Abstract: High‐risk acute leukemia ( AL ) and myelodysplastic syndrome ( MDS ) remain a therapeutic challenge. Unmanipulated haploidentical‐related donor transplantation based on a myeloablative conditioning regimen ( HAPLO ‐ MAC ) and post‐transplant cyclophosphamide ( PT ‐Cy) as prophylaxis against graft vs host disease (Gv HD ) is now a promising rescue strategy that could become universally available. Objective To evaluate the results of HAPLO ‐ MAC with PT ‐Cy in patients with AL and MDS reported to the Haploidentical Transplantation Subcommittee of the Spanish Group for Hematopoietic Transplantation ( GETH ). Patients and methods We report our multicenter experience using an IV busulfan‐based HAPLO ‐ MAC regimen and PT ‐Cy for treatment of 65 adults with high‐risk AL and MDS . Results Engraftment was recorded in 64 patients (98.5%), with a median time to neutrophil and platelet recovery of 16 and 27 days, respectively. The cumulative incidence of grade II ‐ IV acute Gv HD and chronic Gv HD was 28.6% and 27.5%, respectively. After a median follow‐up of 31 months for survivors, the cumulative incidence of non‐relapse mortality and relapse at 2 years was 18.8% and 25%, respectively. Estimated 30‐month event‐free survival and overall survival were 56% and 54.5%, respectively. Conclusion HAPLO ‐ MAC comprising an IV busulfan‐based conditioning regimen enabled long‐term disease control with acceptable toxicity in high‐risk AL and MDS .

Abstract: Extracorporeal photopheresis (ECP) is an efficient and established therapy to treat acute and chronic graft vs host disease (GVHD). Using an “off‐line ” method, the first step (mononuclear cell [MNC] collection) is decisive, as long as a high MNC yield and purity in the collected product is desirable. Two “off‐line ” devices were compared: the COBE Spectra and the Spectra Optia (Terumo BCT), using both continuous and intermittent protocols. Patients and methods Twelve patients with GvHD (7 acute/5 chronic) were enrolled between June 2014 and May 2015 and were alternatively assigned for each procedure to either the COBE Spectra or the Spectra Optia cell separator. Patients characteristics and procedure/product parameters were analyzed. Results Two hundred procedures (100 per device) were included. The Spectra Optia system showed higher total nucleated cells and MNC collection efficiencies (18.6(10.2‐29.7) vs 7.9(4.1‐14.8)% and 43.6(20.3‐59.5) vs 23.3(11.4‐37.1)%, P   〈  .001) and monocyte and lymphocyte collection efficiencies (55.2(17.7‐83.2) vs 22.8(9‐38.9)% and 38.3(26.7‐53.4) vs 22.2(9‐38.9)%, respectively, P   〈  .001). Absolute platelet loss (PL) and PL per liter of blood processed were significantly lower in the Spectra Optia group (22.9(18.3‐28.1) vs 33.6(26.5‐41.1)%, P   〈  .001 and 3.7(3.1‐4.5) vs 4.3(3.5‐4.2)%, P  = .01, respectively). However, granulocyte contamination was higher (4.5(1.3‐36) vs 1.2(0.4‐5.7)%, P   〈  .001) and a higher product haematocrit was obtained with the Spectra Optia (1(0.5‐1.6) vs 0.3(0.2‐0.5)%, P   〈  .001), without an impact on irradiation time. Conclusions In our study, Spectra Optia proved to be safe and effective in collecting MNC with high yield and purity for ECP in GvHD.

