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

Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):e47-54. doi: 10.1016/j.clml.2014.09.006. Epub 2014 Sep 28.

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.

Keywords: Adverse events; Allogeneic stem cell transplantation; Dasatinib; Large granular lymphocyte; Philadelphia-positive ALL.

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biopsy
  • Bone Marrow / pathology
  • Combined Modality Therapy
  • Consolidation Chemotherapy
  • Dasatinib / administration & dosage
  • Dasatinib / adverse effects
  • Dasatinib / therapeutic use*
  • Female
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Induction Chemotherapy
  • Lymphocytes / pathology*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm, Residual
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Recurrence
  • Retrospective Studies
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Dasatinib