scholarly journals Allogeneic Stem Cell Transplantation in a Large Urban Cohort of North-American Adult T-Cell Leukemia/Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Astha Thakkar ◽  
Diego Adrianzen Herrera ◽  
Shafia Rahman ◽  
Zhu Cui ◽  
Angelica D'Aiello ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Private Company ◽  
Advisory Committees ◽  
Post Transplant ◽  
Adult T Cell Leukemia

Introduction: Adult T-cell leukemia lymphoma (ATLL) is a rare hematologic malignancy caused by human T-cell lymphotropic virus (HTLV-1) with dismal cure rates and poor response to conventional chemotherapy. Allogeneic Hematopoietic Stem Cell Transplantation (AlloSCT) is the only therapeutic option which may offer the chance of long-term remission and cures in a subset of patients. We sought to investigate the outcomes of transplantation in one of the largest cohorts in North America. Methods: A retrospective chart review study was conducted using the North-American ATLL and the Hematopoietic Precursor Cell transplantation databases at Montefiore Medical Center from 2011 to 2020. Variables collected include age, sex, ethnicity, ATLL subtype, molecular profile, previous treatments, conditioning regimens, type of transplant, immunosuppressive regimen, progression free survival (PFS) post-transplant and overall survival (OS) post-transplant. Results: Fourteen patients with ATLL who received an AlloSCT from 2011-2020 were identified. Fifty-seven percent (8/14) of patients were male. Seventy-one percent (10/14) of patients were African American and twenty-nine percent (4/14) were Hispanic. Median age was 51 years. Sixty-four percent (9/14) of patients had Stage IV disease at the time of diagnosis. Forty-three percent (6/14) patients had acute and fifty-seven percent (8/14) had lymphomatous ATLL. Almost all patients (92%) were treated initially with EPOCH combination chemotherapy. Twenty-eight percent (4/14) of patients received interferon/zidovudine as bridge-to-transplant. Fifty-seven percent (8/14) of patients achieved complete remission (CR) prior to AlloSCT, 7% (1/14) were in partial remission, and 28% (4/14) were relapsed or refractory. Forty-three percent (6/14) of patients received SCT from a matched-related donor (MRD), 36% (5/14) from a haplo-identical donor and 21% (3/14) from a matched-unrelated donor (MUD). Ninety-three percent (13/14) of patients received a reduced-intensity conditioning (RIC) regimen pre-transplantation. Seven percent (1/14) received a myeloablative conditioning (MAC) regimen. RIC regimens consisted of fludarabine with melphalan +/- anti-thymocyte globulin (ATG) or fludarabine with cyclophosphamide with total-body irradiation in doses less than 500 cGy. Patients receiving haplo-identical SCT also received post-transplant cyclophosphamide (PTCy) for prevention of graft vs host disease (GVHD). The MAC regimen used included busulfan with cyclophosphamide at myeloablative doses. Twenty-eight percent (4/14) of patients relapsed post-alloSCT with a median relapse-free survival of 6 months (range 4-18 months). The median OS of the whole cohort was 27 months (8-82 months). Graft-versus-host disease (GVHD) developed in 28% (4/14) percent of patients. The most common manifestation was skin GVHD. Fifty-percent (7/14) of the patients are surviving to-date. Transplant-related mortality (TRM) at day 100 was 21% (3/14) of patients. Causes of death were complex and included several diagnoses in certain patients. The most frequent diagnoses associated with death were infection (28%), graft failure (14%), GVHD (14%), veno-occlusive disease of the liver (VOD) (7%), disease progression (14%) and unknown due to patient lost to follow-up (14%). The main infectious events included fungal (2), bacterial (1), and COVID-19 (1) infection. Forty-three percent (6/14) of patients remain in complete remission to date. Conclusions: Allogeneic Stem Cell Transplantation offers long-term survival with a TRM of 21% in a disease with an inherently dismal prognosis. AlloSCT using several graft sources, is thus, a safe and well tolerated treatment modality and offers long term remissions. Disclosures Steidl: Pieris Pharmaceuticals: Consultancy; Aileron Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer Healthcare: Research Funding; Stelexis Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Verma:BMS: Consultancy, Research Funding; acceleron: Consultancy, Honoraria; Janssen: Research Funding; Medpacto: Research Funding; stelexis: Current equity holder in private company. Janakiram:ADC Therapeutics, FATE therapeutics, TAKEDA pharmaceuticals: Research Funding.