Abstract: Introduction. The prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Chimeric antigen receptor (CAR) T-cell therapy is approved for R/R DLBCL (≥3 rd line) in Spain since April 2019, based on data from single-arm phase 2 trials that showed complete response (CR) rates between 40-50% and prolonged remissions in 30-40% of patients. Real-world (RW) data from different countries have shown similar efficacy to pivotal trials, but there are no studies focused on the global Spanish experience, including different constructs with a large number of patients and no comparative studies have been carried out in Spain between commercial CAR-T therapy and the standard treatment of the pre-CAR era. Methods This is a multicenter, retrospective, observational study that included all patients with R/R DLBCL treated with CAR-T therapy who were registered in the GELTAMO/GETH database of patients treated with CAR-T therapy in Spain (n=255). The main objective was to analyze efficacy in terms of response rates and survival and analyze prognostic factors influencing survival. In addition, this cohort was compared with a historical population of R/R DLBCL patients from the GELTAMO-IPI study (Montalbán et al, Br J Haematol 2017), treated in the pre-CAR era (n = 158). From both cohorts, refractory patients according to the Scholar-1 criteria (primary refractoriness, refractoriness to last treatment, or early relapse after autologous stem-cell transplant) were identified and included in the comparative analysis. Results Characteristics of the CAR-T group at diagnosis and at infusion are shown in Table 1. From the 255 patients registered, 13 were excluded due to absence of follow up data and 4 for mantle cell lymphoma histology. Finally, 238 patients were included in the intention-to-treat analysis and 226 received the CAR-T infusion (124 axicabtagene ciloleucel, 101 tisagenlecleucel and 1 lisocabtagenemaraleucel). Median time from official approval to infusion was 60 days (34-363), and median time from apheresis to infusion was 46 days (16-349). Regarding adverse events of special interest, 79% of patients had cytokine release syndrome (7% ≥ grade 3), and 32% of patients had neurotoxicity (13.7% ≥ grade 3). Best response rates after CAR-T infusion were: CR 42%, partial response (PR) 27%, stable disease (SD) 7% and progressive disease (PD) 24%. With a median follow up from infusion of 8 months, median progression-free survival (PFS) was 3.5 months (95% CI: 1.9-5), and median overall survival (OS) was not reached, with a 12-month OS of 53% (95% CI: 45-62); 12-month OS and PFS for patients who achieved CR was 86% (Figure 1) and 78% respectively. Factors influencing PFS and OS in the univariate analysis are shown in table 2. In the multivariate analysis, the factors with independent influence on both PFS and OS were R-IPI and Eastern Cooperative Oncology Group-Performance status (ECOG-PS) pre-CAR, and presence of refractory disease to last treatment, as shown in table 3. Regarding the comparative analysis with the historical cohort, the groups were well balanced, except for age and median follow up (Table 4). The survival for this analysis was calculated since the failure to last treatment. Patients treated with CAR T-cells vs standard of care pre-CAR had significantly better PFS (median of 7.9 vs 5.7 months, p=0.002), and OS (median of 16 vs 9.2, p & lt;0.001). Conclusions: We conclude that efficacy results obtained from RW CAR T-cell therapy in Spain are comparable to the pivotal trials. The results of the comparative analysis suggest that the efficacy of CAR-T therapy in refractory patients is superior to that of the treatments available in the pre-CAR era. Figure 1 Figure 1. Disclosures Bastos-Oreiro: F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite: Speakers Bureau; Gilead: Honoraria; BMS-Celgene: Honoraria, Speakers Bureau. Reguera: Janssen, Kite/Gilead, Novartis: Speakers Bureau; BMS-Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees. Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Corral: Gilead: Consultancy; Novartis: Consultancy; Gileqd: Honoraria. Terol: Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Roche: Consultancy; Hospital Clinico Valencia: Current Employment; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; BMS: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel. Ortiz-Maldonado: Kite, Novartis, BMS, Janssen: Honoraria. Mussetti: Gilead: Other: Unspecified, Research Funding; Novartis: Honoraria, Other: Unspecified; Takeda: Honoraria. Luzardo Henriquez: Kyte/Gilead. Takeda. Roche: Honoraria. Sancho: F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers-Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees. Salar: Roche: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Gilead: Research Funding; Janssen: Consultancy, Speakers Bureau. Herrero: Novartis: Consultancy, Honoraria. Sureda: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bluebird: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Support for attending meetings and/or travel; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Mundipharma: Consultancy; GSK: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau. Barba: Novartis: Honoraria; BMS: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Gilead: Honoraria. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria. Martin Garcia-Sancho: Celgene: Honoraria, Other: travel; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Celgene/BMS: Consultancy; Janssen: Honoraria, Research Funding; Servier: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Gilead: Consultancy, Honoraria; Morphosys: Consultancy; Kyowa Kirin: Consultancy; Clinigen: Consultancy; Eusa Pharma: Consultancy; Novartis: Consultancy; Takeda: Honoraria; Incyte: Consultancy; Kern Pharma: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company).

