9.97 g/mg), and 66% of patients had hepatic iron overload. Patients with hepatic iron overload had higher ferritin levels (1181 ng/mL vs. 131 ng/mL, p=0.007) and transferrin saturation (64% vs. 39%, p=0.02), but no differences in NTBI (0.29 microM vs. 0.22 microM, p=0.42). Patients with elevated HIC had a higher prevalence of transfusion dependency but the difference was not significant (50% vs. 33%, p=0.67). Ferritin levels and transferrin saturation correlated with HIC (r = 0.552, p=0.001 [ferritin]; r = 0.609, p=0.001 [transferrin saturation]). Conclusion: T2* MRI can detect iron overload in patients with MDS. Iron overload in MDS cannot be solely explained by transfusion dependent anemia. The study is currently ongoing and updated results will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

Description: Adult Acute Lymphoblastic (ALL) is an aggressive bone marrow neoplasm, associated with a poor outcome in adult patients. The aim of this study is to compare different treatment protocols analyzing complete response after induction treatment (CR), overall survival (OS) and disease free survival (DFS). Statistical analysis was done by SPSS 10.0. The analysis of prognostic factors, protocols and response treatment was done by Pearson’s chi-square. OS and DFS curves were constructed by Kaplan-Meyer method and differences were analyzed by log-rank test. In our institutional department, 102 patients with ALL diagnosed between 1990 and 2005 were treated with one of the follow protocols: BFM 86 modified (BFM 86M) (48/102), OPAL86 (6/102), OPAL87 (40/102) (Linker et cols; 1986Linker et cols; 1987) and CHOP (8/102). The results were analyzed retrospectively. The median follow up was 49 months. CR for BFM 86M, OPAL86, OPAL87 and CHOP was 76,7%, 100% 63,9% and 42,9%, respectively; with no statistically difference (p=0.08). OS was better with BFM 86M than with other protocols (p=0.001). BFM 86M was associated with 4-years DFS of 42,5% (median: 26,4 m) and OS of 49,5% (median: 35,4m). OPAL86, OPAL87 and CHOP had a median survival of 21, 12, and 5,5m respectively. Four-years OS of the patients treated with protocols other than BFM 86M was 16,8%. The distribution of the clinical and laboratory data between the BFM 86M and the other protocols (OP) was compared. Age less than 18y (p=0.05) and L1 ALL (FAB) (p=0.01) were more prevalent in OP group. Myeloid expression antigens (p=0.05) and poor prognosis karyotype (e.g. Ph cromossome) (p=0.08) were more prevalent in BFM 86M group. Age less than 35y (p=0.02), absent of fatigue at diagnosis (p=0.04), CNS not infiltrated (p=0.01) were associated to an early complete remission with OP but not with BFM 86M. Hepatomegaly, at diagnosis, was associated with poor complete remission when patients received BFM 86M protocol (p=0.02). Age less than 18y (p=0.002) and absent of hepatomegaly at diagnosis (p=0.01) were associated with a prolonged survival only in BFM 86M protocol. T-ALL (p=0.04) and infiltration of CNS (p=0.02) were related to worst survival in other protocols (OP) but not in BFM 86M. Bleeding at diagnosis for both BFM 86M and OP were related to short survival (p=0.03; p=0.01).

