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Introducción: el objetivo de tratamiento de primera línea en los pacientes con MM candidatos a trasplante hematopoyético autólogo (TCPH) es lograr la mayor profundidad de respuesta posible, lo que ha permitido prolongar las sobrevidas en este grupo de pacientes (pts). Se disponen de diferentes esquemas de inducción previos al TCPH.Actualmente, el esquema RVd es una de las primeras opciones recomendadas por diferentes guías de tratamiento. No existen datos publicados sobre la eficacia y seguridad sobre RVd como esquema de inducción en Latinoamérica en estudios de evidencia de vida real.Objetivos: nuestro objetivo primario fue describir la eficacia de RVd como inducción previo al TCPH.Además se evaluaron toxicidades relacionadas al tratamiento, sobrevida libre de progresión (SLP) y sobrevida global (SG).Material y métodos: estudio retrospectivo, multicéntrico de 13 centros pertenecientes al GAMM.Se incluyeron pts adultos con MM de reciente diagnóstico candidatos a TCPH tratados con RVd entre abril de 2016 a abril de 2021. Se analizaron las tasas de respuestas según los criterios IMWG-2016 y las toxicidades de acuerdo al CTCAE V4.3.Resultados: se incluyeron 110 pts con una mediana de edad de 58 años (rango 29-71) con 50% de sujetos femeninos y una mediana de seguimiento de 17 meses. 29 pts (27%) presentaron R-ISS 3, 21 pts (19%) alto riesgo citogenético y 11 pts (10%) enfermedad extramedular. La mediana de número de ciclos de RVd recibidos fue 6 (rango 2-10). 15 pts (14%) requirieron plerixafor previo a la recolección de células madres y 14 pts (13%) fallaron a la movilización inicial. La mediana de células CD34+ por kg fue de 4.6 x 106 (RIC 3.21-6.14). Las tasas de respuesta previa al TCPH fueron: 97% de respuesta global (RG), 77% muy buena respuesta parcial (MBRP) o mayor y 40% de respuesta completa (RC). La tasa de RC fue similar entre los pacientes de alto riesgo citogenético vs. riesgo estándar (p:0,39). Las tasas de respuesta post TCPH fueron: 99% RG, 93% MBRP o mayor y 75% de RC. Los eventos adversos de cualquier grado más frecuentes fueron: hematológicos (42%), infecciosos (39%), gastrointestinales (29%) y neuropatía periférica (23%). La SLP a 24 meses fue del 88% para toda la cohorte (IC95% 75-94). En aquellos pts que alcanzaron RC previa al TCPH, la SLP a 24 meses fue del 100% vs 80% en el resto (p: 0.005). La SG a 24 meses es de 95% (IC95% 87-98).Conclusiones: en nuestra cohorte fuera de un ensayo clínico, RVd resultó ser un esquema eficaz con perfil de seguridad adecuado. El TCPH profundizó aún más las tasas de respuesta. Ésta es la primera experiencia sobre el uso de RVd como inducción previa al TCPH en Latinoamérica. Objetivos: nuestro objetivo primario fue describir la eficacia de RVd como inducción previo al TCPH. Además se evaluaron toxicidades relacionadas al tratamiento, supervivencia libre de progresión (SLP) y supervivencia global (SG). Material y métodos: estudio retrospectivo, multicéntrico de 13 centros pertenecientes al GAMM. Se incluyeron pts adultos con MM de reciente diagnóstico candidatos a TCPH tratados con RVd entre abril de 2016 a abril de 2021. Se analizaron las tasas de respuestas según los criterios IMWG-2016 y las toxicidades de acuerdo al CTCAE V4.3. Resultados: se incluyeron 110 pts con una mediana de edad de 58 años (rango 29-71) con 50% de sujetos femeninos y una mediana de seguimiento de 17 meses. 29 pts (27%) presentaron R-ISS 3, 21 pts (19%) alto riesgo citogenético y 11 pts (10%) enfermedad extramedular. La mediana de número de ciclos de RVd recibidos fue 6 (rango 2-10). 15 pts (14%) requirieron plerixafor previo a recolección de células madres y 14 pts (13%) fallaron a movilización inicial. La mediana de células CD34+ por kg fue de 4.6 x106 (RIC 3.21-6.14). Las tasas de respuesta previo al TCPH fueron: 97 % de respuesta global (RG), 77% muy buena respuesta parcial (MBRP) o mayor y 40% de respuesta completa (RC). La tasa de RC fue similar entre los pacientes de alto riesgo citogenético vs. riesgo estándar (p:0,39). Las tasas de respuesta post TCPH fueron: 99% RG, 93% MBRP o mayor y 75% de RC. Los eventos adversos de cualquier grado más frecuentes fueron: hematológicos (42%), infecciosos (39%), gastrointestinales (29%) y neuropatía periférica (23%). La SLP a 24 meses fue del 88% para toda la cohorte (IC95% 75-94). En aquellos pts que alcanzaron RC previo al TCPH, la SLP a 24 meses fue del 100% vs 80% en el resto (p: 0.005). La SG a 24 meses es de 95% (IC95% 87-98). Conclusiones: En nuestra cohorte fuera de un ensayo clínico, RVd resultó ser es un esquema eficaz con adecuado perfil de seguridad. El TCPH profundizó aún más las tasas de respuesta. Esta es la primera experiencia sobre el uso de RVd como inducción previa al TCPH en Latinoamérica.

Las alteraciones citogenéticas (AC) constituyen uno de los factores pronósticos más importantes en los pacientes con mieloma múltiple (MM) permitiendo dividirlos en dos grupos de riesgo (estándar y alto) con diferente pronóstico y enfoque terapéutico. Actualmente las AC que tienen mayor relevancia para la estratificación de los pacientes con MM son: el índice de ploidía, los rearreglos del gen IGH, la inactivación del gen TP53 y las alteraciones del cromosoma 1 (deleción de 1p y/o ganancias de 1q). La técnica de elección para la detección de AC en el MM, tanto al momento del diagnóstico como en las evaluaciones posteriores, es la hibridación fluorescente in situ (FISH) realizada sobre una muestra con muy alta pureza de células plasmáticas (CP). La obtención de CP purificadas puede ser realizada por distintos métodos, de los cuales el que demostró mayor eficiencia es la citometría de flujo multiparamétrica (CFM) o cell sorting. El presente estudio muestra los resultados obtenidos al evaluar la presencia de AC en una cohorte de pacientes con MM de la vida real, comparando dos grupos: grupo S, en los que los estudios por FISH se realizaron sobre la población de células plasmáticas purificadas, y grupo NS en los que se realizaron sobre la muestra entera. Los resultados obtenidos son comparables a los publicados en otras series, y demuestran que la utilización del sorting previo a los estudios por FISH aumenta significativamente la sensibilidad de detección de AC en pacientes con MM, permitiendo una correcta estadificación y evaluación pronóstica, y optimizando las estrategias terapéuticas.

