Abstract BACKGROUND Neurotoxicity is one of the serious and life-threatening complications of CAR-T treatment in patients with diffuse large B-cell lymphoma. Our objective is to identify the findings in brain PET/CT, their evolution over time, and their clinical correlation. We also aim to compare the sensitivity of PET/CT with magnetic resonance imaging (MRI). MATERIAL AND METHODS This prospective study includes 33 patients with diffuse large B-cell lymphoma treated with CAR-T therapy. Whole-body and brain [18F]FDG PET/CT scans were performed pre-treatment and 30 days post-therapy. In cases of suspected immune effector cell-associated neurotoxicity syndrome (ICANS), urgent structural imaging (CT or MRI) and [18F]FDG PET/CT brain scans were conducted, among other tests. RESULTS The mean age was 62±12 years, with a male-to-female ratio of 19:14. 70% of patients (23/33) developed grade 1, 2, or 3 cytokine release syndrome (CRS). 27% (9/33), all with prior CRS, showed symptoms of ICANS (3/9 G1, 3/9 G2 and 3/9 G3 ICANS). The most common symptoms were tremor, disorientation, and bradypsychia, starting on average on the 7th day post-infusion (range 1 to 10). Urgent [18F]FDG PET/CT brain scans were performed on 7 of the 9 ICANS patients, showing diffuse cortical hypometabolism compatible with encephalopathy in 5 (5/7) and no significant findings in 2/7. At the 30-day post-treatment evaluation, complete normalization was observed in 2/5 patients, improvement with persistent mild global cortical hypometabolism in 2/5, and one patient (1/5) died before the 30 days (with G3 ICANS and severe cortical and subcortical hypometabolism on PET imaging). Urgent brain MRI was performed on the 7 patients with ICANS and urgent [18F]FDG PET brain scans, and it was normal in 5/7 and pathological in 2/7 (both with grade 3 ICANS). CONCLUSION [18F]FDG PET/CT brain scan is useful for the diagnosis and follow-up of patients with CAR-T related neurotoxicity (ICANS) and shows greater sensitivity than MRI. Future studies should determine the relationship between acute phase PET findings and long-term prognosis.

Objectives: Our aim was to describe the frequency and severity of infectious complications after chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL). Methods: We retrospectively reviewed clinical records of LBCL patients treated with CD19-targeted CAR T-cell therapy from July/2018 to December/2021 at our institution, and identified all infectious episodes from CAR T-cell infusion until disease progression, death or last follow-up. Results: Overall, 137 patients were included. Thirty six percent had received >= 3 previous lines of therapy and 26% an autologous hematopoietic cell transplantation (auto-HCT). Cytokine release syndrome occurred in 87 (64%) patients. Antibacterial prophylaxis was not used in any patient; only 38% received antifungal prophylaxis. Sixty three infectious events were observed in 41 (30%) patients. Fifty two (83%) of the infectious events had at least one pathogen identified (bacteria [n = 38], virus [n = 11], and fungi [n = 3]). Most of the infectious events occurred during hospitalization for CAR-T treatment. Infection-related mortality was observed in two patients. Independent risk factors for infection included male gender, previous auto-HCT, >= 3 lines of treatment and pre-lymphodepletion neutropenia. Conclusions: Infections after CAR T-cell therapy in patients with lymphoma are frequent but generally not severe. A conservative and tailored antimicrobial prophylaxis seems to be a safe approach.

