Characteristics of patients with development of large granular lymphocyte expansion among dasatinib-treated patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic stem cell transplantation

Yoshikiyo Ito, Toshihiro Miyamoto, Tomohiko Kamimura, Kenichi Aoki, Hideho Henzan, Takatoshi Aoki, Motoaki Shiratsuchi, Koji Kato, Koji Nagafuji, Ryosuke Ogawa, Tetsuya Eto, Hiromi Iwasaki, Koichi Akashi

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)e47-e54
JournalClinical Lymphoma, Myeloma and Leukemia
Volume15
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

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Philadelphia Chromosome
Stem Cell Transplantation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematopoietic Stem Cell Transplantation
Lymphocytes
Protein-Tyrosine Kinases
Pleural Effusion
Combination Drug Therapy
Dasatinib
Therapeutics
Recurrence
Survival

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Characteristics of patients with development of large granular lymphocyte expansion among dasatinib-treated patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic stem cell transplantation. / Ito, Yoshikiyo; Miyamoto, Toshihiro; Kamimura, Tomohiko; Aoki, Kenichi; Henzan, Hideho; Aoki, Takatoshi; Shiratsuchi, Motoaki; Kato, Koji; Nagafuji, Koji; Ogawa, Ryosuke; Eto, Tetsuya; Iwasaki, Hiromi; Akashi, Koichi.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 15, No. 3, 01.03.2015, p. e47-e54.

Research output: Contribution to journalArticle

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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.",
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AU - Kamimura, Tomohiko

AU - Aoki, Kenichi

AU - Henzan, Hideho

AU - Aoki, Takatoshi

AU - Shiratsuchi, Motoaki

AU - Kato, Koji

AU - Nagafuji, Koji

AU - Ogawa, Ryosuke

AU - Eto, Tetsuya

AU - Iwasaki, Hiromi

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N2 - 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.

AB - 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.

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