Abstract: Introduction: Invasive Fungal Infection (IFI) is a serious complication after allogeneic stem cell transplantation (alloSCT). Its incidence and outcome are not well characterized in the setting of peripheral blood, non-manipulated haploidentical stem cell transplantation with postransplant cyclophosphamide (HaploSCT). The aim of the study is to analyze our experience among patients who underwent HaploSCT at our institution and developed an IFI, in order to identify the incidence, risk factors and its impact in survival. Materials and methods: One hundred and thirty-three patients underwent peripheral blood HaploSCT with postransplant cyclophosphamide at our institution between 2011 and 2017. IFI was classified according to the EORTC definitions. Proven and probable IFI were included. Results: Patients´ characteristics are shown in Table 1. Patients received primary antifungal prophylaxis with micafungin from the day before stem cell infusion, during admission and until neutrophil engraftment was stablished. Patients on steroid treatment due to GVHD received prophylaxis with micafungin or posaconazole. Twenty-three episodes of IFI were observed in 20 patients, 10 proven and 13 probable, with a cumulative incidence of IFI of 15% at 500 days. Most commonly isolated organism was Aspergillus spp (5 cases), followed by Candida spp (4 cases: 1 C. kruseii and 3 C. parapsilosis) and Fusarium spp (2 cases). Additionally we observed some isolated cases of Inonotus spp,Mucor spp and Trichosporon Ashii. Pulmonary involvement was the most frequent presentation (11 cases), followed by fungemia (5 cases, 4 Candida and 1 Trichosporon Ashii) and skin-pulmonary involvement (2 cases). Thirteen cases were diagnosed early, in the pre-engraftment period, 5 just after the engraftment and 5 cases developed later. Among patients with late occurrence of IFI, median time of IFI was 220 days, and all of them were associated with GVHD (3 grade III-IV acute GVHD and 2 moderate/severe chronic GVHD). IFI outcome was favorable in 14 out of the 23 documented IFI, with antifungal therapy. Treatment chosen was liposomal amphotericin B in 7 cases, voriconazole in 5 and combined treatment (with amphotericin B and azole) in 6. Death related to IFI was documented in 7 out of the 20 patients, with an IFI mortality cumulative incidence of 6.4%. Prior transplant (OR 4.5, p 〈 0.01) and especially alloHSCT were associated to IFI development (OR 8.2, p 〈 0.01). We did not find any other risk factor associated to IFI, like time of engraftment, disease, conditioning regimen, sequential regimen, grades II-IV GVHD or severe/moderate chronic GVHD. Conclusions: In our experience, cumulative incidence of IFI in the setting of HaploSCT was similar than the one observed in other studies with alloSCT. Mortality associated to IFI in the whole cohort was low (6.4 %). The most significant factor related to IFI development was having received a previous transplant, especially alloSCT. Therefore, this high risk population should be closely monitored and could benefit from prophylaxis with azoles. Disclosures No relevant conflicts of interest to declare.

Abstract: Background: Graft failure (GF) is an unusual but threatening complication after allogeneic HSCT (allo-HSCT). Early diagnosis is crucial for therapeutic interventions to be effective. The monitoring of chimerism in peripheral blood (PB) and T lymphocytes (TL) has shown to contribute in the early detection of this complication. The objective of this study was to describe chimerism dynamics in patients who developed GF after allo-HSCT. Methods: Nineteen patients out of 416 procedures were diagnosed with GF after allo-HSCT since 2003 in our center. Chimerism studies were performed by STR-PCR (AmpFLSTR™ SGM Plus™, Thermo Fisher) in PB and TL weekly since day +14. Patients were classified into three groups: primary GF (absence of neutrophil engraftment by day +28), secondary GF (development of severe cytopenias and progressive mixed chimerism (MC) after initial achievement of neutrophil engraftment), and incipient GF (development of increasing MC with non severe cytopenias) [1]. Relapse/progression was ruled out in all cases. [1] Díez-Martín et al. Bone Marrow Transplant. (2004) 33, 1037-1041. Results: Seven patients were diagnosed with primary GF, 7 with secondary GF and 5 with incipient GF (Table 1). No evident causes of GF were detected in all primary GF cases. Chimerism analysis on day +14, +21 