Tyrosine Kinase Inhibitor Therapy Based on Molecular Monitoring of BCR/ABL Transcript Levels in Allogeneic Hematopoietic Stem Cell Transplant Recipients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
Philadelphia chromosome (Ph) is a reciprocal chromosomal translocation t(9;22）(q34;q11),
which leads to the formation of the BCR/ABL oncogene. Ph is the most frequent cytogenetic
abnormality in ALL characterized by poor outcome. With the BCR/ABL protein TKI, imatinib, in
the combination chemotherapy regimes for newly diagnosed Ph+ ALL, more than 95% of patients
can achieve complete remission(CR)1. Several studies have shown decreased relapse rates and
improved disease-free survival for patients with imatinib-based treatment prior to
allo-HSCT. However, the efficacy of maintenance therapy with imatinib after transplant for
Ph+ ALL patients is still uncertain. In addition, acquired resistance to imatinib is
frequently caused by point mutations in BCR/ABL that inactivate imatinib.
Detection of minimal residual disease (MRD) after transplant is associated with an increased
risk of relapse. Reverse transcription-polymerase chain reaction (RT-PCR) is a sensitive
method for detecting low-level BCR/ABL transcripts to assess MRD in Ph+ ALL. It has been
corroborated by several reports that detection of MRD after SCT was predictive of imminent
In this study, we will evaluate the safety and efficacy of TKI therapy, when initiating
treatment based on BCR-ABL transcript levels after allo-HSCT.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary endpoint assesses the efficacy of TKI therapy. DFS is defined as continuous survival without relapse or death from any cause after HSCT.
Qifa Liu, MD
Nanfang Hospital,Southern Medical University
China: Ethics Committee