scholarly journals T-Cell Replete Peripheral Blood Haploidentical Donor Transplant is Frequently Associated with Cytokine Release Syndrome Which Responds to IL-6 Inhibition—Updated Outcomes Data with Longer Follow-Up

2018 ◽  
Vol 24 (3) ◽  
pp. S314
Author(s):  
Ramzi Abboud ◽  
Michael Slade ◽  
Jesse Keller ◽  
Kathryn Trinkaus ◽  
Camille Abboud ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Donor Transplant

scholarly journals Cytokine Release Syndrome after Peripheral Blood T-Cell Replete Haploidentical Transplantation Is Not Prevented By Dexamethasone and Limits Its Full-Outpatient Conduction

2019 ◽  
Vol 25 (3) ◽  
pp. S136-S137
Author(s):  
Perla R. Colunga-Pedraza ◽  
Andrés Gómez-De León ◽  
Julia E. Colunga-Pedraza ◽  
Paola Santana-Hernández ◽  
Emmanuel Bugarín-Estrada ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Haploidentical Transplantation

scholarly journals Hemophagocytic Lymphohistiocytosis/Macrophage-Activation Syndrome (HLH/MAS) Following Treatment with Tisagenlecleucel

2021 ◽  
Author(s):  
Reyes Maria Martin-Rojas ◽  
Ignacio Gomez-Centurion ◽  
Rebeca Bailen ◽  
Mariana Bastos ◽  
Francisco Diaz-Crespo ◽  
...  
Keyword(s):  
T Cell ◽  
Macrophage Activation ◽  
Mortality Rates ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Unusual Manifestation ◽  
Car T Cell ◽  
Car T ◽  
Diagnosis Criteria

CAR-T cell related HLH/MAS is an unusual manifestation of severe cytokine release syndrome (CRS) with high mortality rates and a challenging diagnosis. The establishment of specific diagnosis criteria is essential, and the combination of several techniques for CAR-T cell follow-up, allows a more precise management of this complication.

scholarly journals Cytokine Release Syndrome after Peripheral Blood T-Cell Replete Haploidentical Transplantation Is Not Prevented By Dexamethasone and Limits Its Full-Outpatient Conduction

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3355-3355
Author(s):  
Perla R. Colunga Pedraza ◽  
Andrés Gómez-De León ◽  
Julia Esther Colunga Pedraza ◽  
Emmanuel Bugarin Estrada ◽  
Paola Santana-Hernandez ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Outpatient Basis ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Median Length ◽  
Transplant Outcomes ◽  
The Impact ◽  
Length Of Hospitalization

