Trial reportCancer immunology, immunotherapy : CII2012
Lymphodepletion is permissive to the development of spontaneous T-cell responses to the self-antigen PR1 early after allogeneic stem cell transplantation and in patients with acute myeloid leukemia undergoing WT1 peptide vaccination following chemotherapy.
Trial report in Cancer immunology, immunotherapy : CII, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- Immunotherapy for acute myeloid leukemia: from allogeneic stem cell transplant to novel therapeutics.Leukemia & lymphoma · 2019Review
- Immunotherapeutic Concepts to Target Acute Myeloid Leukemia: Focusing on the Role of Monoclonal Antibodies, Hypomethylating Agents and the Leukemic Microenvironment.International journal of molecular sciences · 2017Review
- Timing Is Everything: Combining Post-Transplantation Adoptive Cell Therapy and Tumor Vaccines.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2016Article
- Tolerability and Clinical Activity of Post-Transplantation Azacitidine in Patients Allografted for Acute Myeloid Leukemia Treated on the RICAZA Trial.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2016Article
- New approaches for the immunotherapy of acute myeloid leukemia.Discovery medicine · 2015Review
- 5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies.Blood cancer journal · 2014Article
- Generation of tumor antigen-specific T cell lines from pediatric patients with acute lymphoblastic leukemia--implications for immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Article
- New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation.International journal of hematologic oncology · 2013Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
PR1, an HLA-A*0201 epitope shared by proteinase-3 (PR3) and elastase (ELA2) proteins, is expressed in normal neutrophils and overexpressed in myeloid leukemias. PR1-specific T cells have been linked to graft-versus-leukemia (GVL) effect. We hypothesized that lymphopenia induced by chemo-radiotherapy can enhance weak autoimmune responses to self-antigens such as PR1. We measured PR1-specific responses in 27 patients 30-120 days following allogeneic stem cell transplant (SCT) and correlated these with ELA2 and PR3 expression and minimal residual disease (MRD). Post-SCT 10/13 CML, 6/9 ALL, and 4/5 solid tumor patients had PR1 responses correlating with PR3 and ELA2 expression. At day 180 post-SCT, 8/8 CML patients with PR1 responses were BCR-ABL-negative compared with 2/5 BCR-ABL-positive patients (P = 0.025). In contrast, PR1 responses were detected in 2/4 MRD-negative compared with 4/5 MRD-positive ALL patients (P = 0.76). To assess whether the lymphopenic milieu also exaggerates weak T-cell responses in the autologous setting, we measured spontaneous induction of PR1 responses in 3 AML patients vaccinated with WT1-126 peptide following lymphodepletion. In addition to WT1-specific T cells, we detected PR1-specific T cells in 2 patients during hematopoietic recovery. Our findings suggest that lymphopenia induced by chemo-radiotherapy enhances weak autoimmune responses to self-antigens, which may result in GVL if the leukemia expresses the relevant self-antigen.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.