y +28 revealed persistent high percentages of recipient cells before GF were diagnosed, in PB and mainly and earlier in TL (Fig. 1A). Median time to salvage allo-HSCT was 45 days (range 35-77). Two patients were treated with donor lymphocytes infusion (DLI) and five with second allo-HSCT. Five patients achieved engraftment, and six achieved complete chimerism (CC). Six-months OS after salvage was 43%. The 7 patients diagnosed with secondary GF had achieved initial neutrophil engraftment in a median of 17 days (range 13-28). Median time to GF after allo-HSCT was 75 days (range 39-108). Six of them developed CMV reactivation before GF. Chimerism analysis before and at diagnosis of secondary GF, showed persistent high percentages of recipient cells, with a trend towards increasing dynamics in PB and mainly in TL (Fig. 1B). Median time to salvage therapy was 35 days (range 8-817) after GF confirmation. One patient was treated with DLI and six with second allo-HSCT. Five patients achieved engraftment and CC. Six-months OS was 57%. The 5 patients diagnosed with incipient GF showed persistent high percentages of recipient cells, with a trend towards increasing dynamics particularly in TL before and at diagnosis of GF (Fig. 1C). As salvage treatment, patients were treated with immunosuppression withdrawal followed by at least one DLI as salvage theraphy, in a median of 83 days (range 61-126) after allo-HSCT. All patients achieved CC in both PB and TL. Four patients developed grade II-IV GVHD. Six-months OS was 57%. Conclusions: Patients with primary GF presented MC in serial chimerism analysis after allo-HSCT, with persistent high percentages of recipient cells particularly in TC. Patients with secondary and incipient GF showed increasing MC mainly in TC, before GF was established. Early T-cell chimerism dynamics may be the best predictor of GF, allowing early therapeutic interventions. In our experience, timely and individualized second allo-HSCT after GF may improve outcome after primary or secondary GF. On the other hand, early DLI could benefit patients with incipient GF. Disclosures No relevant conflicts of interest to declare.

Abstract: Abstract 4557 BACKGROUND: Natural killer (NK) cells are innate immune effectors that directly lyse virally infected or malignant cells. There are 2 different subsets of NK cells with distinct phenotypic and functional characteristics: the CD56dim subset, which composes 90% of peripheral blood NK cells and has a cytotoxic function, and the CD56bright subset, which cooperates with dendritic cells and T cells in lymph nodes to secrete interferon and promote adaptive immune responses. NK cells are the first donor-derived lymphocyte subset to reconstitute after hematopoietic stem cell transplantation, reaching normal levels after 1 month. Nearly all phenotyping studies of NK subsets after haploidentical hematopoietic stem cell transplantation (HHSCT) reveal a rapid reconstitution of NK cells towards the CD56bright subset. In addition, Y.-J. Chang et al found the highest 2-year survival in patients with a high number of CD56bright NK cells after unmanipulated HHSCT. We analyzed reconstitution of the NK compartment between days 90 and 180 after unmanipulated bone marrow HHSCT with reduced intensity conditioning (RIC). METHODS: Six adults received unmanipulated bone marrow HHSCT after RIC (fludarabine 30 mg/m2 [day –6 to –2], cyclophosphamide 14.5 mg/kg [day –6 and –5] , and busulfan i.v. 3.2mg/kg [day –3]) at our institution between July 2007 and July 2010. Prophylaxis for acute graft-versus-host disease (GvHD) consisted of cyclophosphamide 50mg/kg (days +3 and +4) and cyclosporine A and mycophenolate mofetil from day +5 onwards. We monitored the reconstitution kinetics of circulating NK cells (CD56+, CD3–), and the CD56bright and CD56dim subsets by multiparametric flow cytometry (FC 500 Beckman® Coulter) at day +90 and day +180 after transplantation. Patient characteristics and clinical outcomes are shown in Table 1. 