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INTRODUCTION Tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL) has recently been in the spotlight. The predictive role of immune cells (IC) in peripheral blood (PB), bone marrow (BM) and lymph nodes (LN) has been individually assessed, often using techniques not widely available. However, data regarding the relative prognostic impact of TME in each compartment evaluated simultaneously in DLBCL is still lacking. AIMS To determine the prognostic impact on survival of the monocyte-lymphocyte prognostic score (MLS) in PB and the percentage (%) of IC in the BM and LN measured by flow cytometry (FC) in DLBCL and whether it could improve the conventional risk assessment of the R-IPI. METHODS We retrospectively collected information of patients (pts) with DLBCL and available BM aspiration and LN FC data at diagnosis, treated at our center between 2012 and 2019. Pts were stratified according to the MLS (Wilcox et al, Leukemia 2011) in two groups: low (PB monocyte counts RESULTS 71 pts were included with a median age of 59 years. Table 1 shows frequency analysis of TME variables and R-IPI in our cohort. All pts received immunochemotherapy. Complete remission rate was 82%. Median overall survival (OS) was 120.5 months (m), with a median follow up time of 38.7 m. On univariate analysis, poor R-IPI and TME variables from the 3 compartments: low LN T lymphocyte (TL) %, both high and low BM monocyte (Mo) %, low polyclonal BM B lymphocyte (BL) %, and intermediate-high MLS showed prognostic impact on OS. BM IC levels did not statistically differ in involved vs not involved BM. On multivariate analysis, poor R-IPI, low LN TL %, low BM Mo and polyclonal BL, remained independent predictors of survival (Table 2). Pts with the 4 unfavorable variables showed a median OS of only 4 m and 100% mortality rate. In contrast, in pts with none of these adverse risk variables OS rate was 100% (p CONCLUSIONS Low LN TL %, low BM Mo and polyclonal BL measured by FC were associated with inferior OS in our cohort of DLBCL pts. These TME variables combined with R-IPI can identify both a subgroup of pts with high early mortality rate and a group with excellent long-term prognosis. Immunotherapy with CART cells and BiTEs has shown encouraging results in relapsed refractory DLBCL pts. These strategies could help to improve outcomes in this high risk subset of pts while restoring previously deficient antitumoral immunity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Several studies have disclosed the predictive role of tumor microenvironment (ME) in diffuse large B cell lymphoma (DLBCL). However, there is limited data regarding the prognostic impact of immune cells (IC) in the bone marrow (BM) of DLBCL patients (pts). Regulatory molecules secreted from primary tumor sites may induce a pro-tumorigenic ME within BM, resulting in an impaired systemic immune response that could promote lymphoma survival. AIMS: -To determine the prognostic impact on survival and risk of early relapse (ER) of the % of T lymphocytes (TL), monocytes (Mo), neutrophils, NK cells and polyclonal B lymphocytes (BL) measured by flow cytometry (FC) in pre-treatment BM aspirates of DLBCL pts. METHODS: We selected pts with DLBCL and available BM aspiration FC data at the time of diagnosis who received treatment at our institution between 2012 and 2019. Clinical information was collected from medical records. FC analysis was performed with 8-color FC panels according to international Euroflow protocols. % of TL, Mo, neutrophils, NK cells and polyclonal BL by FC were compared to the normal values determined by Matarraz et al. (Cytometry part B, 2010). All parameters were analyzed as ordinal variables in 3 categories: low, normal and high. Odds ratio for ER (relapse within a year) was calculated using logistic regression. The survival analysis was estimated with Kaplan-Meier method. The comparison between variables was performed through log-rank test and multivariate analysis with Cox regression. RESULTS: A total of 119 pts were included in this retrospective study. Pts characteristics are summarized in Table 1. All pts were treated with immunochemotherapy regimens. Median PFS and OS were not reached, 75th percentile of 12.7 and 27.8 months (m), respectively; with a median follow up time of 30.7 m (range: 3.4-60). ER was documented in 25 pts. Regarding BM IC, pts with normal TL, polyclonal BL and Mo % were significantly associated with superior PFS and OS (figure 1A and table 2). No correlation between BM NK cells or neutrophils levels and outcome was observed. Moreover, BM IC levels did not