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Clinical and Immunologic Responses to Very Low-Dose Vaccination with WT1 Peptide (5 µg/Body) in a Patient with Chronic Myelomonocytic Leukemia

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Abstract

The wild-type Wilms tumor gene, WT1, is overexpressed in myelodysplastic syndrome (MDS) as well as acute myeloid leukemia. In a phase I clinical trial of biweekly vaccination with HLA-A*2402-restricted WT1 peptide for these malignancies, 2 patients with MDS developed severe leukocytopenia in association with a reduction in leukemic blast cells and levels of WT1 messenger RNA (mRNA) after only a single vaccination with 0.3 mg of WT1 peptide. These results indicated that the WT1-specific cytotoxic T-lymphocytes (CTLs) elicited by WT1 vaccination eradicated the WT1-expressing transformed stem or progenitor cells and that MDS patients with little normal hematopoiesis required a new strategy of WT1 vaccination to avoid severe leukocytopenia. We describe the first trial for a 57-year-old male patient with chronic myelomonocytic leukemia who was vaccinated biweekly with a small quantity (5 µg/body) of WT1 peptide. After the start of vaccination, the leukocyte and monocyte counts (13,780/µL and 1930/µL, respectively) gradually decreased to within the normal range in association with a reduction in the WT1 mRNA level. Simultaneously, the percentage of WT1-specific CTLs as measured by the HLA-WT1 tetramer assay increased. This case demonstrates for the first time that vaccination with as little as 5 µg of WT1 peptide can induce WT1-specific immune responses and resultant clinical responses.

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Correspondence to Haruo Sugiyama.

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Kawakami, M., Oka, Y., Tsuboi, A. et al. Clinical and Immunologic Responses to Very Low-Dose Vaccination with WT1 Peptide (5 µg/Body) in a Patient with Chronic Myelomonocytic Leukemia. Int J Hematol 85, 426–429 (2007). https://doi.org/10.1532/IJH97.06194

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  • DOI: https://doi.org/10.1532/IJH97.06194

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