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International Journal of Hematology

, Volume 85, Issue 5, pp 426–429 | Cite as

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

  • Manabu Kawakami
  • Yoshihiro Oka
  • Akihiro Tsuboi
  • Yukie Harada
  • Olga A. Elisseeva
  • Yoshio Furukawa
  • Machiko Tsukaguchi
  • Toshiaki Shirakata
  • Sumiyuki Nishida
  • Hiroko Nakajima
  • Satoshi Morita
  • Junichi Sakamoto
  • Ichiro Kawase
  • Yusuke Oji
  • Haruo Sugiyama
Case report

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.

Key words

Wilms tumor gene WT1 Cancer vaccine Myelodysplastic syndrome (chronic myelomonocytic leukemia) 

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Copyright information

© The Japanese Society of Hematology 2007

Authors and Affiliations

  • Manabu Kawakami
    • 1
    • 3
  • Yoshihiro Oka
    • 2
  • Akihiro Tsuboi
    • 3
  • Yukie Harada
    • 2
  • Olga A. Elisseeva
    • 4
  • Yoshio Furukawa
    • 5
  • Machiko Tsukaguchi
    • 6
  • Toshiaki Shirakata
    • 4
  • Sumiyuki Nishida
    • 4
  • Hiroko Nakajima
    • 4
  • Satoshi Morita
    • 7
  • Junichi Sakamoto
    • 7
  • Ichiro Kawase
    • 2
  • Yusuke Oji
    • 8
  • Haruo Sugiyama
    • 4
  1. 1.Department of MedicineNational Hospital Organization, Osaka Minami Medical CenterOsakaJapan
  2. 2.Department of Respiratory Medicine, Allergy and Rheumatic DiseasesOsaka University Graduate School of MedicineOsakaJapan
  3. 3.Department of Cancer ImmunotherapyOsaka University Graduate School of MedicineOsakaJapan
  4. 4.Department of Functional Diagnostic ScienceOsaka University Graduate School of MedicineOsakaJapan
  5. 5.Department of MedicineFuchu HospitalOsakaJapan
  6. 6.Department of MedicineSakai Municipal HospitalOsakaJapan
  7. 7.Young Leaders’ Program of Medical Administration & International AffairsGraduate School of Medicine Nagoya UniversityNagoyaJapan
  8. 8.Department of Biomedical InformaticsOsaka University Graduate School of MedicineOsakaJapan

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