Abstract: Introduction: Salvage immunochemotherapy (IC), followed by high-dose chemotherapy with autologous stem cell transplantation if chemosensitive is standard-of-care second-line (2L) therapy (tx) for fit patients (pts) with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) when treated with first-line (1L) R-CHOP as shown in the CORAL study. Outcomes following receipt of salvage IC in the 2L setting for pts with DLBCL or high grade B cell lymphoma/B cell lymphoma unclassifiable (HGBL/BCLU) receiving intensive 1L tx remain unknown, and may be worse than those reported in CORAL given prior exposure to higher-dose IC in 1L setting. Here we report the results of a multicenter retrospective analysis of R/R DLBCL and HGBL/BCLU pts treated with intensive 1L tx who receive standard salvage 2L tx. Methods: Inclusion criteria were histologic diagnosis of DLBCL or HGBL/BCLU, R/R disease following 1L tx with R-EPOCH, R-HyperCVAD or R-CODOX-M/IVAC and receipt of 2L tx with R-ICE, R-DHAP, R-DHAC, R-ESHAP or R-GDP. Exclusion criteria were HIV positivity, post-transplant lymphoproliferative disorder, prior chronic lymphocytic leukemia and inadequate data. Therapy was given at the discretion of the treating physician. Progression free survival (PFS) was defined as the interval between time of first relapse or primary refractory disease and disease progression, change in therapy if no disease response or last follow-up in remission, and overall survival (OS) between time of first relapse or primary refractory disease and death or last follow-up while alive. Pts were treated from 2007-2017 and data were censored on 10/15/17. Results: A total of 195 pts treated at 20 US and Canadian academic medical centers were included. Clinicopathologic characteristics at time of R/R disease were 39% age 〉 60 years, 62% male, 77% stage III-IV, 72% elevated LDH, 24% bone marrow (BM) involvement, 28% B symptoms present, 44% extranodal (EN) disease at 〉 1 site, 19% ECOG performance status (PS) 〉 1, 49% with International Prognostic Index score (IPI) ≥3, 46% HGBL/BCLU histology, 49% Ki67 ≥90%, and 61% germinal center (GCB) cell of origin (COO) by Hans algorithm. Of pts with available fluorescence in situ hybridization (FISH) data, 51%, 45% and 30% demonstrated MYC, BCL2 and BCL6 rearrangements (-R), respectively, and 37% were double hit lymphoma (DHL). Tx received in 1L were R-EPOCH in 82%, R-HyperCVAD in 16% and R-CODOX-M/IVAC in 2% of pts. R-ICE was received by 64% and other platinum-containing regimens by 36% as 2L tx. Most (86%) pts relapsed within 12 months (mo) of completion of 1L tx (early) and 58% of pts had primary refractory disease. For all pts, the median length of follow-up was 25.0 mo with a median PFS of 3.0 mo and median OS of 8.0 mo. Overall response rate to 2L tx among all pts was 44% (23% complete response [CR] and 21% partial response [PR] ), and 48% with progressive disease. Pts achieving CR had significantly longer median PFS (32.0 vs 4.0 mo, p = 0.0001) and OS (not reached vs 13.0 mo, p = 0.0004) as compared to pts achieving PR. In pts who achieved CR or PR following 2L tx, 64% received consolidative transplant (42 autologous and 13 allogeneic) and achieved a median PFS and OS of 18.3 mo and 62.0 mo, respectively. As compared to pts relapsing ≥12 mo after completion of 1L tx (late), pts relapsing early were less likely to achieve CR (17% vs. 61%, p=0.0001) and experienced significantly shorter median PFS (2.8 vs. 23.0 mo, p 〈 0.0001) and median OS (6.0 mo vs. not yet reached, p 〈 0.0001). Univariate analysis incorporating clinicopathologic characteristics at the time of relapse demonstrated elevated LDH, stage III-IV disease, IPI ≥3, BM involvement, GCB COO, HGBL/BCLU histology, MYC-R, BCL2-R, DHL and early relapse to have a statistically