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This study investigates early cardiac events (ECE) occurring during the first 180 days after allo-HCT in 416 adults receiving PTCY (n=258) and non-receiving PTCY (n=158). Total body irradiation (TBI) was given to 133 (31.9%) patients, in 111 (83.4%) of them combined with PTCY. The day +180 cumulative incidence function (CIF) of ECE was 8.4%, being heart failure (n=13) and pericardial complications (n=11) as the most prevalent complications. The incidence of ECE was higher in patients receiving PTCY (Day +180 CIF: 11.3% vs. 3.8%, P=0.007), and receiving TBI (Day +180 CIF: 15.0% vs. 5.3%, P0.001). ECEs were more prevalent in haplo-HCTs than in MSD, MUD, and MMUDs allo-HCTs (Day +180 CIF of 17.9%, 6.2%, 8.4% and 7.4%, P=0.005). As for the ECE's risks from the combination of PTCY and TBI, the multivariate analysis reported that patients receiving PTCY without TBI (HR 3.79, P=0.041), those receiving TBI without PTCY (HR 6.01, P=0.027), and patients receiving TBI and PTCY (HR 6.98, P=0.002) were at higher risk for ECE compared with patients receiving neither PTCY nor TBI. Pre-existing cardiac morbidity predicted ECE (HR 5.28, P0.001). However, using high-dose Cy-containing preparative regimens did not increase the risk for cardiac toxicity at +180 days after allo-HCT (HR 0.58, P=0.53). ECE was associated with higher NRM (HR 4.68, P0.001) and lower OS (HR 3.03, P0.001). Considering that PTCY and TBI were predictors for ECE, and the impact of this complication on transplant mortality, the implementation of cardiac monitoring plans could be appropriate in patients receiving these medications.

This study investigates the incidence and predictors for bacterial bloodstream infection (BSI) in 330 adults undergoing allo-HCT, and explores the effect of post-transplantation cyclophosphamide (PTCY) on the probability of presenting this complication. All patients received levofloxacin during the aplastic phase. Only the first episode of BSI was counted as an event. Patients were classified into 2 groups: PTCY-based (n = 200) versus other prophylaxis (n = 130). One hundred twenty-four patients were diagnosed with a first episode of BSI, most of them during the first 30 days (70.2%). Proportions of BSIs caused by Gram-positive bacteria were comparable to those caused by Gram-negative bacteria (48.3% versus 45.9%). The cumulative incidence of BSI was higher in patients receiving PTCY than in those receiving other prophylaxis (days 30 and 100: 35.0% and 37.0% versus 13.1% and 18.5%, P.001). At day 30, the likelihood of BSI was 2.41 (P = .012) times higher in the PTCY group than in the non-PTCY group. The 30-day mortality rate in all patients with BSI was 8.0%, lower (P = .002) in the PTCY group (2.3%) than in the non-PTCY group (21.6%). Finally, the overall survival of patients receiving PTCY and diagnosed with BSI was similar to that of patients without presenting this complication. © 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa‐cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non‐relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow‐up of 14.1 months from CAR T‐cell infusion, median progression‐free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa‐cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses., This article provides real‐world European data on the results of relapsed/refractory large B‐cell lymphoma patients treated with tisagenlecleucel.

Introduction Tisagenlecleucel (tisa-cel) is a second generation, CD19-targeted Chimeric Antigen Receptor (CAR) T-cell therapy for relapsed or refractory (R/R) large B-cell lymphoma (LBCL). The pivotal phase 2 trial JULIET included 93 patients and reported an overall response rate (ORR) of 52% and a complete response rate of 40% among treated patients. However, very little is known regarding its safety and efficacy in the commercial or real-world setting as well as from an intention-to-treat perspective. In our study, we report clinical outcomes of patients with R/R LBCL treated with commercial tisa-cel in 10 Spanish institutions. Methods Data were collected retrospectively from all consecutive patients with R/R LBCL who underwent apheresis for tisa-cel at a Spanish site from December 2018 until June 2020. Evaluable patients included those who received a CAR-T infusion and had at least 1 month of follow-up. Adverse events after infusion were graded according to the ASTCT consensus and efficacy outcomes were assessed according to the Lugano criteria. Efficacy outcomes were calculated in the patients who received a CAR T-cell infusion and in all patients who underwent apheresis for tisa-cel (intention-to-treat). Results During the study period 91 patients with R/R LBCL underwent apheresis for tisa-cel. At the study cutoff, 69 (76%) patients had received a CAR T-cell infusion whereas 22 (24%) had not due to progressive disease (n=10, 45%), pending manufacturing process (n=7, 32%), out of specification (OOS) or manufacturing failure (n=4, 18%), or others (n=1, 5%). Sixty-one patients had at least the first disease response evaluation at 1-month post-infusion. Baseline characteristics of the whole cohort and the infused patients are summarized in Table 1. Among infused patients, median age was 57 years (range 24-77) and 65% were male. Most of the patients had a high-risk International Prognostic Index score (62%), an advanced stage at diagnosis (91%) and were refractory