Cytogenetic abnormalities (CA) such as t(4;14), t(14;16), and del(17p), are associated with a poor prognosis in Multiple Myeloma (MM) patients. However, there is scarce information regarding the Latin-American population. This study aims to analyze the impact of t(4;14), t(14;16), and del(17p) on the progression-free survival (PFS) and overall survival (OS) of transplant-eligible newly-diagnosed MM (NDMM) patients in Latin America. Retrospective survival analysis based on the Grupo de Estudio Latinoamericano de MM (GELAMM) registry, including all adult patients with NDMM harboring CA t(4;14), t(14;16), and/or del(17p). Fifty-nine patients were included; the median age was 57 years, 55.9% males, 22% ISS-I, 25.4% ISS-II, and 47.5% ISS-III. The majority (89.8%) had 1 alteration, whereas 10.2% had del(17p) and t(4;14). The frequencies of CA were del(17p) in 61.0%, t(4;14) in 25.4%, and t(14;16) in 3,4%. Autologous stem cell transplantation (ASCT) was performed in 61.0% of cases. Five-year OS for the entire cohort was 60.8% and 5-year PFS was 28.1%. Bortezomib-based induction regimen (BBR) (P = 0.029), consolidation with ASCT (P0.001), and maintenance therapy (P = 0.004) were associated with an improved 5-year OS. In the multivariate analysis, ASCT was the only variable with a positive impact on OS (HR 0.11, 95% CI 0.033 to 0.34, P0.001). The median PFS presented a non-statistically significant benefit in BBR, ASCT, and maintenance therapy groups. BBR induction, ASCT, and maintenance therapy were associated with improved OS in high-risk NDMM patients.

BACKGROUND Numerous treatment options are available for patients with multiple myeloma (MM). Because of the course of the disease, most patients will experience serial relapse or the MM will become refractory to most of these treatments, leaving patients with few or no treatment options over time. Selinexor, a treatment with a novel mechanism of action, is an oral selective inhibitor of nuclear export (SINE) compound that blocks exportin 1, the major nuclear exporter of tumor suppressor proteins. CASE REPORT In this case series, we report on treatment with the weekly oral administration of selinexor combined with bortezomib and dexamethasone (XVd) in 3 patients from Argentina who were heavily treated (5-7 prior therapies) for MM that relapsed or was refractory to each previous treatment. Two patients had the high-risk cytogenetic abnormality del(17p). All 3 patients experienced efficacy with XVd reaching a best response of partial response or very good partial response. These responses were consistent with those of patients from the BOSTON study who were treated with XVd but were less heavily pretreated (1-3 prior therapies) and had a shorter median time since diagnosis of MM (7 years vs 3.7 years). The 3 patients experienced adverse events (AEs) that included nausea, thrombocytopenia, asthenia, and fatigue, which were similar to the most commonly reported AEs associated with selinexor treatment. CONCLUSIONS With its oral administration, novel mechanism of action, and responses in heavily pretreated patients, selinexor may help to address an important clinical need in the treatment of patients with relapsed/refractory MM.

The aim of this study was to describe clinical and survival characteristics of transplant-eligible multiple myeloma (MM) patients in Latin America (LA), with a special focus on differences between public and private healthcare facilities. We included 1293 patients diagnosed between 2010 and 2018. A great disparity in outcomes and survival between both groups was observed. Late diagnosis and low access to adequate frontline therapy and ASCT in public institutions probably explain these differences. Patients treated with novel drug induction protocols, followed by autologous stem cell transplantation (ASCT) and maintenance, have similar overall survival compared to that published internationally.

Data about treatment outcomes and toxicity in Latin America are scarce. There are differences with central countries based on access to healthcare system and socioeconomic status. Argentinean Society of Hematology recommends bortezomib-based triplets for induction treatment of transplant eligible newly diagnosed multiple myeloma patients. Most common options are CyBorD (cyclophosphamide, bortezomib and dexamethasone) and VTD (bortezomib, thalidomide and dexamethasone). Main goal of our retrospective, multicentric study was to compare very good partial response rate (VGPR) or better after induction treatment in a real-world setting in Argentina. Secondary objectives included comparison of complete response (CR) post-induction and after bone marrow transplantation, grade 3-4 adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Three hundred twenty-two patients were included (median age at diagnosis: 57 years; 52% male; 28% had ISS3; 14% with high-risk cytogenetics; median follow up: 34 months). CyBorD was indicated in 74% and 26% received VTD. In VTD arm, 72.62% of patients achieved at least VGPR vs 53.36% receiving CyBorD (odds ratio, OR: 1.96 [95% confidence interval, CI: 1.08-3.57; P = .026] after adjusting by age, ISS [International Staging System], lactate dehydrogenase levels (LDH) and cytogenetic risk. Difference in VGPR was 19.26% (95% CI: 15-24). CR rate were 35.92% (VTD) vs 22.55% (CyBorD) (adjusted OR: 2.13 [95% CI: 1.12-4.05]). Difference in CR was 13.37% (95% CI: 9.6-17.53). Adverse events (AEs) were more common with VTD (69.05% vs 55.46% for CyBorD; P = .030), especially grade 3-4 neuropathy (P = .005) and thrombosis (P = .001). Thromboprophylaxis was inadequate in 20.24% of patients. Hematological AEs were more common with CyBorD, especially thrombocytopenia (P = .017). PFS and OS at 24 months were not different between treatments. In this real-world setting, VTD was associated with better CR and VGPR than CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina, based on safety profile. Frontline autologous stem cell transplantation improves quality of responses, especially in countries with limited access to new drugs.

Individuals with malignancies and COVID-19 have a lower survival compared with the general population. However, the information about the impact of COVID-19 on the whole hematological population is scarce. We aimed to describe the 30th day overall survival (OS) after COVID-19 infection in patients with a hematological disease in Argentina. A completely anonymous survey from the Argentine Society of Hematology was delivered to all the hematologists in Argentina; it started in April 2020. A cut-off to analyze the data was performed in December 2020 and, finally, 419 patients were reported and suitable for the analysis (average age: 58 years, 90% with malignant diseases). After the COVID-19 diagnosis, the 30-day OS for the whole population was 80.2%. From the entire group (419), 101 (24.1%) individuals required intensive care unit admission, where the 30-day OS was 46.6%. Among allogeneic stem cell transplant recipients, the 30-day OS was 70.3%. Factors associated with a low OS were two or more comorbidities, an active hematological disease and history of chemotherapy. In individuals with the three factors, the 30-day OS was 49.6% while the 30-day OS in those without those factors was 100%. Patients with hematological diseases have a higher mortality than the general population. This group represents a challenge and requires careful decision-making of the treatment in order not to compromise the chances of cure.El presente estudio tuvo por objetivo primario conocer la mortalidad de pacientes con enfermedad hematológica que presentaron infección por COVID-19 en Argentina. Para ello se difundió una encuesta desde la Sociedad Argentina de Hematología (SAH) entre los hematológos para informar sobre los pacientes con enfermedades hematológicas y diagnóstico de infección por SARS- CoV-2, entre el 19/4/2020, y el 7/12/2020. Se incluyeron individuos de todas las edades con diagnóstico de enfermedad hematológica benigna o maligna e infección por SARS-CoV-2 confirmada por técnica de RTPCR. Se analizaron 419 pacientes (mediana 58 años; 90% enfermedades malignas). La supervivencia al día 30 fue de 80.2%. La supervivencia fue menor en aquellos que requirieron internación (74.2%), cuidados intensivos (46.6%) y asistencia respiratoria mecánica (36.8%). Entre los trasplantados alogénicos la supervivencia fue 70.3%. Los factores vinculados a la supervivencia global fueron las comorbilidades, el estado de la enfermedad al momento de la infección y el antecedente de quimioterapia. Se pudo establecer un score en el que aquellos que tuvieron un puntaje de 4 alcanzaron una supervivencia del 49.6% al día 30, mientras que la de los pacientes con score 0 fue del 100% a 30 días. En comparación con la población general, los pacientes con enfermedades hematológicas presentan una mayor mortalidad vinculada al COVID-19, motivo por el cual es primordial definir pautas destinadas a disminuir la exposición de los mismos sin comprometer las posibilidades de beneficiarse del tratamiento de la enfermedad de base.

