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Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation. In experimental models, interleukin-22 promotes epithelial regeneration and induces innate antimicrobial molecules. We conducted a multicenter single-arm phase 2 study evaluating the safety and efficacy of a novel recombinant human interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD. The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. Out of 27 patients, 19 (70%; 80% confidence interval, 56%-79%) achieved a day-28 treatment response, meeting the prespecified primary endpoint. Responders exhibited a distinct fecal microbiota composition characterized by expansion of commensal anaerobes, which correlated with increased overall microbial α-diversity, suggesting improvement of GVHD-associated dysbiosis. This work demonstrates a potential approach for combining immunosuppression with tissue-supportive strategies to enhance recovery of damaged mucosa and promote microbial health in patients with gastrointestinal GVHD. This trial was registered at www.clinicaltrials.gov as NCT02406651.

•Use of the rhIL-22 dimer F-652 with systemic steroids appeared safe and was associated with a high response rate in newly diagnosed GI GVHD.•Patients responding after tissue-targeted therapy with F-652 and corticosteroids demonstrated an expansion of healthy commensal GI flora.

Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, the authors hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. In the 20 days prior to disease onset, GVHD patients had lower abundances of members of the class Clostridia, lower counts of butyrate producers, and lower ratios of strict-to-facultative (S/F) anaerobic bacteria compared with allograft recipients who were free of GVHD. GI GVHD patients showed significant reduction in microbial diversity preonset. Patients with lower GI aGVHD had lower S/F anaerobe ratios compared with those with isolated upper GI aGVHD. In the 20 days after disease onset, dysbiosis was observed only in GVHD patients with GI involvement, particularly those with lower-tract disease. Importantly, Clostridial and butyrate-producer abundance as well as S/F anaerobe ratio were predictors of longer overall survival; higher abundance of butyrate producers and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD.

•Patterns of microbial dysbiosis can be detected in fecal samples of GI aGVHD patients peri-aGVHD onset.•Markers of microbial health pre-GVHD onset are associated with longer survival and lower risk of GVHD-related mortality after allo-HCT.

Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant patients and in a further cross-sectional cohort from an independent transplant center. An additional cross-sectional patient cohort from a third transplant center was analyzed; however, serum (rather than plasma) was available, and the differences in SCFAs observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort and 1 of 2 cross-sectional cohorts explored suggest that the gastrointestinal microbiome may exert immunomodulatory effects in allo-HCT patients at least in part due to control of systemic concentrations of microbe-derived SCFAs.

Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant patients and in a further cross-sectional cohort from an independent transplant center. An additional cross-sectional patient cohort from a third transplant center was analyzed; however, serum (rather than plasma) was available, and the differences in SCFAs observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort and 1 of 2 cross-sectional cohorts explored suggest that the gastrointestinal microbiome may exert immunomodulatory effects in allo-HCT patients at least in part due to control of systemic concentrations of microbe-derived SCFAs.

Introduction:Several new therapeutic agents have been approved in recent years for the treatment of relapsed/refractory (R/R) Large B cell lymphoma (LBCL) (diffuse large B cell lymphoma [DLBCL] and high-grade B cell lymphomas [HGBCL]), such as new monoclonal antibodies (MA), bispecific antibodies (BA) and CAR-T cell therapy. The objective of our study was to evaluate the epidemiology and the use of these new therapies (NT) in Spain and to analyze the impact on survival.

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Background: Oral ruxolitinib is FDA-approved for the treatment of acute and chronic graft-versus-host disease (cGvHD), and ruxolitinib cream has been approved for the treatment of atopic dermatitis and vitiligo. Topical corticosteroids are the mainstay of skin-directed therapy for cutaneous cGvHD but are associated with significant side effects, and may incompletely treat cutaneous cGvHD thereby prompting the use of systemic therapies.

Background :Double-unit cord blood transplantation (dCBT) with intermediate intensity conditioning (Cy50/ Flu150/ Thio10/ TBI400cGy) and cyclosporine-A (CSA)/ mycophenolate mofetil (MMF) graft-versus-host disease (GVHD) prophylaxis has been associated with high progression-free survival (PFS) in adult patients (pts) with hematologic malignancies ( Barker JN et al, Blood Advances 2020). Now, our Center has investigated multiple refinements to further mitigate transplant-related mortality (TRM). Herein, we have analyzed transplant outcomes in these adult dCBT pts to establish an optimized dCBT platform.