statistically differ in involved vs not involved BM. In our cohort, the R-IPI was able to discriminate outcomes in poor and good-very good (G-VG) risk (median OS of 48 m vs. not reached, p R-IPI, BM involvement and BM IC were included in a multivariate analysis. G-VG R-IPI and low BM TL % remained independent prognostic factor of PFS on multivariate analysis with HR of 0.43 (95% CI 0.21-0.89, p: 0.023), and 3.77 (95% CI 1.8-7.92, p The odds of ER was 4 times higher in pts with low BM TL % (95% CI 1.47-10.84, p: 0.006) and 2.8 times higher in pts with low polyclonal BL (95% CI 1.07-7.58, p: 0.036). On the contrary, G-VG R-IPI showed a protective effect with an odds ratio for ER of 0.22 (95% CI 0.08-0.61, p: 0.003). On multivariate analysis both the low BM TL % [OR 5.18 (95% CI 1.45-18.53, p: 0.011)] and the R-IPI subgroup [OR 0.21 in G-VG R-IPI (95% CI 0.06-0.71, p: 0.012)] were predictive of ER. Pts with poor R-IPI were subsequently stratified according to BM TL categories. Pts with low and high TL % had a median PFS of only 9.4 vs 17 m respectively. However, it was unexpectedly not reached in the normal TL subgroup, p: 0.005 (Figure 1B). There was also a trend towards inferior OS in pts with low and high TL (median of 23.1 and 27.8 m respectively vs not reached for the normal subgroup, p: 0.09). CONCLUSIONS: Normal BM % of TL, BL and Mo in DLBCL pts measured by FC was associated with better outcomes in our cohort irrespective of BM involvement. Furthermore, concomitant low BM TL% and poor R-IPI identified a subgroup of pts with extremely poor results. These two variables presented at diagnosis might be used as prognostic factors of early relapse in DLBCL. In the future, therapies that could target the crosstalk between lymphoma cells and the BM ME might represent an encouraging strategy to improve outcomes in DLBCL. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Long-term survival of patients with chronic myeloid leukemia (CML) has significantly improved since the introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs). Several considerations about the side effects, risks and cost associated with the lifetime treatment, have led patients and physicians to explore the possibility of TKI discontinuation after achievement of a sustained deep molecular response (DMR), so-called treatment-free remission (TFR). Several clinical trials show that approximately half of patients who achieve a sustained DMR during TKI treatment maintain molecular remission after suspension of TKIs. There is currently no biomarker that reliably predicts TFR in CML, mainly due to different study designs that have generated inconsistent data. Thus, further investigations are needed to identify factors that consistently favor achievement of TFR. With the aim of developing a biomarker for TFR prediction we analyzed the phenotype of Natural Killer (NK) cells and their relation to successful TKI cessation. METHODS: This analysis was conducted as a substudy of the Argentina Stop Trial. Altogether, 50 consecutive chronic phase CML patients who participated in the clinical trial were recruited from 7 Argentinian centers. Peripheral blood samples were collected before stopping TKI treatment, at month 3, 12 and at any time when MR3.0 was lost. Freshly isolated mononuclear cells from 46 patients were immunophenotyped by staining with CD3, CD16, CD25, CD56, CD57, CD158, NKp30, NKp44, NKp46, NKG2A, NKG2C, NKG2D and PD-1 antibodies and NK cells subpopulations were analyzed by flow cytometry (BD FACS Canto™II). Molecular recurrence-free survival was estimated by the Kaplan-Meier method and compared within groups by the log-rank test. The cutoffs of the numerical variables were optimized according to the log-rank test. Quantitative variables were dichotomized according to receiver operating characteristics (ROC) curves in order to describe sensibility and specificity. Multivariate analysis was performed through Cox proportional hazards model. Main results are provided with hazard ratio (HR) at 6 months and 95% confidence intervals (95% CI). RESULTS: At the time of discontinuation the median proportion of NK cells (CD3-CD56+) among lymphocytes was significantly increased in patients compared with controls (15% vs 9%, P = 0.0016). A significant difference between molecular relapsed vs no-relapsed patients was observed when optimal cutoff (0.43) for CD56bright low and high was determined (at 6 months 74% vs 100% respectively, log rank test, p=0.023). At this time of follow up, no significant difference was observed for CD56dim NK cells. Phenotypic markers for adaptive-like NK cells were analyzed, however, no significant differences were observed between the non-relapsing and relapsing groups. Nevertheless, molecular non-relapsing patients had significantly higher frequencies of PD-1+ NK cells as compared with molecular relapsing patients (at 6 months 85% vs 64%, Log Rank test, P=0.009). Based on the ROC and Youden Index analysis, at 6 months the 1.2 cutoff shows an 80% specificity and 50% sensitivity. Moreover, after multivariable Cox proportional analysis, including age, time of treatment, deep molecular response time, Sokal risk, NK cells and PD-1+ NK cells, the last subpopulation was identified as an independent prognostic factor for molecular-relapse-free survival (Hazard ratio = 3.63; 95% CI 1.3 - 10.1; P=0.014). CONCLUSIONS: The clinical impact of NK cells in patients who have discontinued TKIs is controversial. The effects of TKIs against immune cells, including NK cell subsets, could depend on the type of TKIs; this aspect is particularly relevant in Argentinian treated patients real world, since many different copies of TKIs are routinely used in the clinical setting. Our study is the first, to our knowledge, to report a significant increase in PD-1 expression in NK cells at TKI cessation in patients who do not relapse. Accordingly to recent reports, PD-1 expression is more abundant on NK cells with an activated and more responsive phenotype and does not mark NK cells with an exhausted phenotype. To fully understand how PD-1 on NK cells modulates immune responses we are planning to carry out functional studies. In the future, we are also planning a comprehensive study of immune suppressors, including regulatory T cells and myeloid-derived suppressor cells. Disclosures Moiraghi: Novartis: Speakers Bureau; BMS: Speakers Bureau. Varela:Novartis: Consultancy, Speakers Bureau. Pavlovsky:Varifarma: Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants, Speakers Bureau. Pavlovsky:Pint Pharma: Speakers Bureau; Pfizer: Speakers Bureau; BMS: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

INTRODUCTION: Recent studies have suggested that tumor microenviroment (TME) may play an important role in lymphomagenesis and tumor progression in non-Hodgkin lymphoma. Tumor-infiltrating lymphocytes and myeloid-derived cells could provide valuable prognostic information independent from tumor characteristics alone. In diffuse large B-cell lymphoma (DLBCL) several attempts have been made to capture prognostic variables associated with TME. Peripheral blood monocytes, lymphocytes and natural killer (NK) cells have been shown to predict outcome in DLBCL patients (pts). Immunohistochemistry and gene-expression profile on tissue biopsies have also been studied as prognostic indicators. In this study we assessed the prognostic significance of the percentage of infiltrating T-lymphocytes (TL) and NK cells measured by flow cytometry (FC) in tissue biopsies of DLCBL. AIMS: -To determine the prognostic impact on survival of the percentage of infiltrating TL and NK cells measured by FC in tissue biopsies. -To evaluate whether this variables can provide additional information when superimposed on the R-IPI. METHODS: We selected pts with DLBCL and available tissue biopsy FC data at the time of diagnosis who received treatment at our institution between 2012 and 2018. Clinical information such as age, gender, stage, serum lactate dehydrogenase levels, R-IPI and cell of origin were collected from medical records. FC analysis was performed with 8-color FC panels according to international Euroflow protocols. Percentage of TL and NK-cells in lymph node biopsy by FC was compared to the normal values determined by Battaglia et al (Immunology 2003). Both parameters were analyzed as dichotomized variables: low vs. normal-high. The survival analysis was estimated with Kaplan-Meier method. The comparison between variables was performed through log-rank test and multivariate analysis with Cox regression. RESULTS: A total of 75 pts were included in this retrospective study. Pts characteristic are summarized in Table 1. All pts were treated with immunochemotherapy regimens. Complete remission rate was 82%. Median PFS and OS were 35.2 and 83.2 months respectively, with a median follow up time of 27.8 months (range: 4.3-177.5). In our cohort, the R-IPI was able to discriminate OS and PFS into poor and good-very good risk (median OS of 27.8 months vs. not reached, and median PFS of 12.8 vs. 82.6 months, p A low percentage of TL in lymph node biopsy samples was associated with inferior OS (median OS 34.3 months vs. not reached, p:0.001). This subgroup also had inferior PFS, not statistically significant (median PFS 16 vs. 118 months, p:0.08). Regarding NK-cells, low values had significantly worse OS (median OS 57.4 months vs. not reached, p:0.03). Decreased PFS, not statistically significant, was also found in this subgroup (median PFS of 15.5 vs. 40.4 months, p:0.079). Both the TL and R-IPI remained independent predictors of survival on multivariate analysis with HR of 5.5 (CI 95% 1.88-16.07, p: 0.002), and 5.8 (CI 95% 2.20-15.33, p The percentage of TL in lymph nodes was able to further stratify clinical outcome in all R-IPI categories. In pts in the good-very good R-IPI and normal-high TL risk group no deaths occurred, compared to a median OS of only 22.2 months in pts with poor R-IPI and low TL values (p CONCLUSIONS: Tumor infiltrating TL in lymph nodes of pts with DLBCL measured by FC showed prognostic impact in OS in our cohort. Data obtained from FC is easily acquired and should be taken into consideration when studying TME. Furthermore, the percentage of TL was able to provide additional prognostic information when superimposed on the R-IPI, identifying both a subgroup with an exceptionally good outcome and a very high-risk subset of pts. Early strategies aiming to improve TL in poor risk patients could constitute an appealing approach. Disclosures No relevant conflicts of interest to declare.

Introduction Estimated incidence of cHL in Argentina is 842 cases/year (Globocan 2018). There is no local data regarding response rates (RR) to FL. GATLA (Grupo Argentino de Tratamiento de Leucemia Aguda) reported 3 years progression free survival (PFS) rates of 90% and overall survival (OS) of 98% regardless of stage. HL has a high cure rate; 10% are primary refractory and 30% relapse after achieving complete remission (CR). In stage I-IIa, 5 years OS is estimated around 90% and 60% in stage IV (Ann Hematol 2019). Objectives Primary: To learn the RR, PFS and associated variables after FL of cHL in public (PuI) and private institutions (PrI) in Argentina. Secondary: To learn the OS rates. To study epidemiological characteristics of the patients (Pts) in participating institutions and reveal differences which may affect the response to treatment. Materials and methods Retrospective analysis of consecutive Pts with diagnosis of cHL from 1/1/2008 to 2/1/2019 with available follow up data. Descriptive statistics was performed in clinical variables and histopathological findings. Quantitative variables were expressed as median an interquartile range (IQR) and qualitative variables as total number and percentage (%). Survival rates were estimated by the Kaplan-Meier method and compared by the log-rank test. OS was measured from the date of diagnosis to date of death or last follow-up visit. Results 520 Pts from 7 PuI and PrI in Buenos Aires and Rosario were examined. 22 Pts had nodular lymphocyte predominant HL. Data on the 498 Pts with cHL is presented. Median follow up: 37.4 months (CI95% 17.7-63.5). Pts characteristics: Table 1. The median time from diagnosis to FL was 22 days (IQR 14-42), significantly shorter in PrI (32.5 (IC95% 27-38) vs. 49.3 (IC95% 38.5-60.2); p=0.0027). 96.5% of Pts received ABVD as FL, dose modifications or transitory suspension were required in 17.1%, and 82.1% received all cycles properly. CR was achieved in 83.4% of Pts and partial remission (PR) in 6.3%. The % achieving CR was higher in PrI; more PR were achieved in PuI. 10.3% had progressive disease (PD) at the end-of FL. 85.4% (n=373) had negative end-of-treatment FDG-PET results (DS1-3). Interim PET scan was performed in 70% of Pts (n=357), with 83.8% achieving metabolic CR but only 15.5% (n=70) being treated with response-adapted strategies (6.5% deescalated to AVD). Regarding hematologic toxicity, anemia, neutropenia and thrombocytopenia were found in 28.5%, 56.4% and 7.2% of Pts, respectively. Febrile neutropenia was reported in 9 Pts. 28.6% developed non-hematologic toxicities (41/144 pulmonary toxicity). 51 Pts had primary refractory disease and 69 (14%) relapsed during follow-up (median time to relapse 4.4 months (CI95% 0-13)). 65 Pts died (12.5%), 34 due to lymphoma progression and the remaining 31 due to toxicity. 