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Ito, Sawa, M.D., Ph.D.

Researcher Profiles

Researcher Profiles

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Sawa Ito, M.D., Ph.D.

Sawa Ito, M.D., Ph.D.

The University of Pittsburgh

2023 Funding recipient

Phase 2 study of IFN-y and donor lymphocyte infusion to treat relapsed myeloid malignancies after allogeneic hematopoietic stem cell transplantation

Discovery Research Grant 2023

PROJECT SUMMARY

Allogeneic hematopoietic stem cell transplantation  (alloSCT) can potentially cure the patients with high-risk myelodysplastic syndrome (MDS). Donor-derived immune cells mediated graft- versus-leukemia effect (GVL) and kill abnormal MDS cells. However, GVL failure can lead to the reappearance of abnormal MDS cells (i.e., relapse) even after transplantation. Unfortunately, nearly one-third of the MDS patients die from relapse after alloSCT. Effective therapy has not been established for relapse after transplant.  Based  on  results  from animal studies,  we developed the clinical trial utilizing  the cytokine called “interferon-gamma” to strengthen  the GVL for the patients with myeloid malignancies including MDS and acute myeloid leukemia (AML). Interferon-gamma is approved to treat chronic granulomatous disease,  a rare inherited immunodeficiency; however, interferon-gamma had never before been tested for the treatment of relapsed MDS/AML after alloSCT. In a pilot study, we treated 4 patients with relapsed AML/MDS after alloSCT with interferon-gamma. All patients tolerated interferon-gamma well without unexpected side effects. Three patients achieved complete remissions after treatment with interferon-gamma combined with donor lymphocytes infusion harvested from their original stem cell donor. In this proposal, we plan to treat more patients to confirm the efficacy of the interferon-gamma and  donor lymphocyte combination therapy and perform studies to better understand how interferon-gamma acts on malignant cells. Should this trial confirm the efficacy observed in our pilot study, this would allow more MDS patients to receive alloSCT and eventually improve the survival of MDS patients.

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