Background: Hematological toxicity represents the most frequent high-grade toxicity of CD19 CAR-T, but remains poorly understood. We recently proposed a classification system for CAR-T-related hematotoxicity, defining three unique phenotypes of neutrophil recovery: quick [“Q”] versus intermittent [“I”] versus aplastic [“A”]. Quick: sustained neutrophil recovery without a second dip below an ANC <1000/µL. Intermittent: neutrophil recovery (ANC > 1500/µL) followed by a second dip with an ANC < 1000/µL after day 21. Aplastic: continuous severe neutropenia (ANC < 500/µL) ≥14 days. Multivariable binary logistic regression was applied to analyze clinical metadata. CAR T-cell expansion dynamics were studied during the first 4 months post-CAR-T infusion. The plasma proteome was explored in 58 patients across four time points (day 0, 4, 14, 28) using a 92-protein multiplex proximity extension assay (Olink Bioscience). Progression-free (PFS) and overall survival (OS) were studied via Kaplan-Meier estimates. Results: The distribution of phenotypes was 18%, 42%, and 40% (A vs. I vs. Q). As expected, ‘aplastic’ patients displayed prolonged severe neutropenia (A vs. I vs. Q: 28 vs. 10 vs. 5 days, p < 0.001) and a higher rate of severe infections (40% vs. 22% vs. 18%). On multivariable regression of baseline risk factors (n = 344), the aplastic phenotype was independently associated with the presence of BM infiltration (p = 0.004), low ANC (p = 0.002), and increased ferritin (p = 0.039). When comparing CAR-T expansion among phenotypes, ‘intermittent’ patients displayed the greatest CAR T-cell expansion over time (Figure 1A). Conversely, ‘aplastic’ patients displayed low expansion with an unfavorable relationship between CAR-T expansion and baseline tumor burden (Figure 1B). Serum proteomics revealed higher markers of T-cell suppression, endothelial dysfunction, inflammatory cytokines, and macrophage activation in the ‘aplastic’ phenotype group (Figure 1C). Notably, both PFS and OS was poor in the ’aplastic’patients (1-yr PFS 26%, 1-yr OS 46%). On the other hand, the ‘intermittent’ phenotype, characterized by recurrent neutrophil dips, was associated with superior survival outcomes (1-yr PFS 51%, 1-yr OS 46%). Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies, basic and translational science – Basic and Translational Science - Other Conflicts of interests pertinent to the abstract K. Rejeski Consultant or advisory role: BMS/CELGENE Honoraria: Novartis, BMS/CELGENE Research funding: Kite/Gilead Travel grants: Kite/Gilead

Background: CD19 CAR T cells have significantly improved the prognosis of patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Real-world evidence (RWE) in the US has confirmed outcome data from pivotal trials. In contrast, several European consortia reported inferior real-world response rates and survival. Aims: To understand these divergent outcomes, we sought to characterize differences in patients treated with CD19 CAR T cells in Europe vs. the US. Methods: In this retrospective observational study, we assessed CAR T cell logistics, patient/disease characteristics, toxicities, response, and survival of r/r LBCL patients treated with Axi-cel or Tisa-cel at five EU and one US CAR T center. We evaluated variables for their association with PFS by univariate and multivariate stepwise Cox regression. Results: A total of 386 patients were included (EU: 175, USA: 211). Indeed, the objective response rate was lower in the EU (65% vs. 82% in the US, p<0.001). Median PFS (Fig. 1, 3 vs. 8 months, p<0.001) was significantly shorter for EU compared to US patients. Tisa-cel was applied more frequently in the EU cohort (74% vs. 14%, p<0.001). While severe CRS rates did not significantly differ between cohorts, grade ≥3 ICANS was more