2 years OS rate was 91% (CI95% 88% - 94%) and 85% at 5 years (CI95% 80% - 89%). There was no difference in OS between PrI and PuI (p=0.27); every day of delay in the beginning of FL increased 0.89 (IC95% 0.6-1.8) the risk of achieving PR or PD at the end of FL. 5 years PFS rate was 76% (CI95% 70-81) (figure 1-2: OS according to risk group and PFS). Outcomes were statistically better in women, age younger than 60, non-bulky disease, absence of extranodal disease or risk factors such as leukocytosis, lymphopenia and hipoalbuminemia. Pts with normal ESD, stage I-III, early favorable and advanced favorable stages and Charlson score Conclusions This is one of the largest retrospective cohorts reported in cHL. Epidemiology characteristics, RR, PFS, and associated variables are similar to the ones reported in literature. Five years OS proved to be higher than previously reported. ABVD is the chemotherapy regimen of choice in our country and as our study shows, is well tolerated but not exempt from toxicity. Early FL initiation improves outcome. PET scan was widely used but only 15.5% of the Pts were treated with response adapted strategies. Taking into account that in 47.6% of the Pts toxicity was the main cause of death, the use of PET-guided treatment in our population should be strongly considered. * The first four authors have equal contribution figure 1 Disclosures No relevant conflicts of interest to declare.

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

Summary Objective To evaluate in a multivariate analysis the prognostic factors associated with hematopoietic recovery and the supportive care requirements after autotransplant of progenitor cells (PC) from various sources: bone marrow (BMPC), BMPC & peripheral blood (PBPC), and PBPC alone. Patients and methods A total of 570 patients with hematological malignancies and solid tumors underwent high-dose therapy followed by autotransplant. PBPC were obtained after mobilization with chemotherapy and/or cytokines. One-hundred five patients received BMPC, 217 received BMPC & PBPC and 248 PBPC alone; all of the patients received G-CSF or GM-CSF after infusion. Results In a multivariate analysis the recovery of neutrophils was adversely associated with low numbers of nucleated cells infused (P < 0.13), bone marrow progenitor cell source, and diagnosis of multiple myeloma and acute leukemia (P < 0.001). The factors that adversely affected platelet recovery were low number of nucleated cells and diagnosis of multiple myeloma and acute leukemia (P < 0.001). Conclusion We conclude that BMPC adversely affect neutrophil recovery while low numbers of nucleated cells and diagnosis of multiple myeloma and acute leukemia adversely affect both neutrophil and platelet recovery.

Background. Hematopoietic Stem Cell Transplant Comorbidity Index (HCT.CI) score, described by Sorror, is a useful tool to assess the risk for Non Relapse Mortality (NRM) after Allogeneic HSCT. The impact of this score in Autologous HSCT is still to be confirmed. Aims. To determine the impact of HCT.Ci score in the morbidity and mortality after autologous HSCT, assessing the 100 day morbidity defined as orothraqueal intubation (OTI), dialysis or shock (defined as vasopressors need), 100 day mortality, early morbi-mortality (combined end-point by any of the previous end-point) and long term NRM. Materials and Methods. We retrospectively reviewed 1478 medical records of adult patients who received an autologous HSCT in our centre between October 2002 and April 2016. Median age was 49 years (range 16-74 years), 58% were male, prevalent diseases were Multiple Myeloma (48%), Non Hodgkin Lymphoma (27%) and Hodgkin Lymphoma (18%), 49% were in complete remission, 46% received one chemotherapy scheme before transplant, 41% two schemes and 12% three or more (heavily pre-treated). In respect to conditionings, melphalan was used in 48% of the cases, CBV in 25%, BEAM in 8% as well as BendaEAM. Seventy five percent received an infusion of stem cells CD34+≥3x10.6/kg. Regarding comorbidities, 58% had low risk (LR) HCT.CI (score 0), 32% intermediate risk (IR) (1-2) and 11% high risk (HR) (≥3). For univariate analysis we use Chi2 for dichotomic variables, Kaplan-Meier for Overall Survival (OS) and cumulative incidence for NRM; for multivariate analysis we used logistic regression for dichotomic and Cox regression for time dependant variables. Results. Median follow up was 1.9 years. Early mortality (day 100) was 2.8%, 5.6% required OTI, 4.8% required vassopresors and 2.2% dialysis, 1-3 years NRM and OS were 4.3-5.2% and 89-77% respectively. High risk HCT.Ci patients had a significant increase in 100 day mortality compared to IR and LR (7% vs.3% vs. 2% respectively, p=0.002), OTI (12% vs. 7% vs. 4%, p Conclusions. We observed that HCT.CI had a significant impact on Autologous HSCT treatment related mortality basically due to early toxicity express as 100 day mortality and the three main morbidity outcomes as well as the combined end point. This observation should be confirmed in larger series. Figure 1 Figure 1. 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 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.