to the previous therapy (80%). Median follow-up after CAR T-cell infusion was 4 months (1-16). Fifty-six patients (81%) received bridging therapy before infusion, including chemotherapy in most cases (n=51, 91%). All patients received fludarabine and cyclophosphamide as lymphodepleting chemotherapy. Median time from apheresis to infusion was 53 days (range 29-225). Median infused cell dose was 2.2 x 108 CAR positive viable T-cells (range 0.4-4.2 x 108). Eleven (16%) products were considered OOS although 45% of them were infused. Among the infused patients, 47 (68%) and 9 (13%) developed any grade of cytokine release syndrome (CRS) and neurotoxicity, respectively. Grade >2 CRS and neurotoxicity events occurred in 3 (4%) and 0 patients, respectively. Tocilizumab was administered to 21 (30%) patients and steroids to 13 (19%) patients. Nine (13%) patients required admission to the Intensive Care Unit. By day 100, 2 (3%) patients experienced non-relapse mortality. Other adverse events including infections and tumor lysis syndrome are summarized in table 2. Best response achieved among the infused patients included complete remission in 17 (28%) patients and partial remission in 22 (36%) patients, with an ORR of 64%. Stable disease and progressive disease were the best response in 4 (7%) and 18 (29%) patients, respectively. Considering all patients who underwent apheresis, CR and PR were obtained in 19% and 24% (ORR 43%), respectively. Median progression-free survival (PFS) and overall survival (OS) for infused patients were 3 months (95%CI 2.1-3.4) and 8 months (95%CI 5.7-10.8), respectively. In the univariate analysis, patients with ECOG score >1 (HR 4.3 95%CI 1.5 - 40.9) (p < 0.001) and IPI score >2 (HR 4.8 95%CI 1.6 - 14.4) (p = 0.002) were associated with lower PFS while an ECOG score >1 was also associated with lower OS (HR 3.4 95%CI 1.15 - 34.4) (p = 0.04). In the intention-to-treat analysis for all patients who underwent apheresis, median PFS and OS from apheresis were 4 months (95%CI 2.8-5.8) and 9 months (95%CI 5.8-11.8), respectively. Conclusions Treatment with tisa-cel was able to induce disease response with a good toxicity profile in a population of patients with LBCL treated in a European country. Poor performance status at the time of CAR T-cell infusion was associated with lower PFS and OS. Disclosures Iacoboni: Novartis, Gilead, Celgene, Roche: Honoraria. Guerreiro:Novartis: Honoraria. Mussetti:Novartis, Gilead: Honoraria, Research Funding. Sancho:Roche, Janssen, Celgene, Novartis, Gilead, Sandoz, Mundipharma y Takeda; Advisory y/o consultor para Roche, Janssen, Celgene, Novartis, Gilead, Sandoz, Celltrion y Kern-Pharma.: Honoraria. Hernani:Gilead: Honoraria. Sureda Balari:Takeda: Consultancy, Honoraria, Speakers Bureau; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Incyte: Consultancy; Celgene: Consultancy, Honoraria; BMS: Speakers Bureau; Roche: Honoraria. Martin Garcia-Sancho:Celgene, Eusa Pharma, Gilead, iQuone, Kyowa Kirin, Roche, Morphosys: Consultancy; Roche, Celgene, Janssen, Servier, Gilead: Honoraria. Kwon:Jazz: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Reguera:Celgene, Novartis: Consultancy; Novartis, Gilead: Honoraria. Barba:Novartis, Celgene, Gilead, Pfizer, Amgen, Roche: Honoraria.

The use of post-transplantation cyclophosphamide (PTCY) for graft-versus-host disease (GHVD) prevention is becoming prevalent in the transplantation community when HLA-identical sibling and 10/10 HLA-matched (MUD) and 9/10 mismatched unrelated donors are selected for alloHSCT. However, reported evidence on outcomes from elderly patients receiving PTCY-containing GVHD prophylaxis remains limited. This study aims to compare the outcomes of PTCY- tacrolimus (TK) prophylaxis and conventional GVHD prophylaxis in patients aged50 years undergoing peripheral blood alloHSCT from a single institution. A total of 161 consecutive patients aged50 years undergoing alloHSCT between January 2014 and February 2021 were included. Data were collected retrospectively and updated in December 2021. Patients received grafts from HLA-identical sibling, and from 10/10 and 9/10 HLA matched and mismatched unrelated donors. Overall, median age was 60 years, and 91 (54.8%) received PTCY-TK for GVHD prevention. Time to neutrophil and platelet engraftment was longer in the PTCY-TK group (20 versus 16 days and 19 versus 11 days, P.001). The cumulative incidences of grade II-IV and III-IV acute GVHD (aGVHD) at day 100 and moderate/severe chronic GVHD (cGVHD) at 2 years were 18.2%, 5.7%, and 9.5% for patients receiving PTCY-TK, and 26.0%, 9.6% and 39.5% for those who did not. The multivariate analysis showed that PTCY-TK reduced the probability of grade II-IV aGVHD (hazard ratio [HR] 0.41, P = .035), of cGVHD (any grade: HR 0.43 [P = .014], and of moderate/severe cGVHD [HR 0.15 {P.001}]). At 2 years, the overall survival (65.4% versus 65.6%, P = .472), non-relapse mortality (17.4% versus 13.7%, P = .967), and cumulative incidence of relapse rates (24.2% versus 27.5%, P = .712) were comparable between both cohorts; GVHD-free/relapse-free survival (GRFS) was higher in the PTCY-TK group (2 years: 50.2% versus 21.8%; HR 0.42, P = .001). In patients aged ≥50 years. PTCY-TK was safe and a more effective drug combination than non-PTCY containing GVHD prophylaxis, even with the use of matched and mismatched unrelated donors, and resulted in comparable relapse rates and better GRFS.

