2 results
3 Clinical Utility of Neurocognitive Monitoring During Therapy in Survivors of Childhood Acute Lymphoblastic Leukemia (ALL)
- Rachel M Bridges, Lacey P Hall, Heather M Conklin, Kendra R Parris, Jason M Ashford, Ching-Hon Pui, Sima Jeha, Lisa M Jacola
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 511-512
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Survivors of childhood ALL treated with CNS-directed chemotherapy are at risk for neurocognitive deficits that emerge during treatment and impact functional and quality of life outcomes throughout survivorship. Neurocognitive monitoring is the recommended standard of care for this population; however, information on assessment timing and recommendations for assessment measures are limited. We examined the role of serial neurocognitive monitoring completed during protocol-directed therapy in predicting parent-reported neurocognitive late effects during survivorship.
Participants and Methods:Parents of 61 survivors of childhood ALL completed a semi-structured survey focused on parent perspective of neurocognitive late effects as part of a quality improvement project. Survivors completed protocol-directed treatment for newly diagnosed ALL on two consecutive clinical trials (St. Jude Total Therapy Study 15, 47.5%; Total Therapy 16, 52.5%). The majority of survivors were White (86.9%), 52.5% were male, and 49% were treated for low risk disease. Mean age at diagnosis was 7.77 years (standard deviation [SD] = 5.31). Mean age at survey completion was 15.25 years (SD = 6.29). Survivors completed neurocognitive monitoring at two prospectively determined time points during and at the end of protocol-directed therapy for childhood ALL.
Results:During survivorship, parents reported that 73.8% of survivors experienced neurocognitive late effects, with no difference in frequency of endorsement by protocol (p = .349), age at diagnosis (p = .939), patient sex (p = .417), or treatment risk arm (p = .095). In survivors with late effects, 44.3% sought intervention in the form of educational programming (i.e., 504 or Individualized Education Program). Among the group with late effects, compared to those without educational programming, those with educational programming had worse verbal learning (CVLT Trials 1-5 Total, Mean[SD]; T = 56.36 [11.19], 47.00 [10.12], p = .047) and verbal memory (CVLT Short Delay Free Recall, Z = 0.86 [0.67], -0.21 [1.01], p = .007); Long Delay Free Recall, Z = 0.91 [0.92], -0.25 [1.25], p = .020) during therapy. Compared to those without educational programming, survivors with educational programming had lower estimated IQ (SS = 109.25 [13.48], 98.07 [15.74], p = .045) and greater inattention [CPT Beta T = 56.80 [13.95], 75.70 [22.93], p = .017) at the end of therapy.
Conclusions:Parents report that nearly three quarters of children treated for ALL with chemotherapy only experience neurocognitive late effects during early survivorship, with no difference in frequency by established risk factors. Of those with late effects, nearly half required educational programming implemented after diagnosis, suggesting a significant impact on school performance. Results from neurocognitive monitoring beginning during therapy has utility for predicting educational need in survivors experiencing late effects. Our findings provide direction on the timing and content of neurocognitive monitoring, which is the recommended standard of care for childhood cancer patients treated with CNS-directed therapy.
27 - Development therapeutics
- from Section 3 - Evaluation and treatment
-
- By Sima Jeha
- Edited by Ching-Hon Pui
-
- Book:
- Childhood Leukemias
- Published online:
- 05 April 2013
- Print publication:
- 21 June 2012, pp 616-631
-
- Chapter
- Export citation
-
Summary
Introduction
Most agents currently used in the treatment of leukemia were developed over 30 years ago. The traditional approach to drug discovery and development has been classic single-agent phase I trials that determine a maximally tolerated dose at which efficacy is evaluated in phase II studies prior to incorporation into combination regimens. Responses have been defined by the presence (percentage) or absence of leukemic blasts in the bone marrow based on morphology along with trilineage hematopoietic recovery. With recent advances in molecular and immunologic technology, minimal residual disease (MRD) measurement is increasingly applied in defining response, and novel therapeutic strategies are targeting the leukemia-associated antigens and molecular pathways. The development of new oncology drug classes with novel mechanisms of action brings new challenges. New strategies are needed to efficiently combine immunotherapy and molecular therapy with traditional chemotherapeutics and with each other to maximize leukemic cell kill and minimize toxicity. New definitions of response and relapse are needed to effectively evaluate novel treatments in an era where MRD is increasingly used to assess therapeutic efficacy, and transplant is increasingly performed in patients without full peripheral count recovery. A disciplined application of well-designed clinical trials is needed as new therapeutic options emerge in order to optimize and individualize therapy. Paradigms for the design and conduct of preclinical and early clinical trials are discussed, and novel agents in development are presented in this chapter.
Leukemia as a model for drug development
Leukemia cells are easily accessible for study, allowing assessment of a new agent's activity and providing studies in animal models from which drug dose and schedule dependency can be demonstrated. The concepts of combination chemotherapy, remission induction, and maintenance treatment were all developed in pediatric acute lymphoblastic leukemia (ALL) regimens.