Background The SARS CoV-2 / COVID 19 pandemic has challenged the world's health systems, especially services that treat cancer. The first studies in China showed that cancer patients had a higher risk of becoming infected and dying. Other risk factors for mortality were age over 65 years, male sex, the presence of comorbidity, hypertension, cardiovascular disease, diabetes, and obesity. Data on the specific behavior of patients with multiple myeloma (MM) in the pandemic are scarce. The mechanisms by which MM patients may have a higher mortality are multiple, derived both from the disease itself due to cellular and humoral immunity deficiency as well as from anti-myeloma treatment. The present study aims to establish the behavior of the disease in the pandemic period in Latin America. Methods This is a retrospective case series of in and outpatients with a diagnosis of MM and COVID-19 reported from centers from Latin America between March and July 31, 2020. The analysis of demographic, clinical, laboratory, complications and therapy variables were done using descriptive statistics. A Kaplan Meier survival analysis was performed, with Log Rank statistic. Finally, a Cox regression was performed to identify independent risk factors of worse outcome. Pre-admission characteristics, MM status, and comorbidities constituted the reference model and were used to adjust the association of relevant MM characteristics with mortality. Program used for analysis was SPSS statistics 25. Results Fifty-two patients with COVID-19 and MM from 7 countries were included. Demographic characteristics, comorbidities, infection baseline clinical conditions, treatment, and outcomes are shown in Table 1. The characteristics in terms of MM status are shown in Table 2. When performing the survival analysis, it is evidenced that the survival of the entire cohort at day 49 was 67% Figure 1. When we focus on patients with comorbidities, survival drops to 53.5% +/- 10.6 (CI 95% 53.4 - 99.4 and p value of 0.041) for the same day Figure 2. When performing the obesity analysis, a drop in survival of up to 39% was observed (95% CI 24.448 - 56.76, with p = 0.00001) Figure 3. Adjusted HR for obesity is 5,078 (95% CI 1,389-18,558, α0.014) and mechanical ventilation with a HR of 3,943 (95% CI - 1,296 - 11,998, α0.016) When comparing patients with controlled MM (> PR) versus uncontrolled, the mortality rate was 84% versus 58% respectively (p = 0.109). Comorbidities (presence of either diabetes, arterial hypertension, cardiovascular disease, or "others"), obesity, need of mechanical ventilation, and Conclusions Patients with MM and COVID-19 has an overall mortality of approximately 30% and this is strongly influenced by the presence of comorbidities, uncontrolled disease and need of mechanical ventilation. Survival of patients without comorbidities and controlled disease is good, suggesting that this group of patients would not require modification of MM therapy. The main limitations of our study are its retrospective nature and the low number of patients. It must be highlighted that at the time of the analysis most of Latin American countries were still in the peak of the pandemic. Prospective studies are required to elucidate the behavior of these risk factors in mortality, to optimize the management of patients with MM in this period of the SARS CoV-2 / COVID-19 pandemic. Disclosures Peña: BindingSite: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: 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; Amgen: Speakers Bureau. Abello:Novartis: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Dr. Reddy's: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Idrobo:Abbvie: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Rojas:Novartis: Consultancy; Roche: Honoraria; Sandoz: Honoraria; Abbvie: Honoraria. Remaggi:Takeda: Honoraria; Raffo Argentina: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gador Argentina: Research Funding; Amgen: Honoraria, Research Funding. Alvarado:Celgene: Speakers Bureau; Alexion: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau; Roche: Speakers Bureau. De la Peña-Celaya:Amgen: Speakers Bureau; Janssen: Speakers Bureau; Novartis: Speakers Bureau. Perez:Novartis: Speakers Bureau; Celgene: Speakers Bureau; Roche: Speakers Bureau.

PURPOSE Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) management in Latin America. The primary objective of the Hemato-Oncology Latin America (HOLA) study was to describe patient characteristics and treatment patterns of Latin American patients with MM, CLL, and NHL. METHODS This study was a multicenter, retrospective, medical chart review of patients with MM, CLL, and NHL in Latin America identified between January 1, 2006, and December 31, 2015. Included were adults with at least 1 year of follow-up (except in cases of death within 1 year of diagnosis) treated at 30 oncology hospitals (Argentina, 5; Brazil, 9; Chile, 1; Colombia, 5; Mexico, 6; Panama/Guatemala, 4). RESULTS Of 5,140 patients, 2,967 (57.7%) had NHL, 1,518 (29.5%) MM, and 655 (12.7%) CLL. Median follow-up was 2.2 years for MM, 3.0 years for CLL, and 2.2 years for NHL, and approximately 26% died during the study observation period. Most patients had at least one comorbidity at diagnosis. The most frequent induction regimen was thalidomide-based chemotherapy for MM and chlorambucil with or without prednisone for CLL. Most patients with NHL had diffuse large B-cell lymphoma (DLBCL; 49.1%) or follicular lymphoma (FL; 19.5%). The majority of patients with DLBCL or FL received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. CONCLUSION The HOLA study generated an unprecedented level of high-quality, real-world evidence on characteristics and treatment patterns of patients with hematologic malignancies. Regional disparities in patient characteristics may reflect differences in ethnoracial identity and level of access to care. These data provide needed real-world evidence to understand the disease landscape in Latin America and may be used to inform clinical and health policy decision making.