Background. In our experience, in Argentina, the use of rituximab + chemotherapy in relapsed/refractory CD20+ follicular (FL) non-Hodgkin’s lymphoma results in Methods. Between September 2005 and November 2005, we recruited 10 patients (pts; 6 male/4 female; median age = 56 yr [range: 45–71 yr]) with platelets >100,000/mm3 and bone marrow involvement 5 cm). Three pts were Ann Arbor stage I or II and 7 pts were stage IV. Three pts had received 1–2 cycles of rituximab + chemotherapy and 7 pts had received 3–5 previous cycles. Three pts had undergone autologous transplant. Pts received rituximab 250 mg/m2 IV on days 0 and 7. After the second dose of rituximab, pts received 11 MBq (0.3 mCi) 90Y-Zevalin per kg or 15 MBq (0.4 mCi) 90Y-Zevalin per kg based on platelet counts, with a maximum dose of 32 mCi. Blood counts were monitored weekly until week 10 post-treatment and monthly thereafter. Patient tumor response was reevaluated 3 and 6 months after treatment according to standard criteria. Results. Five pts received a complete dose of 0.4 mCi 90Y-Zevalin per kg and 5 received a reduced dose of 0.3 mCi 90Y-Zevalin per kg. The overall response rate was 60% (CR = 5, PR = 1). Table 1 summarizes the responses. The 5 pts with a CR remained disease-free 8 months later. The pt with a PR progressed with adenopathies and visceromegaly 7 months after treatment. Seven of 10 pts experienced hematologic toxicity: 5 of these 7 pts required G-CSF because of grade 3/4 neutropenia and 3 of these pts developed neutropenic fever. Four of the 7 pts required platelet transfusions and 2 of them required red blood cell transfusions. All 3 pts with previous autologous transplant were in the group with hematologic toxicity. All of these pts required G-CSF and transfusion support, and 2 of these 3 pts were admitted to the clinic for this treatment; hematologic recovery occurred by week 9 post-treatment. Conclusion. The use of 90Y-Zevalin in the relapsed/refractory NHL setting resulted in better response rates and longer disease-free survival than with standard chemoimmunotherapy. Our finding with 50% CR in a heavily pretreated cohort, including 42.8% CR in stage IV pts and 33% CR after autologous transplantation, is encouraging. We are continuing to follow these patients. Table CR PR NR/PD Previous transplant (n=3) 1 1 1 Mantle cell (n=1) 0 0 1 Follicular (n=9) 5 1 3 Tumor volume > 5cm (n=4) 1 0 3 Tumor volume

Patients with stage I-II A non bulky Hodgkin’s lymphoma (HL) are successfully treated with 2–4 cycles of ABVD plus IF radiotherapy (RT). Although the negative impact in DFS and OS of B symptoms and bulky disease(X) is widely accepted, other risk factors such as number of lymph node regions involved or extensive spleen involvement have also been reported. What is the best treatment for such patients? Is radiotherapy necessary? We report here our experience with protocol HD 98 in 62 patients, with stage I–II HL. Since January 98 we have included 30 individuals without risk factors and 32 with one of the following risk factors: B symptoms (n:11), X (n:9), extensive spleen involvement (n:1) and involvement of more than two lymph node regions (n:11). Other patient characteristics were: age: x 31yrs (15–69), sex: females 31, males :31. Ann Arbor stage IA :11, IB :1, IIA: 36, IIB :14. Histologic subtypes were: LP: 4, NS: 42, MC: 15, lymphocyte rich :1. Patients with favourable features received 4 cycles of ABVD plus IFRT, those with unfavourable factors received 6–8 cycles of ABVD plus RT in areas of bulky or residual disease. Results: 59/61 evaluable patients obtained CR or CRu. Two patients were considered primary resistant. Three patients relapsed at 7, 13 and 30 months after completion of treatment. Autologus bone marrow transplant was performed in four patients. The two primary resistant patients relapsed after the transplant and died with proggressive disease. Those patients transplanted in a chemosensitive relapse are currently in CR. With a median follow up of 46m (13–84) 96.7% of the patients are alive, in CR. Conclusions: In our experience patients with unfavourable stages I–II HL are succesfully treated with 6–8 cycles of ABVD. In such patients RT might only be necessary in areas of bulky or residual disease.

