Dataset Information

Induction of Immune Response after Allogeneic Wilms' Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse.

ABSTRACT: Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). Treatment for post-HCT relapse using donor lymphocyte infusion (DLI) has limited utility, particularly in the setting of acute leukemia, and can result in the development of graft-versus-host disease (GVHD). The Wilms' tumor 1 (WT1) gene product is a tumor-associated antigen that is expressed in acute leukemia and other hematologic malignancies, with limited expression in normal tissues. In this pilot trial, we assessed safety and feasibility of a WT1 peptide-loaded donor-derived dendritic cell (DC) vaccine given with DLI designed to enhance and direct the graft-versus-leukemia effect. Secondary objectives were to evaluate immunologic and clinical responses. A total of 5 subjects, median age 17 years (range, 9 to 19 years), with post-HCT relapse were enrolled. Disease subtypes included acute lymphoblastic leukemia (n?=?3), acute myelogenous leukemia (n?=?1), and Hodgkin lymphoma (n?=?1). Successful vaccine production was feasible from all donors. DC vaccination and DLI were well tolerated. One recipient developed grade 1 skin GVHD not requiring systemic therapy. The most common adverse events included grade 1 reversible pain and pruritus at the vaccine injection and delayed-type hypersensitivity (DTH) skin testing sites. There were no grade 3 or higher adverse events related to the research. Immune responses consisted of ELISpot response in 3 recipients and positive DTH tests to WT1 peptide cocktail in 2 subjects. Our study provides 1 of the first attempts to apply tumor-specific vaccine therapy to the allogeneic setting. Preliminary results show the DC-based vaccination is safe and feasible after allogeneic HCT, with a suggestion that this approach can be used to sensitize the repopulated allogeneic-donor immune system to WT1. Future directions may include testing of vaccination strategies in the early post-transplantation setting for relapse prevention.

SUBMITTER: Shah NN

PROVIDER: S-EPMC7499897 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Induction of Immune Response after Allogeneic Wilms' Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse.

Shah Nirali N NN Loeb David M DM Khuu Hahn H Stroncek David D Ariyo Tolu T Raffeld Mark M Delbrook Cindy C Mackall Crystal L CL Wayne Alan S AS Fry Terry J TJ

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20160912 12

Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). Treatment for post-HCT relapse using donor lymphocyte infusion (DLI) has limited utility, particularly in the setting of acute leukemia, and can result in the development of graft-versus-host disease (GVHD). The Wilms' tumor 1 (WT1) gene product is a tumor-associated antigen that is expressed in acute leukemia and other hematologic malignancies, with limit ...[more]

PMID: 27634018

Similar Datasets

Project description:ImportanceThe optimal treatment approach to patients with acute myeloid leukemia (AML) who relapse after an allogeneic hematopoietic cell transplant (allo-HCT) remains elusive. No randomized clinical trial comparing survival outcomes of a second allo-HCT (allo-HCT2) vs donor lymphocyte infusion (DLI) has been conducted to date.ObjectiveTo compare overall survival (OS) after an allo-HCT2 or DLI in relapsed AML after a first allo-HCT.Design, setting, and participantsA retrospective registry study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation involving 418 adults who received an allo-HCT2 (n?=?137) or DLI (n?=?281) for postallograft-relapsed AML. Analysis was assessed on the principle of intent-to-first received intervention. The data were collected from November 21, 2015, to May 15, 2017, and analysis was performed June 1, 2017.Main outcomes and measuresNumber of patients with relapsed AML who are alive after 2 years and 5 years from receiving an allo-HCT2 or DLI.ResultsOf the 418 patients, 228 (54.5%) were men; mean age was 46.2 years (interquartile range, 36.5-56.9 years). There was no apparent difference in OS whether an allo-HCT2 or DLI was prescribed (2-year OS with allo-HCT2, 26%; 5-year OS with allo-HCT2, 19%; 2-year OS with DLI, 25%; 5-year OS with DLI, 15%; P?=?.86). Overall survival was better if either of these procedures was offered when the patient was in complete remission (hazard ratio, 0.55; 95% CI, 0.41-0.74; P?<?.001). Conversely, OS was low for patients relapsing within less than 6 months after an allo-HCT1, regardless of the treatment prescribed (5-year OS: allo-HCT2, 9%; 95% CI, 1%-17% vs DLI, 4%; 95% CI, 1%-8%; P?=?.86).Conclusion and relevanceHeterogeneity of the patient-, disease-, and treatment-related characteristics limit the ability to recommend one approach over another. Findings of this study highlight that best outcomes seem to be achieved in patients relapsing 6 or more months from an allo-HCT1 or those in complete remission at the time of either allo-HCT2 or DLI.

Dataset Information

Induction of Immune Response after Allogeneic Wilms' Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse.

Publications

Induction of Immune Response after Allogeneic Wilms' Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets