Evidence-Based Guidelines for the Use of Tyrosine Kinase Inhibitors in Adults with Philadelphia Chromosome–Positive or Bcr-Abl–Positive Acute Lymphoblastic Leukemia: A Canadian Consensus

Abstract

Adult Philadelphia chromosome–positive (Ph+) or BCR-ABL–positive (BCR-ABL+) acute lymphoblastic leukemia (ALL) is an acute leukemia previously associated with a high relapse rate, short disease-free survival, and poor overall survival. In adults, allogeneic hematopoietic cell transplant in first remission remains the only proven curative strategy for transplant-eligible patients. The introduction of tyrosine kinase inhibitors (TKIS) in the treatment of patients with Ph+ or BCR-ABL+ ALL has significantly improved the depth and duration of complete remission, allowing more patients to proceed to transplantation. Although tkis are now considered a standard of care in this setting, few randomized trials have examined the optimal use of TKIS in patients with Ph+ ALL. Questions of major importance remain, including the best way to administer these medications, the choice of tki to administer, and the schedule and the duration to use. We present the results of a systematic review of the literature with consensus recommendations based on the available evidence.

Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

“…Prior to the era of TKIs, with conventional chemotherapy alone, Ph+ ALL was associated with: high relapse rate, disease-free survival (DFS) not exceeding 10% and for ˂ 12 months, and poor overall survival (OS) [71,80]. When managed with multiagent chemotherapeutic regimens alone, patients with Ph+ ALL have inferior outcomes in terms of remission duration and OS compared with their Ph-ALL patients [73].…”

“…Two thirds of cases of ALL occur in children, while one third of cases occur in adults [71]. Treatment of ALL has produced remarkable improvements in outcome for children but the outlook for adults remains poor [71]. Philadelphia chromosome positive (Ph+) ALL is the most common cytogenetic abnormality found in adults with ALL as it accounts for 25% of ALL cases in adulthood [71][72][73].…”

“…Two thirds of cases of ALL occur in children, while one third of cases occur in adults [71]. Treatment of ALL has produced remarkable improvements in outcome for children but the outlook for adults remains poor [71].…”

“…Treatment with chemotherapy alone or chemotherapy and allogeneic HSCT in adult patients with Ph+ ALL has resulted in 5-year OS between: 45%-53% in patients ˂60 years of age and ˂10% in patients ≥ 60 years of age [71,75].…”

“…Treatment of ALL has produced remarkable improvements in outcome for children but the outlook for adults remains poor [71]. Philadelphia chromosome positive (Ph+) ALL is the most common cytogenetic abnormality found in adults with ALL as it accounts for 25% of ALL cases in adulthood [71][72][73]. However, the prevalence of Ph+ ALL increases with age as follows: ˂ 5% in children, 12%-30% in patients between 18 and 35 years, 40%-44% in patients between 35 and 50 years, and ˃ 50% in patients > 60 years of age [71,[74][75][76].…”