Description: Recently, the IPSS-R has proposed five cytogenetic groups of risk (CGR) based on Schanz et al, 2011, proposal. Nevertheless, nearly 70% of patients belong to lower CGR. Our aim was to characterize the cytogenetic profile of South American (SA) MDS population trying to find differences among Argentine (A) and Brazil (B), both with diverse ethnicity, to evaluate CGR, and to define the impact of more frequent aberrations and of monosomal karyotype (MK) in our population. This is a multicenter retrospective study of 943 SA (634 from A and 309 from B) de novo MDS patients (pts) evaluated from 1981 to 2014. Pts were classified following FAB and WHO criteria. The median age was 69 (15-99) years old with a male/female ratio of (533/410) 1.3. During the follow-up, censored up to receiving a disease modifying therapy (median: 21 months), 159 (17%) evolve to AML and 351 (37%) died. Regarding 130 pts (14%) who received hypomethylating therapy (HMT), 46 (35%) evolved to AML, and 61 (47%) died. Although A population was larger than B series, no differences were observed concerning to: CGR distribution according to the IPSS (p=0.565) and to the IPSS-R (p=0.343), percentage of abnormal karyotypes (42%-A vs 40%-B; p=0.499), and presence of deletions and/or monosomies (77%-A vs 80%-B, p=0.700). B showed a higher proportion of karyotypes involving, at least, one chromosome Y, 5, 7, 8 and/or 20 (83% vs 73%-A, p=0.039), mostly due to a higher proportion of 5q- (39% vs 22%-A, p

Description: ALL is an aggressive bone marrow neoplasm, mainly associated with a poor outcome in adult patients. The aim of this study is to describe clinical, laboratory and prognostic factors in 102 patients treated in one institutional department from 1990 to 2005, retrospectively. Adult ALL subtype L3 (FAB) or B-IV (EGIL) was excluded. Statistical analysis was done by SPSS 10.0.The association of features and prognosis was assessed by Pearson’s chi-square. OS and DFS curves were constructed by Kaplan-Meier method and the differences were analyzed by the log-rank test. Mean age was 30,6 (12 to 82) years and 55,9% was male. Clinical findings, at diagnosis, were fatigue (55,9%), splenomegaly (56,9%), hepatomegaly (54,6%), lymphadenopathy (52,6%), fever (38,8%), bone pain (28,6%), bleeding (27,5%) and headache (15,3%). Involvement of CNS was detected in 11(10,8%) patients and testicular involvement was observed in one patient. Cutaneous infiltration occurred in one patient immunophenotyping T-IV(group b). Kidney and pulmonary infiltration, documented by biopsy, was found in 2 and 1 patients respectively. At diagnosis; mean blood values were 8,5g/dl, 84.341/mm3 and 76.275/mm3 for hemoglobin, leukocytes and platelets respectively. 98,7% of the patients presented with lymphoblasts in peripheral blood. FAB classification was L1 and L2, 50% each. B and T-ALL was observed in 69,7% and 30,2% respectively. One case was identified as biphenotypic B and T leukemia. Karyotype analysis was performed in 40 cases, Ph chromosome was identified in 20% (8/40) of the cases. Others abnormalities were hyperdiploid karyotype (6/40); t(4;11) in 2 cases; t (1;19) and t(10;11) each one with 1 case. Patients were treated with different protocols: BFM 86 modified (BFM 86M) in 47,1% (48/102) of the patients, OPAL86 and OPAL87 protocols (Linker e cols) in 45,1% (46/102) and CHOP in 7,8% (8/102). Ten patients died in early induction phase and 70,6% (65/92) were in complete remission after induction treatment. Age less than 35 years (p=0.021), CNS not infiltrated (p= 0.022) and immunophenotyping B1 and B3 (p=0.018) were associated with a better induction response in a univariated analysis. The first two parameters were associated with a high probability of complete response (p=0.041 and 0.034, respectively) in a multivariate analysis. In a median follow up of 49 months, we have observed a four-years OS of 30,4% (median 19 months). Univariate analysis of OS showed that age less than 35 and mainly less than 18 years (p=0.01), absent bleeding and hepatomegaly at diagnosis (p=0.0022; p=0.029), early time to complete remission (p=0.0001) and treatment protocol BFM 86M (p=0.0034) were associated with better survival. In a multivariate analysis age 〉35y, presence of hepatomegaly or bleeding at diagnosis were associated with poor OS, and were used to created a prognosis score. Patients with none to one adverse factor have a significantly better survival than patients with more than one (p=0.0001). We have observed in our population a DFS of 27% in 4 years with a median DFS of 18,9 months. Only fever, at diagnosis, was an adverse factor related to DFS in univariate analysis (p=0.0057).