Practical guidance for the management of acute lymphoblastic leukemia in the adolescent and young adult population

Abstract

The outstanding therapeutic progress achieved with modern pediatric regimens in childhood acute lymphoblastic leukemia (ALL) led efforts to explore whether a similar treatment approach could be equally effective and safe in older patients, starting initially with older adolescents and young adults (AYA), variably defined in different studies by an age between 15-18 and 25-39 years. Several comparative and noncomparative trials of this type have been carried out during the last two decades, enrolling thousands of patients. Almost without exception, the new strategy improved patients' outcomes compared with traditional adult treatments in B-lineage and T-lineage Philadelphia (Ph) chromosome-negative B-ALL, while the use of tyrosine kinase inhibitors (TKI) led to comparative progress in Ph+ ALL, a former high-risk subset more typically observed in older age groups. At present, highly effective pediatric-based regimens warrant 5-year survival rates of 60-70% in AYA patients. In view of these data, the same approach was progressively extended to older patients, improving the results up to 55 years of age. Issues of treatment compliance and drug-related toxicity have thus far prevented a comparable therapeutic advancement in patients aged >55 years. This critical review updates and summarizes with pertinent examples this global, positive therapeutic change, and examines how to promote further progress with new targeted therapies that include novel immuno-therapeutics and other agents developed against the many molecular dysfunctions detectable in various ALL subsets. Substantial progress is expected to occur soon, bringing AYA survival figures very close to that of children, and also to improve the outcome of ALL at all ages.

Global burden and trend of acute lymphoblastic leukemia from 1990 to 2017

“…Benefiting from developments of intensified chemotherapy as well as immunotherapeutic strategies such as Rituximab and chimeric antigen receptor T-cell therapy, the clinical outcomes of ALL patients have been significantly improved [ 8 – 10 ]. At the present stage, the 5-year survival rate of children with ALL is over 90% [ 11 ]. However, the clinical outcomes of ALL vary in different age groups and countries.…”

MRD-Based Therapeutic Decisions in Genetically Defined Subsets of Adolescents and Young Adult Philadelphia-Negative ALL

“…In all these studies, the diagnostic characteristics of AYA ALL, genetics in first place, were intermediate between those observed in children and older adults. Overall, once the challenge of improving the outcome of AYA patients was correctly perceived and the first innovative trials demonstrated the advantages of using modern pediatric rather than historical adult programs, the new approach was rapidly adopted by virtually all cooperative adult ALL Study Groups worldwide [ 9 , 15 , 16 , 17 ] and is highly recommended at present. All these topics are considered in the following sections.…”

Genetic Profile and Clinical Implications of PDGFRB Fusion in Adult B-Cell Acute Lymphoblastic Leukemia: A Retrospective Analysis

“…The minimal residual disease (MRD) was analyzed in the bone marrow by ow cytometry (Beckman Coulter Ireland, Navios, Flow 10-color antibody panels). Consolidation regimen: Consolidation chemotherapy was based on high-dose methotrexate (MTX) and cytarabine (Ara-C), 10 and 3 cases were combined with TKI therapy (Table 2). Chimeric antigen receptor-modi ed T cell (CAR-T) therapy: CAR-T cells were derived from autologous lymphocyte.…”