Yoshikiyo Ito1, Toshihiro Miyamoto2, Tomohiko Kamimura3, Kenichi Aoki4, Hideho Henzan5, Takatoshi Aoki3, Motoaki Shiratsuchi6, Koji Kato7, Koji Nagafuji8, Ryosuke Ogawa4, Tetsuya Eto5, Hiromi Iwasaki9, Koichi Akashi7. 1. Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Japan; Department of Hematology, Harasanshin Hospital, Fukuoka, Japan. 2. Department of Medicine and Biosystemic Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. Electronic address: toshmiya@intmed1.med.kyushu-u.ac.jp. 3. Department of Hematology, Harasanshin Hospital, Fukuoka, Japan. 4. Department of Hematology, Japan Community Health care Organization Kyushu Hospital, Kitakyushu, Japan. 5. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan. 6. Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. 7. Department of Medicine and Biosystemic Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. 8. Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. 9. Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan.
Abstract
INTRODUCTION: Widespread use of tyrosine kinase inhibitors (TKIs) in combination with chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-SCT) has totally changed the existing treatment strategies for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). However, the prognosis after relapse after allo-SCT is still dismal. PATIENTS AND METHODS: We analyzed the clinical outcome of therapy using dasatinib, a second-generation TKI, in 9 patients with relapsed Ph(+)ALL after allo-SCT. Dasatinib was initiated at a median time of 168 days after allo-SCT at dosages ranging from 20 mg to 100 mg daily. RESULTS: Six of 9 patients manifested a marked increase in large granular lymphocytes (LGLs), but all 6 patients discontinued dasatinib because of adverse events (AEs) such as pleural effusion. Four of 6 patients resumed dasatinib, and 3 of them have been alive with molecular complete remission and a persistent increase of LGLs. CONCLUSION: Our results demonstrated that dasatinib therapy can induce LGL expansion accompanied by AEs, but this phenomenon can be associated with long-term survival benefit in a proportion of relapsed Ph(+)ALL patients after allo-SCT.
INTRODUCTION: Widespread use of tyrosine kinase inhibitors (TKIs) in combination with chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-SCT) has totally changed the existing treatment strategies for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). However, the prognosis after relapse after allo-SCT is still dismal. PATIENTS AND METHODS: We analyzed the clinical outcome of therapy using dasatinib, a second-generation TKI, in 9 patients with relapsed Ph(+)ALL after allo-SCT. Dasatinib was initiated at a median time of 168 days after allo-SCT at dosages ranging from 20 mg to 100 mg daily. RESULTS: Six of 9 patients manifested a marked increase in large granular lymphocytes (LGLs), but all 6 patients discontinued dasatinib because of adverse events (AEs) such as pleural effusion. Four of 6 patients resumed dasatinib, and 3 of them have been alive with molecular complete remission and a persistent increase of LGLs. CONCLUSION: Our results demonstrated that dasatinib therapy can induce LGL expansion accompanied by AEs, but this phenomenon can be associated with long-term survival benefit in a proportion of relapsed Ph(+)ALL patients after allo-SCT.