This study examined the impact of prednisone (PDN) on cytomegalovirus (CMV) infection after allogeneic stem cell transplantation (allo-SCT) according to donor and recipient CMV serostatus. Seventy-five patients underwent allo-SCT from June 2010 to July 2012. The risk of CMV infection according to donor and recipient serostatus was defined as follows: high risk (HR; D-/R+), intermediate risk (IR; D+/R+ and D+/R-), and low risk (D-/R-). Forty-five patients (60%) developed CMV infection, and 46 patients (61%) received steroids (PDN ≥ 1 mg/kg/day) to treat acute graft-versus-host disease. CMV infection was more common in those treated with steroids than in those not treated with steroids (70% versus 44%, respectively, P .05). Overall, 40% of patients had recurrent CMV infection (50% PDN versus 24% no PDN, P .05). Steroids had no impact on the incidence of CMV infection or its recurrence in HR patients; however, steroids did prolong the need for antiviral treatment. The incidence of CMV infection in IR patients was higher in those receiving PDN (80% PDN versus 41% no PDN, P = .01); recurrence rates were also higher (55% PDN versus 18% no PDN, P = .02). We analyzed CMV-specific immune reconstitution in the first 22 patients of the series and observed that patients on steroids had lower levels of CMV-specific lymphocytes TCD8 (P .05 on days +60, +100, and +180) and that CMV-specific immune reconstitution (defined as lymphocytes CD8/IFN ≥ 1 cell/µL) was achieved later (after day +100 post-SCT) in the steroid group.

BACKGROUND AND OBJECTIVES CD19-directed chimeric antigen receptor (CAR)-T-cell therapy is associated with early cytopenia in approx. 80% of patients and late cytopenia in 40% of patients. To date, the transfusion profile of patients undergoing these therapies has not been described. Our objectives are: To define the transfusion profile of CAR-T therapy in our setting.To evaluate clinical variables related to the intensity and duration of cytopenias. METHODOLOGY This is an observational, prospective, single centre study. Adult patients with lymphoproliferative disorders and acute lymphoblastic leukaemia proposed for CAR-T therapy from August 2019 to March 2021 were included. RESULTS 68 patients were included in the CAR-T cell therapy program. Table 1 describes patients characteristics. Forty-seven received CART therapy, apheresis was not performed in 7 cases (progression n=6, withdrawal of consent n=1), product was not infused in 9 patients due to disease progression and 5 patients are awaiting infusion. Cytokine release syndrome (CRS) occurred in 79% of patients, 25% developed grade≥2 and median time to onset was 2 days (IQR, 1-4 days). Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 33% of patients, 16% were grade≥3 and median time to onset was 7 days (IQR, 6-8 days). Median duration of hospital admission was 14 days (IQR, 12 to 21 days). None of the 47 infused patients had neutropenia or anemia in the transfusion range prior to lymphodepletion. 94% (44/47) developed grade ≥3 neutropenia, with a median duration of 14.5 days (IQR, 9.75 to 36 days). G-CSF was administered to 21 patients, with a median time on G-CSF of 115 days (IQR, 27-258 days). A total of 239 red blood cells units (RBC) have been transfused, median 3.5 RBC/patient (IQR, 0 to 7.5 RBC / patient). 70% of this consumption occurred in the first 30 days after infusion. Before CAR T cell infusion, 2 patients had a platelet count 20x10 9/L was 17 days (IQR, 4-54 days) and > 50x10 9/L was 39 days (IQR, 20-79 days). 62% of patients received ≤2 platelet concentrates (PC). However, 21% had long-term thrombocytopenia (> 30 days). This group received a median of 15 PC (IQR, 12-27). The amount of PC used was 198, 52% were administered in the first 30 days. Eltrombopag was indicated in 9 of the 25 patients with grade ≥3 thrombocytopenia, doses never exceeded 75 mg/day. No serious bleeding (WHO grade ≥2) was observed. Factors related to severe thrombocytopenia were female (74% vs 42%, p=0.036), CRS (61% vs 0%, p=0.019), ICANS (80% vs 43%, p=0.020) and use of steroids (92% vs 67%, p=0.003). We found no relationship with underlying disease or status, prior treatment lines, prior autologous transplantation, CAR-T product, duration of lymphopenia, time and duration of CRS or ICANS. With a median follow-up of 167 days (IQR, 73-303 days), 26% of patients died, causes of death were infections n=2 and disease progression n=10. Three months after the procedure, there were 30 evaluable patients for response and 64% remained in remission (47% CR, 17% PR). CONCLUSIONS A high percentage of patients receiving CAR T cell therapy present long-term cytopenias. Reserves of irradiated blood components must be foreseen. Development of CRS and ICANS could be prognostic factors for the development of long-term grade ≥3 thrombocytopenia. Studies are needed on the use of thrombopoietin receptor agonists to reduce the duration of thrombocytopenia, although effective doses could be higher than those used in idiopathic immune thrombocytopenia. Figure 1 Figure 1. Disclosures Reguera: Janssen, Kite/Gilead, Novartis: Speakers Bureau; BMS-Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees. Perez-Simon: JANSSEN, TAKEDA, PFIZER, JAZZ, BMS, AMGEN, GILEAD: Other: honorarium or budget for research projects and/or participation in advisory boards and / or learning activities and / or conferences.

