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Asparaginase, an important treatment component for acute lymphoblastic leukemia (ALL), causes severe hepatotoxicity in some patients. Levocarnitine is a mitochondrial co-factor that can potentially ameliorate the mitochondrial toxicity of asparaginase. In this retrospective case series, we describe the clinical presentation and management of six pediatric and young adult patients (mean age 12.7, range 9–24 years) with ALL who developed Grade 3–4 hyperbilirubinemia following administration of asparaginase as part of induction/re-induction therapy. Five of these patients were treated with levocarnitine with subsequent improvement of hyperbilirubinemia, while one patient was given levocarnitine prophylactically during induction and developed Grade 3 hyperbilirubinemia, but did not require therapy adjustments or delays. Increased awareness in the pediatric oncology community regarding asparaginase-associated hepatic toxicity and the potential role of levocarnitine in management is warranted.

Remarkable improvements in survival rates have made childhood acute lymphoblastic leukemia (ALL) a success story within pediatric oncology. The excellent outcomes for many patients with ALL have resulted in part from risk stratification based on well-established clinical and disease features of prognostic significance. Despite the progress that has been observed, relapses occur unpredictably, and treatment can be associated with acute and long-term toxicity. This has prompted efforts to better tailor ALL therapy in individual patients. In recent years, there has been a growing expansion in our knowledge of underlying disease biology as well as inherent patient characteristics, and this has contributed to a movement toward more personalized ALL therapy. In this article, we have focused on examples of how comprehensive genomic analyses are being utilized to individualize childhood ALL treatment as well as how these analyses may be further leveraged in the future.

Glucocorticoids are an integral component of therapy for acute lymphoblastic leukaemia (ALL), but usage differs between cooperative group protocols. All groups use glucocorticoids during induction but vary on whether to use dexamethasone or prednisone. Issues to consider in the choice of induction steroid include impact on event-free and overall survival, acute morbidity such as infection risk, diabetes, and behavioural disturbances and long-term complications such as avascular necrosis. It is generally agreed that dexamethasone is the steroid of choice for groups using a delayed intensification phase, but dosing schedules (intermittent versus continuous) vary. There is no consensus on the potential benefit of steroid administration during maintenance therapy. This review will summarize the current available data on steroid use in paediatric ALL, highlighting outcomes as well as major toxicities.

Acute lymphoblastic leukemia (ALL) affects all agegroups, although it is much more common inpediatric patients, with a peak incidence betweenthe ages of 1 and 4 years and a median age of 13 yearsat diagnosis (Surveillance, Epidemiology and EndResults [SEER] 2003–2007 data). While deregula-tion of pathways that control cell proliferation,differentiation, and survival contributes to its patho-genesis, the precise etiology of ALL is not yetunderstood. Many patients with ALL are in factchildren, and few have predisposing genetic syn-dromes or known carcinogenic exposures, such asionizing radiation or chemotherapeutic agents.Therefore increasing attention is being placed onidentifying underlying factors that increase thesusceptibility to the development of ALL. Folatemetabolism is essential to numerous cellular pro-cesses, including DNA and RNA synthesis as well asmethylation reactions involving homocysteine andDNA [1,2]. Rapidly dividing cells, therefore, havehigh folate requirements, and polymorphisms infolate-related genes can alter the amount or distribu-tion of this substrate available to cells. This has ledinvestigators to examine possible associations be-tween polymorphisms in the wide variety of genesinvolved in folate metabolism and the developmentof ALL. While there is a growing body of literatureexamining such associations, the results are not allconcordant.In this issue of Leukemia and Lymphoma,Yang et al. record the results of their study evaluatingsuch associations in the Han Chinese population [3].This study reports on polymorphisms in ninedifferent folate-related genes in both adult andpediatric patients with ALL and found that in thepopulation studied, variations in RFC1 (reducedfolate carrier 1) and MTRR (methionine synthasereductase) confer an increased risk for developingadult ALL while MTHFR (methylenetetrahydrofo-late reductase) and ABCG2 (ATP-binding cassettesub-family G member 2) polymorphisms confer adecreased risk. No significant associations werefound between polymorphisms in any of the genesstudied and the risk of pediatric ALL.The most studied folate-related gene variants todate, in relation to ALL risk, are the 677C4T and1298A4C polymorphisms in MTHFR. While thereare conflicting results from various studies, severalmeta-analyses suggest a reduced risk of adult ALLwith the homozygous TT genotype but perhaps lessof a risk reduction with this genotype in pediatricpopulations [1,4,5], similar to what was observed byYang et al. in their report here [3]. There have beenseveral studies in pediatric populations, however,which identified a reduced risk of pediatric ALL withthe 677T allele [2,6]. Fewer studies are available onother genes involved in folate metabolism, and theresults in different populations vary. In general,though, studies that evaluated polymorphisms inRFC1 found a significantly increased relative risk ofALL in patients with the 80G4A variant [2,7],similar to the results reported by Yang et al. [3]. On

C-reactive protein (CRP) is an acute phase reactant that is a reliable marker of systemic inflammation and has been associated with increased morbidity and mortality following hematopoietic stem cell transplantation (HSCT) in adults. In this study, we evaluated whether early elevations of CRP were associated with various complications and nonrelapse mortality following HSCT in pediatric patients. Seventy pediatric patients had CRP levels drawn at regular time points during the first week following their transplants. Patients were followed for 100 days following transplant, and transplant-related complications were documented. Patients who subsequently developed severe infections had higher median CRP values than those without severe infections (median 8.03 mg/dL versus 1.64 mg/dL, P = .0008) as did those who suffered nonrelapse mortality compared with those who did not (12.6 mg/dL versus 2.44 mg/dL, P = .02). These findings suggest that elevated CRP values may be useful as a marker of individual pediatric patients with a higher risk for treatment-related morbidity and mortality.