scholarly journals Feasibility and Outcomes of T-Cell Depleted Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory AML and High Risk MDS

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3324-3324
Author(s):  
Satyajit Kosuri ◽  
Sang Mee Lee ◽  
Hongtao Liu ◽  
Mylove Mortel ◽  
Lucy A Godley ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees

Background: Survival in patients (pts) with relapsed/refractory (R/R) acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) is dismal. Treatment options are limited; however, a proportion of these individuals can be rescued by allogeneic stem cell transplantation (allo-SCT). Historically, allo-SCT, especially for R/R myeloid diseases, has used myeloablative regimens and no T-cell depletion (TCD) to maximize graft-versus-leukemia effect, often restricting this approach to younger and fit pts with matched donors. The aim of this study was to investigate outcomes of in vivo T-cell depleted stem cell transplantation (TCD-SCT) in a high-risk AML and MDS population. Methods: We performed a retrospective analysis of 141 patients with R/R AML (n=108)/high risk MDS (RAEB or CMML, n=33) who received TCD-SCT at our center from 2002-2015. Median age was 55 years (18-71) with 37 (26%) pts older than 60. Patients underwent in vivo TCD with alemtuzumab or ATG and 117 (88%) received reduced-intensity conditioning (RIC). Alemtuzumab was generally given as 100 mg total divided over 5 days whereas rabbit ATG dosing included days -1, - 3, -5 (+/- on day -7). Alemtuzumab usually partnered with matched related (n=65; 46%) or unrelated (n=53; 38%) peripheral blood stem cell (PBSC) grafts whereas ATG mostly was a component of umbilical cord grafts combined with a CD34 selected haploidentical donor (haplo-cord) (n=23; 16%). Prognostic factors such as age, HCT-CI, CIBMTR score (Duval 2010), revised disease risk index (R-DRI), donor type and pre-transplant disease status were analyzed. Multivariate cox regression models were considered from forward selection for factors with a p value <0.1 in univariate analysis. Results: Table 1 summarizes baseline characteristics. Among the 141 R/R AML or high risk MDS pts, AML predominated (77%). Sixty six (47%) pts had primary induction failure (PIF), 42 (37%) had relapse and 33 (23%) had high risk MDS. Eighty three pts (59%) had peripheral blasts at time of TCD-SCT. Cumulative incidence (CI) of relapse for all pts was 53% and non-relapse mortality was 28% at 2 yrs. Two and 5 yr PFS rates for the group were 19% and 11%, respectively. Two and 5 yr OS rates for the group were 30% and 18%, respectively. Figure 1 shows OS by disease type. Day 100 mortality was 18%. Twenty one percent developed Grade 2-4 acute GVHD (aGVHD) (6% Grade 3-4), and only 5% developed chronic GVHD (cGVHD) requiring therapy. Figure 2 shows CI of cGVHD amongst disease types. Differences in 2yr survival outcomes were not significant among prognostic factors. Specifically, age 60+ vs younger was not prognostic (PFS 24% vs 17% p=0.4, OS 29% vs 29% p=0.7). Likewise, haplo-cord did not differ relative to matched donors in outcomes (PFS 18% vs 26% p=0.2, OS 35% vs 29% p=0.5). Conclusions: Although novel therapeutic approaches are emerging for R/R AML and high risk MDS, allo-SCT remains an established option for long-term disease control. In our analysis, outcomes after in vivo TCD-SCT in R/R AML and high-risk MDS pts treated with RIC mirror published historical results (Duval 2010, Schlenk 2010) but with low rates of cGVHD. The lack of significant difference in survival outcomes amongst age groups and donor sources suggests RIC with in vivo TCD can also be utilized as a platform in older individuals and those with alternative donors. With high relapse rates in this population, better pre-transplant disease reduction, minimal residual disease monitoring and post-transplant maintenance will be critical to increase long-term cures. Disclosures Liu: Agios: Honoraria; Arog: Other: PI of clinical trial; BMS: Research Funding; Karyopharm: Research Funding; Novartis: Other: PI of clinical trial. Larson:Novartis: Honoraria, Other: Contracts for clinical trials; Agios: Consultancy; Celgene: Consultancy. Odenike:Oncotherapy: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Astra Zeneca: Research Funding; Astex Pharmaceuticals: Research Funding; NS Pharma: Research Funding; Gilead Sciences: Research Funding; Janssen Oncology: Research Funding; Agios: Research Funding; CTI/Baxalta: Research Funding. Stock:Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; UpToDate: Honoraria; Research to Practice: Honoraria. Kline:Merck: Honoraria; Merck: Research Funding. Riedell:Bayer: Honoraria, Speakers Bureau; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding. Van Besien:Miltenyi Biotec: Research Funding. Bishop:Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Artz:Miltenyi: Research Funding.