INTRODUCTION The continuous refinement of transplant techniques has lead to a reduction of transplant-related toxicity resulting on an increasing number of allogeneic hematopoietic cell transplantation (alloHCT) performed in older patients. Since 2014, post-transplant cyclophosphamide (PTCy) with tacrolimus (PTCy-TK), alone, has been progressively implemented at our Institution as GvHD prophylaxis for related, matched and mismatched unrelated donor transplantation (MRD, MUD, MMUD). The experience has proved that the use of this prophylaxis induces effective GvHD prevention without increased relapsed rates (Pedraza et al, 2021). Secondary to the encouraging results obtained from the use of PTCy-TK at our Institution, and considering that older patients with hematological disorders are a group of patients with higher risk to develop transplant-related toxicity, this study compares, as far as we know, the results provided by the use of PTCy-TK with conventional GVHD prophylaxis in a consecutive cohort of patients older than 50 years. METHODS Between January 2014 and June 2020, 147 adults with hematological malignancies and > 50 years underwent alloHCT either from MRD or UD at our Institution. Seventy-two (48.9%) patients received PTCy 50 mg/kg/day IV on day +3 and +4, followed by TK, initiated at a dose of 0.03/kg/24h IV on day +5 and titrated to achieve a therapeutic level of 5-15mg/mL. Other GvHD prophylaxes combined calcineurine inhibitors combined with methotrexate, mycophenolate mofetil, or sirolimus, and anti-thymocyte globulin was added especially when MMUD were selected. Data were collected retrospectively and updated in June 2021. Overall survival (OS) and GvHD-Free/Relapsed free survival (GRFS) were considered the main outcome variables, and the cumulative incidence of GvHD was calculated accounting relapse and dead as competing events. In order to analyze the independent impact of PTCy-TK prophylaxis on OS and GRFS, a multivariate Cox regression analysis was performed including GvHD prophylaxis, Disease Risk Index, and transplant year (dichotomized with a cut-off in 2017, given the marked increase of PTCy-TK after this year) as explanatory variables together with other variables with prognostic value in the univariate analysis. RESULTS Baseline characteristics of patients classified according to the GvHD prophylaxis are reported in Figure 1. The two cohorts of patients according to GvHD prophylaxis are well balanced. Peripheral blood was the predominant stem cell source in the vast majority (97%). Of note, 53 out of 72 patients receiving PTCy-TK were transplanted between July 2017 and December 2020. And UD was used in more than 90% of PTCy-TK alloHCT, compared to 44% of alloHCT with other prophylaxes. The median of days for neutrophil (20 vs 16, p OS (1-y: 72.1% vs 66.7%, HR 0.98; p=0.91), NRM (1-y: 18.1% vs 13.3%, HR 1.20; p=0.63), and relapse rates (1-y: 18.1% vs 22.9%, HR 0.86, P=0.65) were similar in both groups (PTCy-TK and other GvHD prophylaxis, respectively). However, PTCy-TK significantly resulted into an improved GRFS (1-y: 52.6% vs 30.7%, HR 1.68, p=0.01). A multivariate analysis confirmed the independent favorable impact of PTCy-TK prophylaxis on GRFS (HR 0.58, p=0.01), but not on OS (Figure 1). CONCLUSIONS PTCy-TK, alone, is an effective GVHD prophylaxis for alloHCT when related and UD are selected. The use of this innovative combination provides superior GRFS than the use of conventional GvHD prophylaxis in older adults undergoing alloHCT, with comparable transplant-related mortality and relapse rates. GRFS is a composite endpoint considered a surrogate outcome of health-related quality of life, and the improvement of this parameter is remarkable in PTCy-TK alloHCT, especially for older patients. Figure 1 Figure 1. Disclosures Lozano: Grifols: Honoraria; Terumo BCT: Honoraria, Research Funding; Macopharma: Research Funding. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Esteve: Novartis: Consultancy, Research Funding; Abbvie: Consultancy; Astellas: Consultancy; Jazz: Consultancy; Novartis: Research Funding; Pfizer: Consultancy; Bristol Myers Squibb/Celgene: Consultancy.

Background: Autologous chimeric antigen receptor-T (CAR-T) cells that target BCMA (BCMA-CARs) have emerged as a promising treatment for multiple myeloma (MM). Current clinical protocols dictate that BCMA-CAR therapy is only used after patients have repeatedly relapsed. However, at this stage, the immunosuppressive nature of advanced MM and/or side-effects of the previous therapies cause T cell dysfunction and an unfavourable phenotype, such as exhaustion, senescence and loss of early memory cells. An alternative and convenient pool of 'fitter' T cells are apheresis products that are routinely collected to obtain progenitor cells for autologous stem cell transplantation (ASCT), an intervention that is often carried out early in MM treatment. However, to mobilise the progenitor cells, patients are treated with G-CSF, which could have negative effects on T cells such as reduce proliferation, impair CD8 + T cell function and induce regulatory T cell (Treg) expansion. Whether this has an effect on the BCMA-CARs generated from these T cells, however, is unknown. Therefore, we aimed to establish whether G-CSF treatment had detrimental effects on T cell phenotype, and moreover, to ascertain whether BCMA-CARs that are generated from these T cells were impaired compared to those produced from T cells prior to G-CSF infusion. Methods: T cells were isolated from the blood of 9 patients with MM before and after 4 days of subcutaneous G-CSF administration (PRE G-CSF and POST G-CSF, respectively) prior to peripheral blood CD34 + cell harvesting for an ASCT as consolidation after first-line induction treatment. Following stimulation with anti-CD3/anti-CD28 beads and IL-2, T cells were transduced with ARI2h, an anti-BCMA CAR produced at our institution that is currently being explored in a clinical trial for relapsed/refractory MM (NCT04309981). Freshly-isolated T cells or expanded ARI2h cells were analysed by flow cytometry for markers of cell identity, activation, dysfunction and memory, or alternatively, challenged with an MM cell line (ARP-1 or U266) and then tested for cytokine production and cytotoxic ability. In addition, PRE and POST G-CSF ARI2h CARs were injected into ARP-1 tumour-bearing mice to assess their in vivo function. Results: Firstly, the phenotype of PRE G-CSF and POST G-CSF T cells, before CAR production, was analysed to identify effects of G-CSF treatment. Interestingly, there were fewer POST G-CSF CD8 + T cells with a stem cell memory (CCR7 +CD45RA +CD95 +) phenotype, but the proportion of naïve (CCR7 +CD45RA +CD95 -) cells and other memory populations was not significantly different. Moreover, POST G-CSF T cells had a lower CD4:CD8 ratio, but did not contain more senescent-like cells or display evidence of pre-activation or increased expression of exhaustion markers. Due to the known effect of G-CSF on CD4 + Treg expansion, the percentage of Tregs was also compared between the PRE G-CSF and POST G-CSF samples, but no difference was observed. Following T-cell activation and CAR transduction, comparable transduction efficiencies and proliferation rates were obtained. Likewise, the in vitro function of PRE G-CSF and POST G-CSF ARI2h cells, as determined by assessing their cytotoxic response to MM cell lines and ability to produce effector molecules such as granzyme B, was similar. To test the in vivo function of ARI2h CAR-T cells expanded from PRE G-CSF and POST G-CSF samples, they were injected into a murine xenograft model of advanced MM. Mice administered with both PRE and POST G-CSF ARI2h cells survived longer than those given untransduced T cells (p=0.015 and p=0.039, respectively), but there was no difference in the longevity of mice between the PRE G-CSF and POST G-CSF groups (p=0.990) (Figure 1). The similarity of the in vitro and in vivo function of PRE and POST G-CSF ARI2h cells was reflected in the phenotype of the CAR-T cells after ex vivo expansion, with cells from both groups displaying equal levels of activation, exhaustion, and importantly for CAR-T cell activity, memory/effector phenotype. Conclusions: The in vitro and in vivo functions of ARI2h CAR-T cells when generated from either PRE G-CSF or POST G-CSF samples were comparable, despite G-CSF administration decreasing the CD8 + stem cell memory pool. Overall, we conclude that T cells from apheresis products, performed to collect G-CSF-mobilised peripheral blood progenitor cells for ASCT, are suitable for BCMA-CAR manufacture. Figure 1 Figure 1. Disclosures Lozano: Grifols: Honoraria; Terumo BCT: Honoraria, Research Funding; Macopharma: Research Funding. Fernandez de Larrea: BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Research Funding; GSK: Honoraria; Sanofi: Consultancy; Janssen: Consultancy, Honoraria, Research Funding.