Data about treatment outcomes and toxicity in Latin America are scarce. There are differences with central countries based on access to healthcare system and socioeconomic status. Argentinean Society of Hematology recommends bortezomib-based triplets for induction treatment of transplant eligible newly diagnosed multiple myeloma patients. Most common options are CyBorD (cyclophosphamide, bortezomib and dexamethasone) and VTD (bortezomib, thalidomide and dexamethasone). Main goal of our retrospective, multicentric study was to compare very good partial response rate (VGPR) or better after induction treatment in a real-world setting in Argentina. Secondary objectives included comparison of complete response (CR) post-induction and after bone marrow transplantation, grade 3-4 adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Three hundred twenty-two patients were included (median age at diagnosis: 57 years; 52% male; 28% had ISS3; 14% with high-risk cytogenetics; median follow up: 34 months). CyBorD was indicated in 74% and 26% received VTD. In VTD arm, 72.62% of patients achieved at least VGPR vs 53.36% receiving CyBorD (odds ratio, OR: 1.96 [95% confidence interval, CI: 1.08-3.57; P = .026] after adjusting by age, ISS [International Staging System], lactate dehydrogenase levels (LDH) and cytogenetic risk. Difference in VGPR was 19.26% (95% CI: 15-24). CR rate were 35.92% (VTD) vs 22.55% (CyBorD) (adjusted OR: 2.13 [95% CI: 1.12-4.05]). Difference in CR was 13.37% (95% CI: 9.6-17.53). Adverse events (AEs) were more common with VTD (69.05% vs 55.46% for CyBorD; P = .030), especially grade 3-4 neuropathy (P = .005) and thrombosis (P = .001). Thromboprophylaxis was inadequate in 20.24% of patients. Hematological AEs were more common with CyBorD, especially thrombocytopenia (P = .017). PFS and OS at 24 months were not different between treatments. In this real-world setting, VTD was associated with better CR and VGPR than CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina, based on safety profile. Frontline autologous stem cell transplantation improves quality of responses, especially in countries with limited access to new drugs.

Context: BIA-ALCL is a new entity included in the 2016 WHO classification. It represents less than 10% of breast lymphomas. There are approximately 500 cases reported worldwide. BIA-ALCL is considered an indolent disease with excellent outcomes, but there is a subset of patients with a more aggressive course. Objective: To describe the main characteristics and outcomes of BIA-ALCL patients in Argentina. Design: This is a cross-sectional observational study. We collect patient data with a digital form fulfilled by different doctors among several healthcare institutions in Argentina. Data were provided by hematologists, pathologists, and plastic surgeons. The first case was reported in 2009 and the last in November 2019. Setting: This study was set in a referral Hemato-Oncologist centre. Patients or other participants: Inclusion criteria: Patients with BIA-ALCL diagnosis confirmed by histopathological study. The patients were diagnosed in Argentina and were reported by a physician. Interventions: No interventions were done because this was an observational study. Main outcome measures: No outcomes were measured because this was an observational study. Results: Twelve cases were registered. All patients were female. The median age was 48 years (33 to 66), and 100% of implants were textured. The median time between the implant surgery and the diagnosis was 8.5 years. In 8 (66%) patients the first symptom was late seroma. Seven (58%) patients were stage I at diagnosis, 3 (33%) stage III, and 1 (8%) stage IV. The diagnosis was achieved by fine-needle aspiration of periprosthetic fluid in 5 (41%) patients, mass biopsy in 4 (33%), and lymph-node biopsy in 3 (25%). All samples were CD30+ and ALK-. Surgical treatment was performed in all patients. Six (50%) patients also received chemotherapy with CHOP-based regimens. One patient received brentuximab+CHP and autologous stem cell transplantation. All patients are currently in complete remission. Conclusions: The characteristics of our reported patients were similar to those in international studies. We do not know the incidence and features of this disease in Latinomerica because of the lack of publications; thus, that is the value of this first report. Considering the scarcity of knowledge on the behaviour of this lymphoma, more research and follow-up are required to adequately treat this disease.

Background Multiple myeloma (MM) is a heterogeneous disease that is most frequently diagnosed in the elderly. Therefore, data on clinical characteristics and outcomes in the young population are scarce and it is recognized that it remains incurable even in this group of patients. We present here the outcomes of patients under 40 years old cohort in Latin-American countries. On behalf of GELAMM (Grupo de Estudio Latino-Americano de Mieloma Múltiple). Methods Retrospective international multicenter cohort study. We analyzed MM patients under 40 years old who received treatment in 6 Latin-American countries, between 2010 and 2018. Demographics and disease features were analyzed using descriptive statics. We examined treatment characteristics and response rates. The overall survival (OS) of the entire cohort was analyzed using Kaplan-Meier curves. Results Eighty-six patients of 6 countries were analyzed (Table1). The mean age was 35.4 years old, and 60% were male. The most frequent monoclonal component type was IgG followed by light chain MM. Risk determined by ISS was distributed in almost equal percentages. The most frequent cytogenetic alteration was the t (4;14) that was found in four patients out of 25 evaluated. The missing data were greater than 70%. Skeleton-related events were the most frequent clinical feature, followed by anemia and renal failure. Plasmacytomas and fractures were present in more than 20 percent of cases. With regard to treatment, VCD / CyBorD was the most used regimen, followed by VTD. The overall response rate (ORR) was 63%. Fifty-three patients received high dose therapy and autologous stem cell transplantation (62%). Only 8% received post-transplant consolidation, and 45% received maintenance therapy. The median OS of the entire cohort was 45 months, and a plateau in the survival curve was not observed, suggesting that patients continue relapsing over the time. Conclusion In this Latin American multicenter study, we found that the young population with MM has similar presentation characteristics to those of elderly patients. A significant amount of information is lost regarding the risk characterization, especially in regard with cytogenetics. With respect to treatment, less than half of the patients achieve very good partial response or better. It is striking that more than a third of this young patients did not access to high doses of chemotherapy and bone marrow transplantation. Maintenance therapy is offered to less than half patients. The median OS is lower than in other series of patients younger than 40 years, even than in the elderly cohorts. Prospective multicentric studies are required to elucidate the behavior of the disease in this group of patients. Disclosures Peña: Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights. Rojas:Novartis: Membership on an entity's Board of Directors or advisory committees; Pfeizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Abello:Takeda: Other: Participation in advisory board meeting. Gomez-Almaguer:Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau.