common in US patients (25% vs. 9%, p<0.001), likely reflecting the more frequent use of of Axi-cel. In terms of baseline characteristics, median LDH (321 vs. 272 U/l, p=0.02) and ferritin levels (682 vs. 449 ng/ml, p=0.002) were significantly higher in the EU cohort. EU patients received fewer treatment lines (p=0.004), though the percentage of prior auto-SCT (35% vs. 18%, p<0.001) and active/history of CNS disease (17% vs. 7%, p=0.005) was higher. Analysis of CAR-T logistics revealed longer EU vein-to-vein intervals (43 vs. 28 days, p<0.001). The proportion of patients receiving “holding” therapy, defined as lymphoma treatment between indication-to-CAR and apheresis, was comparable between EU and US centers (22% vs. 27%, p=0.32). However, significantly more patients were treated with bridging therapy (between apheresis and transfusion) in the EU (89% vs. 69%, p<0.001). In univariate analyses, shorter PFS was associated (p<0.05) with lack of response to the latest therapy, longer indication-to-CAR intervals, higher ECOG, stage III/IV disease, IPI, extranodal disease (END), higher LDH, ferritin, CRP levels, and Tisa-cel use. On multivariate regression (n=319), ECOG (adjusted HR 1.4), ferritin (HR 1.5), refractory disease (HR 1.5), END (HR 1.4), and Tisa-cel use (HR 1.5) represented independent risk factors. Of note, the aggregate of these four independent baseline risk factors (ECOG, ferritin, refractory disease, END) did not significantly differ between EU vs. US patients (p=0.18), indicating that product choice likely influenced the observed differences in PFS. Interestingly, although Axi- vs. Tisa-cel did not confer different outcomes for patients with 0-1 risk factors (p=0.47), Axi-cel led to significantly improved PFS compared to Tisa-cel in patients with 2-4 risk factors (p<0.001). Image:Summary/Conclusion: This is the first analysis to comprehensively compare CAR T cell treatment characteristics in Europe vs. the US in a large real-world cohort. Response rates and PFS were significantly inferior in the EU, potentially due to the use of Tisa-cel in adverse-risk patients. Our data suggest that Tisa- and Axi-cel are equally effective in low-risk patients (≤1 risk factor - ECOG, ferritin, refractory disease, END), but that Axi-cel facilitates improved outcomes in patients with 2-4 risk factors, with a representative toxicity profile.

Background: Real-world evidence has underlined the role of hematological toxicity and infections in driving the toxicity burden of CD19 CAR-T. We have recently developed a classification system for post-CAR-T hematotoxicity, identifying three unique phenotypes of neutrophil recovery (Rejeski et al Blood 2021). However, their prognostic impact remains poorly understood. Aims: We sought to understand potential pathomechanisms underlying hematopoietic recovery patterns, and characterize their influence on toxicity and clinical outcomes. Methods: In this multicenter retrospective observational study, we analyzed 316 pts. receiving Axicabtagene ciloleucel (n=194) or Tisagenlecleucel (n=122) for R/R LBCL in a real-world setting. The phenotypes of neutrophil recovery were defined as follows: 1) Quick Recovery: sustained neutrophil recovery without a second dip below an ANC<1000/µl. 2) Intermittent Recovery: neutrophil recovery (ANC>1500/µl) followed by a second dip with an ANC<1000/µl after day 21. 