INTRODUCTION The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis has decreased the rates of this complication, resulting on an improvement of transplant-related toxicity and survival. Secondary to its efficacy, the use of PTCy has been almost universally integrated for allogeneic hematopoietic cell transplantation (alloHCT), independently of the selected donor source. Clinical decisions in alloHCT are supported by the use of prognostic scores for outcome prediction. However, capability of prediction by diverse scores can vary depending on their features and on the composition of the study cohort. Additionally, the continuous innovation on alloHCT techniques and practices leads to an ongoing need to update risk indices aimed at improving risk stratification of patients undergoing alloHCT. This study explores the predictive capacity of different prognostic scores routinely used in alloHCT, in a contemporaneous cohort of adults undergoing peripheral blood (PB) alloHCT using PTCy-based GvHD prophylaxis. METHODS Between 2014 and 2020, 230 consecutive adults with hematological malignancies underwent PB-alloHCT with PTCy-based GvHD prophylaxis at our Institution. Data related to Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), Karnosfky Performance Status (KPS), Disease Risk Index (DRI), European Bone Marrow Transplantation (EBMT) score, and Endothelial Activation and Stress Index (EASIX) were collected retrospectively. Complete information was available for 216 patients. Overall survival (OS) was considered the main outcome variable. Patients were grouped into two risk groups based on the optimal cut-off value for each score. In the case of EASIX, 1.578 was the most discriminating cut-off for OS. The score discrimination for OS was measured independently for each index using the receiver operating characteristic curve (AUC) calculated using receiver operating characteristic (ROC) curves, and determined at different time-points after alloHCT. RESULTS Of the 216 patients included, the median age was 52 years (range: 18-70), acute myeloid leukemia (36.1%) was the most prevalent baseline diagnosis, 42.1% of adults underwent reduced-intensity conditioning alloHCT, 69.4% received grafts from unrelated donors, and 23.0% from haploidentical donors. With a median follow-up of 22.6 months, 24.1% patients relapsed, and 2-y OS and non-relapse mortality were 67.3% and 19.9%. DRI, HCT-CI, KPS, and EASIX successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. HCT-CI [(score>3 (vs 0-3): HR 2.02, p1.578 (vs ≤ 1.578): HR 1.73, p 55%). DRI was the most accurate prognostic index during the entire post-transplant period (median AUC ranges > 60%). KPS score was found to be a useful predictor of mortality up to the first year after alloHCT and with the highest prognostic accuracy at 3 months (AUC 67.09%). HCT-CI score was found to present a better discrimination capacity once elapsed 6 months after alloHCT and with a peak of prediction capacity at 2 years (AUC 60.3%). EASIX, when measured at the pre-transplant evaluation, demonstrated to have acceptable predictive ability during the entire post-transplant period (median AUC > 55%), and with a peak of prediction at 3 months (AUC 62.6%). The EBMT score had the lowest predictive capacity in our analysis (Figure 1). CONCLUSION: This study validates, for the first time, the risk stratification capacity for OS of DRI, HCT-CI, KPS, and EASIX in PB-alloHCT with PCTy-based prophylaxis. Interestingly, the prediction accuracy of the prognostic scores differed depending on the time-period. This result can be taken into consideration to enhance the applicability of these scores and refine the clinical decisions taken based on the information provided from their use in routine clinical practice. Figure 1 Figure 1. Disclosures Lozano: Terumo BCT: Honoraria, Research Funding; Macopharma: Research Funding; Grifols: Honoraria. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Esteve: Novartis: Consultancy, Research Funding; Astellas: Consultancy; Jazz: Consultancy; Pfizer: Consultancy; Novartis: Research Funding; Abbvie: Consultancy; Bristol Myers Squibb/Celgene: Consultancy.

With recent novel therapies, cancer survival has improved and chemotherapy-induced cardiac toxicity including left ventricular dysfunction and heart failure has a greater potential impact on long-term outcomes. Hence, the prevention of cardiotoxicity should be an important objective when planning the therapy of cancer patients. Different pharmacologic and nonpharmacologic approaches have been shown to be effective in small trials, most of them in patients treated with anthracyclines. Treatment of cardiovascular risk factors, the implementation of a healthy lifestyle, and changes in the administration of anthracyclines have been shown to be effective to prevent cardiotoxicity, as is the administration of antioxidants such as dexrazoxane, and some cardiovascular drugs such as ACE-inhibitors and beta-blockers. Ongoing studies are analyzing the effects of these drugs on anthracycline- and trastuzumab-induced cardiotoxicity. Nevertheless, the future of the prevention of cardiac toxicity should include the study of the exact mechanism of toxicity of each cardiotoxic drug and the genetic individual susceptibility of each patient. With this information, correct risk stratification could be performed when planning the initial therapy and new drugs with less cardiotoxicity could be developed. Also, the diagnostic and prognostic value of different cardiac biomarkers and of imaging techniques for each cardiotoxic drug should be established. Finally, further large randomized studies are needed to confirm the results of prior pilot studies on the effects of cardioprotective drugs.