Background Multiple myeloma (MM) is a frequent hematologic malignancy. The current gold standard frontline strategy includes a proteasome inhibitor (PI)-based induction, followed by autologous stem cell transplant (ASCT). Access to novel drugs in Latin America (LA) is limited. ASCT is available in most countries, but real access to it is highly heterogeneous. Data regarding patients´ outcomes in candidates to ASCT in the region is scarce. The aim of this study was to describe clinical characteristics and outcomes of MM transplant eligible patients in LA countries. Material and Methods Retrospective international multicenter cohort study. Consecutive MM transplant- eligible patients diagnosed between 2010 and 2018 from participating centers in Chile, Argentina, Ecuador, Mexico, Colombia, and Uruguay were included. Data were collected from clinical records in a standardized report form. We analyzed clinical characteristics at diagnosis and frontline therapy outcomes, including ASCT. Transplant-eligible patients were defined as fit patients younger than 66 years old. Active MM and response to treatment were defined according to current IMWG criteria. Inclusion criteria: 1.- Patients with newly diagnosed active MM between 2010 and 2018. 2.- Older than 18 years, and younger than 66 years. 3- Candidates for ASCT according to the evaluation of the attending physician Exclusion criteria: 1- Lack of minimum data in the clinical history 2- Plasma cell leukemia, AL amyloidosis or solitary plasmacytoma. 3- HIV infection 4-No consent and/or Ethics Committee approvals. Statistical analysis A descriptive statistic has been done. Comparisons of characteristics between groups was made usingT-student, Chi2 or ANOVA, as appropriate. Survival analysis was performed using Kaplan-Meier curves. Comparisons of survival between groups were made by the logarithmic recording method and the calculations of the risk relationships by Cox regression. Statistical analysis was performed by using STATA 13. Results We included 1293 patients in the study, 363 from Chile, 395 from Argentina, 209 from Colombia, 45 from Ecuador, 151 from Mexico, and 130 from Uruguay. The main characteristics at diagnosis and therapeutic strategies are shown in Table 1. Optimal response (sCR, CR and VGPR) was achieved in 38% of the patients in the cyclophosphamide, bortezomib, and dexamethasone (CyBorD) group, in 46% in the bortezomib, thalidomide, and dexamethasone (VTD) group, and in 36% in the cyclophosphamide, thalidomide, and dexamethasone (CTD) group, the 3 main induction regimens used. Only 53% of patients finally received ASCT. Significant differences were found between both groups, private and public institutions, regarding burden of symptoms, ISS staging, access to PI based induction, ASCT completion and adequate maintenance, with patients from the latter being more symptomatic, and receiving suboptimal therapy. FISH analysis was performed in less than 50% of patients, both in the public and private setting. With a median follow up of 34 months (range 1-113), median overall survival (OS) was 86 months. The 5-year progression free survival (PFS) was 38% and 5- year overall survival (OS) was 64%. When comparing public vs private settings, 5 year OS was 45% vs 80%, with a median OS of 56 months vs not reached, respectively (P In the multivariable analysis renal failure (p=0.03), achieving less than VGPR response (p Conclusion This is the largest report on transplant eligible patients with MM in LA. Great inequities are shown between public and private health systems. Survival in transplant-eligible patients is lower than that described in other regions. Only one third of patients had FISH performed. This means that very few patients are treated with a risk-based induction in LA. Patients in the public setting are diagnosed with a more symptomatic disease, probably due to a late diagnosis. OS is significantly worse in the public setting. This might be explained by the significant differences in access to PI-based induction, ASCT and maintenance between private and public institutions, with patients from the latter receiving suboptimal frontline therapy and maintenance. Reasons for 47% of potential candidates not being transplanted merit further analysis. Table 1 Disclosures Peña: Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfeizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Abello:Takeda: Other: Participation in advisory board meeting. Gomez-Almaguer:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

Hematopoietic stem cell transplantation (HSCT) with sibling donors (s.d.) is a life-saving intervention for patients with hematologicalmalignancies. Numerous genetic factors have a role in transplant outcome. Several functional polymorphisms have been identifiedin TGF-β1 gene, such as single-nucleotide polymorphism (SNP) at +29C4T within exon 1. Two hundred and forty five patient/donorpairs who underwent a s.d. HSCT in our centers were genotyped for this SNP. In the myeloablative cohort, +29CC donors wereassociated with an increase in severe chronic GvHD (32% vs 16%, hazard ratio (HR) 9.0, P = 0.02). Regarding survival outcomes,+29CC patients developed higher non relapse mortality (NRM) (1?5 years CC 28?32% vs TC/TT 7?10%; HR 5.1, P = 0.01). Recipientsof +29TT donors experienced a higher relapse rate (1?5 years TT 37?51% vs TC 19?25% vs CC 13%?19%; HR 2.4, P = 0.01) witha decreased overall survival (OS) (1?5 years TT 69?50% vs TC/CC 77?69%; HR 1.9, P = 0.05). Similar to previous myeloablativeunrelated donors HSCT results, we confirmed that +29CC patients had higher NRM. In addition we found that +29TT donors mightbe associated with a higher relapse rate and lower OS. These results should be confirmed in larger series. Identification of theseSNPs will allow personalizing transplant conditioning and immunosuppressant regimens, as well as assisting in the choice of themost appropriate donor. Fil: Berro, Mariano. Universidad Austral; Argentina Fil: Palau Nagore, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Rivas, M. M.. Universidad Austral; Argentina Fil: Longo, P.. Universidad Austral; Argentina Fil: Foncuberta, Cecilia. Instituto Alexander Fleming; Argentina Fil: Vitriu, Adriana. Instituto Alexander Fleming; Argentina Fil: Remaggi, Guillermina. Fundaleu; Argentina Fil: Martinez Rolón, Juliana. Fundaleu; Argentina Fil: Jaimovich, Gregorio. Fundación Favaloro; Argentina Fil: Requejo, Alejandro. Fundación Favaloro; Argentina Fil: Feldman, Leonardo. Fundación Favaloro; Argentina Fil: Padros, Karín. Fundación Favaloro; Argentina Fil: Rodriguez, María Beatriz. Fundación Favaloro; Argentina Fil: Shaw, B. E.. Medical College Of Wisconsin; Estados Unidos Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Kusminsky, Gustavo. Universidad Austral; Argentina