Stem Cell Transplantation Can Provide Durable Disease Control in Blastic Plasmacytoid Dendritic Cell Neoplasia (BPDC): A Retrospective Study From the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3077-3077
Author(s):  
Sascha Dietrich ◽  
Damien Roos-Weil ◽  
Ariane Boumendil ◽  
Emanuelle Polge ◽  
Jian-Jian Luan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Nk Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Advisory Committees

Abstract Abstract 3077 Blastic plasmacytoid dendritic cell neoplasm (BPDC), formerly known as blastic NK cell lymphoma, is a rare hematopoietic malignancy preferentially involving the skin, bone marrow and lymph nodes. The overall prognosis of BPDC is dismal. Most patients show an initial response to acute leukemia-like chemotherapy, but relapses with subsequent drug resistance occur in virtually all patients resulting in a median overall survival of only 9–13 months. However, anecdotal long-term remissions have been reported in young patients who received early myeloablative allogeneic stem cell transplantation (alloSCT). We therefore performed a retrospective analysis of patients identified in the EBMT registry in order to evaluate the outcome of autologous stem cell transplantation (autoSCT) or alloSCT for BPDC. Eligible were all patients who had been registered with a diagnosis of BPDC or Blastic NK cell lymphoma and had received autologous stem cell transplantation (autoSCT) or alloSCT in 2000–2009. Centres were contacted to provide a written histopathology and immunophenotyping report and information about treatment and follow-up details. Patients who did not have a diagnostic score ≥ 2 as proposed by Garnache-Ottou et al. (BJH 2009) were excluded. RESULTS: Overall, 139 patients could be identified in the database who fulfilled the inclusion criteria (alloSCT 100, autoSCT 39). Of 74 patients for whom the requested additional information could be obtained, central review confirmed the diagnosis of BPDC in 39 patients (34 alloSCT, 5 autoSCT). The 34 patients who had undergone alloSCT had a median age of 41 years (range: 10–70 years), were transplanted from a related (n=11) or unrelated donor (n=23); received peripheral blood stem cells (n=9), bone marrow stem cells (n=19) or cord blood (n=6); and had been treated with a reduced intensity conditioning regimen (RIC, n=9) or myeloablative conditioning (MAC, n=25). Nineteen of 34 patients were transplanted in CR1. After a median follow up time of 28 months (range: 4–77+ months), 11 patients relapsed (median time to relapse: 8 months, range: 2–27 months) of whom 8 died due to disease progression. 9 patients died in the absence of relapse. No relapse occurred later than 27 months after transplant. Median disease free survival (DFS) was 15 months (range: 4–77+ months) and median overall survival (OS) was 22 months (range: 8–77+ months; Figure 1a). However, long-term remissions of up to 77 months after alloSCT could be observed. Patients allografted in CR1 tended to have a superior DFS (p=0.119) and OS (p=0.057; Figure 1b). MAC was associated with a better OS (p=0.001) which was attributable to the significantly higher non-relapse mortality (NRM) rate of patients after RIC (p=0.014), who had been significantly older (age RIC: 56 years, age MAC: 36 years, p=0.0014). The relapse rate was not different in patients after RIC and MAC, respectively. However, there was no survivor after RIC. Median age in the autoSCT group was 47 years (range: 14–62 years). Three of 5 patients were transplanted in CR1 of whom 1 patient relapsed after 8 months, 1 patient experienced treatment related mortality and 1 patient remained in CR for 28 months. The 2 remaining patients had more advanced disease at autoSCT and relapsed 4 and 8 months thereafter. CONCLUSION: AlloSCT is effective in BPDC and might provide curative potential in this otherwise incurable disease, especially when performed in CR1. However, it remains to be shown by prospective studies if the potential benefit of alloSCT in BPDC is largely due to conditioning intensity, or if there is a relevant contribution of graft-versus-leukemia activity. Disclosures: Tilly: Seattle Genetics, Inc.: 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, Research Funding, Speakers Bureau, Travel/accommodations/meeting expenses; Genentech: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; Janssen Cilag: Speakers Bureau.

