Hematopoietic stem cell transplantation for T315I-mutated chronic myelogenous leukemia

Ann Transplant. 2010 Apr-Jun;15(2):68-70.

Abstract

Background: The T315I mutation of BCR/ABL gene is known to produce complete resistance of chronic myelogenous leukemia (CML) to all currently available BCR/ABL inhibitors. The data suggesting poor median survival of these patients may indicate that they should be primary candidates for allogeneic stem cell transplantation (alloSCT). However, evidence on efficiency of this treatment modality in CML with T315I mutation is lacking.

Case report: A 25-year-old patient was diagnosed with Philadelphia chromosome positive CML in accelerated phase. As he did not have an HLA-identical sibling or fully-matched unrelated bone marrow donor, treatment with low dose tyrosine kinase inhibitor - imatinib was initiated. Despite satisfactory hematological remission, he failed to achieve complete cytogenetic remission within the first year of treatment. Moreover, despite escalation of imatinib dosage, the disease relapsed after further 3 months of treatment. Molecular studies revealed T315I mutation of BCR/ABL gene. He responded poorly to interferon alpha (IFN-alpha) and we decided to perform alloSCT from a partially mismatched (8/10 HLA allele match) unrelated donor. The course of transplantation was complicated by staphylococcal sepsis, grade I skin acute GvHD and limited chronic skin GVHD. However, the goal of alloSCT was achieved and the patient remains in complete molecular remission at week +68 post-transplantation.

Conclusions: The clinical course of this case supports the idea that allogeneic hematopoietic transplantation is a viable treatment option for patients with CML bearing T315I mutation.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Drug Resistance, Neoplasm / genetics
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / genetics
  • Genes, abl*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Leukemia, Myeloid, Accelerated Phase / drug therapy
  • Leukemia, Myeloid, Accelerated Phase / genetics
  • Leukemia, Myeloid, Accelerated Phase / therapy
  • Male
  • Mutation, Missense*
  • Protein Kinase Inhibitors / pharmacology
  • Remission Induction
  • Transplantation, Homologous

Substances

  • Protein Kinase Inhibitors
  • Fusion Proteins, bcr-abl