Introduction: There are scarce data regarding treatment outcomes and toxicity in Latin American countries. Argentina is the second largest country in the region and the fourth most populated one. National Guidelines from the Argentinean Society of Hematology (SAH) recommends the use of bortezomib based triplets for induction treatment in transplant eligible newly diagnosed Multiple Myeloma patients. Objective: To compare response rates and adverse events after induction treatment with Cyclophosphamide Bortezomib and Dexamethasone (CyBorD) or Bortezomib Thalidomide and Dexamethasone (VTD) outside of clinical trials in a Latin American country. Methods: Retrospective multicentric cohort study. All centers participating in the Argentinean Multiple Myeloma Study Group (GAMM) were invited to participate in the study. Eligible patients were 75 years of age or younger, with a diagnosis of Multiple Myeloma according to the IMWG 2014 criteria, transplant eligible, treated with at least one cycle of CyBorD or VTD as induction therapy in the time period from December 2012 until December 2017. Main exclusion criteria were amyloidosis, plasma cell leukemia and previous neuropathy. Patients were identified from local registries at each center and included consecutively in the study database. Epidemiological and clinical data were obtained from medical records and collected in a standardized clinical report form. Patients were followed from diagnosis until death or lost to follow up. Response was evaluated according to IMWG Response Criteria 2016. Adverse events were graded by CTCAE 4.3. Comparisons of response rates were performed using a Chi2 test and differences in rates were expressed as proportions with 95% confidence intervals (CI). Crude odds ratios (OR) and OR adjusted by potential confounders were calculated using a logistic regression model. Kaplan Meier method was used to estimate progression free survival (PFS) and overall survival (OS). Stata 13 software was used. Results: A total of 322 patients from 15 centers in Argentina were included in the study. The median age at diagnosis was 57 years (range 26-74), 52% (167) of the patients were male, 18% (58) had renal failure, 28% (85) ISS 3 , 7% (22) extramedullary disease, and 14% (46) high risk cytogenetics. Median time of follow up was 34 months (IQR 21-58). CyBorD was the most common treatment, indicated as induction therapy in 74% (238) of the cases. The characteristics of the patients were similar in both groups except age and LDH levels. The median number of cycles was 5 (range 1-12). Bortezomib was administered once per week in 85% (272) of the patients and subcutaneously in 86% (276) with no differences between both treatment arms. The median cumulative cyclophosphamide dose per month was 1.5 g (IQR 1.5-2.4) and thalidomide dose per day was 100 mg. In the VTD arm, 72,62% (61) of the patients achieved at least very good partial response (VGPR) vs 53.36% (127) with CyBorD [OR of 2.31 (CI 1.35 - 3.99) p=0.002]. The difference in VGPR was 19.26% (CI 15 - 24). Complete response rate (CR) was 35.92% in patients treated with VTD vs 22.55% with CyBorD [OR of 1.87 (CI 1.04 - 3.35) p=0.03). The difference in CR was 13,37% (CI 9.6 -17.53). There was no difference in overall response rate (ORR) with 94.05% vs 91.18% (p=0.406). Adverse events were more common with VTD (69.05% vs 55.46% p=0.030), especially neuropathy grade 3 - 4 (7.14% vs 1.26% p=0.005) and thrombosis (13.10 % vs 3.36 % p=0.001). Deep venous thrombosis prophylaxis was inadequate in 20.24% of the patients. Hematologic adverse events were more common with CyBorD, especially thrombocytopenia (5.95% vs 16.39% p=0.017). Autologous stem cell transplantation (ASCT) was performed in 78% (249) of patients. There was 5% (17) stem cell mobilization failure, all in the CyBorD arm. Response rates after ASCT with VTD and CyBorD induction treatment were: 76.19 vs 73.11% VGPR (p=0.580) and 48.53% vs 40% CR (p=0.20). Maintenance treatment was indicated in 67.86% (57) and 65.13% (155) patients respectively (p=0.650). The PFS at 24 months was 83% (CI 71-90) with VTD vs 72% (CI 66-78) [(HR 0.92 (CI 0.59 - 1.42) p 0.715] and OS 96% (CI 87-99) vs 91% (86-94) respectively [(HR 1.2 (CI 0.62 - 2.32) p 0.587]. Conclusions: VTD has better CR and VGPR compared to CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina based on safety profile. The optimal number of induction treatment cycles remains to be determined. Disclosures Schutz: Takeda: Honoraria, Research Funding; Sanofi Aventis: Research Funding; Roche: Research Funding; Glaxo: Research Funding; Janssen: Honoraria, Research Funding; Varifarma: Honoraria. Shanley:Brystol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Fantl:Janssen: Consultancy, Honoraria, Research Funding; Varifarma/Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Research Funding; Roche: Research Funding; Tecnofarma: Honoraria; BMS: Consultancy, Honoraria; Glaxo: Research Funding.

Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative approach for patients with myelodysplastic syndrome (MDS).In this multicenter retrospective study, we analyzed the outcome of adult patients with MDS who underwent AHSCT in Argentina and evaluated the prognostic factors associated with progression-free survival (PFS), overall survival (OS), cumulative incidence (CI) of relapse, and non-relapse mortality (NRM).We analyzed data from 87 adults (median age: 43 years, range 18-66) who underwent SCT after myeloablative (n = 60) or non-myeloablative conditioning (n = 27), and from related (n = 62) or unrelated (n = 25) donors. For all patients, unadjusted 4-year PFS and OS were 37% and 38%, respectively; no significant differences were found between recipients of related or unrelated donors. One-year CI of relapse and NRM were 21% and 20%, respectively. In the multivariate analysis, intermediate disease risk index (DRI) and acute graft versus host disease AGVHD of all grades (I-IV) were independent variables associated with better PFS and lower relapse CI; only intermediate DRI was associated with better OS.AHSCT is a feasible procedure in Argentina, with more than 30% of the patients achieving long-term survival. Recipients with unrelated donors had at least similar outcome than those with related donors. DRI may be useful to identify patients at higher risk of relapse after transplantation.

Background To establish stringent complete remission (SCR) in patients with multiple myeloma (MM), it is currently recommended to obtain a normal serum free light chains (sFLC) ratio. The appearance of serum oligoclonal bands (OB) after autologous stem cell transplantation (ASCT) is considered a favorable prognostic factor. The objective of this study was to examine sFLC for assessing SCR in patients with MM, and ASCT with OB. We also examined how capillary electrophoresis (CE) compares with agarose gel electrophoresis (Aga) in identifying oligoclonal bands. Methods Out of 238 patients studied in our institution between April 1992 and December 2008 a serum protein electrophoresis (SPE) was performed by means of CE and sFLC determination on 37 patients with MM in complete remission (CR), ASCT and OB presence were assigned by conventional Aga electrophoresis and IF. Results Statistically significant differences (SSD) were found when comparing CE vs. Aga, regarding BO visualization in SPE, favoring the latter. In connection with sFLC, the group of patients with an abnormal ratio presented elevated values in the γ-globulin zone of the SPE, whereas the group of patients with a normal ratio of sFLC presented with normal values resulting in SSD between the groups. Conclusions It is essential to perform immunofixation to certify the presence of OB, especially if CE is used as it is difficult to distinguish them using this method. A normal sFLC was observed in most of the patients with OB and normal values of the SPE γ-globulin zone. The above-mentioned information might demonstrate a limitation of sFLC test in SCR evaluation for patients with MM, ASCT and CR if OB has been detected.