3) Aplastic: continuous severe neutropenia (ANC<500/µl) ≥14 days. Multivariate analysis was performed as stepwise binary logistic regression for the aplastic vs. non-aplastic phenotypes. Variables with a p<0.2 on univariate analysis were included. Clinical outcomes were studied via Kaplan-Meier estimates. Serum cytokines were analyzed using the Ella automated immunoassay system (ProteinSimple) in 70 pt. from Moffitt Cancer Center. The plasma proteome was characterized in a further 38 pts. from the LMU Munich across four time points (day 0, 4, 14, 28) using a 92-protein multiplex proximity extension assay (Olink Bioscience). Results: The overall distribution of the ‘quick’ (Q), ‘intermittent’ (I) and ‘aplastic’ (A) phenotypes was 40%, 41%, and 19%, respectively. Prior to lymphodepletion, ‘aplastic’ patients displayed increased systemic inflammation (median ferritin 1168 ng/ml), impaired hematopoietic function (median platelet count 101 G/l) and high tumor burden (median LDH 344 U/l). ‘Aplastic’ patients displayed a longer median duration of severe neutropenia, (A vs. I vs. Q: 28 vs. 10 vs. 5 days, p<0.001), higher rate of severe infections (A vs. I vs. Q: 40% vs. 22% vs. 18%), and a trend towards higher 1-year non-relapse mortality (A vs. I: 10% vs. 4%, p=0.09). Progression-free (PFS) and overall survival (OS) was poor in the ‘aplastic’ patients (Fig. 1, 1-yr PFS 24%, 1-yr OS 48%). On the other hand, ‘intermittent’ patients exhibited the best survival outcomes (HR for PFS, I vs. A: 0.46, 95% CI 0.32-0.69). Median PFS was 3 vs. 4 vs. 20 months (A vs. Q v. I, p<0.001); median OS was 8 vs. 23 months vs. not reached (A vs. Q v. I, p=0.0025). On multivariate regression (n=316), the aplastic phenotype was primarily driven by baseline ECOG (OR=1.6, p=0.05), ferritin (OR=2.5, p=0.01), ANC (OR=0.3, p=0.01), and hemoglobin (OR=0.8, p=0.04). Of note, high-grade CRS/ICANS and CAR product were not associated with the aplastic phenotype. Initial analyses of inflammatory patterns revealed higher peak IL-15 levels and an increased ratio of ANG2 to ANG1 in ‘aplastic’ patients in both cohorts, with ANG-1 levels decreasing over time. Image:Summary/Conclusion: Hematopoietic recovery patterns impact disease outcomes after CD19 CAR-T. Surprisingly, a phenotype associated with recurrent neutrophil dips (i.e. prolonged cytopenia) was associated with improved survival outcomes. The poor-risk ‘aplastic’ phenotype was driven by baseline inflammation and hematopoietic function, and characterized by progressive endothelial dysfunction. Further mechanistic exploration is warranted and ongoing.

Data are scarce on cytomegalovirus (CMV) replication in patients receiving CD19-directed chimeric antigen receptor (CAR) T cell treatment. Here we describe the incidence, severity, and management of CMV infection in patients with aggressive B cell lymphoma treated with CAR T cell therapy. In this retrospective observational study, we analyzed CMV viral load and its clinical impact in patients with aggressive B cell lymphoma receiving CAR T cell therapy between July 2018 and December 2021 at a single center. Patients with a negative baseline CMV IgG or a previous allogeneic stem cell transplantation were excluded. CMV replication was determined in whole blood. Overall, 105 patients met the study's inclusion criteria. Ten patients presented with CMV replication before CAR T cell infusion and were analyzed separately. Forty-two of the remaining 95 patients (44%) had at least 1 positive CMV determination, with a viral load >1000 IU/mL in 21 patients (22%). Four patients in the main cohort (N = 95) and 4 patients in the preinfusion replication group (N = 10) achieved a viral load >10,000 IU/mL. Only 7 patients received preemptive anti-viral treatment. No CMV end-organ disease was reported. The sole independent risk factor associated with CMV vire-mia >1000 IU/mL was dexamethasone treatment (odds ratio, 8.4; 95% confidence interval, 2.4 to 36.6; P = .002). Based on our findings, we designed an algorithm for CMV management in this setting. CMV replication is relatively frequent in patients with aggressive B cell lymphoma receiving CART cell therapy. It is usually self-limited and not