Abstract
Acute leukemia is the most common cancer in childhood; in particular, acute lymphoblastic leukemia (ALL) represents roughly up to 80% of all cases of acute leukemias in children. Survival of children with ALL has dramatically improved over the last few decades, and is now over 90% (versus 40% of adult patients) in developed countries, except for in infants (i.e., children < 1 year), where no significant improvement was registered. Philadelphia positive ALL (Ph+ALL) accounts for around 3% of cases of childhood ALL, its incidence increasing with patient’s age. Before the era of tyrosine-kinase inhibitors (TKIs), pediatric Ph+ALL showed a worse prognosis in comparison to other forms of ALL, and was managed with intensive chemotherapy, followed, whenever possible, by allogenic hematopoietic stem cell transplantation (HSCT) in first morphological complete remission. TKIs have revolutionized the current clinical approach, which involves combinations of imatinib plus standard chemotherapy that can abrogate the negative prognostic impact conferred by the presence of BCR/ABL1 rearrangement, resulting in the probability of event-free survival (EFS) being significantly better than that recorded in the pre-TKI era. Long-term follow-up confirms these data, questioning the role of a real advantage offered by HSCT over intensive chemotherapy plus TKI in all Ph+ALL pediatric patients. Imatinib was the first generation TKI and the prototype of targeted therapy, but over the years second- (dasatinib, nilotinib, bosutinib) and third-generation (ponatinib) TKIs showed a capacity to overcome resistance to imatinib in Ph+ hematological neoplasms. Given the effectiveness of the first-in-class TKI, imatinib, also the second-generation TKI dasatinib was incorporated in the treatment regimens of Ph+ALL. In this manuscript, we will discuss the role of this drug in pediatric Ph+ALL, analyzing the available data published to date.
Highlights
Through the application of reliable prognostic factors and riskoriented treatment protocols, almost 85% of children with newly diagnosed acute lymphoblastic leukemia (ALL) can be cured today
These improved patient outcomes in childhood ALL are due to many factors, including a better knowledge of the molecular lesions responsible for disease occurrence, monitoring of minimal residual disease (MRD), which represents a surrogate biomarker of leukemia cell sensitivity to chemotherapy, refined risk-adapted chemotherapy treatment and better results in patients given allogeneic hematopoietic stem cell transplantation (HSCT)
The outcome of refractory/relapsed ALL (r/rALL) remains, even nowadays, unsatisfactory and treatment must be diversified according to subsequent risk of treatment failure for children experiencing leukemia recurrence [8, 9]
Summary
Acute leukemia is the most common cancer in childhood; in particular, acute lymphoblastic leukemia (ALL) represents roughly up to 80% of all cases of acute leukemias in children. Philadelphia positive ALL (Ph+ALL) accounts for around 3% of cases of childhood ALL, its incidence increasing with patient’s age. Long-term follow-up confirms these data, questioning the role of a real advantage offered by HSCT over intensive chemotherapy plus TKI in all Ph+ALL pediatric patients. Given the effectiveness of the first-in-class TKI, imatinib, the second-generation TKI dasatinib was incorporated in the treatment regimens of Ph+ALL. In this manuscript, we will discuss the role of this drug in pediatric Ph+ ALL, analyzing the available data published to date
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
