Tatsunori Ishikawa1, Nobuharu Fujii2, Masahide Imada3, Michinori Aoe3, Yusuke Meguri4, Tomoko Inomata4, Hiromi Nakashima4, Keiko Fujii5, Shohei Yoshida4, Hisakazu Nishimori4, Ken-Ichi Matsuoka4, Eisei Kondo4, Yoshinobu Maeda4, Mitsune Tanimoto4. 1. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan; Division of Transfusion, Okayama University Hospital, Okayama, Japan. 2. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan; Division of Transfusion, Okayama University Hospital, Okayama, Japan. Electronic address: nfujii@md.okayama-u.ac.jp. 3. Department of Laboratory Medicine, Okayama University Hospital, Okayama, Japan. 4. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan. 5. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan; Department of Laboratory Medicine, Okayama University Hospital, Okayama, Japan.
Abstract
BACKGROUND: Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. CASE REPORT: Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation. We observed a powerful graft-versus-leukemia (GVL) effect accompanied by an evident Wilms tumor antigen 1 (WT1)-specific CD8 T-cell response. Remission continued for 15 months, but finally the patient relapsed. The kinetics of the WT1-specific CD8 T cells were inversely associated with WT1 messenger RNA (mRNA), suggesting a WT1-driven GVL effect. DISCUSSION: A difference of T-cell phenotype between the whole T cells and the WT1-specific CD8 T cells was observed. It is of note that the memory phenotype of the WT1-specific T cell was limited and decreased early. The immunoescape mechanism was partly supported by loss of the memory phenotype due to failure of expansion and differentiation. CONCLUSION: Our data suggested that a WT1-specific T-cell response at least partly contributes to the GVL effect induced by Aza + DLI. A strategy for maximizing and maintaining the memory phenotype of the CTL may be required for durable remission.
BACKGROUND:Azacitidine (Aza) and donor lymphocyte infusion (DLI) therapy has recently been reported as an effective salvage therapy for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite the high response rate and relatively long period of remission, most patients relapse again. The immunologic mechanism of the response and limited efficacy remain unknown. CASE REPORT: Aza + DLI therapy was performed for a patient with therapy-related MDS (t-MDS), who had relapsed after allogeneic peripheral blood stem cell transplantation. We observed a powerful graft-versus-leukemia (GVL) effect accompanied by an evident Wilms tumor antigen 1 (WT1)-specific CD8 T-cell response. Remission continued for 15 months, but finally the patient relapsed. The kinetics of the WT1-specific CD8 T cells were inversely associated with WT1 messenger RNA (mRNA), suggesting a WT1-driven GVL effect. DISCUSSION: A difference of T-cell phenotype between the whole T cells and the WT1-specific CD8 T cells was observed. It is of note that the memory phenotype of the WT1-specific T cell was limited and decreased early. The immunoescape mechanism was partly supported by loss of the memory phenotype due to failure of expansion and differentiation. CONCLUSION: Our data suggested that a WT1-specific T-cell response at least partly contributes to the GVL effect induced by Aza + DLI. A strategy for maximizing and maintaining the memory phenotype of the CTL may be required for durable remission.