scholarly journals Reconstitution of T-cell-mediated immunity in patients after allogeneic stem cell transplantation

2020 ◽  
Vol 65 (1) ◽  
pp. 24-38
Author(s):  
N. N. Popova ◽  
V. G. Savchenko
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cell Mediated Immunity ◽  
Term Survival ◽  
Post Transplant

Background. The timely reconstitution of the donor-derived immune system is a key factor in the prevention of such post-transplant complications as graft versus host disease, relapse or secondary tumours and various infections. These complications affect the long-term survival of patients after allogeneic stem cell transplantation.Aim — to describe the main stages of T Cell–mediated immune recovery in patients after allogeneic stem cell transplantation.General findings. T-cell–mediated immunity is responsible for anti-infective and anti-tumour immune response. The early post-transplant period is characterized by the thymus-independent pathway of T-cell recovery largely involving proliferation of mature donor T cells, which were transplanted to the patient together with hematopoietic stem cells. To a lesser extent, this recovery pathway is realized through the expansion of host naïve and memory T cells, which survived after conditioning. Thymus-dependent reconstitution involves generation of de novo naïve T cells and subsequent formation of a pool of memory T-cells providing the main immunological effects — graft versus tumour and graft versus host reactions. A better understanding of the T-cell immune reconstitution process is important for selecting optimized pre-transplant conditioning regimens and patient-specific immunosuppressive therapy approaches, thus reducing the risks of post-transplant complications and improving the long-term survival of patients after allogeneic stem cell transplantation.

scholarly journals Haplo-Cord Transplantation Vs Unrelated Donor Stem Cell Transplantation in Patients with AML/MDS Older Than 50

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1235-1235 ◽  
Author(s):  
Joanna Rhodes ◽  
Koen van Besien ◽  
Hongtao Liu ◽  
Usama Gergis ◽  
Stephanie B. Tsai ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Post Transplant