Background: Steroid-refractory (SR) gastrointestinal acute GVHD (GI aGVHD) is a serious complication after allogeneic hematopoietic transplantation (allo-HCT), and subsequent lines of treatment following steroid failure are often ineffective. The JAK 1/2 inhibitor ruxolitinib is the only FDA-approved treatment for SR aGVHD, and patients for whom ruxolitinib is not effective or not tolerated have limited therapeutic options and high mortality. Interleukin-22 (IL-22) is a tissue-protective IL-10-family cytokine that has been shown to support intestinal mucosa after damage, directly signaling to the intestinal epithelium and promoting its survival, regeneration, and production of innate antimicrobial molecules. F-652, a recombinant human (rh)IL-22 fusion protein composed of an IL-22 dimer and IgG2 Fc fragment, has recently been studied in a phase 2 trial for patients with newly diagnosed lower GI aGVHD, demonstrating a promising day 28 treatment response rate and improved gut microbial health. Given this, we examined F-652 administration in 3 patients with severe SR GI aGVHD.

Background and Significance:Allogeneic hematopoietic cell transplantation (alloHCT) is a curative immunotherapy for patients with hematologic disorders. However, graft-versus-host-disease (GVHD) is a major limitation to the success of alloHCT, with chronic GVHD (cGVHD) as the leading cause of morbidity and mortality. The pleomorphic nature of cGVHD makes the diagnosis and patient management challenging for clinicians; thus, patient-reported symptoms often guide in diagnosing and determining the severity of cGVHD. Our current understanding of cGVHD is largely based on data from registries, single-institution prospective studies, and the cGVHD Consortium with representation from tertiary care academic centers. Prospective studies including patient-reported outcomes and a focus on a more representative and generalizable sample of patients with cGVHD are needed to better understand cGVHD symptoms, disease burden, and practice patterns for management.This trial in progress focuses on broad patient-centered assessment of post-alloHCT medical and psychosocial complications and patient-reported caregiver involvement in a diverse and contemporary patient population. This study uses multiple organ- or system-directed patient-reported outcome measures (PROMs) to help identify cGVHD symptoms, severity, and impact on patient quality of life including financial impact. The primary objective of THRIVE is to assess the clinical course and burden of cGVHD, including diagnosis and severity recorded in electronic case report forms (eCRFs) and PROMs. Secondary objectives include measuring healthcare resource utilization and patient economic and employment impact associated with cGVHD management, as well as patient-reported organ-specific symptoms.

Background:In patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT), low gastrointestinal (GI) microbial diversity is associated with risk of bloodstream infections (BSIs), acute graft-versus-host disease (aGvHD), and death. SER-155 is an investigational cultivated microbiome therapeutic rationally designed to improve clinical outcomes in allo-HCT patients by preventing pathogen domination, promoting epithelial barrier integrity, and reducing colonic inflammation. SER-155-001 is a 2-part, Phase 1b study evaluating the safety, tolerability, pharmacokinetics, and efficacy of SER-155 in adults undergoing allo-HCT. Here, we present preliminary safety and tolerability data from the open-label Cohort 1 through Day 100 post HCT.

Background :Double-unit cord blood transplantation (dCBT) is standard therapy for patients with acute myelogenous leukemia (AML) who do not have suitable adult donors. We & others have reported low relapse rates & high progression free survival (PFS) in dCBT recipients suggesting robust CB-derived graft-versus-leukemia effects. However, the efficacy of dCBT in high-risk AML as determined by ELN genetic risk & pre-transplant minimal residual disease (MRD) status has not been performed to date.

Introduction

Background

While cord blood transplantation (CBT) is an effective therapy for hematologic malignancies, acute graft-versus-host disease (aGVHD) is a leading cause of transplant-related mortality (TRM). We investigated if biomarkers could predict aGVHD and TRM after day 28 in CBT recipients. Day 28 samples from 113 CBT patients were analyzed. Suppressor of tumorigenicity 2 (ST2) was the only biomarker associated with grades II-IV and III-IV aGVHD and TRM. Day 180 grade III-IV aGVHD in patients with high ST2 levels was 30% (95% confidence interval [CI], 18-43) vs 13% (95% CI, 5-23) in patients with low levels (P= .024). The adverse effect of elevated ST2 was independent of HLA match. Moreover, high day 28 ST2 levels were associated with increased TRM with day 180 estimates of 23% (95% CI, 13-35) vs 5% (95% CI, 1-13) if levels were low (P= .001). GVHD was the most common cause of death in high ST2 patients. High concentrations of tumor necrosis factor receptor-1, interleukin-8, and regenerating islet-derived protein 3-α were also associated with TRM. Our results are consistent with those of adult donor allografts and warrant further prospective evaluation to facilitate future therapeutic intervention to ameliorate severe aGVHD and further improve survival after CBT.

While cord blood transplantation (CBT) is an effective therapy for hematologic malignancies, acute graft-versus-host disease (aGVHD) is a leading cause of transplant-related mortality (TRM). We investigated if biomarkers could predict aGVHD and TRM after day 28 in CBT recipients. Day 28 samples from 113 CBT patients were analyzed. Suppressor of tumorigenicity 2 (ST2) was the only biomarker associated with grades II-IV and III-IV aGVHD and TRM. Day 180 grade III-IV aGVHD in patients with high ST2 levels was 30% (95% confidence interval [CI], 18-43) vs 13% (95% CI, 5-23) in patients with low levels (P = .024). The adverse effect of elevated ST2 was independent of HLA match. Moreover, high day 28 ST2 levels were associated with increased TRM with day 180 estimates of 23% (95% CI, 13-35) vs 5% (95% CI, 1-13) if levels were low (P = .001). GVHD was the most common cause of death in high ST2 patients. High concentrations of tumor necrosis factor receptor-1, interleukin-8, and regenerating islet-derived protein 3-α were also associated with TRM. Our results are consistent with those of adult donor allografts and warrant further prospective evaluation to facilitate future therapeutic intervention to ameliorate severe aGVHD and further improve survival after CBT.

We investigated the unit characteristics associated with engraftment after double-unit cord blood (CB) transplantation (dCBT) and whether these could be reliably identified during unit selection. Cumulative incidence of neutrophil engraftment in 129 myeloablative dCBT recipients was 95% (95% confidence interval: 90-98%). When precryopreservation characteristics were analyzed, the dominant unit CD34+cell dose was the only characteristic independently associated with engraftment (hazard ratio, 1.43; P= .002). When postthaw characteristics were also included, only dominant unit infused viable CD34+cell dose independently predicted engraftment (hazard ratio, 1.95; P< .001). We then examined the determinants of infused viable CD34+cell dose (precryopreservation count, postthaw recovery, and postthaw viability) in 402 units thawed at our center. This revealed close correlation between precryopreservation and postthaw CD34+cell counts (r2= 0.73). Median CD34+cell recovery was 101%, although it ranged from 12% to 1480%. Notably, units from non–Netcord Foundation for the Accreditation of Cellular Therapy (Netcord-FACT)–accredited banks were more likely to have low recovery (P< .001). Furthermore, although median postthaw CD34+cell viability was 92%, 33 (8%) units had <75% viable CD34+cells. Units from non–Netcord-FACT–accredited banks and units with cryovolumes other than 24.5 to 26.0 mL were more likely to have poor postthaw viability. Precryopreservation CD34+cell dose and banking practices should be incorporated into CB unit selection.

We investigated the unit characteristics associated with engraftment after double-unit cord blood (CB) transplantation (dCBT) and whether these could be reliably identified during unit selection. Cumulative incidence of neutrophil engraftment in 129 myeloablative dCBT recipients was 95% (95% confidence interval: 90-98%). When precryopreservation characteristics were analyzed, the dominant unit CD34+ cell dose was the only characteristic independently associated with engraftment (hazard ratio, 1.43; P = .002). When postthaw characteristics were also included, only dominant unit infused viable CD34+ cell dose independently predicted engraftment (hazard ratio, 1.95; P < .001). We then examined the determinants of infused viable CD34+ cell dose (precryopreservation count, postthaw recovery, and postthaw viability) in 402 units thawed at our center. This revealed close correlation between precryopreservation and postthaw CD34+ cell counts (r2 = 0.73). Median CD34+ cell recovery was 101%, although it ranged from 12% to 1480%. Notably, units from non–Netcord Foundation for the Accreditation of Cellular Therapy (Netcord-FACT)–accredited banks were more likely to have low recovery (P < .001). Furthermore, although median postthaw CD34+ cell viability was 92%, 33 (8%) units had <75% viable CD34+ cells. Units from non–Netcord-FACT–accredited banks and units with cryovolumes other than 24.5 to 26.0 mL were more likely to have poor postthaw viability. Precryopreservation CD34+ cell dose and banking practices should be incorporated into CB unit selection.

