Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Abstract

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is characterized by expression of oncogenic fusion product BCR-ABL1, resulting from reciprocal translocation between chromosomes 9 and 22 [t(9;22)(q34;q11.2)]. Previously perceived to confer poor outcome with at least 10 % lower chance of remission than standard-risk ALL. With the advent of targeted BCR-ABL specific tyrosine-kinase inhibitors (TKIs), higher remission rates were achieved, thus allowing more patients to proceed with the definitive treatment modality--allogeneic hematopoietic stem cell transplantation (alloHSCT). Prime challenges to treatment of Ph+ ALL include appropriate integration of TKIs into remission induction chemotherapeutic regimes, appropriate understanding and implementation of BCR-ABL monitoring for guiding therapeutic intervention(s), and minimizing transplant-related toxicities.