Abstract Introduction: Our center has implemented an outpatient-based peripheral blood haploidentical HSCT (haplo-HSCT) program since 2012. Cytokine release syndrome (CRS) associated with T-cell replete haplo-HSCT is characterized by fever and high levels of inflammatory cytokines with symptom onset typically occurring early after cell infusion, coinciding with maximal in vivo T-cell expansion. In this study, we report our analysis of CRS development after T cell-replete haplo-HSCT after using prophylactic dexamethasone and focusing on the impact of CRS on hospitalization and transplant outcomes in our outpatient program. Methods: In this retrospective study, adult patients undergoing a T-cell replete haplo-HSCT at our transplant center between January 2016-2018 were included. CRS was defined and graded using the criteria described by Lee et. al. Conditioning was based on fludarabine 25 mg/m2/day (day -5 to -3), cyclophosphamide 350 mg/m2/day (day -5 to -3), and oral melphalan 50-100 mg/m2 (day -2 to -1). For graft-versus-host disease (GVHD) prophylaxis we used post-transplant cyclophosphamide (PTCy) 50 mg/kg on days +3 and +4 as well as mycophenolate mofetil and either cyclosporine or tacrolimus starting on day +5. All patients received dexamethasone 8 mg IV on day 0 to +2 as prophylaxis against CRS. Disease-risk index (DRI) and HCT-Comorbidity Index (HCT-CI) were calculated based on established definitions. The primary objective was to evaluate the incidence of CRS with dexamethasone prophylaxis during an outpatient-based peripheral blood haplo-HSCT. Secondary objectives were to describe factors associated with CRS and to determine the impact of CRS on transplant outcomes and hospitalizations. Results: There were 42 patients included; the median age was 32.5 years (range, 16-66). The median DRI score was 3 (range, 1-4). The most common underlying diagnosis was acute lymphoblastic leukemia (n=14, 33%), followed by acute myeloid leukemia (n=8, 19%), and lymphoma (n=7, 16.6%). Conditioning was myeloablative (n=33, 79%) or reduced-intensity (n=9, 21%). Thirty patients (71.4%) developed CRS. CRS severity was grade 1-2 in 28 patients (66.7%) and grade 3 in 2 patients (4.8%). Median day of onset occurred on day +2 (range 0-4) and usually resolved after PTCy on day +5 (range, 1-11). The incidence of CRS was not associated with recipient age, number of CD34+ cells infused, DRI score, baseline HCT-CI score, and conditioning intensity. Time to neutrophil and platelet engraftment was not different in patients with CRS compared with patients without. Hospitalization was required in 36 cases (87%) while 6 patients (13%) were followed in a fully-outpatient basis, including 2 patients with grade 1 CRS. The median length of hospitalization was 13 days (range, 0-50) for patients with CRS and 8 days for patients without CRS (range, 0-44). The most common signs and symptoms besides fever were gastrointestinal manifestations (36.6%), hypoxemia (30%), fluid-responsive hypotension (16%) while 2 patients required vasopressors. Conclusion: The completely ambulatory conduct of haplo-HSCT was limited by the development of CRS. However, even in patients who developed CRS median length of hospitalization was short. CRS was common despite dexamethasone prophylaxis although most CRS were of grade 1 or 2. None of the factors evaluated were associated with CRS development in this context, and CRS did not influence time to engraftment, cumulative incidence of acute or chronic GVHD. New strategies are required to prevent CRS and prevent hospitalizations associated with haplo-HSCT. Disclosures Gomez-Almaguer: AbbVie: Consultancy; Novartis: Consultancy.

Preliminary analysis of a phase 1/2 study of NEXI-001 donor-derived multi-antigen-specific CD8+ T-cells for the treatment of relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2538-2538
Author(s):  
Monzr Al Malki ◽  
Sumithira Vasu ◽  
Dipenkumar Modi ◽  
Miguel-Angel Perales ◽  
Donna Bui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Cellular Therapy ◽  
Human Study ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Allogeneic Hct ◽  
Over Time

2538 Background: Allogeneic HCT is a potentially curative therapy for many patients with AML that relies on a graft-versus-leukemia (GvL) effect. Patients who relapse after allogeneic HCT have a poor prognosis and few treatment options. Donor lymphocyte infusion (DLI) can achieve a GvL effect in some patients, however, efficacy is frequently associated with the development graft-versus-host disease (GVHD). There is a substantial need for treatment approaches that enhance the benefit of GVL while decoupling toxicities associated with GVHD. Methods: We report ongoing results from a first-in-human study (NCT04284228) of a non-genetically engineered, donor-derived adoptive cellular therapy product, NEXI-001, which contains multiple populations of CD8+ T cells that recognize different HLA 02.01-restricted peptides from the WT1, PRAME, and Cyclin A1 antigens. NEXI-001 contains T cell memory subtypes that combine anti-tumor potency with long-term persistence. Results: At the time of this analysis, 7 patients with relapsed AML after allogeneic HCT were enrolled. Five Patients were treated with single infusions of NEXI-001 at three different dose levels: 50, 100 and 200 million. Currently, the median follow-up is 5 months. Significantly, GVHD, cytokine release syndrome, neurotoxicity, or NEXI-001-related adverse events were not observed. NEXI-001 treatment resulted in reductions in red blood cell and platelet transfusions and increased donor chimerism. Decreases in myeloblasts in bone marrow and peripheral blood and reduction in the size of an extramedullary myeloid sarcoma were suggestive of an anti-leukemia effect (Table). Correlative studies indicate that NEXI-001 CD8+ cells undergo a rapid proliferation after infusion and are also associated with a robust hostlymphocyte recovery that occurs as quickly Day 3 after infusion. NEXI-001 infused CD8+T cells are detectable by multimer staining in peripheral blood of patients and proliferate over time. TCR sequencing analyses determined that infused NEXI-001 cells contain T cell clones that were undetectable in the peripheral blood of patients at baseline but were detected in blood and bone marrow and persist over time. Conclusions: NEXI-001 has the potential to enhance GvL effect without the associated toxicities of GVHD, cytokine release syndrome, and neurotoxicity. Due to these encouraging results, the trial will proceed with an evaluation of repeated NEXI-001 dosing Clinical trial information: NCT04284228. [Table: see text]

