Chronic myelogenous leukemia presenting with central nervous system infiltration, successfully treated with central nervous system-directed chemotherapy followed by allogeneic stem cell transplantation

Int J Hematol. 2018 Dec;108(6):640-646. doi: 10.1007/s12185-018-2511-6. Epub 2018 Aug 4.

Abstract

With the introduction of tyrosine kinase inhibitors (TKIs), prognosis of chronic myelogenous leukemia (CML) has improved dramatically. However, treatment for blast phase (BP) CML remains a challenge. CML infiltration of the central nervous system (CNS) is particularly rare and no effective treatment strategy has been established. The present case reports a 30-year-old man presenting with sensory deafness. Marked leukocytosis with p210 BCR-ABL1 mRNA positivity and Philadelphia chromosome detected by bone marrow biopsy confirmed the diagnosis of CML. Dura thickening in brain MRI and immature cells with Philadelphia chromosome in spinal fluid confirmed CNS invasion of CML and he was diagnosed with BP-CML. Two cycles of hyper-CVAD/MA (cyclophosphamide, vincristine, doxorubicin and dexamethasone/ high-dose methotrexate and cytarabine) therapy with dasatinib and concomitant intrathecal chemotherapy induced complete cytogenetic response and remission of CNS involvement. Bone marrow transplantation from an unrelated HLA-mismatched donor was performed and complete molecular response in bone marrow and complete remission in CNS disease was achieved. To our knowledge, this the first report of BP-CML with CNS infiltration at initial diagnosis, and shows that CNS-directed chemotherapy with dasatinib followed by allogeneic hematopoietic stem cell transplantation is useful in the treatment for BP-CML with CNS invasion in the TKI era.

Keywords: Allogeneic hematopoietic stem cell transplantation; Blast phase; Central nervous system; Chronic myelogenous leukemia; Tyrosine kinase inhibitor.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers
  • Biopsy
  • Bone Marrow / pathology
  • Central Nervous System Neoplasms / diagnosis
  • Central Nervous System Neoplasms / secondary*
  • Central Nervous System Neoplasms / therapy*
  • Combined Modality Therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Biomarkers