Abstract
During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.
Highlights
The best contemporary chemotherapy for childhood acute lymphoblastic leukemia (ALL) yields 5-year overall survival (OS) rates above 90%, which reflects intensified chemotherapy with treatment stratification directed by the somatic mutations and early response to chemotherapy, better use of conventional anti-leukemic agents, and improved supportive care, including broad-spectrum antibiotics to combat opportunistic infections[1,2]
Whereas recent high-throughput, cost-effective technologies have revolutionized our insight into the somatic mutational landscape of ALL, disease pathogenesis, and drug resistance mechanisms[5], our understanding of non-infectious chemotherapy-associated acute toxicities remains limited, including how to prevent and treat them
This review summarizes recent advancements in the exploration of non-infectious, chemotherapy-associated acute toxicities and outlines strategies for future research
Summary
The best contemporary chemotherapy for childhood acute lymphoblastic leukemia (ALL) yields 5-year overall survival (OS) rates above 90%, which reflects intensified chemotherapy with treatment stratification directed by the somatic mutations and early response to chemotherapy, better use of conventional anti-leukemic agents, and improved supportive care, including broad-spectrum antibiotics to combat opportunistic infections[1,2]. Many patients with a late relapse or a second cancer have a fair chance of cure[212,213], whereas chronic toxicities are generally irreversible and challenge patients’ ability to live a normal adult life[214] This calls for new endpoint measures that include both survival and quality of life, which will require common strategies for toxicity capture and Abbreviations 6-MP, 6-mercaptopurine; AAP, asparaginase-associated pancreatitis; ALL, acute lymphoblastic leukemia; CNS, central nervous system; HD, high dose; HPA, hypothalamic-pituitary-adrenal; hSCT, hematopoietic stem cell transplantation; MRI, magnetic resonance imaging; MTX, methotrexate; NMDAR, N-methyl-Daspartate receptor ON, osteonecrosis; OS, overall survival; PEG, polyethylene glycol; PRES, posterior reversible encephalopathy syndrome; PTWG, Ponte di Legno Toxicity Working Group; SLS, stroke-like syndrome; SOS, sinusoidal obstruction syndrome; TE, thromboembolism; UNL, upper normal limit. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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