Background: Consolidation chemotherapy for adult patients with acute myeloid leukemia (AML) who have achieved a complete response after induction treatment is associated with prolonged, severe neutropenia and a high incidence of infections. In our center, patients were historically followed up during the neutropenic period at the day care unit, usually every 2 or 3 days, where they had routine laboratory tests, blood transfusions, central venous catheter management and medical checkups. Since this strategy was associated with a high incidence of febrile episodes that lead to hospital readmissions with some patients dying due to infectious complications, we designed a specific program for patients with AML receiving consolidation therapy including a specialized at-home management. Patients and Methods: Since March 2011, all consecutive patients with AML without significant co-morbidities or active febrile complications who received consolidation chemotherapy and lived within 60 minutes of the hospital were included in the at-home program (AHP). During the neutropenic period, a specialized nurse took care of every patient daily, either visiting the patient at home or by phone. A record of the vital signs, routine laboratory tests, central venous catheter management and administration of intravenous medication was kept regularly by the nurse. Antibiotic prophylaxis consisted of oral levofloxacin (500 mg daily), oral posaconazole (200 mg, three times per day) and intravenous ceftriaxone during the neutropenic ( Results: Up until February 2014, 29 out of 31 (94%) patients were included in the AHP, with a total of 60 episodes. Only 2 patients were excluded from the program, one because of lack of informed consent and the other due to an active febrile complication. The control group consisted of 40 out of 42 (98%) patients (56 episodes in total), who received consolidation treatment following the standard outpatient from May 2004 to March 2011. Median duration of severe neutropenia was of 11 (4-34) days in the AHP group compared with 18 (2-55) days in the control group (p Conclusion: At-home management after administration of consolidation therapy in adult patients diagnosed with AML is feasible in most patients. It is associated to a lower incidence of febrile complications and readmissions, contributing to increase safety for patients and optimizing hospital resources. Table Control Group(N= 56) AHP Group(N= 60) p Period of inclusion May/04-Mar/11 Mar/11-Feb/14 - Patients, n 40 29 - Included/candidate patients, n (%) 40/42 (98%) 29/31 (94%) - Episodes, n 56 60 - Included/candidate episodes, n (%) 54/57 (95%) 60/63 (95%) - Gender (M/F) 21/19 8/21 0.05 Age, median (range), years 52 (16-68) 56 (19-71) n.s. Neutropenia duration, median (range), days 18 (2-55) 11 (4-34) Disclosures No relevant conflicts of interest to declare.

Introduction and objectives: There is increasing knowledge on the relevance of danger signals activating the innate immune system in the pathogenesis of graft-versus-host disease (GvHD). Uric acid (UA) is a known danger signal that is released from injured cells during conditioning for allogeneic stem cell transplantation (alloSCT). UA has been identified to enhance dendritic cells maturation and to amplify T-cell responses. Previous reports analyzing the relationship between UA and acute GvHD (aGvHD) have shown controversial results (Ann Hematol 2015; 94: 139; Biol Blood Marrow Transplant 2014; 20: 730).The objective of this study is to investigate the association between UA levels pre-alloSCT and aGvHD. Patients and methods: We retrospectively analyzed data from 548consecutive patients who received an alloSCT from January 2007 to December 2014 on four institutions. The cumulative incidence of aGvHD over the first 100 days post-alloSCT was estimated in the framework of competing risks by taking relapse or death without relapse as competing events. The association between pre-alloSCT UA levels (measured between day -7 and day 0), dichotomized at the median value, and the incidence of aGvHD was investigated by calculating the subhazard rate (SHR) according to Fine & Gray (J Am Stat Assoc 1999; 94: 496). Results: Patients (median age 46y, range 16-67; 66% male) were transplanted for acute leukemia (51%), lymphoproliferative syndrome (22%), myelodysplastic syndrome (12%), multiple myeloma (8%), and other causes (7%). Disease status at the time of alloSCT was 49% complete remission, 17% partial response and 31% active disease. Fifty-one percent patients received alloSCT from related donors, 41% from unrelated donors, and 8% from alternative donors (cord blood units or haploidentical donors). The source of stem cells was peripheral blood in 84% patients. Fludarabine-based reduced intensity conditioning (RIC) regimens were used in 54% of transplants and myeloablative (MAC) in 46%. Most patients received immunosuppression with calcineurin inhibitors in combination with methotrexate (MAC) or mycophenolate mofetil (RIC). Sixteen percent also received ATG. Most patients (82%) received allopurinol 300 mg/day through conditioning regimen until day 0 of transplant. The median serum UA level prior to stem cells infusion was 3.7 mg/dL (range 0.7-8.8). Serum levels of UA (mg/dl) were higher in males than in females (4 vs. 3, p=0.0001), in patients submitted to RIC as compared with MAC alloSCT (4 vs 3.3, p=0.0001), in those not receiving ATG for GvHD prophylaxis (3.8 vs. 2.9, p=0.0002) and in the minority of patients not treated with allopurinol (4.7 vs. 3.3, p=0.0001). By day +100 post-alloSCT, 222 patients had been diagnosed of aGvHD II-IV, 79 had relapsed and 72 had died from causes unrelated to relapse or GvHD. The cumulative incidence of aGvHD II-IV was 40% (95% CI: 35%-44%) whereas the incidence of competing events (death or relapse) amounted to 11% (95% CI: 8%-13%). Patients with levels of UA above the median had an increased incidence of aGvHD II-IV (SHR: 1.4, 95% CI: 1.1-1.8; p=0.015) at the univariate analysis. However, such relationship vanished after multivariate adjustment for other factors associated with the peri-alloSCT UA levels and/or the risk of aGvHD (e.g. age, sex, type of donor, type of alloSCT, GvHD prophylaxis). Additional exploratory and subgroup analyses did not find any relationship between UA levels neither severe aGvHD (grades III/IV), early aGvHD (before day +60) nor type of conditioning regimen (RIC vs. MAC). Conclusions: There is a weak association between higher peri-alloSCT levels of uric acid and increased incidence of aGvHD. Nevertheless, our results suggest that such associations reflect confounding effects rather than causal factors and, therefore, they do not support interventions aimed at preventing aGvHD by reducing uric acid levels. Disclosures No relevant conflicts of interest to declare.