significant increased hazard ratio (HR) for progression. All of these factors, as well as EN disease at 〉 1 site, B symptoms, ECOG PS 〉 1 and Ki67 ≥90%, but not BCL2-R, demonstrated a statistically significant increased HR for death. Multivariate analysis demonstrated only early relapse to have a statistically significant increased HR for progression (HR 2.47, p=0.024) and death (HR 5.90, p=0.001). Conclusion: Relapse 〈 12 mo from completion of intensive 1L tx is associated with extremely poor outcomes in pts with DLBCL and HGBL/BCLU treated with standard salvage 2L tx. Novel therapeutics, including chimeric antigen receptor-modified T cell (CART) tx, should be investigated as 2L tx in this pt population. Figure. Figure. Disclosures Maddocks: Pharmacyclics: Research Funding; BMS: Research Funding; Teva: Honoraria; AstraZeneca: Honoraria; Novartis: Research Funding; Pharmacyclics/Janssen: Honoraria; Merck: Research Funding. Wagner-Johnston:Novartis: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ASTEX: Research Funding; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Merck: Research Funding; JUNO: Honoraria, Membership on an entity's Board of Directors or advisory committees. Karmali:Gilead: Speakers Bureau; AstraZeneca: Speakers Bureau. Kahl:Genentech: Consultancy; Juno: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy; Gilead: Consultancy; Acerta: Consultancy; CTI: Consultancy; Abbvie: Consultancy; AstraZeneca: Consultancy. Cohen:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioInvent: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Reddy:MEI Pharma: Research Funding. Ramchandren:Seattle Genetics: Consultancy, Research Funding; Pharmacyclics LLC an AbbVie Company: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Merck: Research Funding; Janssen: Consultancy, Research Funding. Diefenbach:Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Incyte: Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding; Denovo: Research Funding; Acerta: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy. Olszewski:TG Therapeutics: Research Funding; Genentech: Research Funding; Spectrum Pharmaceuticals: Consultancy, Research Funding. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding. Hill:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Seattle Genetics: 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; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Assouline:Roche: Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding; BMS: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Landsburg:Curis: Consultancy, Research Funding; Takeda: Consultancy.

Abstract: Patients with aggressive non‐Hodgkin lymphoma who fail intensive first‐line immunochemotherapy within 12 months experience poor outcomes with standard salvage immunochemotherapy. Standard‐of‐care and experimental therapies currently offered in the third‐line setting or later should be investigated earlier in this patient group.

Abstract: Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data are for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. This is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC-MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial–mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓ in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, IL6 STAT3 signaling, and response to hypoxia via HIF1A targets (↑ in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis.

Abstract: Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1–196), the 3‐year progression‐free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3‐year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper‐CVAD or auto‐SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p  = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.

