ALL in which the Philadelphia chromosome is present
Last reviewed 01/2018
The presence of the Philadelphia chromosome in patients with ALL is a poor prognostic factor:
- occurs in 20-30% of adult ALL and in 3% of childhood ALL (1)
- prior to the advent of tyrosine kinase inhibitors (TKI), Ph+ ALL was associated
with a very poor prognosis despite the use of intensive chemotherapy and frequently
hematopoietic stem-cell transplantation (HSCT) in first remission
- development of TKIs revolutionized the therapy of Ph+ ALL. Addition
of the first generation ABL1 class TKI imatinib to intensive chemotherapy
dramatically increased the survival for children with Ph+ ALL and established
that many patients can be cured without HSCT (2)
- development of TKIs revolutionized the therapy of Ph+ ALL. Addition
of the first generation ABL1 class TKI imatinib to intensive chemotherapy
dramatically increased the survival for children with Ph+ ALL and established
that many patients can be cured without HSCT (2)
- in patients with ALL and a Philadelphia chromosome:
- 1/3 - have M-bcr (major breakpoint-cluster region) rearrangements (resulting in a 210-kd protein) similar to those in patients with CML
- 2/3 - have m-bcr (minor breakpoint-cluster region) rearrangements with a consequent 190-kd protein
- outcome for patients with either variant is equally poor
Reference:
- Editorial.Acute lymphoblastic leukaemia - progress in children, less in adults.NEJM (1993);329:1343-44.
- Bernt KM, Hunger SP.Current Concepts in Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Front Oncol. 2014 Mar 25;4:54.