ALBERT

Description: Abstract 1888 Myelodysplastic Syndrome (MDS) comprises a group of heterogeneous hematological disorders with variable risk of leukemic evolution (LE) and short survival (SV). Around 40–50% of patients show abnormal karyotype at diagnosis and cytogenetic findings are an independent prognostic factor in MDS. Although the International Prognostic Scoring System (IPSS) differentiated 3 cytogenetic categories of risk (CCR), the Intermediate one is heterogeneous. The aim of this study was to characterize the cytogenetic profile, to test its prognostic value and to evaluate cytogenetic groups of risk in the Argentinean MDS population. Also, we tried to ascertain whether some abnormalities could be segregated from their respective CCR. This is a multicenter retrospective analysis of 488 primary Argentinean patients with MDS evaluated from 1984 to 2008 (including 183 patients from the Pilot Study for MDS Registry organized by the Argentinean Society of Hematology). Patients' distribution according to French-American-British classification (FAB) was: 235 Refractory Anemia (RA), 50 RA with Ringed Sideroblasts (RARS), 121 RA with excess of Blast (RAEB), 27 RAEB in transformation (RAEBt) and 55 Chronic Myelomonocytic Leukemia (CMML). The median age was 69 (17-92) years with a gender ratio (M/F) of 1.3. During the follow-up (mean: 25 months (m), range: 1–266 m), 110 (22.5%) underwent LE and 217 (44.5%) patients died. Age, sex, percentage of bone marrow blast, hemoglobin level, platelets count, number of cytopenias, LDH level and red blood cell transfusion requirements were significant predictive variables for prognosis (Kaplan-Meier and Long-Rank test, p

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: Abstract 4582 Introduction: Introduction of imatinib mesylate has changed the approach towards bone marrow transplantation in Chronic Myeloid Leukemia (CML). Historically considered as a curative therapeutic option, with a probability of disease free survival ranging from 40 to 60%. Its indicated use has been restricted to patients with treatment failure to prior tyrosin-kinase inhibitors or blast crisis. Objective: To assess the outcome of patients with CML who undergo BMT Materials and methods: 66 patients who underwent allogeneic BMT between the years 1994 and 2011 in two health care facilities were analyzed. 63 (93%) were performed between 1994 and 2005. At the time of transplantation, patient status was: 56 patients in 1st Chronic Phase and 10 in advanced phases. Fourteen patients received Unrelated Donor BMT and 37 had Related Donor BMT. Transplant risk was assessed, based on the European Bone Marrow Transplantation (EBMT) score (sc). The conditioning regimens which were used included: for patients in chronic phase, cyclophosphamide (Cy) and busulfan (Bu) and for patients in accelerated phase etoposide (VP 16) was added to the previous regimen, and for unrelated donors BuCy + ATG or alentuzumab was used. Prophylaxis for Graft vs Host Disease (GVHD) was performed with a two-drug regimen (cyclosporine, methotrexate), with or without methylprednisone. Result: 66 patients were recorded (28 female/38 male), with a mean age of 35 years at the time of transplantation (range 8–55). The source of Stem Cell was bone marrow in 60 patients and peripheral blood in 6 patients. 43% of patients developed GVHD: (29 patients) according to clinical criteria established by the European Cooperative Group. Overall Survival (OS) was 50% with a mean follow-up of 48 months. Analyzed according to the EBMT risk score, OS was 64% in the 0–2 score group and 31% in patients with a 3–5 score. Procedure-related mortality was 16%, and the most frequent causes included: hepatic veno-occlusive disease, infections, GVHD, and graft failure. Conclusions: BMT in patients with CML has been substantially reduced since the introduction of tyrosin-kinase inhibitors. In our experience, this shows its healing potential with an extended follow-up and a prolonged survival. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Hodgkin´s Lymphoma (HL) is a highly curable disease. However, there are still patients with primary refractory disease or who relapse after first-line treatment, or even after high-dose chemotherapy with hematopoietic cell rescue. Allogeneic stem cell transplant (ASCT) is therapeutic for this patients. Objective To analyze the experience with relapsed HL patients that received ASCT with reduced intensity conditioning (RIC)regimen in 8 Argentine Medical Centers. Design and Population We performed a retrospective multicenter analysis from data obtained from medical records. Fifty-four patients with relapsed HL who received ASCT had a median age of 26years. The relationship between male / female was 1/1. Only 3 patients (5.5%) at the time of transplant had a performance status〉 1 according to ECOG. Ninety-six percent of the patients had received previously autologous transplant. Most patients 43 (80%) received an identical sibling donor