Abstract: Introduction Relapses involving the central nervous system (CNSrel) occur in ~5% of patients (pts) with aggressive non-Hodgkin lymphoma (NHL) in the rituximab era (Ghose et al, Clin LML 2015) with rates exceeding 10% in high risk groups (Villa et al, Ann Onc 2010; Schmitz et al, JCO 2016). CNSrel are generally thought to occur in the first 4-6 months from diagnosis. Prophylaxis (PPx) administration, route, and frequency are not standardized, and the impact of PPx on CNSrel risk is incompletely understood. Methods We performed a multicenter retrospective analysis of pts with aggressive NHL (excluding Burkitt's) without known CNS involvement (inv) who received single-route CNS PPx with during front-line (FL) anthracycline-based therapy (tx) from 2013-2019 across 19 US academic institutions. Recipients of chemotherapy for prior CLL or indolent NHL were ineligible. Method, frequency, and outcomes of CNS PPx administration were evaluated, with significance assessed by various statistical methods via two-tailed P & lt;0.05. Results 1030 patients were identified who met eligibility criteria. Clinical features included median age 61 years (yrs; range 16-86), 40.9% female, ECOG PS 0-1 82.8%, elevated LDH 65.3%, & gt;1 extranodal (EN) site 42.3%, stage 3/4 disease 79.2%. NHL histologies included diffuse large B cell (DLBCL; 75.2%), high grade B cell (16.3%), transformed follicular lymphoma (5.6%) and 3% other; among pts with DLBCL, 46.4% had germinal center (GCB) subtype and 40.5% had non-GCB. 26.2% (n=210) of evaluable pts had double-hit lymphoma (DHL). Among pts with known HIV status, 7.2% (n=65) were HIV-positive. 85.7% had EN inv; common sites included bone (35.4%), liver (13.7%), gastrointestinal (12.7%), lung (11.8%), and marrow (11.5%). FL regimens included RCHOP (45.9%), REPOCH (46.5% total; 79.1% with dose-adjustment), 7.6% other. PPx was given intravenously (IV) in 20% of pts vs 77% intrathecally (IT), over a median 2.9 vs 4.1 doses respectively; see Table 1 for factors associated with PPx route. PPx was generally well-tolerated, with 10.7% PPx-related toxicity reported; see Table 2. CNSrel after FL tx was 5.3% overall without significant difference by PPx route (7% IV vs 5% IT, p=0.178). This lack of difference between PPx routes was observed in all subgroup analyses performed, including by: age, stage, histology, number of EN sites, individual EN site inv, elevated LDH, CNS-IPI, DHL status, HIV status, FL regimen, number of PPx doses. There was no significant difference in anatomic site(s) of CNSrel by PPx route. CNSrel occurred bimodally: 24% by end of FL tx vs 76% delayed (average 2.3 yrs, range 0.4-5.2 yrs). Rates of CNSrel were significantly higher with CNS-IPI high vs moderate risk (8.3 vs 4.1%, p=0.03; Figure 1), elevated LDH (6.9 vs 2.6%, p=0.007) and multiple inv EN sites (7.5% for 2+ vs 4% for 0-1, p=0.01); each additional EN site further increased risk (p=0.03 for trend; Figure 2). Increased CNSrel was noted in pts with testis (13.7 vs 5%, p=0.004) and liver inv (11.1 vs 4.6%, p=0.002) vs those without inv at respective sites. No significant difference was noted at other EN sites, including renal/adrenal (4.8 vs 5.6%, p=0.71), marrow (8.9 vs 5.1%, p=0.09), or lung (8.6 vs 5.1%, p=0.12). All EN site-CNSrel correlations were unchanged when accounting for PPx route. With median follow-up of 2.3 yrs, median PFS and OS for the overall group have not been reached; 2-yr PFS and OS were 70 and 85% respectively. PFS and OS were each predicted by CNS-IPI (p & lt;0.0001) and maintained significance when separated by PPx route. 196 deaths were reported, including 122 disease-related and 34 tx-related (TRM). There was no significant difference in TRM by PPx route (1.9% IV vs 3.6% IT, p=0.24). Death due to progression was more common following IT PPx (13.3% vs 7.9% IV; HR 1.72, p=0.04), driven primarily by DH status (adjusted PPx HR: 1.54, p=0.11). In those with CNSrel, subsequent relapse and/or death was common (n=41, 74.5%) regardless of initial PPx route or salvage tx. Median survival after CNSrel diagnosis was poor (7.1 months, range 1 day-5.3 yrs) and was significantly inferior to those with non-CNSrel (HR 1.488, p=0.03). Conclusion Use of single-route ppx demonstrated similar CNSrel vs established outcomes for this population in the rituximab era, with no difference by PPx route. CNSrel remains a rare but devastating complication, with greater risk even after single-route PPx in those with higher EN burden and inv of key EN sites. Disclosures