Highly diverse bacterial populations inhabit the gastrointestinal tract and modulate host inflammation and promote immune tolerance. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. We examined the impact of intestinal diversity on subsequent mortality outcomes following transplantation. Fecal specimens were collected from 80 recipients of allo-HSCT at the time of stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and microbial diversity was estimated using the inverse Simpson index. Subjects were classified into high, intermediate, and low diversity groups and assessed for differences in outcomes. Mortality outcomes were significantly worse in patients with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and 67% for low, intermediate, and high diversity groups, respectively (P = .019, log-rank test). Low diversity showed a strong effect on mortality after multivariate adjustment for other clinical predictors (transplant related mortality: adjusted hazard ratio, 5.25; P = .014). In conclusion, the diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal microbiota may be an important factor in the success or failure in allo-HSCT.

Highly diverse bacterial populations inhabit the gastrointestinal tract and modulate host inflammation and promote immune tolerance. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. We examined the impact of intestinal diversity on subsequent mortality outcomes following transplantation. Fecal specimens were collected from 80 recipients of allo-HSCT at the time of stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and microbial diversity was estimated using the inverse Simpson index. Subjects were classified into high, intermediate, and low diversity groups and assessed for differences in outcomes. Mortality outcomes were significantly worse in patients with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and 67% for low, intermediate, and high diversity groups, respectively (P= .019, log-rank test). Low diversity showed a strong effect on mortality after multivariate adjustment for other clinical predictors (transplant related mortality: adjusted hazard ratio, 5.25; P= .014). In conclusion, the diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal microbiota may be an important factor in the success or failure in allo-HSCT.

Infant acute lymphoblastic leukemia harboring the fusion mixed-lineage leukemia (MLL)-AF4 is associated with a dismal prognosis and very brief latency. Our limited understanding of transformation by MLL-AF4 is reflected in murine models, which do not accurately recapitulate the human disease. Human models for MLL-AF4 disease do not exist. Hematopoietic stem or progenitor cells (HSPCs) represent probable targets for transformation. Here, we explored in vitro and in vivo the impact of the enforced expression of MLL-AF4 in human cord blood-derived CD34+ HSPCs. Intrabone marrow transplantation into NOD/SCID-IL2Rγ−/− mice revealed an enhanced multilineage hematopoietic engraftment, efficiency, and homing to other hematopoietic sites on enforced expression of MLL-AF4. Lentiviral transduction of MLL-AF4 into CD34+ HSPCs increased the in vitro clonogenic potential of CD34+ progenitors and promoted their proliferation. Consequently, cell cycle and apoptosis analyses suggest that MLL-AF4 conveys a selective proliferation coupled to a survival advantage, which correlates with changes in the expression of genes involved in apoptosis, sensing DNA damage and DNA repair. However, MLL-AF4 expression was insufficient to initiate leukemogenesis on its own, indicating that either additional hits (or reciprocal AF4-MLL product) may be required to initiate ALL or that cord blood-derived CD34+ HSPCs are not the appropriate cellular target for MLL-AF4-mediated ALL.