Introduction: MCL is a mature B-cell neoplasm characterized by t(11;14) (q13;q32) and cyclin D1 (CCND1) overexpression. Molecular studies have revealed other alterations in cell-cycle regulation, DNA damage response and cell survival pathways, with a landscape of somatic mutations being recently identified. CNS involvement is a well known complication, occurring in 4-26% of MCL at five years, with an ominous significance. Although different clinical variables have been identified as risk factors for CNS infiltration, the biological parameters related to this complication have not been extensively studied. The aim of the study was to explore the biological parameters associated with CNS involvement in a multicentre and retrospective series of MCL patients. Patients and Methods: 285 patients (M:74%; 64 yr) diagnosed of MCL between 1990-2014 (median survival of 4 years) were analysed. In addition to standard clinico-biological variables, IGHV mutational analysis, chromosomal alteration studies and Sanger sequencing of NOTCH1 , NOTCH2 , TP53 , BIRC3 , WHSC1 , MEF2B , MLL2 , TLR2 and PRDM1 were performed. Results: CNS involvement was observed in 15/285 MCL patients (5.2%), with a 5-yr risk of 9.1% (95%CI: 4.6-13.6), one patient at diagnosis, and at first or second/ulterior progressions in 7 cases each. The clinical, pathological and molecular risk factors identified are detailed in the Table. In addition to what has been already described, CNS involvement was usually observed in MCL cases with a clinical nodal presentation (p=0.05). In fact, no indolent MCL with a non-nodal presentation developed this complication during the follow-up period. No differences were observed in the risk of CNS involvement between patients treated in first-line with conventional or high-dose intense treatment (5-yr risk: 6.1%+/-6% vs. 10.7%+/-10.6%, p =ns). Regarding the biological features, no differences in terms of the IGHV mutational status were observed in cases developing CNS involvement compared to the others (75% vs. 68.7%, using 97% identity cut-off). Similarly, the IGHV gene usage of CNS involved cases corresponded to the more frequent IGHV genes observed in MCL (usually IGHV 1-18, IGHV 3-23, IGHV 4-34, IGHV 4-59). Although not significant, a predominance of high number copy number alterations (CNA) (>4) could be observed in the genetic study of MCL cases with CNS involvement as could be expected for the enrichment in blastoid variants (up to 50% of these cases). In fact, we did not observe any case with CNS involvement among those cases with 3 or less CNA. CNS involvement was not related to common poor prognosis genetic alterations such as 9p, 11p and 17p losses, but the presence of 8q gains was associated with a higher risk of CNS involvement ( p =0.05). We did not find any significant association between CNS involvement and the large number of oncogenic mutations studied. Conclusions: CNS involvement in MCL is associated with initial aggressive clinico-biological characteristics. Non-nodal MCL cases with a low number of genetic alterations did not present CNS involvement. Finally, the presence of 8q gains was associated with a higher risk of CNS infiltration. | Initial Clinical Features | Category | N | 5 yr-CNS involvement (%, 95%CI) | HR | p | | ----------------------------- | -------- | ------------ | ---------------------------------------- | --- | ----- | | Performance status (ECOG) | > 1 | 8/51 | 41.5 (+/-28) | 4.2 | .003 | | ≤ 1 | 7/128 | 9.4 (+/-5.5) | | Nodal disease | Yes | 14/185 | 13.3 (+/-7.6) | 6.1 | .05 | | No | 1/77 | 1.4 (+/-2.7) | | Hemoglobin (g/L) | < 105 | 12/93 | 24.7 (+/-14.7) | 3.2 | .05 | | ≥ 105 | 3/78 | 5.3 (+/-6.3) | | LDH | > ULN | 4/89 | 27.1(+/-19.4) | 6.7 | ULN | 11/114 | 21.6 (+/-14.9) | 3.5 | .04 | | < ULN | 3/66 | 8.7(+/-10) | | Molecular & Pathological data | | | | | | | Histological variant | Blastoid | 6/58 | 17.3 (+/-13.7) | 3.5 | .02 | | Others | 8/156 | 1.3 (+/-7.2) | | Ki-67 | > 30% | 5/44 | 17.5 (+/-14.9) | 3.6 | .06 | | ≤ 30% | 3/61 | 6.7 (+/-9.4) | | SOX11 | Positive | 8/153 | 2.9 (+/- 5.7) | 2.6 | ns | | Negative | 1/42 | 2.1 (+/-2.4) | | IGHV | ≥97% | 6/109 | 9.5 (+/-9.6) | 1.9 | ns | | 4 | 2/87 | 3.9 (+/-5.7) | 1.1 | ns | | ≤ 4 | 1/44 | 2.3 (+/-4.3) | | Chromotripsis | Yes | 1/17 | 12.5 (+/-22) | 3.2 | ns | | No | 2/106 | 1.9 (+/-2.7) | | 8q gain | Yes | 2/30 | 13.1(+/-19) | 7.5 | .05 | | No | 2/97 | 1 (+/-1.96) | Table CNA: copy number alteration; IGHV: immunoglobulin heavy chain; LDH: Lactate dehydrogenase Disclosures No relevant conflicts of interest to declare.