Kahl: Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy. Spinner:Notable Labs: Honoraria. Advani:Celgene, Forty Seven, Inc., Genentech/Roche, Janssen Pharmaceutical, Kura, Merck, Millenium, Pharmacyclics, Regeneron, Seattle Genetics: Research Funding; Astra Zeneca, Bayer Healthcare Pharmaceuticals, Cell Medica, Celgene, Genentech/Roche, Gilead, KitePharma, Kyowa, Portola Pharmaceuticals, Sanofi, Seattle Genetics, Takeda: Consultancy. Voorhees:AstraZeneca: Research Funding. Grover:Genentech: Research Funding; Tessa: Consultancy. Huntington:Genentech: Consultancy; Novartis: Consultancy; Celgene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Pharmacyclics: Honoraria; Bayer: Consultancy, Honoraria; DTRM: Research Funding; Astrazeneca: Honoraria; AbbVie: Consultancy. Spurgeon:Beigene: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy, Research Funding; VelosBio: Consultancy, Research Funding; Cardinal Health: Honoraria; Verastem: Research Funding; Genmab: Research Funding; AstraZeneca: Research Funding; Acerta: Research Funding. Olszewski:Spectrum Pharmaceuticals: Research Funding; Genentech, Inc.: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding. Landsburg:Seattle Genetics: Speakers Bureau; Morphosys: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Triphase: Research Funding. Kamdar:Roche: Research Funding. Caimi:Kite Pharma: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board, Research Funding; Verastem: Other: Advisory Board; Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Celgene: Speakers Bureau. Karmali:Takeda: Research Funding; BeiGene: Speakers Bureau; AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau. Stephens:Pharmacyclics: Consultancy; Innate: Consultancy; Verastem: Research Funding; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; Gilead: Research Funding; Arqule: Research Funding; Juno: Research Funding; MingSight: Research Funding; Acerta: Research Funding; Beigene: Consultancy. Smith:Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; TG Therapeutics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy; Karyopharm: Consultancy, Research Funding; FortySeven: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding. Khan:Celgene: Research Funding; Pharmacyclics: Honoraria; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; Janssen: Honoraria. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy. Portell:Bayer: Consultancy; Xencor: Research Funding; BeiGene: Consultancy, Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; TG Therapeutics: Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding.

Abstract: Background: Plasmablastic lymphoma (PBL) is a rare subtype of Non-Hodgkin Lymphoma with a well-known association with HIV infection. The outcomes of PBL patients are typically described with high relapse rates and poor prognosis. (Loghavi S, J Hematol Oncol. 2015; Morscio J, Am J of Pathol. 2014; Castillo JJ, Clin Lymphoma Myeloma Leuk. 2011; Castillo JJ, Am J Hematol. 2008) There has been a paucity of data suggesting that limited stage disease (Ann Arbor stage I-II) may have a more favorable prognosis. However, due to the rarity of this disease there have been no large-scale reviews to confirm this. Thus, many patients with limited stage disease are subject to the aggressive therapy recommendations based on the poor outcomes of PBL patients as a whole. (Loghavi S, J Hematol Oncol. 2015; NCCN Guidelines, version 2.2020; Al-Malki MM, BBMT. 2014) We attempted to determine the treatment patterns and outcomes of patients with limited stage PBL. Methods: We conducted a multi-center (13 US academic centers) retrospective study of patients with limited stage (Ann Arbor stage I-II) Plasmablastic lymphoma. Determination of limited stage and diagnosis of PBL was determined by the investigators at each individual center. Patients diagnosed between 1/1/1990 and 6/1/2018 were included. Baseline demographic, clinical, laboratory, pathology, and outcomes data were extracted by retrospective chart review. Kaplan Meier was utilized for time to event analysis. Results: Baseline characteristics are included in table 1. A total of 80 patients were identified with limited stage disease. With a median follow up of 34 months the 3-yr Progression free survival (PFS) and overall survival (OS) was 71.9% and 78.7% respectively (Figure 1A and 1B). Patients that received frontline chemotherapy with (n=29) and without RT (n=36) had a 3-yr PFS and OS of 84.6% and 96.2% as compared to 64.5% and 70.8%, respectively (Figure 2A and 2B; Figure 3A and 3B). The Hazard ratio (HR) for