Donor lymphocyte infusions in AML and MDS: Enhancing the graft-versus-leukemia effect

Ortí, Guillermo; Barba, Pere; Fox, Laura; Salamero, Olga; Bosch, Francesc; Valcárcel, David

doi:10.1016/j.exphem.2016.12.004

Cited by 61 publications

(50 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current speculation is that, in contrast to unstimulated DLI, the larger numbers of lymphocytes, CD34 cells, natural killer (NK) cells, as well as cytokines, contained in G-PBSCs may contribute roles in promoting haematopoietic recovery. [13,22]. However, in this study, there was no signi cant difference in the recovery of blood parameters in the GPBSCs infusion group compared with the uninfused group, although similar levels of donor chimerism were observed in this study, which was consistent with the previous study of leukaemia.…”

Section: Discussionsupporting

confidence: 91%

HLA-Mismatched GPBSCs infusion therapy in refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: A observational study from a single center

Song

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory state. Epstein–Barr virus (EBV) infection associated HLH (EBV-HLH) is one of the most common secondary HLH and suffers a very poor prognosis. Allo-HSCT is often required for refractory EBV-HLH, but some patients still cannot proceed to the next allo-HSCT due to various factors. This study aimed to observe the efficacy of HLA-mismatched granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (GPBSCs) infusion for refractory EBV-HLH. Methods: A retrospective case-control study of refractory EBV-HLH patients with GPBSCs infusion from HLA-mismatched donors after chemotherapy (as GPBSCs group) and sole chemotherapy (as control group) was performed. Efficacy was evaluated 2 and 4 weeks and all patients were followed up until 1 March 2018.Results: There were 18 cases who accepted infusion between March 2016 and Sep 2017 and 19 were randomly selected from refractory EBV-HLH patients who underwent salvage therapy during the same period for the control group. In GPBSCs group, WBC (p=0.017), Fbg (p=0.040), ferritin (p=0.039) improved significantly after treatment. The overall response rate was 66.7% (CR 22.2%, PR 44.4%). However, there is no significant differences in changes of WBC, HGB, PLT, TG, Fbg, Ferritin, AST, ALT, T-bil between two groups. Only the Fbg level was recovered better in the GPBSCs infusion group (p=0.003). In the GPBSCs group, EBV-DNA decreased significantly after 2 weeks (p=0.001) and 4 weeks (p=0.012) after treatment, and the effect of the decrease was significantly better than that of the chemotherapy alone group in 2 weeks but not 4 weeks (p2w=0.011, p4w=0.145). The median survival time in the infusion group was 20.4 weeks [95%CI 10.9, 29.9], and the median survival time in the control group was 10.8 weeks [95%CI 0-24.34]. In the short-term, the infusion group’s survival rate was better (2-month 88.89% vs. 52.63%, p=0.008; 3-month 83.33% vs. 47.09%, p=0.012), but there was no difference in OS (p=0.287). Conclusions: Infusing GPBSCs combined with chemotherapy is effective, especially in decreasing EBV-DNA, performs better than chemotherapy alone, and improve short term survival rate. GPBSCs infusion is suggested as a bridging treatment method to allo-HSCT.

show abstract

Section: Discussionsupporting

confidence: 91%

HLA-Mismatched GPBSCs infusion therapy in refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: A observational study from a single center

Song

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Perhaps the most common method is dose escalation, or increasing doses with each subsequent DLI in order to improve outcomes . Though a clearly defined endpoint is not always possible, some continue dose escalation until the patient develops GVHD to offer the best opportunity for clinical response …”

Section: DLImentioning

confidence: 99%

Harnessing the immune system after allogeneic stem cell transplant in acute myeloid leukemia

Sterling

Webster

2020

American J Hematol

View full text Add to dashboard Cite

Allogeneic stem cell transplantation (allo-SCT) is the most successful and widely used immunotherapy for the treatment of acute myeloid leukemia (AML), as a result of its anti-leukemic properties driven by T cells and natural killer (NK) cells, leading to a graft-vs-leukemia (GVL) effect. Despite its essential role in AML treatment, relapse after allo-SCT is common and associated with a poor prognosis. There is longstanding interest in developing immunologic strategies to augment the GVL effect posttransplant to prevent relapse and improve outcomes. In addition to prophylactic maintenance strategies, the GVL effect can also be used in relapsed patients to reinduce remission. While immune checkpoint inhibitors and other novel immune-targeted agents have been successfully used in the post-transplant setting to augment the GVL effect and induce remission in small clinical trials of relapsed patients, exacerbations of graft-vs-host disease (GVHD) have limited their broader use. Here we review advances in three areas of immunotherapy that have been studied in post-transplant AML: donor lymphocyte infusion (DLI), immune checkpoint inhibitors, and other monoclonal antibodies (mAbs), including antibody-drug conjugates (ADCs) and ligand receptor antagonists. We also discuss additional therapies with proposed immunologic mechanisms, such as hypomethylating agents, histone deacetylase inhibitors, and the FLT3 inhibitor sorafenib.

show abstract

“…This strategy did reduce relapse rates (compared with their previous work) without affecting the incidence of acute GVHD, but was associated with an increase in chronic GVHD [81,82]. Because of the GVL effect of DLI, some groups have incorporated infusions into transplantation protocols to reduce relapse [2,83]. In high-risk patients undergoing myeloablative TCD HSCT, DLI can be administered to improve donor chimerism and prevent relapse [84].…”

Section: DLImentioning

confidence: 99%

“…In patients with leukemia, the transplanted immune system has the ability to recognize abnormal leukemia cells and kill them. This "graft-versus-leukemia" (GVL) effect explains why some patients with high-risk disease are able to achieve long-term cure after HSCT [2].…”

Section: Introductionmentioning

confidence: 99%

Cellular Immunotherapy for Hematologic Malignancies: Beyond Bone Marrow Transplantation

Cirillo

Tan

Sturm

et al. 2018

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Immunotherapy has changed treatment practices for many hematologic malignancies. Even in the current era of targeted therapy, chemotherapy remains the backbone of treatment for many hematologic malignancies, especially in acute leukemias, where relapse remains the major cause of mortality. Application of novel immunotherapies in hematology attempts to harness the killing power of the immune system against leukemia and lymphoma. Cellular immunotherapy is evolving rapidly for high-risk hematologic disorders. Recent advances include chimeric antigen-receptor T cells, mesenchymal stromal/stem cells, dendritic cell tumor vaccines, cytokine-induced killer cells, and virus-specific T cells. The advantages of nontransplantation cellular immunotherapy include suitability for patients for whom transplantation has failed or is contraindicated, and a potentially less-toxic treatment alternative to transplantation for relapsed/refractory patients. This review examines those emerging cellular immunotherapies that are changing treatment paradigms for patients with hematologic malignancies.

show abstract

Donor lymphocyte infusions in AML and MDS: Enhancing the graft-versus-leukemia effect

Cited by 61 publications

References 102 publications

HLA-Mismatched GPBSCs infusion therapy in refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: A observational study from a single center

HLA-Mismatched GPBSCs infusion therapy in refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: A observational study from a single center

Harnessing the immune system after allogeneic stem cell transplant in acute myeloid leukemia

Cellular Immunotherapy for Hematologic Malignancies: Beyond Bone Marrow Transplantation

Contact Info

Product

Resources

About