Meeting Challenges in the Long-Term Care of Children, Adolescents, and Young Adults with Acute Lymphoblastic Leukemia.

PURPOSE OF REVIEW: To discuss the long-term view of treating and following pediatric, adolescent, and young adult patients with acute lymphoblastic leukemia (ALL) - with review of what can be done to prevent, monitor for, and treat complications of therapy. RECENT FINDINGS: Pediatric, adolescent, and young adult oncology patients, including those with ALL, are living longer with higher overall survival rates as treatments and supportive care for these patients continue to improve. These patients are burdened by the risk of significant health and quality of life consequences as a result of their treatment.. For these patients, the late effects of treatment can be life-threatening, such as secondary cancers or cardiotoxicity, or life-altering with respect to quality of life. The goal of this paper is to review the current literature, research, and surveillance guidelines regarding the late effects of ALL therapy, to outline what can be done to mitigate the toxic effects of oncology treatment, and to extend life expectancy and improve quality of life for our patients. We review risk factors and interventions available to prevent and treat cardiovascular disease, secondary malignancies, endocrine complications (obesity, osteoporosis, infertility, and premature menopause), cognitive effects, and effects on functioning and mortality.

Current approaches in the grading and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy.

With immunotherapy innovations for cancer treatment, in particular chimeric antigen receptor (CAR) T cells, becoming more successful and prevalent, strategies to mitigate and manage their toxicities are required. Anti-CD19 CAR T-cell therapy has revolutionized the treatment of relapsed/refractory pediatric and adult acute lymphoblastic leukemia and refractory adult non-Hodgkin lymphoma, resulting in the expanded use of CAR T cells in multicenter trials and as US FDA-approved products. Cytokine release syndrome (CRS) and CAR-associated neurotoxicity, which can occur independently or concurrently with CRS, are two potentially life-threatening toxicities of CAR T-cell therapy. In this review, we will focus on describing the pathophysiology behind CRS, the proposed definitions of and grading systems for CRS, and innovative options for treating this potentially lethal systemic inflammatory condition.

Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival.

High lethality rates associated with metastatic cancer highlight an urgent medical need for improved understanding of biologic mechanisms driving metastatic spread and identification of biomarkers predicting late-stage progression. Numerous neoplastic cell intrinsic and extrinsic mechanisms fuel tumor progression; however, mechanisms driving heterogeneity of neoplastic cells in solid tumors remain obscure. Increased mutational rates of neoplastic cells in stressed environments are implicated but cannot explain all aspects of tumor heterogeneity. We present evidence that fusion of neoplastic cells with leukocytes (for example, macrophages) contributes to tumor heterogeneity, resulting in cells exhibiting increased metastatic behavior. Fusion hybrids (cells harboring hematopoietic and epithelial properties) are readily detectible in cell culture and tumor-bearing mice. Further, hybrids enumerated in peripheral blood of human cancer patients correlate with disease stage and predict overall survival. This unique population of neoplastic cells provides a novel biomarker for tumor staging, as well as a potential therapeutic target for intervention.