Nonmyeloablative allogeneic stem-cell transplantation can induce sustained regression of metastatic renal-cell carcinoma in patients who have had no response to conventional immunotherapy.
Key Points
Allogeneic CD19-CAR VSTs are well tolerated by patients with relapsed B-cell malignancies post-HSCT. At periods of CD19-CAR VST persistence, these cells demonstrate antitumor activity.
The hepatitis of the hepatitis-associated aplastic anemia does not appear to be caused by any of the known hepatitis viruses. We recommend immunosuppressive treatment for patients who do not have an HLA-matched related donor available for bone marrow transplantation. Several features of the syndrome suggest that it is mediated by immunopathologic mechanism.
We describe the safety and immunogenicity of a combined vaccine of 2 leukemiaassociated antigenic peptides, PR1 and WT1. Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocytemacrophage colony-stimulating factor. Patients were reviewed weekly for 4 weeks to monitor toxicity and immunologic responses. Toxicity was limited to grades 1 to 2. Using peptide/HLA-A*0201 tetramers and intracellular interferon-␥ staining, CD8 ؉ T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination. To monitor the kinetics of vaccine-induced CD8 ؉ T-cell responses and disease regression after vaccination, absolute PR1 and WT1 ؉ CD8 ؉ T-cell numbers and WT1 expression were studied weekly after vaccination. Responses occurred as early as 1 week after vaccination. After vaccination, the emergence of PR1 or WT1 ؉ CD8 ؉ T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect. Conversely, loss of response was associated with reappearance of WT1 transcripts (P < .01). This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic.
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