Infant acute lymphoblastic leukemia harboring the fusion mixed-lineage leukemia (MLL)-AF4 is associated with a dismal prognosis and very brief latency. Our limited understanding of transformation by MLL-AF4 is reflected in murine models, which do not accurately recapitulate the human disease. Human models for MLL-AF4 disease do not exist. Hematopoietic stem or progenitor cells (HSPCs) represent probable targets for transformation. Here, we explored in vitro and in vivo the impact of the enforced expression of MLL-AF4 in human cord blood-derived CD34+HSPCs. Intrabone marrow transplantation into NOD/SCID-IL2Rγ−/−mice revealed an enhanced multilineage hematopoietic engraftment, efficiency, and homing to other hematopoietic sites on enforced expression of MLL-AF4. Lentiviral transduction of MLL-AF4 into CD34+HSPCs increased the in vitro clonogenic potential of CD34+progenitors and promoted their proliferation. Consequently, cell cycle and apoptosis analyses suggest that MLL-AF4 conveys a selective proliferation coupled to a survival advantage, which correlates with changes in the expression of genes involved in apoptosis, sensing DNA damage and DNA repair. However, MLL-AF4 expression was insufficient to initiate leukemogenesis on its own, indicating that either additional hits (or reciprocal AF4-MLL product) may be required to initiate ALL or that cord blood-derived CD34+HSPCs are not the appropriate cellular target for MLL-AF4-mediated ALL.

No relevant conflicts of interest to declare.

Background:Venetoclax (ven) combined with azacitidine (aza/ven), decitabine (dec/ven), and low-dose cytarabine (LDAC/ven) is approved as frontline therapy for older or otherwise unfit AML patients (pts) and also frequently used for pts with relapsed/refractory (RR)-AML. However, clinical outcomes of AML pts who receive an allogeneic stem cell transplant (alloSCT) after ven combination (ven combo) therapy are unclear.

Background.GVHD is a frequent complication within the 1styear after allogeneic stem cell transplantation (allo-HCT). Recipients of reduced intensity (RI) and non-myeloablative (NMA) conditioning combined with calcineurin inhibitor (CNI)-based GVHD prophylaxis, frequently develop GVHD in the context of immunosuppression taper. Ixazomib is an oral proteasome inhibitor (PI) that has demonstrated immunomodulatory properties, inhibition of pro-inflammatory cytokines, anti-tumor activity, and has a wide safety profile. We hypothesized that secondary GVHD prophylaxis using ixazomib, will facilitate CNI taper without increase in GVHD frequency and severity, maintaining graft-versus-tumor (GVT) effect, and a safety profile.

Bachy: Beigene: Membership on an entity's Board of Directors or advisory committees; Roche, Gilead: Consultancy; Amgen: Research Funding; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria. Camus:PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); JANSSEN: Honoraria; AMGEN: Honoraria. Thieblemont:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bristol-Myers Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Hospira: Research Funding; Incyte: Honoraria; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Bayer: Honoraria. Casasnovas:Amgen: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses, Research Funding; Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy, Honoraria. Ysebaert:Roche: Consultancy; AbbVie: Consultancy; Janssen: Consultancy. Guidez:BMS: Honoraria; CELGENE: Honoraria; TAKEDA: Honoraria; JANSEN: Honoraria; AMGEN: Honoraria; Service Hématologie et Thérapie cellulaire CHU POITIERS: Current Employment. Kim:JJ: Research Funding; Celltrion: Research Funding; Kyowa Kirn: Research Funding; Donga: Research Funding; Mundipharma: Research Funding; Pfizer: Research Funding; F. Hoffmann-La Roche: Research Funding. Lim:National Cancer Centre Singapore: Current Employment. André:Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Johnson & Johnson: Research Funding; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Novartis: Consultancy, Research Funding; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Karyopharm: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Takeda: Consultancy; Celgene: Other, Research Funding; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy; Seattle Genetics: Consultancy. Martin Garcia-Sancho:Celgene, Eusa Pharma, Gilead, iQuone, Kyowa Kirin, Roche, Morphosys: Consultancy; Roche, Celgene, Janssen, Servier, Gilead: Honoraria. Penarrubia Ponce:Novartis: Consultancy; Takeda: Consultancy, Honoraria; Janssen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Servier: Honoraria; HOSPITAL CLINICO UNIVERSITARIO DE VALLADOLID: Current Employment; Abbvie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy; Celgene: Consultancy, Honoraria; Incyte: Consultancy. Staber:msd: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Celgene/ BMS: Consultancy, Honoraria. Trotman:BeiGene: Research Funding; Takeda: Research Funding; F. Hoffmann-La Roche: Research Funding; Celgene: Research Funding; PCYC: Research Funding. Hüttmann:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Other: Travel expenses; University Hospital Essen, University of Duisburg-Essen, Essen, Germany: Current Employment; Seattle Genetics: Research Funding; Lead Discovery Center GmbH: Consultancy; Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead: Honoraria. Gaulard:Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); INNATE PHARMA: Research Funding; TAKEDA: Consultancy, Honoraria, Research Funding; CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris: Current Employment. Delfau-Larue:MUNDIPHARMA: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); ROCHE: Honoraria; GILEAD: Honoraria; AMGEN: Honoraria. De Leval:Lausanne University Hospital & Lausanne University Institute of Pathology: Current Employment; Lunaphore Technologies SA: Consultancy, Honoraria; Abbvie: Honoraria; Roche Diagnostics: Honoraria. Meignan:ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Li:BMS: Current Employment, Current equity holder in publicly-traded company. Morschhauser:F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Servier: Consultancy. Delarue:Celgene International, a BMS company: Current Employment; BMS: Current equity holder in private company.Romidepsin is not approved for patients with previously untreated PTCL.

