At the intersection between children and older adults, the care of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) poses unique challenges and issues beyond those ...faced by other age groups. Although the survival of AYA patients is inferior to younger children, growing evidence suggests that AYA patients have improved outcomes, with disease-free survival rates of 60% to 70%, when treated with pediatric-based approaches. A holistic approach, incorporating a multidisciplinary team, is a key component of successful treatment of these AYA patients. With the appropriate support and management of toxicities during and following treatment, these regimens are well tolerated in the AYA population. Even with the significant progress that has been made during the last decade, patients with persistence of minimal residual disease (MRD) during intensive therapy still have a poor prognosis. With new insights into disease pathogenesis in AYA ALL and the availability of disease-specific kinase inhibitors and novel targeted antibodies, future studies will focus on individualized therapy to eradicate MRD and result in further improvements in survival. This case-based review will discuss the biology, pharmacology, and psychosocial aspects of AYA patients with ALL, highlighting our current approach to the management of these unique patients.
The author of this article summarizes which, when, where, and how students take introductory economics. Among students who began college in 2012, 74 percent never took economics, up from 62 percent ...in 2004. Fifteen percent of beginning college students in 2012 took some economics, and 12 percent were one-and-done students. About half of introductory economics students never took another economics class, and only about 2 percent majored in economics. The characteristics of one-and-done and some economics students are generally similar and closer to one another than to students with no economics. The implication is that efforts to diversify the profession should focus at least in part on attracting students who would otherwise not take introductory economics.
Treatment outcomes among survivors of cancer diagnosed during adolescence and early young adulthood have not been characterised independently of survivors of cancers diagnosed during childhood. We ...aimed to describe chronic health conditions and all-cause and cause-specific mortality among survivors of early-adolescent and young adult cancer.
The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study with longitudinal follow-up of 5-year survivors diagnosed with cancer before the age of 21 years at 27 academic institutions in the USA and Canada between 1970 and 1999. We evaluated outcomes among survivors of early-adolescent and young adult cancer (aged 15–20 years at diagnosis) and survivors diagnosed at age younger than 15 years (matched on primary cancer diagnosis, including leukaemia, lymphoma, CNS tumours, neuroblastoma, Wilms tumour, soft-tissue sarcomas, and bone cancer) by comparing both groups to siblings of the same age. Mortality was ascertained with the National Death Index. Chronic health conditions were classified with the Common Terminology Criteria for Adverse Events. Standardised mortality ratios (SMRs) were estimated with age-specific, sex-specific, and calendar year-specific US rates. Cox proportional hazard models estimated hazard ratios (HRs) for chronic health conditions and 95% CIs.
Among 5804 early-adolescent and young adult survivors (median age 42 years, IQR 34–50) the SMR compared to the general population for all-cause mortality was 5·9 (95% CI 5·5–6·2) and among 5804 childhood cancer survivors (median age 34 years; 27–42), it was 6·2 (5·8–6·6). Early-adolescent and young adult survivors had lower SMRs for death from health-related causes (ie, conditions that exclude recurrence or progression of the primary cancer and external causes, but include the late effects of cancer therapy) than did childhood cancer survivors (SMR 4·8 95% CI 4·4–5·1 vs 6·8 6·2–7·4), which was primarily evident more than 20 years after cancer diagnosis. Early-adolescent and young adult cancer survivors and childhood cancer survivors were both at greater risk of developing severe and disabling, life-threatening, or fatal (grade 3–5) health conditions than siblings of the same age (HR 4·2 95% CI 3·7–4·8 for early adolescent and young adult cancer survivors and 5·6 4·9–6·3 for childhood cancer survivors), and at increased risk of developing grade 3–5 cardiac (4·3 3·5–5·4 and 5·6 4·5–7·1), endocrine (3·9 2·9–5·1 and 6·4 5·1–8·0), and musculoskeletal conditions (6·5 3·9–11·1 and 8·0 4·6–14·0) when compared with siblings of the same age, although all these risks were lower for early-adolescent and young adult survivors than for childhood cancer survivors.
Early-adolescent and young adult cancer survivors had higher risks of mortality and severe and life threatening chronic health conditions than the general population. However, early-adolescent and young adult cancer survivors had lower non-recurrent, health-related SMRs and relative risks of developing grade 3–5 chronic health conditions than childhood cancer survivors, by comparison with siblings of the same age, which were most notable more than 20 years after their original cancer. These results highlight the need for long-term screening of both childhood and early-adolescent and young adult cancer survivors.
National Cancer Institute and American Lebanese-Syrian Associated Charities.
Although economics' share of Bachelor's degrees awarded in the United States has been flat for over a decade, its share of second majors is growing. This paper documents trends and correlations in ...disciplines' shares of first and second majors for Bachelor's degrees conferred in the United States during 2001-2014. First majors in math, engineering, computer science, and technology and in the life and medical sciences (now the modal major among female students) are complements to second majors in economics. Encouraging double majoring in economics among students in these disciplines could grow and diversify the economics discipline while also benefiting graduates.