Background Response to TKI is the most important predictor of survival in CML and its early acquisition predicts the achievement of deep molecular responses (MR) (Baccarani et al. Blood 2013). In current ELN recommendations, the optimal time point to achieve Major Molecular Response (MMR) is defined at 12 months (mo) after diagnosis of CML however, not achieving MMR is not a failure criterion at any time point (Saussele et al, Blood 2014). There are controversies about when CML therapy must be changed in pts who do not achieve MMR after 12 mo of treatment. We wonder if pts achieving late MMR are less likely to achieve deep MR or are at risk of progression to accelerated phase (AP) or blast crisis (BC). Objectives We aim to identify predictive factors for achievement of deep MR and improvement of failure-free survival (FFS). Other objective was to determine if delay in MMR acquisition predicts outcomes in order to justify an optimal landmark for changing TKI reducing the risk of failure. Methods Between 2000 and 2015, 122 consecutive adult pts with CP CML were treated with various TKI modalities. Adherence (ADH) monitoring occurred in every visit and was reported in medical records, optimal ADH defined as >90% of dose completed. Cytogenetic and MR were defined according to ELN definitions and followed the procedures as described elsewhere (Cross et al. Leukemia 2012). In particular, BCR-ABL Results From 122 pts diagnosed with CP CML, 110 pts received 1st line imatinib (IM) 400mg daily and constitute the basis of the analysis. Median age was 48 years (14-82), 65% were males, 82% low Sokal score. With a median follow-up of 107 mo (IQR 69.5-141) 82% pts are still on initial IM, 4.5% died and 1.8% were lost to follow-up. A total of 20 pts (18%) discontinued Imatinib, 9% due to intolerance and 9% due to failure. At 15 years, FFS was 88% and OS 95%.The proportion of pts treated with IM who achieved CCyR at 6mo and MMR at 12mo was 84% and 38% respectively. Median-time to achieve MMR and MR4.0 was 2.6 and 3.6 years respectively. By logistic regression analysis CCyR at 6mo OR 5,6 (95% CI 1,6-19,00), MMR at 12mo OR 5,3 (95% CI 1,4-21,0), ADH OR 7,0 (95% CI 1,3-37,0) and not MMR at 24mo OR 2,5 (95% CI 0,9-7,2) resulted independent predictors for achieving MR4.0 and confirm earlier observations. In Cox model of proportional hazards for risk of failure, time to achieve MMR HR 1,02 (95% CI 1,01-1,04), ADH HR 6.1 (95% CI 1,38-26,8), and Sokal HR 4,7 (95% CI 1,12-19,3) were independent predictors of failure. Time to achieve MMR is a continuous variable, so the HR associated with it, is equivalent to a 2% monthly increase in the risk of failure. To calculate HR in other time intervals, the product of the coefficient model (B) and time of interest (in mo) were used as an exponent of the base of the natural logarithm (e). Not reaching MMR at 12 mo correlates with higher risk of failure: hazard-risk (HR) 1.30, (95% CI 1.28-1.30) and the risk increases with every passing year not achieving MMR (Table 1). Table 1.Time to MMR as predictor of progressionNo MMR achievement in different time intervalsHRCI 95%After 12 mo of TKI1,30(1,3-1,3)After 24 mo of TKI1,70(1,7-1,7)After 30 mo of TKI2,21(2,2-2,2)After 60 mo of TKI3,74(3,7-3,8) Conclusions The prognostic value of CCyR at 6mo and MMR at 12mo was confirmed. The association between early MMR and deep MR was confirmed. In this long-term follow-up Latin American real-world cohort of patients ADH was also an early predictor for achievement of deep MR. Although good responses are obtained with IM, some patients still progress, this is the reason why it is necessary to identify those who will relapse so as to consider a change in treatment to another TKI at a convenient time point. Time to achieve MMR, ADH, and Sokal Risk score were independent predictors of failure. Not achievement of MMR at 12mo correlates with increased risk of failure. The risk increases annually in proportion to the time delay. Patients who are delayed in reaching MMR should be controlled closely. Disclosures Pavlovsky: Novartis: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau. Pavlovsky:Novartis - Bristol: Speakers Bureau.

Allogeneic hematopoietic stem cell transplantation (HSCT) using sibling donors is a life-saving intervention for patients with hematological malignancies. It is recognized that numerous genetic factors in both patient and donor play a role in the outcome of the procedure. TGF beta 1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes. Several functional polymorphisms have been identified in TGF-B1 gene, such as a single nucleotide polymorphism (SNP) at codon 10 of exon 1. We have previously published significant impact of this SNP on unrelated donor (UD) transplant outcome, predominantly on Non Relapse Mortality (NRM) and acute Graft-vs.-Host-Disease (aGVHD). To date there are no published data in large sibling donor HSCT cohorts looking at survival outcomes. We have hypothesized that TGF-B1 SNP may influence the outcome of sibling donor HSCT similarly to UD. Preliminary data were presented at ASH meeting 2014. Two hundred and seventeen patient/donor pairs who underwent a sibling donor HSCT in our centers were genotyped for the presence of a SNP at codon 10 (rs1982073) by an allele-specific PCR. Transplants took place between January 2000 and January 2015 and the median follow up time was 4.4 years. Median age was 33 years and 58% were male. The prevalent diagnoses were acute myeloid leukemia 64 (29%), acute lymphoid leukemia 49 (23%), lymphoproliferative disorders 28 (13%), myelodysplastic syndrome 26 (12%) and myeloproliferative neoplasm 20 (9%). Early stage of the disease was determined in 42%. Myeloablative conditioning regimens were used in 58% of transplants; the source was PBSC in 90% of the patients. The patients' observed SNP frequencies were TT 23%, TC 55% and CC 22%, and for the donors were 26%, 53% and 21% respectively. No significant impacts were observed in the full cohort analysis. When we analyzed the myeloablative cohort, significant differences were founded. Similarly to what we observed in UD, codon 10 CC patients had a significant increase in 1 year treatment related mortality (32% vs. 9%, p=0.01) and Non Relapse Mortality (NRM) (1-3 years CC 31-31% vs. TC/TT 8-13%, Gray's test p=0.04) (figure 1). A very interesting finding was in donor's genotype. Codon 10 TT donor's receptors experienced a significant increase in aGVHD (72% vs. 49%, p=0.03), with 56% of this grades 2-4. Interestingly this group had no protection in terms of relapse, but the opposite, although not significant (1-3 years TT 36-40% vs. TC 17-34% vs. CC 9-13%, Gray's test p=0.1). Finally TT donors had a significant decrease in Overall Survival (OS) compared to other genotypes (1-3 years TT 69-50% vs. TC/CC 77-69%, log-rank p=0.04) (figure 2). No differences were observed in donor genotype in terms of NRM. Besides confirming that as in UD, patient codon 10 CC had an increase in NRM, we conclude that in sibling donor-myeloablative HSCT codon 10 TT donors might be associated with an increase in aGVHD with no protection in relapse and a significant decrease in OS. These results should be confirmed in larger series. Identification of these SNPs pre-transplant will allow for transplant conditioning and immunosuppression regimens to be tailored to the individual patient, as well as assisting in the most appropriate choice of donor. Disclosures No relevant conflicts of interest to declare.