PFS and OS for chemo (reference) vs chemo-RT was 0.47 (95% CI 0.18-1.3; P=0.131) and 0.18 (95% CI 0.04-0.84; p=0.029) respectively. The HR for PFS and OS for CHOP (n=14, reference) vs EPOCH (n=33) based regimens was 0.37 (95% CI 0.11-1.2; p=0.106) and 0.36 (95% CI 0.079-1.6; p=0.182) respectively. Patients with stage I/IE disease (n=56) had a 3-yr PFS and OS of 73.1% and 81.2% respectively. Patients with stage II/IIE disease (n=24) had a 3-yr PFS and OS of 69.3% and 73.4% respectively. Patients that received aggressive treatment (n=17) with Hyper-CVAD based regimens and/or Auto-SCT as consolidation had a 3-yr PFS and OS of 63.6% and 72.7% respectively. Patients with concomitant HIV (n=16) had a 3-yr PFS and OS of 80.8% and 77.4% respectively. Seven patients received RT alone and 6 patients had surgical resection alone as frontline therapy; 1 patient received no therapy; 1 patient received HAART therapy only and remains in CR without any other treatment for PBL 29 months after diagnosis. There were 8 deaths (10%) related to PBL, 3 deaths (4%) related to treatment of PBL (2 during frontline chemo and 1 upon relapse with salvage chemo), and 9 deaths (11%) related to other causes. The 3-yr lymphoma free survival (LFS) of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (without including treatment related mortality (TRM) as an event) was 89.1%, 85.2%, and 100% respectively. The 3-yr LFS survival of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (including TRM as an event) was 85.1%, 80.0%, and 96.2% respectively. Discussion: Here we report the largest review to our knowledge of limited stage PBL. Outcomes appear to be excellent with 3-yr PFS and OS of 71.9% and 78.7% respectively and a 3-yr LFS of 89.1% (85.1% when attributing TRM as an event). There was no obvious benefit to receiving aggressive therapy with H-CVAD based regimens and/or Auto-SCT. Although this is a small, uncontrolled sample size the HR for OS was improved in patients receiving frontline chemo-RT vs chemo alone 0.18 (95% CI 0.04-0.84; p=0.029). However, this did not take into account TRM with or progression while receiving frontline chemotherapy. Patients who were HIV+ had similar PFS and OS outcomes compared to the entire cohort. This retrospective study clearly demonstrates the favorable outcomes in this patient population, especially in those able to receive definitive therapy for their disease. Disclosures Hess: ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS, AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Patel:Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Nektar: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Poseida: Research Funding; Cellectis: Research Funding; Oncopeptides: Consultancy; Janssen: Consultancy, Research Funding. Nowakowski:Nanostrings: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Kymera: Consultancy; Denovo: Consultancy; Kite: Consultancy; Celgene/BMS: Consultancy, Research Funding; Roche: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding. Chavez:Bayer: Consultancy; AbbVie: Consultancy; BeiGene: Speakers Bureau; Morphosys: Consultancy, Speakers Bureau; Merck: Research Funding; AstraZeneca: Speakers Bureau; Celgene: Consultancy; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Karyopharm: Consultancy; Verastem: Consultancy; Pfizer: Consultancy. Hill:Beigene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Maddocks:Pharmacyclics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding. Wagner-Johnston:ADC Therapeutics, Regeneron, CALIB-R, Verastem: Membership on an entity's Board of Directors or advisory committees. Kahl:AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy. Alderuccio:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member; Oncinfo: Honoraria; Inovio Pharmaceuticals: Other: Family member; Foundation Medicine: Other: Family member; Puma Biotechnology: Other: Family member; OncLive: Honoraria. Lossos:Janssen Biotech: Honoraria; Verastem: Consultancy, Honoraria; Janssen Scientific: Consultancy, Other; Seattle Genetics: Consultancy, Other; Stanford University: Patents & Royalties; NCI: Research Funding. Portell:Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding. Landsburg:Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Takeda: Research Funding; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Speakers Bureau. Castillo:TG Therapeutics: Research Funding; Beigene: Consultancy, Research Funding; Kymera: Consultancy; Janssen: Consultancy, Research Funding; Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding.

