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Tumour lysis syndrome (TLS) describes the metabolic derangements that occur with tumour breakdown following the initiation of cytotoxic therapy. TLS results from the rapid destruction of malignant cells and the abrupt release of intracellular ions, nucleic acids, proteins and their metabolites into the extracellular space. These metabolites can overwhelm the body's normal homeostatic mechanisms and cause hyperuricaemia, hyperkalaemia, hyperphosphaetemia, hypocalcaemia and uraemia. TLS can lead to acute renal failure and can be life-threatening. Early recognition of patients at risk and initiation of therapy for TLS is essential. There is a high incidence of TLS in tumours with high proliferative rates and tumour burden such as acute lymphoblastic leukaemia and Burkitt's lymphoma. The mainstays of TLS prophylaxis and treatment include aggressive hydration and diuresis, control of hyperuricaemia with allopurinol prophylaxis and rasburicase treatment, and vigilant monitoring of electrolyte abnormalities. Urine alkalinization remains controversial. Unfortunately, there have been few comprehensive reviews on this important subject. In this review, we describe the incidence, pathophysiological mechanisms of TLS and risk factors for its development. We summarise recent advances in the management of TLS and provide a new classification system and recommendations for prophylaxis and/or treatment based on this classification scheme.

Key Points Donor-derived anti-CD19-CAR T cells cause regressions of refractory malignancies after allogeneic transplantation.

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Chronic active EBV disease (CAEBV) is

Although reduced intensity (RIC) and nonmyeloablative (NMA) conditioning regimens have been used for over a decade, their relative efficacy versus myeloablative (MA) approaches to allogeneic hematopoietic cell transplantation (HCT) in patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) is unknown. We compared disease status, donor, graft and recipient characteristics with outcomes of 3731 MA with 1448 RIC/NMA procedures performed at 217 centers between 1997 and 2004. Five year univariate probabilities and multivariate relative risk (RR) outcomes of relapse, transplant related mortality (TRM), disease free survival (DFS) and overall survival (OS) are reported. Adjusted OS at 5 years was 34%, 33%, and 26% for MA, RIC and NMA transplants, respectively. NMA conditioning resulted in inferior DFS and OS but there was no difference in DFS and OS between RIC and MA regimens. Late TRM negates early decreases in toxicity with RIC and NMA regimens. Our data suggest higher regimen intensity may contribute to optimal survival in patients with AML/MDS, suggesting roles for both regimen intensity and graft vs. leukemia in these diseases. Prospective studies comparing regimens are needed to confirm this finding and determine the optimal approach to patients who are eligible for either MA or RIC/NMA conditioning.

Immune effector cell (IEC) therapies offer durable and sustained remissions in significant numbers of patients with hematological cancers. While these unique immunotherapies have improved outcomes for pediatric and adult patients in a number of disease states, as ‘living drugs,’ their toxicity profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), differ markedly from conventional cancer therapeutics. At the time of article preparation, the US Food and Drug Administration (FDA) has approved tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel, all of which are IEC therapies based on genetically modified T cells engineered to express chimeric antigen receptors (CARs), and additional products are expected to reach marketing authorization soon and to enter clinical development in due course. As IEC therapies, especially CAR T cell therapies, enter more widespread clinical use, there is a need for clear, cohesive recommendations on toxicity management, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of common toxicities in the context of IEC treatment, including baseline laboratory parameters for monitoring, timing to onset, and pharmacological interventions, ultimately forming evidence- and consensus-based recommendations to assist medical professionals in decision-making and to improve outcomes for patients.

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