Jennifer L. McNeer

The optimal use of steroids in paediatric acute lymphoblastic leukaemia: no easy answers.

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.

Early Elevation of C-Reactive Protein Correlates with Severe Infection and Nonrelapse Mortality in Children Undergoing Allogeneic Stem Cell Transplantation

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.

Psychological morbidities in adolescent and young adult blood cancer patients during curative‐intent therapy and early survivorship

Adolescents and young adults (AYAs) with cancer face unique psychosocial challenges. This pilot study was aimed at describing the prevalence of psychological morbidities among AYAs with hematologic malignancies during curative‐intent therapy and early survivorship and at examining provider perceptions of psychological morbidities in their AYA patients.

Acute lymphoblastic leukemia in young adults: which treatment?

Purpose of review Acute lymphoblastic leukemia (ALL) is the most common and one of the most curable malignancies in children; however, it presents unique challenges in adolescents and young adults (AYAs). The purpose of this review is to discuss factors that contribute to the outcome disparities in AYAs with ALL as well as approaches that can be taken to optimize the care of this patient population. Recent findings AYAs with ALL are unique and have outcomes that have lagged behind those observed in children with ALL. Contributing factors to the challenges faced by this group include distinctive disease biology, different drug pharmacology and toxicity profiles, and complex psychosocial and socioeconomic factors. Several clinical trials conducted worldwide have demonstrated that treatment with pediatric protocols significantly improves outcomes in the AYA population. Summary Initiatives to improve outcomes for AYAs with ALL include treatment with pediatric regimens tailored to be delivered without excessive toxicity and in centers with the necessary supportive care and medical services to address the specific needs of this population. As more is understood about the unique disease biology of AYA ALL, targeted therapeutic approaches may offer promise for the future.

Adoption of pediatric-inspired acute lymphoblastic leukemia regimens by adult oncologists treating adolescents and young adults: A population-based study.

Studies have demonstrated superior outcomes for adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) who are treated using pediatric versus adult therapeutic regimens. To the best of our knowledge, whether adult oncologists in the United States have adopted this approach to ALL in AYA patients is currently unknown. The objective of the current study was to provide a population‐based description of ALL treatment patterns in AYA individuals over the past decade.

Outcomes in adolescents and young adults with Hodgkin lymphoma treated on US cooperative group protocols: An adult intergroup (E2496) and Children's Oncology Group (COG AHOD0031) comparative analysis

There is no clear consensus between pediatric and adult providers about the treatment of adolescents and young adults (AYAs) with Hodgkin lymphoma (HL).

Acute lymphoblastic leukemia and lymphoblastic lymphoma in adolescents and young adults

Compared to younger and older age groups, the incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) has increased more in the adolescent and young adult (AYA) population, the cause of which is unknown. As of the last decade, only half of the AYA patients with these diseases were surviving 10 years. Strong evidence exists that favors “pediatric” treatment regimens for AYAs compared to “adult” treatment regimens in terms of survival rates, hospitalization time, toxicities, late effects, and quality of life both during and after treatment. Targeted agents are clinically accessible for certain subsets of patients with Philadelphia‐like ALL, the incidence of which peaks in AYAs. Treatment teams must appreciate the complex psychosocial underpinnings in these patients in order to maximize compliance with the prolonged and complex treatment plans during the AYA years.

RCSD1 - ABL2 fusion resulting from a complex chromosomal rearrangement in high-risk B-cell acute lymphoblastic leukemia

RCSD1–ABL2 fusion resulting from a complex chromosomal rearrangement in high-risk B-cell acute lymphoblastic leukemia Gordana Raca, Sandeep Gurbuxani, Zhiyu Zhang, Zejuan Li, Madina Sukhanova, Jennifer McNeer & Wendy Stock a Department of Medicine, The University of Chicago, Chicago, IL, USA b Department of Pathology, The University of Chicago, Chicago, IL, USA c Department of Pediatrics, The University of Chicago, Chicago, IL, USA Published online: 09 Jun 2015.

The complex interplay between folate metabolism and risk of acute lymphoblastic leukemia

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

Diagnostic evaluation of RNA sequencing for the detection of genetic abnormalities associated with Ph-like acute lymphoblastic leukemia (ALL).

Abstract Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a molecular subtype of high-risk B-cell ALL characterized by formation of abnormal gene fusions involving tyrosine kinase (TK) and cytokine receptor genes and activation of TK signaling. Because of the diversity of associated genetic changes, the detection of Ph-like ALL cases currently requires multiple cytogenetic and molecular assays; thus, our goal was to develop a consolidated workflow for detecting genetic abnormalities in Ph-like ALL. We found that total and targeted RNA sequencing (RNAseq)-based approach allowed the detection of abnormal fusion transcripts (EBF1-PDGFRB, P2RY8-CRLF2, RCSD1-ABL1, and RCSD1-ABL2). The bioinformatics algorithm accurately detected the fusion transcripts without prior input about possible events. Additionally, we showed that RNAseq analysis enabled evaluation for disease-associated sequence variants in expressed transcripts. While total RNAseq can be a second tier approach allowing discovery of novel genetic alterations, the targeted RNAseq workflow offers a clinically applicable method for the detection of fusion transcripts.