Background:Patients with COVID-19 have an increased risk of thromboembolic disease, this has been partly attributed to an excessive inflammatory response that is associated with hypercoagulability; patients develop thrombotic complications with rates of 6.4% in non-critically ill and 15 to 31 % in critically ill patients. With this data some clinicians have incorporated thromboprophylaxis with higher dose heparin into the management of this patients, to date there´s no information of the effect of this intervention.

Background: Peripheral T-cell lymphoma (PTCL) is an aggressive form of non-Hodgkin lymphoma (NHL) that is typically associated with a poor prognosis. Romidepsin is a histone deacetylase inhibitor approved by the US Food and Drug Administration for patients with PTCL who have received at least 1 prior therapy (J Clin Oncol. 2012;30:631). Presented here is the final analysis of a phase III randomized study comparing romidepsin + cyclophosphamide, doxorubicin, vincristine, and prednisone (Ro-CHOP) with CHOP in patients with previously untreated PTCL.

Dahi: Kite: Consultancy. Giralt:TAKEDA: Research Funding; JAZZ: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Research Funding; MILTENYI: Consultancy, Research Funding; KITE: Consultancy; NOVARTIS: Consultancy, Honoraria, Research Funding; OMEROS: Consultancy, Honoraria; ACTINUUM: Consultancy, Research Funding. Sauter:Bristol-Myers Squibb: Research Funding; GSK: Consultancy; Gamida Cell: Consultancy; Celgene: Consultancy, Research Funding; Kite - a Gilead Company: Consultancy; Precision Biosciences: Consultancy, Research Funding; Genmab: Consultancy; Novartis: Consultancy; Spectrum Pharamaceuticals: Consultancy; Sanofi-Genzyme: Consultancy, Research Funding; Juno Therapeutics: Consultancy, Research Funding. Perales:Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Medigene: Membership on an entity's Board of Directors or advisory committees, Other; NexImmune: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Other; Cidara Therapeutics: Other; Takeda: 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; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; Miltenyi Biotec: Research Funding; Kite/Gilead: Honoraria, Research Funding; Incyte Corporation: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; MolMed: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ponce:Ceramedix: Membership on an entity's Board of Directors or advisory committees; Generon: Membership on an entity's Board of Directors or advisory committees; Kadmon: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding.

Although several CXC chemokines have been shown to induce angiogenesis and play roles in tumor growth, to date, no member of the CC chemokine family has been reported to play a direct role in angiogenesis. Here we report that the CC chemokine, monocyte chemotactic protein 1 (MCP-1), induced chemotaxis of human endothelial cells at nanomolar concentrations. This chemotactic response was inhibited by a monoclonal antibody to MCP-1. MCP-1 also induced the formation of blood vessels in vivo as assessed by the chick chorioallantoic membrane and the matrigel plug assays. As expected, the angiogenic response induced by MCP-1 was accompanied by an inflammatory response. With the use of a rat aortic sprouting assay in the absence of leukocytic infiltrates, we ruled out the possibility that the angiogenic effect of MCP-1 depended on leukocyte products. Moreover, the direct effect of MCP-1 on angiogenesis was consistent with the expression of CCR2, the receptor for MCP-1, on endothelial cells. Assessment of supernatant from a human breast carcinoma cell line demonstrated the production of MCP-1. Treatment of immunodeficient mice bearing human breast carcinoma cells with a neutralizing antibody to MCP-1 resulted in significant increases in survival and inhibition of the growth of lung micrometastases. Taken together, our data indicate that MCP-1 can act as a direct mediator of angiogenesis. As a chemokine that is abundantly produced by some tumors, it can also directly contribute to tumor progression. Therefore, therapy employing antagonists of MCP-1 in combination with other inhibitors of angiogenesis may achieve more comprehensive inhibition of tumor growth.

