The cell composition of infused donor lymphocyte has different impact in different types of allogeneic hematopoietic stem cell transplantation

DLI is an effective strategy for patients with recurrent hematological malignancies after allogeneic hematopoietic SCT (allo-HSCT). DLI has been widely applied to boost the graft vs tumor (GVT) or GVL effects. However, given the potentially severe complications associated with conventional DLI and transient GVL effect, new strategies for DLI are emerging. In this review, we have discussed the recent important studies on DLI as a prophylactic or therapeutic modality for relapsed hematological disorders after allo-HSCT. The strategies to separate GVL from GVHD have also been discussed. Leukemia-targeting therapy and lymphodepletion combined with DLI, and prophylactic DLI after allo-HSCT are often employed for patients with high risk of relapse, which has been reviewed as well. In addition, we have also discussed the issues on DLI to be further addressed, such as the doses, timing and frequency of DLI in different clinical settings, leukemic antigen-specific DLI as well as how to augment GVL effect while attenuating GVHD.

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“…Meanwhile, this study points a new direction for the development of cellular therapies by manipulating the components of infused cells. 104 …”

Section: Gvhd and Gvl After DLImentioning

confidence: 99%

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

Chang

Zang

Xia

2015

Bone Marrow Transplant

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“…However, a greater number of CD14+ cells was an independent risk factor for II-IV aGvHD (HR = 1.758, p = 0.034) in haploidentical allo-SCT. These data show that the cell composition of DLI provides a novel approach for the development of cellular therapies by manipulating the components of infused cells [58].…”

Section: Biology Of Therapeutic DLImentioning

confidence: 78%

Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients

Greiner

Götz

Bunjes

et al. 2019

JCM

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Allogeneic stem cell transplantation (allo-SCT) is the preferred curative treatment for several hematological malignancies. The efficacy of allo-SCT depends on the graft-versus-leukemia (GvL) effect. However, the prognosis of patients with relapsed acute myeloid leukemia (AML) following allo-SCT is poor. Donor lymphocyte infusion (DLI) is utilized after allo-SCT in this setting to prevent relapse, to prolong progression free survival, to establish full donor chimerism and to restore the GvL effect in patients with hematological malignancies. Thus, there are different options for the administration of DLI in AML patients. DLI is currently used prophylactically and in the setting of an overt relapse. In addition, in the minimal residual disease (MRD) setting, DLI may be a possibility to improve overall survival. However, DLI might increase the risk of severe life-threatening complications such as graft-versus-host disease (GvHD) as well as severe infections. The transfusion of lymphocytes has been tested not only for the treatment of hematological malignancies but also chronic infections. In this context, manipulated DLI in a prophylactic or therapeutic approach are an option, e.g., virus-specific DLI using different selection methods or antigen-specific DLI such as peptide-specific CD8+ cytotoxic T lymphocytes (CTLs). In addition, T cells are also genetically engineered, using both chimeric antigen receptor (CAR) genetically modified T cells and T cell receptor (TCR) genetically modified T cells. T cell therapies in general have the potential to enhance antitumor immunity, augment vaccine efficacy, and limit graft-versus-host disease after allo-SCT. The focus of this review is to discuss the different strategies to use donor lymphocytes after allo-SCT. Our objective is to give an insight into the functional effects of DLI on immunogenic antigen recognition for a better understanding of the mechanisms of DLI. To ultimately increase the GvL potency without raising the risk of GvHD at the same time.

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“… 11 In a study by Zhao et al of 194 patients undergoing allo-HSCT, the patients received mobilized DLI for various clinical reasons and the results showed that infusion with a dose of CD14-positive cells at greater than the 50th percentile was associated with a lower incidence of hematological relapse and longer disease-free survival after mobilized DLI. 5 …”

Section: Strategies and Treatment Options For Relapsed All Following mentioning

confidence: 99%

“… 1 For patients with ALL who relapse after allo-HSCT, the treatment options are limited and the clinical course and prognostic factors affecting outcome have not been well characterized. 2 , 3 Although a better understanding of the graft-versus-tumor/graft-versus-leukemia (GVL) effect, 4 minimal residual disease (MRD), and donor leukocyte infusions (DLIs) 5 have been achieved in recent decades, predicting ALL relapse after allo-HSCT and finding strategies to overcome ALL relapse remain critical to clinical practitioners. The aim of this article is to review the current concepts regarding risk factors, prevention, and treatment of ALL relapse following allo-HSCT.…”

Section: Introductionmentioning

confidence: 99%

Prophylaxis and treatment of acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation

Chen

Campbell

Chen

2015

OTT

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Relapse of acute lymphoblastic leukemia remains a major cause of death in patients following allogeneic hematopoietic stem cell transplantation. Several factors may affect the concurrence and outcome of relapse, which include graft-versus-host disease, minimal residual disease or intrinsic factors of the disease, and transplantation characteristics. The mainstay of relapse prevention and treatment is donor leukocyte infusions, targeted therapies, second transplantation, and other novel therapies. In this review, we mainly focus on addressing the impact of graft-versus-host disease on relapse and the prophylaxis and treatment of acute lymphoblastic leukemia relapse following allogeneic hematopoietic stem cell transplantation. We also make recommendations for critical strategies to prevent relapse after transplantation and challenges that must be addressed to ensure success.

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The cell composition of infused donor lymphocyte has different impact in different types of allogeneic hematopoietic stem cell transplantation

Cited by 5 publications

References 29 publications

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients

Prophylaxis and treatment of acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation

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