Strategies for Improving the Efficacy of Donor Lymphocyte Infusion Following Stem Cell Transplantation

Stamouli, Maria; Gkirkas, Konstantinos; Tsirigotis, Panagiotis

doi:10.2217/imt.15.100

Cited by 11 publications

(9 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another important protocol in lymphocyte engineering is the use of DLI for cytomegalovirus (CMV) reactivation, as well as other disorders related to immune deficiency. DLI may also improve the graft-versus-tumor (GVT) or graft-versus-leukemia effect of an allogeneic stem cell transplantation [ 24 , 25 ]. In the current paper we aim to approach the ICU patient that presents following a diagnosis with a hematological disease and treated mainly through the use of CAR-T cells, DLI, as well as similar novel technologies.…”

Section: Introductionmentioning

confidence: 99%

Genetically enhanced T lymphocytes and the intensive care unit

Tat

Constantinescu

et al. 2018

Oncotarget

View full text Add to dashboard Cite

Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells have emerged as a new modality for cancer immunotherapy due to their potential efficacy against hematological malignancies. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in lymphocyte T cell activation subsequent to antigen binding. In present-day medicine, four generations of CAR-T cells are described depending on the intracellular signaling domain number of T cell receptors. DLI represents a form of adoptive therapy used after hematopoietic stem cell transplant for its anti-tumor and anti-infectious properties. This article covers the current status of CAR-T cells and DLI research in the intensive care unit (ICU) patient, including the efficacy, toxicity, side effects and treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Genetically enhanced T lymphocytes and the intensive care unit

Tat

Constantinescu

et al. 2018

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Its major complication was the high risk of graft-versus-host-disease, which is associated with a donor lymphocyte reaction against host antigens [29]. Its efficacy is nonetheless assessed as disappointing.…”

Section: To Enhance the Cytotoxic Effect: Potential Therapies Are Promentioning

confidence: 99%

“…As a result, T cells are not appropriately activated in vivo to induce an antitumor response. To improve the efficacy of DLI, multiple methods have been used: costimulation with CD3/CD28 and activation ex vivo [30], enrichment of donor T cells with leukemia-specific antigens (WT1) [31] or tumor-specific and host-restricted minor histocompatibility complex antigens [29,32].…”

Section: To Enhance the Cytotoxic Effect: Potential Therapies Are Promentioning

confidence: 99%

Immunotherapy in Pediatric Acute Leukemia: A Novel Magic Bullet or an Illusory Hope?

Barełkowska¹,

Derwich²

2017

Unique Aspects of Anti-Cancer Drug Development

View full text Add to dashboard Cite

The last decade became the renaissance for investigating and exploring the potential role of immunotherapy in pediatric acute leukemia (AL). It is beyond question that there is an interaction between innate immune system and hematological malignancy. Leukemia cells inhibit the host immune response according to multiple mechanisms, but exploiting the innate immune system mechanisms can overcome the resistance to the conventional treatment. What is the role of immunotherapy in pediatric AL treatment? Does it have the potential to substitute or combine the standard chemotherapy? What is the best possible timing to take advantage of immune interventions? This review is considered to follow through the possible treatment options including their foundation, strong and weak points, but also information about possible implementation into the clinical practice.

show abstract

“…[4][5][6][7] Preemptive interventions, including withdrawal of immunosuppressants and donor lymphocyte infusion (DLI), can prevent graft rejection and improve clinical outcomes of patients with malignancy that develop MC after HSCT. [8][9][10] Several recombinant human cytokines, selected based on their immunomodulatory effects, have also been applied to patients with a tendency toward relapse. For example, interferon-α (IFN-α) has been reported to stimulate dendritic cells, natural killer cells, and T cells to produce anticancer effect.…”

Section: Introductionmentioning

confidence: 99%

Prediction, management, and prognosis of mixed chimerism after hematopoietic stem cell transplantation in transfusion‐dependent pediatric thalassemia patients

Chen

Zhan

et al. 2020

Pediatric Transplantation

View full text Add to dashboard Cite

Background: Early-onset mixed chimerism (MC) with a high proportion of residual host cells is considered a signal of graft rejection in patients undergoing allogenic hematopoietic stem cell transplantation for transfusion-dependent thalassemia. In order to prevent graft rejection and minimize the risk of treatment-related graft-versus-host disease (GVHD), we established a hierarchical management system based on chimerism analysis. Method: This retrospective study provides a comprehensive review of the characteristics, interventions, and outcomes of the 38 patients who developed MC after transplantation among the 144 pediatric thalassemia patients between July 2007 and January 2019 at our center. Results: A sibling donor, a blood type-matched donor, conditioning regimens without fludarabine, and transplants containing <10 × 10 8 total nucleated cells/kg were identified to be associated with the development of MC. Among the 38 patients developing MC, only four patients rejected the grafts. The response rate to donor lymphocyte infusion (DLI, only for patients receiving sibling donor transplantation) and cytokine immunomodulation without DLI was 70.6% and 42.9%, respectively. Patients that developed GVHD after DLI or cytokine therapy had a more significant increase in donor cell chimerism (16%, range 0%-35%) than those without (8.5%, range −21% to 40%, P = .049). However, even when treatment-related GVHD was included, patients with MC had a lower cumulative incidence of total acute GVHD than patients with complete donor chimerism (29.2% vs 48.0%, P = .030). Conclusions: Interventions based on chimerism analysis were effective in preventing graft rejection and did not increase treatment-related GVHD in thalassemia patients with MC.

show abstract

Strategies for Improving the Efficacy of Donor Lymphocyte Infusion Following Stem Cell Transplantation

Cited by 11 publications

References 69 publications

Genetically enhanced T lymphocytes and the intensive care unit

Genetically enhanced T lymphocytes and the intensive care unit

Immunotherapy in Pediatric Acute Leukemia: A Novel Magic Bullet or an Illusory Hope?

Prediction, management, and prognosis of mixed chimerism after hematopoietic stem cell transplantation in transfusion‐dependent pediatric thalassemia patients

Contact Info

Product

Resources

About