scholarly journals T-Cell Replete Peripheral Blood Haploidentical Donor Transplant (HID) Using Immunogenic Dose of Cyclophosphamide (Cy) with Fludarabine (Flu)/Melphalan (Mel) Results in Enhanced Cytokine Release Syndrome (CRS) with Robust Immune Recovery & Low Relapse Rate

2018 ◽  
Vol 24 (3) ◽  
pp. S409-S410
Author(s):  
Yasser Khaled ◽  
Jason Chandler ◽  
Diwura Owolabi ◽  
Joshua D. Boss ◽  
Joel F. Gradowski
Keyword(s):  
T Cell ◽  
Relapse Rate ◽  
Peripheral Blood ◽  
Immune Recovery ◽  
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 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]

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

scholarly journals Cytokine release syndrome and neurological event costs in lisocabtagene maraleucel–treated patients in the TRANSCEND NHL 001 trial

2021 ◽  
Vol 5 (6) ◽  
pp. 1695-1705
Author(s):  
Jeremy S. Abramson ◽  
Tanya Siddiqi ◽  
Jacob Garcia ◽  
Christine Dehner ◽  
Yeonhee Kim ◽  
...  
Keyword(s):  
Health Care ◽  
T Cell ◽  
B Cell Lymphoma ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
System Perspective ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T ◽  
Grade 3

Abstract Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell–specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.gov as #NCT02631044.

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