Abstract Haplo-cord Transplantation Vs Unrelated Donor Stem Cell Transplantation In Patients with AML/MDS older than 50 Between 2007 and 2013, 109 patients with AML/MDS who were 50 years and older and had no HLA- matched related donor underwent allogeneic hematopoietic stem cell transplant. 64 had an HLA identical unrelated donor and received fludarabine/melphalan/alemtuzumab conditioning and post transplant tacrolimus for graft vs host disease (GVHD) prophylaxis. 45 underwent haplo-cord (HC) SCT with fludarabine/melphalan/ thymoglobulin; post-transplant tacrolimus and MMF. We compared patient characteristics and transplant outcomes between both groups. (Table 1) Age distribution and ASBMT risk category were similar. There were more patient's with AML in the HC group. (P=0.01) Time to neutrophil recovery, treatment related mortality (TRM), relapse rate, progression free survival (PFS) and overall survival (OS) were nearly identical between the two groups. Time to platelet recovery was on average 5 days longer after HC (p=0.05) The incidences of acute and chronic GVHD were very low in both groups, in part due to the use of in-vivo T cell depletion. HC transplant with reduced intensity conditioning is a curative treatment for older patients with AML/MDS who lack HLA identical unrelated donors. Despite inclusion of many patients with high risk features, nearly two thirds were estimated to be alive one year after transplant and very few had chronic GVHD. Haplo-cord grafts are more readily available, a potential advantage over MUD grafts in situations where transplant is needed urgently. TableMatched Unrelated DonorHaplo Cord PN6445Age (range)62 (50-73)62 (50-74)AML/MDS45/2041/5 0.01ASBMTLow/Int /High21/6/3015/10/200.7KPS 9090Time to ANC >50010110.1Time to Plt >2018230.05PFS@ 1 Y (95% CI)46 (34-58)41 (26-56)0.6OS@ 1 Y (95% CI)57 (44-70)64 (49-79)0.8Cum Inc TRM @100 d (95% CI)9 (2-16)9 (0-18)0.2Cum Inc TRM @ 1 Y(95% CI)25 (14-36)29 (15-44)0.2Cum Inc Relapse @ 1Y (95% CI)30 (18-42)26 (12-40)0.5Cum Inc AGVHD @ 100 D (95% CI)25 (14-36)29 (13-43)0.7Cum Inc CGVHD @ 1 Y (95% CI)6 (0-12)7 (0-15)0.9 Disclosures van Besien: Miltenyi: Research Funding. Mark:Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Artz:Miltenyi: Research Funding.

scholarly journals Local and Systemic Effects of Immune Checkpoint Blockade on Relapsed Myeloid Malignancies Following Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 34-35
Author(s):  
Livius Penter ◽  
Yi Zhang ◽  
Alexandra Savell ◽  
Srinika Ranasinghe ◽  
Teddy Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Cell Infiltration ◽  
Advisory Committees ◽  
T Cell Infiltration