associated with end-organ disease. Patients receiving dexamethasone or harboring CMV replication before infusion might benefit from active surveillance and preemptive treatment strategies. (c) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Background: CD19-directed CAR-T cell therapies (tx) demonstrate efficacy in patients (pts) with B-cell malignancies. However, despite positive outcomes with currently approved CAR-T cell tx, many patients fail to respond or relapse after initial response. YTB323 is an autologous CD19-directed CAR-T cell tx generated by the innovative T-Charge™ platform, which demonstrates high potency, preserves T-cell stemness in the final product, and takes <2 d to manufacture. Aims: T-Charge™ is expected to prolong CAR-T cell persistence and yield higher response rates and durability. Methods: These data from the ongoing Phase I, multicenter, dose-escalation study (NCT03960840) focus on safety and efficacy of YTB323 in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Eligible pts had measurable disease at enrollment, ECOG 0-1, and r/r DLBCL after ≥2 lines of prior tx. Pts received single-dose YTB323 at targeted dose levels (DL) 1 (2.5×106 CAR+ cells), DL2 (12.5×106 CAR+ cells), DL3 (25×106 CAR+ cells), or DL4 (40×106 CAR+ cells). Results presented here focus on DL1 and DL2. The primary endpoints are to identify a recommended dose for subsequent trials and characterize the safety and dose-limiting toxicities. Secondary endpoints include overall response rate (ORR) by local investigator assessment and cellular kinetics. Results: As of August 20, 2021, 20 pts with r/r DLBCL received YTB323: 4 at DL1 and 16 at DL2. Median age was 65 y, 65% received 2 prior lines of tx, and 35% had prior SCT. The median follow-up for pts in DL1 and DL2 was 20 and 7 months, respectively. Of 20 pts evaluable for safety, all experienced at least 1 adverse event (AE) of any Grade (Gr) and 80% at least 1 AE Gr ≥3. One pt (25%) experienced Gr 1 cytokine release syndrome (CRS) at DL1, and 5 (31%) pts experienced CRS at DL2, including 4 (25%) Gr 1 or 2 and 1 (6%) Gr 4 (Lee et al, 2014), which met protocol defined DLT criteria at DL2. Tocilizumab and corticosteroids were used for CRS management in 4 (80%) and 2 (40%) pts at DL2, respectively. Median time to CRS onset was 10 d (range, 1-17 d). Five pts (25%) had neurological events (NE), of which the majority were Gr 1. Median time to onset and resolution of NE was 7 and 12 d, respectively. Five pts died on trial (beyond 30 d); 3 pts died due to disease progression (1 at DL1, 2 at DL2), and 1 pt each due to sepsis (1 at DL1) and intestinal hemorrhage (1 at DL2). At DL1, ORR and complete response (CR) rate were both 75%. At DL2, ORR and CR rates were 81% and 75%, respectively. Of the 15 pts who received YTB323 at DL2 at least 3 mo prior to the data cutoff, CR rate at mo 3 was 73% (95% CI, 44.9%-92.2%) (Figure). Median time to peak YTB323 expansion was ~16 d and coincided with cytokine peak. YTB323 expansion (Cmax and AUC0-28d) with 12.5×106 CAR+ cells (DL2) was comparable to a median tisagenlecleucel dose of 312×106 CAR+ cells in pts with DLBCL, a 25-fold lower median dose (Awasthi R, et al. 2020). Limited data indicate that CAR expression was detectable by flow cytometry for at least 9 mo at DL2. T-Charge™ allowed preservation of CD4 and CD8 naive/stem memory T cells in the final product according to flow cytometry. Bulk RNAseq analysis demonstrated that YTB323 retained a naive stem-like gene signature. Image:Summary/Conclusion: YTB323 is a potent new CAR-T cell tx with distinct cellular kinetics, encouraging early efficacy results across DL1 and DL2, and a manageable safety profile. Updated results will be presented at the meeting along with a recommended dose for subsequent trials.