Allogeneic hematopoietic stem cell transplantation (HSCT) using sibling donors is a life-saving intervention for patients with hematological malignancies. It is recognized that numerous genetic factors in both patient and donor play a role in outcome. TGF beta 1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes. Several functional polymorphisms have been identified in TGF-B1 gene, such as a single nucleotide polymorphism (SNP) at codon 10 of exon 1. We have previously published significant impact of this SNP on unrelated donor (UD) transplant outcome, predominantly on Non Relapse Mortality (NRM) and acute Graft-vs.-Host-Disease (aGVHD). To date there are no published data in large sibling donor HSCT cohorts that analyze survival outcomes. We have hypothesized TGF-B1 SNP may influence the outcome of sibling donor HSCT similarly to UD. One hundred and sixty six patient/donor pairs who underwent a sibling donor HSCT in our centers were genotyped for the presence of a SNP at codon 10 (rs1982073) by an allele-specific PCR. The transplant took place between January 2000 and March 2014 and the median follow up time was 4.4 years. Median age was 33 years and 59% were male. The prevalent diagnoses were acute myeloid leukemia 54 (32%), acute lymphoid leukemia 33 (20%), lymphoproliferative disorders 24 (14%), myelodysplastic syndrome 21 (13%), myeloproliferative neoplasm 9 (5%), and 42% were in early stage. Myeloablative conditioning regimens were used in 58% of transplants; the source was PBSC in 93.3% of the patients. The patients' observed SNP frequencies were TT 22%, TC 56% and CC 22%, and for the donors were 25%, 57% and 18% respectively. No significant impacts were observed in the full cohort analysis. When we analyzed the myeloablative cohort significant differences were founded. Wild-type donors (TT) experienced a significant increase in relapse incidence compared to other genotypes (1-3 years TT 37-41% vs. TC 15-23% vs. CC 0-0%, Gray's test p=0.01), with a significant decrease in disease free survival (DFS) (1-3 years TT 53-39% vs. TC/CC 73-65%, log-rank p=0.04) and overall survival (OS) (1-3 years TT 64-46% vs. TC/CC 77-67%, log-rank p=0.04) (figures). No differences in terms of NRM were founded. We conclude that in sibling donor-HSCT TGF-B1 wild-type donors might be associated with an increase in relapse and subsequent decrease in DFS and OS. These results should be confirmed in larger series. Identification of these SNPs pre-transplant will allow for transplant conditioning and immunosuppression regimens to be tailored to the individual patient, as well as assisting in the most appropriate choice of donor. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Materials and Methods We retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplant (HSCT) in 9 centers from Argentina. We evaluated the following characteristics: sex, age, diagnosis, stage, comorbidities (according to the HCT-CI score), type of donor, histocompatibility, source, conditioning and immunosupression. We analyzed the incidence and severity of acute Graft-vs-Host disease (aGVHD) with Chi Square, Overall Survival (OS) and Disease Free Survival (DFS) with Kaplan Meier and Relapse, Non Relapse Mortality y chronic GVHD (cGVHD) with CI. For multivariate analysis (MA) we included variables that in univariate had a p Results Patients characteristics are listed in table 1. Between January 1997 and July 2013, 137 transplants were performed in adults older than 50 years, with a median follow up 1.3 years. Acute GVHD incidence was 41% (19% were grade II and 7.3% III-IV). The only variable associated with aGVH clinically significant (G II-IV) was AML that was protective (14% vs 35%, p Conclusion HSCT is a valid therapeutic option for older patients. In this retrospective analysis of patients older than 50 years, we found that the main risk factors that impact in transplant outcome are patients comorbidities and not age, whereas transplant related toxicities increase with the number of comorbidities and therefore decrease OS and DFS. Beyond the fact that certain disease experienced more aGHVD (AML) or cGVHD and higher NRL (MPN) the other factor significantly related in transplant outcome was the use of tacrolimus vs CSA. Disclosures: No relevant conflicts of interest to declare.

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.

Introduction MF is a myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, cytopenias and constitutional symptoms. Since the identification of JAK2V617F mutation and development of anti JAK molecules, the course of the disease has changed. Ruxolitinib is a JAK1 and JAK2 inhibitor recently approved for patients (pts) with primary and secondary MF. In Argentina, pts could access the ruxolitinib through CUP. Analysis of this multicenter protocol provides a preliminary data set, follow up and efficacy results. Objectives To assess the efficacy (reduction in spleen size/improvement in constitutional symptoms) and toxicity. To investigate risk groups modifications during follow-up. Methods In Argentina, 36 pts with myelofibrosis, including primary MF (PMF) and post polycythemia vera (PPV) received ruxolitinib through CUP regardless of JAK2 mutational status. Study period: September 2011 to June 2013. The participating physicians provided information of the disease characteristics by completing a data form. Splenomegaly was evaluated by physical exam, and constitutional symptoms were categorized as present or absent. Retrospective analysis was performed based on data at baseline (n 36), after 3 months (n 30), 6 months (n 24) and 12 months (n 14). Results Median follow-up is 10 months (1-20). The median age is 65 years (30-79), 64% were men and 36% women. There were 72% positive for the JAK2 V617F mutation, 69% had PMF and 31% Post-PV. At admission 89% of pts had received ≥1 lines of therapy for MF prior to ruxolitinib: hydroxyurea 77%, thalidomide 26%, erythropoietin 23%, others: corticosteroids, interferon, anagrelide, danazol, busulfan, splenic radiation, cytarabine, and 6-mercaptopurine. The distribution of risk category according to DIPSS was: 61% high, 19% Intermediate 2, 17% Intermediate 1, and 3% low. Median value for spleen size was 15 cm (4-33) below the costal margin. Constitutional symptoms were present in 71% of the patients and 33% were transfusion dependent. ECOG (Eastern Cooperative Oncology Group) was zero 28%, one 44%, two 22%, three 3%, and four 3%. The median hemoglobin, leucocytes and platelets was 10 g/dl (4.8-15.2); 13, 4 x 109/L (3.6-64) and 217 x 109/L (75-850), respectively. Peripheral blood blasts ≥ 1% in 44% of pts. Ruxolitinib therapy was initiated at 40 mg/d in 16 pts (50%), 30 mg/day in 9 pts (28%), and at a lower dose in the minority of pts. The median value for spleen size at 3, 6 and 12 months was 10, 8 and 6.5 cm, representing decrease of 20%, 41% and 42% from baseline, respectively (fig 1.). In 13 of 29 pts (45%) spleen size decreased ≥ 50% in 3 months. Constitutional symptoms not present at 3, 6 and 12 months in 79%, 100% and 87% of pts, respectively. Improvement in ECOG class was noted in 73%, 69 % and 73% at the above mentioned time points, respectively. Persistence of transfusion dependence at 3, 6 and 12 months was seen in 33, 24 and 27% of the patients. Hemoglobin median levels during treatment (g/dL): at baseline 10.1, at 3 months 8.5, at 6 months 9.7, and at 12 months 9.5. During follow-up, 27% pts shifted to a lower risk group, 2 pts (7%) to a higher group due to worsening anemia, and 67% did not change its category. Hematologic adverse events (AE) were anemia and thrombocytopenia in 8 pts (Grade 1 and Grade 3 according to CTCAE v4.0), 31% of pts required dose adjustment. There were no suspensions of medication because of cytopenia. Others AE > 10% were: headache, musculoskeletal pain, and diarrhea ( Conclusion Ruxolitinib is an effective therapy that reduced spleen size and improved constitutional symptoms with an acceptable toxicity profile in this group of pts. During follow up at 12 months, a quarter of pts shifted to a lower risk group. Our data is consistent with previous reports Disclosures: Barreyro: GSK: Employment. Enrico:Bristol Myers Squibb: Speakers Bureau; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees. Lanari Zubiaur:Novartis: Membership on an entity’s Board of Directors or advisory committees. Pavlovsky:Novartis: Consultancy. Sackmann:Novartis: Membership on an entity’s Board of Directors or advisory committees. Bengió:Novartis: Member advisory Board Myelofibrosis Other.

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.