Abstract
Acute lymphoblastic leukemia (ALL) in infants has a significantly inferior outcome in comparison with older children. Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has plateaued in recent years. Historically, infants were treated on risk-adapted childhood ALL protocols. These studies were pivotal in identifying the need for infant-specific protocols, delineating prognostic categories and the requirement for a more unified approach between study groups to overcome limitations in accrual because of low incidence. This subsequently led to the development of collaborative infant-specific studies. Landmark outcomes have included the elimination of cranial radiotherapy following the discovery of intrathecal and high-dose systemic therapy as a superior and effective treatment strategy for central nervous system disease prophylaxis, with improved neurodevelopmental outcome. Universal prospective identification of independent adverse prognostic factors, including presence of a mixed lineage leukemia rearrangement and young age, has established the basis for risk stratification within current trials. The infant-specific trials have defined limits to which conventional chemotherapeutic agents can be intensified to optimize the balance between treatment efficacy and toxicity. Despite variations in therapeutic intensity, there has been no recent improvement in survival due to the equilibrium between relapse and toxicity. Ultimately, to improve the outcome for infants with ALL, key areas still to be addressed include identification and adaptation of novel prognostic markers and innovative therapies, establishing the role of hematopoietic stem cell transplantation in first complete remission, treatment strategies for relapsed/refractory disease and monitoring and timely intervention of late effects in survivors. This would be best achieved through a single unified international trial.
Highlights
INTRODUCTIONThe majority of first relapses occurred early (within months of diagnosis) and was the primary cause of death.[14] the probability of isolated central nervous system (CNS) relapse on Cancer Group (CCG)-1883 was lower (3.0%) as compared with CCG-107 (8.2%),[15] and was similar to a historical control (CCG-160) that used cranial radiotherapy (5%).[14] This led to the conclusion that compared with cranial radiotherapy, the combination of intrathecal and high-dose systemic therapy represented a superior and effective treatment strategy for prevention of CNS disease, with improved neurodevelopmental outcome.[14,17] Analysis of combined data from both studies identified several prognostic factors associated with poor outcome, including age o6 months at diagnosis, with the most inferior outcome in those o3 months, CD10 negativity, failure of morphological remission on day marrow, white blood cell (WBC) 450 Â 109/l at diagnosis and presence of the t(4;11) mixed lineage leukemia (MLL) rearrangement.[14]
Acute lymphoblastic leukemia (ALL) is the most common malignancy occurring in children and adolescents, accounting for B20% of cancers in patients younger than 20 years of age.[1,2] Remarkable therapeutic advances have been made since Sidney Farber first reported temporary remission in five children with acute leukemia using the folate antagonist, aminopterin, in 1948.3 The 5-year overall survival (OS) exceeds 90%, with significant improvements in survival for subgroups according to age, sex, race, immunophenotype and National Cancer Institute risk status.[4]
Survival of infants with ALL continues to remain significantly inferior to older children
Summary
The majority of first relapses occurred early (within months of diagnosis) and was the primary cause of death.[14] the probability of isolated CNS relapse on CCG-1883 was lower (3.0%) as compared with CCG-107 (8.2%),[15] and was similar to a historical control (CCG-160) that used cranial radiotherapy (5%).[14] This led to the conclusion that compared with cranial radiotherapy, the combination of intrathecal and high-dose systemic therapy represented a superior and effective treatment strategy for prevention of CNS disease, with improved neurodevelopmental outcome.[14,17] Analysis of combined data from both studies identified several prognostic factors associated with poor outcome, including age o6 months at diagnosis, with the most inferior outcome in those o3 months, CD10 negativity, failure of morphological remission on day marrow, WBC 450 Â 109/l at diagnosis and presence of the t(4;11) MLL rearrangement.[14]. Age o6 months, presence of CNS disease and hyperleukocytosis at diagnosis identified as independent adverse prognostic factors
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.