Background: An impaired humoral and cellular immunogenicity to the mRNA SARS-CoV-2 vaccines has been reported in patients diagnosed with hematologic malignancies. Data regarding the effectiveness of SARS-CoV-2 vaccination on COVID-19 evolution an immunocompromised population are still scarce. Aims: To compare disease severity and mortality in a real-life cohort according to the vaccination status of patients diagnosed with hematologic malignancies developing COVID-19 disease. Methods: We retrospectively collected clinical data from the patients with a current or prior history of hematologic malignancy in the last 5 years at Vall d´Hebron Hospital whom suffered a SARS-CoV-2 infection. Patients were unvaccinated between March 2020 and May 2021, and partially or completely vaccinated between May 2021 and January 2022. The primary endpoint was COVID-related mortality according to vaccination status. Secondary endpoints included rate and length of hospitalization, ICU admission, need for supplemental oxygen including high flow oxygen therapy and mechanical ventilation, and severity of COVID-19 disease. Results: Overall, 113 vaccinated and 81 unvaccinated patients developed COVID-19. Both groups were similar in age (median 69 and 72 years, respectively), gender predominance, diagnosis (mainly lymphoproliferative diseases [58% and 53%]), and administered active treatment (mostly anti-CD20 monoclonal antibodies [38% and 37%]). In contrast, more patients received active treatment (78% vs. 48%; p=<0.001) in the vaccinated cohort. Vaccinated patients developed infection by the delta variant in 27% (17/62) and by the omicron variant in 73% of the sequenced cases (45/62). Genotype analysis of the variant in unvaccinated cases is ongoing. Despite the fact that 96% of patients received 2 vaccine doses and 73% also a third boost dose, in only 67% (59/88) of patients basal IgG anti-spike antibodies were detected after vaccination. In comparison with the unvaccinated cohort of patients, vaccinated patients had less severe (17% vs. 42%; p=0.01) and critical (13% vs 28%; p=0.03) COVID-19 infection, lower rates of hospitalization (42% vs. 90%; p=<0.001) with shorter length of stay (median 13 days (IQR 7-34) vs. 11 days (IQR 6-16), and fewer patients needed supplemental oxygen (34% vs. 73%; p=0). Admission rates to ICU were similar between both cohorts. Finally, mortality rate was lower in the vaccinated patients in comparison with the unvaccinated cohort (HR: 0.19 (95%CI 0.09, 0.38); p=<0.001). Of note, in hospitalized patients only, the mortality of the vaccinated cohort was also lower (HR: 0.38 (95%CI 0.19, 0.76); p=0.007). Among vaccinated patients who suffered a severe/critical infection, 52% did not have vaccine seroconversion. Of the vaccinated patients who died (11/113), 6/8 had negative anti-S IgG, 5/9 were infected by the delta variant and 4/9 by omicron, and 10/11 were on active treatment (5/11 with monoclonal antibodies). Image:Summary/Conclusion: In our series, despite the heterogeneity of infection by different viral variants and treatment availability for COVID-19 during the evolution of the pandemic, vaccination has been widely effective at reducing need of hospitalization, severity and mortality of the SARS-CoV-2 infection in hematological patients. Nevertheless, a subgroup of vaccinated patients remains with an adverse outcome and requires further identification and management improvement.

BACKGROUND Patient outcomes are poor for aggressive B-cell non-Hodgkin's lymphomas not responding to or progressing within 12 months after first-line therapy. Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for diffuse large B-cell lymphoma after at least two treatment lines. METHODS We conducted an international phase 3 trial involving patients with aggressive lymphoma that was refractory to or progressing within 12 months after first-line therapy. Patients were randomly assigned to receive tisagenlecleucel with optional bridging therapy (tisagenlecleucel group) or salvage chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT) (standard-care group). The primary end point was event-free survival, defined as the time from randomization to stable or progressive disease at or after the week 12 assessment or death. Crossover to receive tisagenlecleucel was allowed if a defined event occurred at or after the week 12 assessment. Other end points included response and safety. RESULTS A total of 322 patients underwent randomization. At baseline, the percentage of patients with high-grade lymphomas was higher in the tisagenlecleucel group than in the standard-care group (24.1% vs. 16.9%), as was the percentage with an International Prognostic Index score (range, 0 to 5, with higher scores indicating a worse prognosis) of 2 or higher (65.4% vs. 57.5%). A total of 95.7% of the patients in the tisagenlecleucel group received tisagenlecleucel; 32.5% of the patients in the standard-care group received autologous HSCT. The median time from leukapheresis to tisagenlecleucel infusion was 52 days. A total of 25.9% of the patients in the tisagenlecleucel group had lymphoma progression at week 6, as compared with 13.8% of those in the standard-care group. The median event-free survival in both groups was 3.0 months (hazard ratio for event or death in the tisagenlecleucel group, 1.07; 95% confidence interval, 0.82 to 1.40; P = 0.61). A response occurred in 46.3% of the patients in the tisagenlecleucel group and in 42.5% in the standard-care group. Ten patients in the tisagenlecleucel group and 13 in the standard-care group died from adverse events. CONCLUSIONS Tisagenlecleucel was not superior to standard salvage therapy in this trial. Additional studies are needed to assess which patients may obtain the most benefit from each approach. (Funded by Novartis; BELINDA ClinicalTrials.gov number, NCT03570892.).