Oral ruxolitinib has been successfully used for the treatment of acute and chronic graft-versus-host disease (cGvHD) and topical ruxolitinib has demonstrated efficacy in clinical trials for vitiligo, atopic dermatitis, and psoriasis.

Background:Understanding disparities in allograft access is a prerequisite to interpret outcomes. Moreover, while alternative donors extend access, the extent to which there are racial disparities in availability of optimal donors is not established.

Microbial diversity is associated with improved outcome in patients receiving allogeneic hematopoietic cell transplantation (allo-HCT), however, the mechanism underlying this observation is unclear. Unconventional T cells recognize specific metabolites of bacterial biosynthesis and their role in the post-HCT immunity has not yet been fully clarified. Here we have performed an observational study (n = 174 patients) using 16S rRNA sequencing of early post-HCT patient stool samples (day 7-21 after HCT) paired with multiparameter flow cytometry (performed at day 30 and day 100 after HCT) to explore the relationship between the intestinal microbiome early after HCT and the unconventional T cell populations in circulation. Our data extend findings of other groups suggesting that mucosal-associated invariant T (MAIT) cells are dependent on a diverse microbiome and are also associated with favorable allo-HCT outcome. In addition, we report for the first time that the Vδ2 subset of γδ T cells is positively correlated with MAIT cells as well as independent predictors of favorable transplant outcome.

The current standard of care to prevent graft versushost disease (GVHD) after HLA mismatched unrelated donor (URD) allogeneic hematopoietic cell transplantation (HCT) is tacrolimus, methotrexate (MTX) and anti-thymocyte globulin (ATG). Recently, an approach based on administration of post-transplant cyclophosphamide (PT-Cy) demonstrated promise in a prospective trial for HLA mismatched URD HCT. Here, we compared tacrolimus/MTX/ATG (ATG group) treatment, with that of PT-Cy, mycophenolate mofetil, and tacrolimus or sirolimus (PT-Cy group) after HLA mismatched URD HCT, at two academic centers with similar peri-transplant supportive care practices.

Gomes: Xbiome: Current Employment. Zappasodi: iTeos Therapeutics: Consultancy; Astra Zeneca: Research Funding; Bristol Myers Squibb: Research Funding. Ponce: CareDx: Consultancy, Honoraria; Takeda Pharmaceuticals: Research Funding; Generon Pharmaceuticals: Consultancy; Kadmon pharmaceuticals: Consultancy, Honoraria; Ceramedix: Consultancy, Honoraria; Seres Therapeutics: Consultancy, Research Funding. Giralt: JENSENN: Membership on an entity's Board of Directors or advisory committees; SANOFI: Membership on an entity's Board of Directors or advisory committees; AMGEN: Membership on an entity's Board of Directors or advisory committees; PFIZER: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; JAZZ: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees; Actinnum: Membership on an entity's Board of Directors or advisory committees. Peled: Seres: Other: Intellectual Property Rights, Research Funding and Travelfees; DaVolterra: Consultancy; Other: Other: Jonathan U. Peled had filed intellectual property applications related to the microbiome (referencenumbers #62/843,849, #62/977,908, and #15/756,845); MaaT Pharma: Consultancy. Perales: Cidara: Honoraria; Celgene: Honoraria; Merck: Honoraria; MorphoSys: Honoraria; Nektar Therapeutics: Honoraria, Other; Equilium: Honoraria; Karyopharm: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Kite/Gilead: Honoraria, Other; Medigene: Honoraria; Novartis: Honoraria, Other; Sellas Life Sciences: Honoraria; Servier: Honoraria; Miltenyi Biotec: Honoraria, Other; Omeros: Honoraria; Incyte: Honoraria, Other; NexImmune: Honoraria. van den Brink: Rheos: Honoraria; Merck & Co, Inc: Honoraria; Therakos: Honoraria; Amgen: Honoraria; GlaskoSmithKline: Other: has consulted, received honorarium from or participated in advisory boards; Synthekine (Spouse): Other: has consulted, received honorarium from or participated in advisory boards; Kite Pharmaceuticals: Other; Notch Therapeutics: Honoraria; Nektar Therapeutics: Honoraria; Priothera: Research Funding; Wolters Kluwer: Patents & Royalties; Juno Therapeutics: Other; Frazier Healthcare Partners: Honoraria; DKMS (nonprofit): Other; Seres: Other: Honorarium, Intellectual Property Rights, Research Fundingand Stock Options; Forty-Seven, Inc.: Honoraria; Lygenesis: Other: has consulted, received honorarium from or participated in advisory boards ; WindMILTherapeutics: Honoraria; Pharmacyclics: Other; Jazz Pharmaceuticals: Honoraria; Novartis (Spouse): Other: has consulted, received honorarium from or participated in advisory boards; Da Volterra: Other: has consulted, received honorarium from or participated in advisory boards; Ceramedix: Other: has consulted, received honorarium from or participated in advisory boards ; MagentaTherapeutics: Honoraria; Pluto Therapeutics: Current holder of stock options in a privately-held company, Other: has consulted, received honorarium from or participated in advisory boards .

