Abstract
Introduction: The Philadelphia chromosome (Ph) is the most common cytogenetic abnormality associated
with adult acute lymphoblastic leukemia (ALL) occurring in 20% to 40% of patients.
It is also detected in 2% to 5% of children with ALL. Historically, patients with
Ph-positive ALL carried a dismal prognosis, with poor response to most chemotherapy
combinations, short remission durations, and long-term disease-free survival rates
of 10% to 20%. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized
therapy of Ph-positive ALL. Materials and Methods: This retrospective and descriptive single center study was carried out based on data
retrieved of 508 patients treated for ALL from 2007 to 2014. Of these thirty patients
were Ph-positive ALL and were available for analysis, and these patients were included
in the study. Ph-positive ALL was defined as ALL carrying the t(9;22) translocation
on standard karyotype and/or fluorescent in situ hybridization analysis and/or positivity
for BCR-ABL fusion transcript detection by real-time quantitative polymerase chain
reaction (RQ-PCR) analysis. Patients were treated with combination chemotherapy and
oral TKIs and responses were classified as either CR defined by the absence of circulating
blasts and <5% marrow blasts on a bone marrow examination done at the end of induction
chemotherapy or failure, including persistent disease and early death. Results: There were 30 (5.9%) cases of Ph-positive ALL out of a total of 508 cases of ALL
with a median age of 27.5 years (range: 7-55). The choice of first line TKI was Imatinib
in 25 (83.3 %) patients and Dasatinib in 1 (3.3 %) patient. Fourteen patients (46.6
%) had a CR, 3 (10 %) had a partial response (PR), 8 (26.6 %) had persistence of disease
at the end of induction chemotherapy. The overall survival in those who received sequential
chemotherapy followed by TKI (n = 4) was 28.5 months (95% CI 10.78 to 46.21 months) compared with 13.98 months (95%
CI 6.04 to 21.97 months) for patients who received concurrent chemotherapy and TKI
(n = 20); log rank (Mantel Cox) X 2 = 8.33, P = 0.040), however limited sample precluded meaningful subgroup analysis. Conclusion: The results of our study showed that we still have a long way to go to match outcomes
of western published series, even when the same treatment protocol is used, probably
due to the underutilization of Allogeneic SCT as an option in first CR.
Key words
Acute lymphoblastic leukemia - chemotherapy - overall survival - Philadelphia chromosome