The relapse post ABMT is a terminal stage complication in HD. The allogenic transplant contributes to a different therapeutic approach through the immune anti tumor effect of the Graft versus Host Disease (GVHD) The NST variant of the procedure diminishes the risks of transplant related mortality (TRM) and is associated with induction of mixed hematopoietic chimerism when either HLA-identical sibling or unrelated donor are used, and that powerful GVT effects can be achieved against advanced chemotherapy/resistant hematology disease. The feasibility, risk and effectiveness of the NST, is analyzed in 13 patients with relapsed HD after ABMT. Seven women and six men with a median age of 26 years old. They had received ≥ of 3 therapeutic lines that included the high doses and the ABMT. The period betwen the diagnosis to NST, had a median time of 36 months. The patients were conditioned with Fludarabine based schemes plus: Melphalan 8, Cyclofosfamide 3, TBI 1, Busulfan 1. The sources of stem cells were, with a HLA-identical sibiling donors in 12 patients, and in 1 with non related donor. 4 patients died due to complications associated with the BMT (TRM 28 %): shock 2, sepsis 1, thrombotic microangiophaty 1. Half of the patients developed some form of GVHD, or it was induced by donor lymphocytes infusion. With an average follow up of 15 months (range: 1–56), 7 patients are alive, 5 of them developed GVHD and are in CR, the other 2 have a short follow up (28 and 75 days). Of 4 patients who progressed only 1 present GVHD. The NST is a feasible procedure in HD relapsed post ABMT. The TRM is 28 %. In this group there is a clear relationship between the control of HD and the appearance of GVHD.

TCRBCL is a large B - cell lymphoma with a prominent reactive T cell proliferation. More common in males in the fourth decade of life, usual clinical presentation includes generalized adenopathies and bone marrow involvement. More localized presentation is frequently misdiagnosed as Hodgkin’s (HL) or T - cell lymphoma. Cases resistant to anthracyclines (A) pose a medical dilemma. We present here a patient initially misdiagnosed as HL who showed nodal relapse after ABVD and was resistant to conventional chemotherapy. Case report: CP is a 45 years old gentleman who presented with left axillaries adenophaties. A lymph node biopsy was diagnosed as lymphocyte predominant HL (LPHL) stage IA. Treated with 3 cycles of ABVD plus involved field radiation therapy, he relapsed in the margin of the radiation field soon after treatment was completed. A new biopsy showed TCRBCL. A review of the first biopsy was also consistent with TCRBCL. Treated with Promace/Cytabom the patient experience a spleen relapse which was resistant to ESHAP. With a gross hypo dense image in the spleen, treatment with R was started at a dose of 375 mg sqm2 weekly for four weeks. Disappearance of the splenic mass on the CT scan prompted us to perform a splenectomy. The pathologic study revealed a residual 8 mm lesion. The patient is currently without evidence of disease 40 months after the splenectomy. In total he received 6 doses of R. Interestingly an additional patient with TCRBCL originally misdiagnosed as ABVD resistant HL, showed a durable partial remission after treatment with R. In conclusion: due to our experience we think that it might be worth including R in the front line treatment of TCRBCL.