Recent updates on bispecific T-cell engager (BiTE) antibodies in relapsed and refractory multiple myeloma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20034-e20034
Author(s):  
Abdul Rafae ◽  
Ahsan Wahab ◽  
Hamid Ehsan ◽  
Joshua Christy ◽  
Tabinda Saleem ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Hematological Malignancies ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Good Tolerability ◽  
Refractory Multiple Myeloma ◽  
Dose Levels ◽  
Bispecific T Cell Engager

e20034 Background: Bispecific T-cell engager (BiTE) antibodies are currently being studied for various hematological malignancies including relapsed and refractory multiple myeloma (RRMM). BiTE antibodies that target CD3 on T cells and antigens GPRC5D, BCMA or FcRH5 on myeloma cells are being studied in RRMM patients (pts). Methods: A comprehensive literature search was done on Pubmed, Embase, and Cochrane. The data presented in various conferences (ASH, ASCO) were also included. Results: Six clinical trials are currently evaluating anti-BCMA, anti CD3 BiTE in RRMM. Madduri et al. reported ORR of 39% in 49 pts treated with REGN5458 an anti BCMA and CD3 BiTE antibody. Grafall et. al reported an ORR of 73% with Teclistamab at 1500µg/kg SC. Harrison et al. reported ORR of 83% in 9 pts treated with 9mg of AMG 701. Lesokhin et al. reported an ORR of 33% among 18 RRMM pts at all dose levels and ORR of 75%. at dose level of 215μg/kg weekly (n=4), and 360 μg/kg weekly (n=4). Rodriguez et al. reported an ORR of 80% among 15 RRMM pts treated with TNB-383B at the dose of 40-60mg IV every 3 weeks. Topp et al reported an ORR of 70% among 10 pts treated with AMG420/BI-836909 at MTD of 400µg/d. Chari et al reported results of Talquetamab which targets GPRC5D which showed an ORR of 66% in 55 evaluable pts. ORR at RP2D (405 µg/kg SC) was 69% in 19 pts treated at this dose. Cohen et al reported results on BFCR4350A, an anti FcRH5 BiTE which showed an ORR of 53% at dose ≥3.6/20mg Q3W. Cytokine release syndrome (CRS) is a serious side effect of BiTE antibodies and was reported in 39%, 64%, 65%, 61%, 45%, 38%, 54% and 76% in studies by Madduri et al, Grafall et al., Harrison et al., Lesokhin et al., Rodriguez et al., Topp et al., Chari et al., and Cohen et al., respectively. Most of the CRS cases were grade 1-2 and resolved either by themselves or required treatment with tocilizumab and steroids. Other most common side effects are reported in table. Conclusions: The most recent data on BiTE antibodies in RRMM has shown promising results with good tolerability. However, the trials are ongoing and a longer follow up is needed.[Table: see text]

scholarly journals Peripheral Blood Grafts for T Cell–Replete Haploidentical Transplantation Increase the Incidence and Severity of Cytokine Release Syndrome

2018 ◽  
Vol 24 (8) ◽  
pp. 1664-1670 ◽  
Author(s):  
Renju V. Raj ◽  
Mehdi Hamadani ◽  
Aniko Szabo ◽  
Marcelo C. Pasquini ◽  
Nirav N. Shah ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Haploidentical Transplantation
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