Abstract: Background. Type 1 diabetes mellitus (T1DM) is an autoimmune disease. A safe induction of an autoimmunity-free status may become a promising therapy. We hypothesize that intense immuno- and myelosuppression followed by autologous hematopoietic stem cell (HSC) rescue is an option to establish a lasting immunetolerance by eliminating auto-reactive lymphocytes and thus facilitate a possible recovery of autologous insulin production. Aims. Evaluate the HSC mobilization, infusion and engraftment in T1DM patients. Patients and Methods. Between January of 2004 and July of 2006 15 T1DM patients (12 male/3 female), with no more than 6 weeks after the first episode of hyperglycemia, were selected and enrolled. Their median age was 17 years old (range 14–31). HSC were mobilized into the peripheral blood (PB) by cyclophosphamide (Cy) 2g/m2 and filgrastim (G-CSF) 10 μg/kg/day. Peripheral blood stem cells (PBSC) were collected by leukapheresis using COBE Spectra (Gambro BCT, Lakewood, CO) blood cell separator. Collected PBSC were mixed with a cryoprotectant solution (autologous plasma and 10% dimethyl-sulfoxide (DMSO)), then frozen and stored in a mechanical freezer (−80°C). The CD34+ cell were counted using the ISHAGE protocol by a FACSort flow cytometer and CellQuest software packages (Becton Dickinson, San Jose, CA, USA). The conditioning regimen was Cy 200mg/kg and anti-lymphocyte globulin (4.5mg/kg). The protocol and the consent form were approved by the institution and the national ethics committees. Results. All results are expressed as median (range), except when specified. The collection was done on the 7th day (7–9) after the chemotherapy. The pre-apheresis values were: WBC (×103/μL) 7.9 (2.6–56.0); Hct (%) 37.4 (30.9–44.7); platelets (×103/μL) 177 (87–295); CD34+ (μL) 80.9 (36.5–167.6). The blood volemia processed and apheresis duration (min) were 2.8 (2.0–3.1) and 235 (177–280), respectively. Five patients (33.3%) experienced mild adverse reactions related to G-CSF administration (osteo-muscular pain and headache) and six (40%) related to citrate infusion (paresthesia and tremors), although thirteen (86%) had received prophylactic intravenous calcium infusion. The final yield values were: volume (mL) 210 (170–273); WBC (×108/Kg) 6.0 (3.0–14.9); Hct (%) 5.0 (3.3–9.0); CD34+ (×106/kg) 9.6 (5.8–22.5). Fourteen patients have already been transplanted. The time between cryopreservation and infusion was 21 days (13–35). The dose of DMSO infused was 0.4 mL/kg (0.0–0.5) (one patient received washed PBSC). All patients presented mild complications related to infusion: 13 (93%) nausea or vomiting, 8 (57%) flushing, 5 (36%) abdominal pain, 4 (29%) headache and 3 (21%) dyspnea, but only one needed oxygen supplementation. None of the patients presented complications like renal failure, hepatic insufficiency or cardiac arrhythmias. The time to reach granulocytes recovery (500/μL) was 9 days (7–10). Conclusions. The present data suggest that HSC mobilization in T1DM patients are very effetive, precocious and provide a good collection of CD34+ cells. The infusion of PBSC is a safe and reliable procedure with a low incidence of severe side effects and early engraftment. These results could be explained by a good bone marrow function as these patients had never been submitted to any kind of myelo or immunosuppressive therapy.

Abstract: Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.