Politikos: Merck: Research Funding; ExcellThera, Inc: Other: Member of DSMB - Uncompensated. Giralt: AMGEN: Membership on an entity's Board of Directors or advisory committees; PFIZER: Membership on an entity's Board of Directors or advisory committees; JENSENN: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; SANOFI: Membership on an entity's Board of Directors or advisory committees; JAZZ: Membership on an entity's Board of Directors or advisory committees; Actinnum: Membership on an entity's Board of Directors or advisory committees. Gyurkocza: Actinium Pharmaceutical Inc.: Research Funding. Perales: Omeros: Honoraria; Novartis: Honoraria, Other; NexImmune: Honoraria; Nektar Therapeutics: Honoraria, Other; MorphoSys: Honoraria; Miltenyi Biotec: Honoraria, Other; Merck: Honoraria; Medigene: Honoraria; Kite/Gilead: Honoraria, Other; Karyopharm: Honoraria; Incyte: Honoraria, Other; Equilium: Honoraria; Cidara: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Sellas Life Sciences: Honoraria; Servier: Honoraria; Takeda: Honoraria. Ponce: Ceramedix: Consultancy, Honoraria; Takeda Pharmaceuticals: Research Funding; CareDx: Consultancy, Honoraria; Kadmon pharmaceuticals: Consultancy, Honoraria; Seres Therapeutics: Consultancy, Research Funding; Generon Pharmaceuticals: Consultancy.

Jimenez: AbbVie: Research Funding; Takeda: Research Funding. Perales: MorphoSys: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria; Merck: Honoraria; Equilium: Honoraria; Miltenyi Biotec: Honoraria, Other; Medigene: Honoraria; Kite/Gilead: Honoraria, Other; Incyte: Honoraria, Other; Cidara: Honoraria; Takeda: Honoraria; Nektar Therapeutics: Honoraria, Other; Servier: Honoraria; Sellas Life Sciences: Honoraria; Omeros: Honoraria; NexImmune: Honoraria; Novartis: Honoraria, Other. Sauter: Precision Biosciences: Consultancy; Genmab: Consultancy; Celgene: Consultancy, Research Funding; Kite/Gilead: Consultancy; Bristol-Myers Squibb: Research Funding; GSK: Consultancy; Gamida Cell: Consultancy; Novartis: Consultancy; Spectrum Pharmaceuticals: Consultancy; Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding. Beitinjaneh: Kite/Gilead: Other: Ad Board Event Attendee. Ponce: CareDx: Consultancy, Honoraria; Ceramedix: Consultancy, Honoraria; Seres Therapeutics: Consultancy, Research Funding; Kadmon pharmaceuticals: Consultancy, Honoraria; Takeda Pharmaceuticals: Research Funding; Generon Pharmaceuticals: Consultancy.Off-label use of Cyclophosphamide for Graft-versus-Host Disease prevention will be discussed in the abstract.