Philadelphia-Positive B-Acute Lymphoblastic Leukemia: Does it Differ from Philadelphia Negative One?
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- Category: Vol. 85, September 2017
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Philadelphia-Positive B-Acute Lymphoblastic Leukemia: Does it Differ from Philadelphia Negative One?, FATMA G. ABD EL-NASSER, RAAFAT ABD EL-MALEK, SOMAYA EL-DEEB and NEEMAT M. KASSEM
Abstract
Background: Approximately one-fourth of adult Acute Lymphoblastic Leukemia (ALL) expresses the oncogenic protein BCR-ABL1 that results from the t (9;22) chromosome translocation known as the Philadelphia (Ph) chromosome. Formerly seen as a poorly tractable therapeutic problem; Ph-positive (Ph+) ALL is associated with at least a 10% lower chance of Complete Remission (CR) than Ph-negative (Ph–) disease and with an extremely poor prognosis overall. However, multiple clinical trials of BCR-ABL-specific Tyrosine Kinase Inhibitors (TKIs) have conclusively demonstrated significantly superior initial responses resulting in higher CR rates without additional toxicity.
Purpose: Little evidence exists regarding the prevalence, clinical outcomes and molecular response of adult patients with Ph+ versus Ph– B-ALL in our country. The aim of our study was to explore the presence of minor BCR-ABL (P190) gene in Egyptian B-ALL patients and correlate it with treatment outcome.
Patients and Methods: Quantitative assessment of minor BCR-ABL gene expression was performed by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) in 48 Egyptian B-ALL patients. All patients received classic ALL treatment in addition to TKI (Imatinib) in the minor BCR-ABL +ve patients.
Results: Only Ten patients (21%) were positive for minor BCR-ABL. Concerning molecular response, minor BCR-ABL fusion gene was expressed in mRNA of patient leukocytes (Mean ± SD=0.006±0.006), with a 3 log reduction from baseline ratio after receiving treatment. Disease Free Survival (DFS) was significantly higher among Ph+ve patients than Ph-ve patients (p=0.049).
Conclusion: In conclusion, the TKIs have significantly improved outcomes for adult patients with Ph-positive ALL, with the use of imatinib in combination with intensive che-motherapy early in the treatment course. Over the coming years, the treatment of adult ALL will certainly change from disease-type to molecular-target type and from risk-stratified treatment schedules to more personalised therapies. More specific therapies and new immunotherapy-based approaches are the most promising advances for improving prognosis and reducing treatment-related morbidity.