6 patients who underwent allogeneic HLA-identical sibling HSCT with RIC during the same period were used as controls. RESULTS: After HHSCT, NK cells reached normal levels in all patients but one at day +90, with a median number of NK cells of 111/mm3 (range, 25–195/mm3). At day +180 the median number of NK cells was 92/mm3 (range, 4–272/mm3). When we analyzed the absolute number of CD56bright and CD56dim subsets at day +90, we observed 2 patterns: Two patients showed skewed NK cell reconstitution towards CD56bright (Patient no. 3: 54 CD56bright/mm3; 11 CD56dim/mm3. Patient no. 4: 70 CD56bright/mm3; 17 CD56dim/mm3). Three patients reconstituted with a CD56dim/CD56bright ratio towards the CD56dim cell subset, similar to that of healthy adults (Patient no. 1: 17 CD56bright/mm3; 178 CD56dim/mm3. Patient no. 5: 9 CD56brigh/mm3; 135 CD56dim/mm3. Patient no. 6: 20 CD56bright/mm3; 116 CD56dim/mm3). One patient did not achieve adequate NK cell reconstitution (Patient no. 2: 15 CD56bright/mm3; 10 CD56dim/mm3). In contrast, in the control group, an increase in the CD56bright NK cell subset was not observed in any of the patients at any point. It is worth noting that 2 of the 3 patients with better clinical outcome (no GvHD, no relapse), namely patients no. 3 and no. 4 were the ones with skewed NK cell reconstitution towards the CD56bright NK cell subset. The other patient with a better clinical outcome (patient no. 6) had a normal CD56dim/CD56bright ratio at day +90. However, he showed an early CD56bright reconstitution (363 CD56bright/mm3; 34 CD56dim/mm3) in an additional determination on day +30. NK cell subsets reconstitution kinetics is shown in Figure 1. CONCLUSIONS: In our experience, NK cell reconstitution is adequate after RIC unmanipulated bone marrow HHSCT. Some patients recovered with a high proportion of CD56bright NK cells, as previously reported in other studies on HHSCT. Although limited by the sample size, our results are consistent with the previously observed survival advantage of patients with high early levels of CD56bright NK cells after unmanipulated haploidentical transplantation. Disclosures: No relevant conflicts of interest to declare.

Abstract: Introduction Graft versus host disease (GVHD) is the main cause of morbi-mortality after allogeneic stem cell transplantation (allo-SCT). Despite considerable advances in our understanding of the pathophysiology, nowdays anticipation of GVHD is an unresolved matter. Several single-nucleotide polymorphisms (SNPs) in cytokine genes have shown to be associated with donor-recipient alloreactivity and, ultimately, with SCT outcome. In the present study, we propose a novel predictive model based on both clinical and genetic (SNP) variables applying an innovative estimation linear regression model, the least absolute shrinkage and selection operator (LASSO), in a large cohort of HLA-identical sibling donor allo-SCT. Patients and Methods The study evaluated 25 SNPs in 12 genes (Table 1) in genomic DNA obtained from PB samples from 273 patients with available acute GVHD (aGVHD) data and 213 patients with chronic GVHD (cGVHD) data included in the DNA Bank of the Spanish Group for Hematopoietic Stem Cell Transplantation (GETH) and their HLA-identical sibling donors. Each SNP was assessed for different models of transmission (recessive, dominant, co-dominant and additive), producing 25 SNPs x 4 models = 100 variables. Clinical variables known to influence the development of GVHD were also considered (Table 1). Univariate regression analysis was performed using Cox regression (data not shown). Multivariant analysis was made with LASSO, an innovative estimation method for linear regression models which is able to select a set of optimal predictors from a large set of potential predictor variables and was considered as a variables selection method under the estimation of a Logit regression model. In this model, the strength of the penalty term is controlled by a smoothing parameter (λ), which is chosen by maximizing the area under ROC curve (AUC) and the correct classification rate (CCR). The statistical model was fitted (goodness-of-fit assessment) by randomly selecting the 85% of the data (the so-called "training set"), and the predictive ability was computed with the remaining 15% (the so-called "testing set"). In order to evaluate the performance and the prediction ability of each model, training and testing samples were randomly selected a total of 100 times. The distribution of the CCR and the AUC over the 100 samplings, were shown by means of box plots and statistical summary in the results data. Finally, for prediction purposes, we considered a cut-off value according to the proportion of Y=1 in the sample (0.28 for grades II-IV aGVHD, 0.11 for grades III-IV aGVHD and 0.30 for extensive cGVHD). Results The best model to predict aGVHD II-IV included 11 genetic variables and no clinical variables with a CCR