OBJECTIVE To compare the efficacy and safety of CD34+ selected ex vivo T-cell cell depletion (TCD) versus post-transplant cyclophosphamide, sirolimus and mycophenolate mofetil (PTCy-Sir-MMF) as GVHD prophylaxis. METHOD We retrospectively included patients who underwent allo-HSCT with either TCD (n = 38) or PTCy-Sir-MMF (n = 91). RESULTS Cumulative incidence of neutrophil and platelet recovery was 92% vs 99% (p = 0.06) and 89% vs 97% (p = 0.3) in TCD and PTCy-Sir-MMF, respectively. Cumulative incidences of aGHVD grade II-IV, III-IV and moderate to severe cGVHD were 11% vs 19% (p = 0.2), 3% vs 2% (p = 0.9) and 3% vs 36% (p <0.001) in TCD and PTCy-Sir-MMF, respectively. The 2-year non-relapse mortality, relapse, disease-free and overall survival was 25% vs 8% (p = 0.01), 20% vs 16% (p = 0.2), 55% vs 76% (p = 0.004), 57% vs 83% (p = 0.004) for TCD and PTCy-Sir-MMF, respectively. Cumulative incidence of cytomegalovirus and Epstein-Barr infection requiring therapy was 76% vs 40% (p < 0.001) and 32% vs 0% (p < 0.001) in TCD and PTCy-Sir-MMF, respectively. PTCy-Sir-MMF platform showed faster T-cell reconstitution. CONCLUSION PTCy-Sir-MMF provides better survival outcomes but is associated with higher risk of cGVHD compared to TCD.

Reduced-intensity conditioning (RIC) and t-cell depletion (TCD) through CD34+ selection without the use of post-transplant immunosuppression are 2 strategies used to reduce non-relapse mortality (NRM) in older patients after allogeneic hematopoietic cell transplantation (allo-HCT). CORRESPONDING AUTHOR: Miguel-Angel Perales, M.D., Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 298, New York, NY 10065 USA, peralesm@mskcc.org, Fax: 212-717-3500, Phone: 212-639-8682, Or, Pere Barba, M.D., Servicio de Hematologia, Hospital Universitari Vall d’Hebrón. Universitat Autònoma de Barcelona, Pg. Vall Hebron 119, 08035., Barcelona, SPAIN, pebarba@vhebron.net, Phone: +34.93.274.64.14. AUTHOR CONTRIBUTIONS Conception and Design: Pere Barba, Miguel-Angel Perales, Rodrigo Martino. Collection of data: Pere Barba, Christina Cho, Albert Esquirol, Lucía Lopez-Corral, Molly Maloy, José Luís Piñana, María Laura Fox. Data analysis and interpretation: Qin Zhou, Sean Devlin, Pere Barba, Miguel-Angel Perales Manuscript writing: All authors Final approval of manuscript: All authors Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author manuscript Biol Blood Marrow Transplant. Author manuscript; available in PMC 2019 October 18. Published in final edited form as: Biol Blood Marrow Transplant. 2018 May ; 24(5): 964–972. doi:10.1016/j.bbmt.2017.12.804. A uhor M anscript