Measurable residual disease (MRD) is the most powerful independent predictor of risk of relapse and long-term survival in adults and children with acute lymphoblastic leukemia (ALL). For almost all ...patients with ALL there is a reliable method to evaluate MRD, which can be done using multi-color flow cytometry, quantitative polymerase chain reaction to detect specific fusion transcripts or immunoglobulin/T-cell receptor gene rearrangements, and high-throughput next-generation sequencing. While next-generation sequencing-based MRD detection has been increasingly utilized in clinical practice due to its high sensitivity, the clinical significance of very low MRD levels (<10-4) is not fully characterized. Several new immunotherapy approaches including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T-cell therapies have demonstrated efficacy in eradicating MRD in patients with B-ALL. However, new approaches to target MRD in patients with T-ALL remain an unmet need. As our MRD detection assays become more sensitive and expanding novel therapeutics enter clinical development, the future of ALL therapy will increasingly utilize MRD as a criterion to either intensify or modify therapy to prevent relapse or de-escalate therapy to reduce treatment-related morbidity and mortality.
We examine determinants of coauthorship behavior and how coauthorship relates to research productivity and other career outcomes for academic economists. We supplement a unique dataset containing ...economics Doctor of Philosophy (PhD) graduates' demographic, PhD program, advisor, and other characteristics with measures of their coauthorship behavior and research productivity. Significant gender differences in the formation and effects of coauthorship are found. Students with female advisors and women from lower‐ranked programs had a higher propensity to coauthor, and coauthorship is associated with more research output and more publications in top economics journals. However, women received less credit toward tenure when coauthoring with men or advisors.
Background
Inotuzumab ozogamicin (InO) is an antibody‐drug conjugate used for adults with relapsed/refractory B‐cell precursor (BCP) acute lymphoblastic leukemia (ALL). The INotuzumab Ozogamicin ...trial to inVestigAte Tolerability and Efficacy (INO‐VATE) previously reported improved outcomes with InO versus standard‐of‐care (SoC) chemotherapy. This article reports the final INO‐VATE results (≥2 years of follow‐up) and additional analyses of patient characteristics associated with improved outcomes.
Methods
Between August 27, 2012, and January 4, 2015, this multicenter, parallel, open‐label, phase 3 trial randomized 326 adults with relapsed/refractory ALL to InO (n = 164) or SoC (n = 162); 307 received 1 or more doses of the study drug (164 in the InO arm and 143 in the SoC arm).
Results
The complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) rate was higher with InO versus SoC (73.8% vs 30.9%; 1‐sided P < .0001), with consistent CR/CRi rates across patient subgroups. The median overall survival (OS) was 7.7 months with InO and 6.2 months with SoC, with 2‐year OS rates of 22.8% and 10.0%, respectively (overall hazard ratio, 0.75; 97.5% confidence interval CI, 0.57‐0.99; 1‐sided P = .0105). The predictors of OS with InO were the best minimal residual disease status, baseline platelet count, duration of first remission, achievement of CR/CRi, and follow‐up hematopoietic stem cell transplantation (HSCT; all 2‐sided P values < .05). More InO arm patients proceeded directly to HSCT after achieving CR/CRi before any follow‐up induction therapy (39.6% 95% CI, 32.1%‐47.6% vs 10.5% 6.2%‐16.3%; 1‐sided P < .0001). The most frequent all‐grade and grade 3 or higher adverse events in both arms were hematologic. Veno‐occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) was more frequent with InO (23 of 164 14.0% vs 3 of 143 2.1%).
Conclusions
In patients with relapsed/refractory BCP ALL in INO‐VATE, InO was associated with a greater likelihood of CR/CRi across key patient subgroups, and it served as a bridge to HSCT. Potential VOD/SOS risk factors must be considered when InO treatment decisions are being made.
All key subgroups of patients with relapsed or refractory CD22‐positive B‐cell precursor acute lymphoblastic leukemia have the potential to benefit from inotuzumab ozogamicin in comparison with the standard of care (intensive chemotherapy). In the future, the combination of inotuzumab ozogamicin with other therapies may provide improved outcomes.
What do we know about how well graduate teaching in economics addresses cognitive challenges to learning? In short, very little. There is a dearth of research that investigates how graduate student, ...program and professor characteristics, and choices impact graduate student learning and other outcomes. Some of the broader literature on graduate education in economics includes findings that can be linked to Chew and Cerbin's cognitive challenges to provide suggestive evidence, but many open research questions remain. Research is needed to understand whether improvements like clear communication, clear requirements and expectations, better advising, and adopting a learning-driven approach to graduate courses would mitigate cognitive challenges to learning and improve graduate education in economics.
Although paid family leave (PFL) has the potential to improve labor market and other outcomes for mothers, there is also concern that PFL might also lead to discrimination against women of ...childbearing age. We examine the impact of California's paid family leave law (CA‐PFL) on labor market outcomes over time during the post‐law decade, as well as the law's effect for groups with differing levels of education. Results indicate that the law had negligible impacts on young women's labor force participation, unemployment duration, and earnings, but persistent small negative impacts on their relative employment. The negative employment impacts are concentrated among college‐educated women, for whom the law is associated with a 2–3 percentage point decrease in labor force participation and a 1–2 percentage point decline in employment. The CA‐PFL does not appear to have impacted the relative labor force participation, employment, unemployment duration, or earnings of less‐educated young females.
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