Relapse after allogeneic hematopoietic stem cell transplantation (HSCT) remains an unmet medical need. The ETCTN 9204 study evaluated in 71 study subjects if immune checkpoint blockade with anti-CTLA-4 (Ipilimumab (Ipi), n = 43) or anti-PD-1 (Nivolumab (Nivo), n = 28) antibodies could stimulate graft-versus-leukemia (GvL) responses in this setting. We focused mainly on patients (pts) with relapsed AML/MDS, which constituted the majority of pts (n = 38; 54%). Ipi induced both long-term complete remissions (CR; n = 3) and transient CRs (TR; n = 3), while Nivo did not generate any CRs, but 4 patients demonstrated partial remissions (PR). To define the molecular features associated with response to Ipi, we performed bulk transcriptomic analyses of formalin-fixed paraffin-embedded biopsies of sites of AML/MDS involvement (n = 35) collected before and after Ipi treatment from 13 pts. Our analysis of matched pre- and post-Ipi samples of patients with CRs identified 50 differentially expressed genes. By gene ontology analysis, these were enriched for signatures of 'lymphocyte activation' and 'antigen-receptor signaling'. Principal component analysis using these genes separated post-Ipi CR samples as a distinct cluster, transcriptionally apart from pre-Ipi CR samples and from non-responder (NR, n = 15) pre and post-Ipi samples. Of note, post-Ipi CR samples were similar to both pre- and post-Ipi TR samples as well as samples from GvHD/toxicity biopsies (n = 9). Consistent with these findings, we detected increased CD8+ T cell abundance post-Ipi in CR but not NR samples with CIBERSORTx (pre vs post, median score 0.043 vs. 0.56, p &lt; 0.01). Likewise, reconstruction of T cell receptor (TCR) CDR3 sequences using the tool TRUST showed an increase in TCR clonotypes per million reads post-Ipi in CR samples (pre vs post, median 0.33 vs. 1.65, p &lt; 0.05). In sum, response to CTLA-4 blockade is characterized by transcriptional evidence of T cell infiltration and activation within the tumor microenvironment, with similar gene programs observed in the setting of GvHD. To determine if the changes within tissue sites following Ipi are also observed in peripheral blood (PB), we analyzed the immunophenotype and TCR repertoire of T cells from serially collected PB samples from pts with AML/MDS (n = 14) or non-myeloid malignancy (n = 6). In responders and non-responders, exposure to Ipi was associated with decreased naïve, increased effector memory, and increased expression of HLA-DR on central memory T cells (p &lt; 0.05), consistent with T cell differentiation and activation. From 9 of 14 AML/MDS pts (CR = 4, NR = 5), bulk TCR sequencing before and after 1 cycle of Ipi yielded 572,017 PB TCR sequences. Only 776 clonotypes demonstrated significant change in frequency, and these TCRs were detected in greater proportion among responders (613/776 versus NR 163/776, p &lt; 0.01). Thus, Ipi alters the differentiation states of circulating T cells irrespective of response and leads to higher TCR repertoire turnover in CR patients. Of the AML patients achieving PR following Nivo, we also observed transcriptional evidence of CD8+ T cell infiltration in one patient. This signature, however, was not detected in a second such patient. In a separate instance, we had the opportunity to dissect the molecular features of a partial response in a patient with JAK2V617F+ secondary AML following Nivo through single-cell RNA and ATAC-sequencing (scRNA-seq and scATAC-seq, 10x Genomics) of PB mononuclear cells collected serially across 6 timepoints. In total, we analyzed the transcriptomes and chromatin accessibility data from of 27,777 and 28,713 individual cells, respectively. At time of response, non-exhausted CD4+ T cells expanded while both exhausted CD8+ T cells and a malignant subpopulation with increased expression of PD-L1 and features of megakaryocytic differentiation preferentially contracted. The subsequent expansion of a PD-L1- malignant population at progression suggests that decreased leukemic PD-L1 expression was associated with relapse. Altogether, these data highlight the molecular and cellular features of successful reinvigoration of GvL using CTLA-4 blockade, from increased local T cell infiltration and activation in the leukemic microenvironment to peripheral T cell turnover. In addition, the selection of therapy-resistant subclones after PD-1 blockade underscores the need for further high-resolution studies of GvL responses. Disclosures Zeiser: Novartis: Honoraria; Incyte: Honoraria; Malinckrodt: Honoraria. Ritz:Rheos Medicines: Consultancy; LifeVault Bio: Consultancy; Infinity Pharmaceuticals: Consultancy; Falcon Therapeutics: Consultancy; Avrobio: Consultancy; Kite Pharma: Research Funding; Talaris Therapeutics: Consultancy; Equillium: Research Funding; Amgen: Research Funding; TScan Therapeutics: Consultancy. Neuberg:Madrigak Pharmaceuticals: Current equity holder in publicly-traded company; Celgene: Research Funding; Pharmacyclics: Research Funding. Soiffer:alexion: Consultancy; Gilead: Consultancy; Be the Match/ National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Rheos Therapeutics: Consultancy; Juno: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Mana Therapeutics: Consultancy; Precision Bioscience: Consultancy; VOR Biopharma: Consultancy; Kiadis: Membership on an entity's Board of Directors or advisory committees; Cugene: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees. Liu:GV20 Oncotherapy: Consultancy, Membership on an entity's Board of Directors or advisory committees; 3DMed Care: Consultancy; Sanofi: Research Funding; Takeda: Research Funding. Davids:AbbVie: Consultancy; Gilead Sciences: Consultancy; Sunesis: Consultancy; BeiGene: Consultancy; AstraZeneca: Consultancy, Research Funding; Syros Pharmaceuticals: Consultancy; Research to Practice: Honoraria; Pharmacyclics: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Verastem: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Janssen: Consultancy; Surface Oncology: Research Funding; Novartis: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Eli Lilly: Consultancy; Zentalis: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Research Funding; Merck: Consultancy; Ascentage Pharma: Consultancy, Research Funding. Wu:Pharmacyclics: Research Funding; BionTech: Current equity holder in publicly-traded company. OffLabel Disclosure: Ipilimumab and Nivolumab were tested in the setting of relapsed hematological malignancies after allogeneic stem cell transplantation.

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