transplant. All patients receiving unrelated donor transplants had in vivo lymphocyte depletion as prophylaxis of graft versus host disease. Forty-three patients (79.6%) received as a conditioning regimen Fludarabine + Melphalan. The disease status at transplant was: complete remission (CR) 33%, partial remission (PR) 54%, stable disease / progressed (SD / PD) 13%. Results With a median follow up of 2.7 years, actuarial overall survival (OS) at 1 and 5 years was 65% and 20% respectively and disease free survival (DFS) at 1 and 5 years was 35 % and 18% respectively. The incidence of acute GVHD grade II-IV was 31%. Patients in CR at the time of transplant showed significant differences compared with those who were not in CR in DFS (1-5 years 52-27% vs 19-14%, p=0.01), OS (1-5 years 76-38% vs 59-13%, p=0.02) and non relapsed mortality (NRM) (1-5 years 6-12% vs 34-39%, p=0.04). Age, PS, the use Fludarabine + Melphalan as conditioning regimen, unrelated donor, aGVHD, were not variables that modified the overall survival and disease-free survival. Conclusion The ASCT with RIC regimen is a feasible therapeutic option in patients with HL, especially in patients who can achieve CR. The low rate of DFS is still an issue in this setting, may be new drugs may help in optimizing pretransplant response status to improve patients’ outcome. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3804 Poster Board III-740 Background Epigenetic therapy with a hypomethylating agent is becoming the standard of care in some intermediate and high-risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML). Aims This multicenter, open label, single-arm study evaluated the efficacy and safety of the 5-day decitabine (DACOGEN, Janssen Cilag Farmaceutica S.A. and Eisai Inc.) dosing regimen in patients with MDS and CMML on a “Real World Program”. Methods Eligible patients were enrolled at different sites from South Korea and Argentina. A report prepared ad-hoc was completed. WHO classification was taken into account, as well as International Prognostic Scoring System (IPSS), performance status by ECOG, co-morbidities, previous treatments and IWG 2006 criteria. Efficacy was evaluated with at least 2 cycles. Inclusion Criteria: ≥18 years of age; de novo or secondary MDS; all WHO Subtypes and CMML type 1 and type 2. Exclusion Criteria: Acute Myeloid Leukemia (AML) or other progressive malignant disease. All patients received decitabine 20 mg/m2 IV over 1 hour x 5 days, with cycles repeated every 4 weeks. Results One hundred sixteen patients enrolled (Intend-To Treat) and 99 were evaluable: median age 64, 73% male, 93% de novo MDS, median time from diagnosis 9 months, and 19% with prior chemotherapy treatment. WHO classification was: RA 1%; RARS 2%; RCMD 25%; RCMDRS 4%, RAEB-1 12%; RAEB-2 28%; MDSu 1%; CMML type-1 17% and type-2 9%. IPSS: High (17%), Int-2 (25%), Int-1 (55%) and Low (3%). Co-morbidities were described in 51%. This report includes data from a 24-month follow-up period. Patients received a median of 5 cycles (range 1-13), with 42% receiving ≥6 cycles. Overall improvement rate in the evaluable population was 35% by IWG 2006 criteria (19% CR + 4% mCR + 4% PR + 8% HI) and the rate of stable disease or better was 50%. Median time to first and best response was 2.2 and 3.9 months respectively. 37% of patients died during study period. Adverse events attributed to the study drug were febrile neutropenia (59%), thrombocytopenia and bleeding (18%), asthenia (30%), fatigue (12%), and eosinophilia (4%). Three patients received an Allo Stem Cell Transplant after achieving CR and did well. Two percent of patients responded after cycle 4. Four patients withdrew decitabine after getting CR, they relapsed and re-treatment was successful. Twenty-one percent of patients developed AML during follow-up. Conclusions Decitabine showed a prompt clinical activity and the overall improvement rate was 35%. This drug had a manageable toxicity profile. Previous chemotherapy treatment was an unfavorable risk factor. Although delayed response has been observed (2%), no less than 4 cycles should be given. Relapse was a rule after withdrawing treatment, so keeping dosing and interval is really important. This treatment was very active in CMML and allowed patients to be transplanted in a better condition. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2031 Background: The role of High-Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT) as salvage therapy in relapsed Follicular Lymphoma (FL) has been questioned since the introduction of Rituximab in the treatment of FL. Our objectives were to evaluate the long-term event-free survival (EFS) and overall survival (OS) rates of patients with relapsed or refractory FL who received HDT and ASCT as salvage therapy. Our secondary objective was to compare EFS of patients who received ASCT before and after 2002 (the year Rituximab become fully available for use in our country). Patients and Methods: We conducted a retrospective analysis of 123 consecutive patients with relapsed or refractory FL who had received HDT and ASCT as salvage therapy in five Argentinean transplant centers from 1992 to 2012. Results: One hundred twenty tree patients (median age: 48 years, range: 23–72) were transplanted, 71 (58%) male, 37/106 (35%) had FL Grade 1, 47/106 (44%) FL Grade 2 and 22/106 (21%) FL Grade 3; 75/102 (73%) of patients have a stage III-IV disease at the moment of diagnosis and 27/102 (26%) have a disease stage I-II. Before transplantation 78/121 (64%) patients were in Complete Response (CR), 42/121 (35%) were in Partial Response (PR) and one patient had a Progressive Disease. Fifty four patients (44%) were transplanted before 2002 (before Rituximab era in our country). The conditioning regimens used were CBV 94 (76%), BEAM/BEAC 27 (22%), others regimens two patients; only one patient received TBI containing conditioning regimen and was excluded for conditioning regimen PFS curve calculation. The median time from FL diagnosis to ASCT was 29 (range 1–300) months. The transplant related mortality (until day 90 after ASCT) was 5%. With a median follow-up of 52 (range 0–247)months, the median EFS was reached at 44 months and a plateau on the EFS curve was evident starting at 6 years after ASCT. The 10 years-projected EFS was 36% (Figure 1). The median OS was not reached during follow-up. Median EFS for patients who were transplanted before 2002 (before Rituximab era) and for those who were transplanted after 2002 was 41 months and 47 months respectively [HR 1.01; IC (0.61–1.65); p=0.97]. EFS rates difference was not statically significant between patients who previously transplantation have achieved a CR or a PR, median EFS 47 and 68 months respectively [HR 0,94; IC (0,56–1,58); p= 0,82]. There was no difference in EFS rates between patients who received CBV as conditioning regimen and patients who received BEAM/BEAC, median EFS 57.6 months and 16.3 months respectively [HR 0.67; IC (0,34–1.35); p=0.2]. The median EFS rate for patients with FL Grade 1, FL Grade 2 and FL grade 3 were 58, 44 and 16 months respectively, P for trend = 0.78. Seven cases (5,7%) of secondary malignancies were detected, six cases (6/94; 6,4%) in patients who received CBV as conditioning regimen (urotelial carcinoma, pancreas carcinoma, lynfoprolipherative disorders, non-melanoma skin malignancies and prostate carcinoma) and one case (1/27; 3,7%) in patients who received BEAM (urotelial carcinoma), p=0,85; there were no reports of secondary myelodysplastic syndromes/acute myeloid leukemia. Conclusion: In this study, 50% of the patients analyzed were free from progression after 44 months of ASCT and approximately a 30% of patients achieve long term remission. According to this, patients with relapsed or refractory FL can achieve long-term EFS with HDT followed by ASCT. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4850 Background The Secondary Myelodysplastic Syndrome (sMDS) represents a severe complication in the treatment of cancer. They are associated to the use of alkylating agents, radiation and immunosuppressive therapy. Their prognosis is unfavorable. Conventional chemotherapy is mainly palliative whereas allogenic bone marrow transplantation allows the cure of a small percentage of cases. Aims: To characterize and to describe the clinical presentation, therapeutic conduct and evolution in sMDS. This results where compared with those of primary MDS (pMDS) in patients enrolled into the observational study of Sociedad Argentina de Hematología from January 2007 to June 2009 Methods There were analyzed 253 patients with diagnosis of MDS. sMDS correspond to 12.2 % (31/253)of the total, mean age 71 years old (r 23-84), relation M: F of 1:2.8 (being 1:2.2 in pMDS). Previous pathologies were: solid tumors in 17 patients (54%); 6 prostate Ca, 5 breast Ca, 4 GI Ca, 1 thyroid Ca, 1 bladder Ca, 1 pharynx Ca. Hematology malignancies were found in 7 patients: 2 Non Hodgkin Lymphoma, 2 Hodgkin Lymphoma, 1 Myeloma Multiple, 1 Chronic Myelomonocyticleukemia, 1p aplastic anemia. Six patients (23%) received immunosuppressive treatment for kidney transplantation, Wegener disease and glomerulonephritis. 85% of the patients received previous chemotherapy and/or radiotherapy. Result: There were analyzed 217 karyotypes (85.7%), 25 in the sMDS group and 189 in the pMDS, abnormal karyotypes in 14/25 (56%) vs 55/189 (29%) (p=0.006), complex karyotypes (unfavorable): 6/25 (24%) vs 8/189 (7%) (P=0.002). Twenty eight patients requiered treatment 28/31 (90.3%) vs 167/222 (75.2%) (p=0.09), transfusional therapy 23/31 (77.55%) vs 93/222 (42%) (p=0.001). Hypomethylating agents were used in 22,5% in sMDS vs 21,1% in pMDS and Erythropoyetin in 45,2% vs 48,6%. With a median follow up of 136 days (r:4-650), 8/31 progressed to AML (25.8%) vs 28/222 (13%) (p=0.005). Fourteen patients (45%) were death vs 47/222 (20.6%) (p=0.005); 17/31 (54.8%) of patients were alive in the sMDS group and 153/189 (80%) in the pSMD group (p= 0.005). Summary and Conclusions sMDS constituted 12.2% of the total of MDS that were reported. This entity has in our experience presence of unfavorable karyotype in more than the 50% of the cases, greater transfusion request, greater evolution to acute myeloid leukemia with high mortality and greater mortality than pMDS. This results confirm the bad prognosis of sMDS. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4454 Introduction: CML represents 15% all of oncohematologic diseases in adults. IM changed the history of the disease. At one year of treatment, the emblematic IRIS study showed Major Cytogenetic Responses (MCyR) of approximately 87% and Complete Cytogenetic Responses (CCyR) of around 76%, with PFS to accelerated phase or blast crisis of 97.7% and 91.5%, respectively. Objective: To assess treatment characteristics and responses in a group of patients treated with IM in clinical practice. Materials and Method: 113 medical records of patients with CML diagnosed between 1998–2011 from two institutions in the Argentine Republic were retrospectively analyzed. Result: Mean population age was 46 years old (r 18–73) 65 male, 48 female. 97% in chronic phase, the rest in accelerated phase. 31% presented comorbidities at diagnosis. Cytogenetic abnormalities at diagnosis, in addition to the classic t(9:22), included: trisomy 8 and double Philadelphia chromosome in 4 tests. Only 7 patients had qualitative BCR/ABL determined at diagnosis. 25% had received interferon, patients received IM 400 mg and only 2% received 300 or 600 mg doses. 2.6% of patients did not achieve CHR. Cytogenetic responses assessed at any time of treatment were: Major: 12%, Minor 20%, Complete 51%, None 3%, 14% were not assessed. With a mean follow-up time of 46 months, the overall survival was 75%. 10% of patients progressed to BC/AP, 11 % of patients died due to disease-related causes or comorbidities. Conclusions: With a mean follow-up time of 46 months for chronic phase CML, treatment with IM achieved complete cytogenetic responses in 51% of patients, and progression occurred in 10% of patients. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4838 Background Myelodysplastic Syndromes (MDS) are so heterogeneous, that new prognostic scoring systems are being continuously developed to help choose the best treatment strategy. The International Prognostic Scoring System (IPSS) excludes secondary MDS, prior therapy and Chronic Myelomonocytic Leukemia (CMML) with leucocytosis. Recently, a new risk model has been published by Kantarjian et al. (Cancer 2008; 113; 6; 1351) that is applicable to all MDS patients. Aims To validate this new risk model in our MDS population. Methods We analyzed 253 patients reported from 15 centers in our country from Jan 2007 through Jun 2009. We took into account age, performance status (PS), hemoglobin, platelets, leucocytes, bone marrow blasts, karyotype, and transfusion requirements. The new model divided patients into 4 prognostic groups: Low Risk (LR): 0-4; Intermediate-1 (I-1): 5-6; Intermediate-2 (I-2): 7-8; and High Risk (HR): ≥9. We assessed the prognostic impact of this New Risk Model and compared results to IPSS. Mortality Rate and AML progression risk were analyzed. Results 164 patients were evaluable, mean age 69 (R 21-92), primary MDS: 144, and secondary MDS: 20. Risk Group assessment for the new score: LR (34%), I-1 (31%), I-2 (18%), and HR (17%). The mean Follow-up was 22 months; Results are shown in table and graphic. Conclusion Even though our sample is not considerably big, and follow-up is short, we confirmed 4 categories with different prognosis and found a close correlation with Mortality Rate. This New Scoring System allowed us to identify Low Risk IPSS patients with different outcomes, highlighted the importance of adding new prognostic factors like age and performance status, refined the cut-offs of thrombocytopenia and anemia, and recognized the adverse impact of prior transfusions needs. Graphic Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma subtype seen in Western countries. However, data on FL from Latin America (LATAM) are scarce. We aimed at better understanding the clinical features, treatment patterns and outcomes of patients with FL from LATAM. Methods: This is a retrospective study that included all consecutive patients with a pathological diagnosis of FL at 18 participating centers from 12 LATAM countries. All cases were reviewed by specialized pathologists at their respective participating centers. Pertinent clinical, pathological and treatment data were collected. Responses were assessed per the Lugano criteria. Time to first treatment, progression-free survival after first treatment (PFS1) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: A total of 763 patients were included in this analysis. On clinical features, 51% of patients were ≥60 years, 46% were male, 29% had extranodal involvement, 27% had bulky disease (≥6 cm in diameter), 68% had stage III/IV disease, 21% had hemoglobin