for patients who developed (CCR1) aGVHD II-IV of 63.6% (Figure 2). The best model to predict aGVHD III-IV included 20 genetic and 7 clinical variables with a CCR1 for aGVHD III-IV of 100%. The best model to predict extensive chronic GVHD included 10 genetic and 3 clinical variables with a CCR1 for extensive cGVHD of 80%. On the other hand, predictive models with only clinical variables showed a poorer CCR1 for patients who developed aGVHD II-IV, aGVHD III-IV and extensive cGVHD (55.6%, 50% and 66.7% respectively; Figure 1). Based on the results from LASSO multivariate analyses, a risk score was calculated for grades II-IV and III-IV aGVHD as well as for cGVHD and extensive cGVHD. Patients were categorized into two groups: low risk (below the cut-off value) and high risk (above the cut-off). Such risk model was able to stratify patients who develop grades II-IV aGVHD (p 〈 0.001), grades III-IV aGVHD (p 〈 0.001) and extensive cGVHD (p 〈 0.001) more consistently than models only considering clinical variables (Figure 2). Conclusions Identification of biomarkers useful for the estimation of the risk of GVHD constitutes an unmet need in the clinical management of GVHD. The novel predictive model proposed here, based on clinical and genetic factors, allows significantly improved anticipation of aGVHD III-IV (100% accuracy) and extensive cGVHD (80%) after HLA-identical sibling donor allo-SCT. This approach would allow a personalized risk-adapted clinical management of patients after transplantation. Disclosures No relevant conflicts of interest to declare.

Abstract: Abstract 4859 BACKGROUND: Most patients with classical Hodgkin's Lymphoma (CHL) are cured with primary treatment. However, a proportion of them fail to first line treatment needing to be rescued with subsequent lines of chemotherapy and/or autologous or allogeneic stem cell transplantation (auto-SCT and allo-SCT, respectively). The identification of clinical and biological characteristics of these patients at diagnosis is still a challenge and most prognostic systems fail to identify a proportion of patients with worse prognosis. In this context, different groups are currently analyzing several biological markers as determinants of clinical outcome. It has been reported that Bcl-2 immunohistochemical expression in Hodgkinxs Reed Sternberg cells (HRSC) might confer a worse prognosis. OBJETIVE: To analyze clinical outcomes following 1st line chemotherapy according to Bcl-2 expression at diagnosis of CHL. PATIENTS AND METHODS: CHL patients, older than 16 years old, receiving at least 1 line of treatment, were retrospectively studied for Bcl-2 expression in diagnostic samples. For this purpose, tissue sections were immunostained and semiquantitatively assessed for this marker. Cumulative incidence (CI) of treatment failure, treatment failure free survival (TfFS) and overall survival (OS) were defined as primary outcomes. Treatment failure was considered when a different treatment regimen was set up due to relapse after CR or failing to achieve CR following 1st line. RESULTS: 103 patients (55 Bcl-2 positive patients and 48 Bcl-2 negative patients) were analyzed. Main patient and clinical features are shown in Table 1. Both cohorts were well balanced for the main prognostic factors. At a median follow up of 36m (2-221), 34m (2-140) for Bcl-2 negative patients and 38m (4.5-221) for Bcl-2 positive patients, CI of 3 years treatment failure was 19% and 50% for the negative and positive cohorts, respectively (p=0.02). 3 years TfFS after diagnosis was 75% for Bcl-2 negative patients vs 47% for Bcl-2 positive patients (p=0.1). Within the cohort of Bcl-2 negative patients, 9/48 (19%) underwent auto-SCT as part of rescue treatment while 18/55 (33%) of Bcl-2 positive patients received an SCT (13 auto-SCT and 5 allo-SCT) and 3 of them, a second SCT (allo) for the treatment of post-auto-SCT relapse. 3 years OS was 84.5% for negative and 86% for positive patients (p=NS). CONCLUSIONS: According to these preliminary results, Bcl-2 expression in HRSC at diagnosis may constitute an independent biological prognostic marker in CHL patients, seemingly associated with worse outcome and need of second line chemotherapy. More studies and a longer follow up is needed in order to confirm that aggressive treatment strategies such as SCT may overcome the negative impact in survival of Bcl-2 expression in this population. Disclosures: No relevant conflicts of interest to declare.