Breaking News
September 25, 2018 - Hybrid theranostic complex shows high therapeutic efficacy against tumor cells
September 25, 2018 - FDA Issues Statement Reaffirming the Positive Benefit-Risk Profile of Nuplazid (pimavanserin) for Patients with Hallucinations and Delusions Associated with Parkinson’s Disease Psychosis
September 25, 2018 - 5 obstacles parents commonly face in child obesity treatment and how to overcome them
September 25, 2018 - Immunologist to study how Chikungunya causes devastating effects in older adults
September 25, 2018 - Rural borderland communities vulnerable to high stress impacting mental and physical health
September 25, 2018 - SNMMI announces recipients of 2018-2020 Wagner-Torizuka Fellowship
September 25, 2018 - Common painkiller not effective in controlling chronic pain after traumatic nerve injury
September 25, 2018 - New therapeutic vaccine helps immune cells fight HPV-related head and neck cancer
September 25, 2018 - Environmentally-induced gene activity influences IQ test performance
September 25, 2018 - Biogen and Eisai announce results of LTE Phase 1b study of aducanumab for treating MCI
September 25, 2018 - FDA Approves Copiktra (duvelisib) Capsules for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Follicular Lymphoma
September 25, 2018 - Medical device company settles US case over false claims
September 25, 2018 - Trying to get answers: One woman’s quest for a diagnosis
September 25, 2018 - Lung cancer patients treated with invasive surgery more likely to become chronic opioid users
September 25, 2018 - Oxford VR raises £3.2m to boost innovation in VR for mental health problems
September 25, 2018 - Gene therapy approach could help treat mitochondrial diseases
September 25, 2018 - Few Yogurt Products Qualify As Low-Sugar
September 25, 2018 - Eye disease can cause blindness, and it’s on the rise
September 25, 2018 - Pawnshop density linked to gun-related suicides, Stanford study finds
September 25, 2018 - Pioneering procedure for common prostate condition offered by The London Clinic
September 25, 2018 - Number of people with respiratory diseases likely to increase if UK air pollution remains unchecked
September 25, 2018 - FARXIGA receives positive results in Phase III DECLARE-TIMI 58 cardiovascular outcomes trial
September 25, 2018 - New program to reduce harmful stress effectively improves mood in cancer patients
September 24, 2018 - Florence’s Lingering Threat: Mold – Drugs.com MedNews
September 24, 2018 - For professional baseball players, faster hand-eye coordination linked to batting performance
September 24, 2018 - Bill for later school start times is defeated, but Stanford sleep specialist isn’t
September 24, 2018 - For Heart Failure Patients, Mitral Valve Procedure Improved Outcomes
September 24, 2018 - Successful recovery from addiction means more than achieving abstinence
September 24, 2018 - New nanoplatform technology may reverse drug-resistance in renal cell carcinoma
September 24, 2018 - October 1918 marks the centenary of Spanish Flu that claimed more lives than World War I
September 24, 2018 - LGBT community reports more number of poor mental health days than general population
September 24, 2018 - New research suggests power of zebrafish as tool for cancer drug discovery
September 24, 2018 - New study finds height as possible risk factor for developing varicose veins
September 24, 2018 - Researchers compare weight loss results of online and in-person diabetes prevention program
September 24, 2018 - New HER2 PET Study Uses Affibody’s ABY-025 Tracer to Individualize Breast Cancer Treatment
September 24, 2018 - Drug combination offers more effective care for patients suffering miscarriage
September 24, 2018 - Tallness linked to varicose veins, Stanford study says
September 24, 2018 - For Heart Failure Patients, Mitral Valve Procedure Improved Outcomes
September 24, 2018 - Ecstasy drug makes octopuses more social
September 24, 2018 - Immediate compression therapy could cut risk of complications after deep-vein thrombosis
September 24, 2018 - Transcatheter mitral valve repair reduces mortality for patients with mitral regurgitation
September 24, 2018 - First intracranial aneurysm patients treated with BRAVO Flow Diverter after CE mark approval
September 24, 2018 - ‘Physicians of the mouth’? Dentists absorb the medical billing drill
September 24, 2018 - People more likely to believe those with confident tone of voice than with accent
September 24, 2018 - Harmony Biosciences Presents 5-Year Data On Pitolisant At International Narcolepsy Symposium
September 24, 2018 - Blood test may identify gestational diabetes risk in first trimester
September 24, 2018 - Height may be risk factor for varicose veins | News Center
September 24, 2018 - King’s commemorates opening of new NMR facility with one-day symposium
September 24, 2018 - Eisai receives approval for partial label change of DC Bead device for transcatheter arterial embolization
September 24, 2018 - Using multi-level approach to reduce underage drinking among youths on rural reservations
September 24, 2018 - High-resolution genomic map gives scientists unprecedented view of brain development
September 24, 2018 - Researchers find impact of neurobehavioral symptoms on employment in adults with TBI
September 24, 2018 - Alexion announces positive results from Phase 3 PREVENT study of Soliris in patients with NMOSD
September 24, 2018 - First evaluation of benefits, harms of Alzheimer’s screening for family members of older adults
September 24, 2018 - Ancora Heart announces positive data of study evaluating AccuCinch Ventricular Repair System
September 24, 2018 - Children of mothers using cannabis may start using it at an earlier age, finds study
September 24, 2018 - Gilead Sciences plans to launch authorized generic versions of Epclusa and Harvoni in the US
September 24, 2018 - Most patients who underwent transcatheter valve replacement experience prosthesis-patient mismatch
September 24, 2018 - Lumos acquires license for LUM-201 drug that promotes secretion of growth hormone
September 24, 2018 - New study provides basis for Air Canada to change its facial hair policy for aircrew
September 24, 2018 - Infant walkers lead to thousands of emergency visits for babies
September 24, 2018 - Genes predicting person’s height may provide clues about causes of varicose veins
September 24, 2018 - EPA Plan Will Maintain Carbon Emissions From Power Plants
September 24, 2018 - Characterizing pig hippocampus could improve translational neuroscience
September 24, 2018 - Element3 Health reports social and mental engagement play key role in overall health
September 24, 2018 - Paralympic medalists support Fight for Sight’s unique virtual event
September 24, 2018 - ADCETRIS drug receives approval in Japan as frontline treatment option for Hodgkin lymphoma
September 24, 2018 - Public awareness of urological conditions found to be alarmingly low across Europe
September 24, 2018 - Fitter Folks Suffer Milder Strokes: Study
September 24, 2018 - Novel botulinum toxin compound relieves chronic pain
September 24, 2018 - CHMP recommends approval of Gilenya for treatment of multiple sclerosis in children, adolescents
September 24, 2018 - National Friendly’s private medical insurance is a hit with women living in the South East
September 24, 2018 - Academics receive prestigious awards for achievements in blood pressure research
September 24, 2018 - Obese pregnant women can restrict weight gain safely with proper nutrition guidance
September 24, 2018 - CHMP adopts positive opinion of Takeda’s ALUNBRIG for treatment of ALK+ non-small cell lung cancer
September 24, 2018 - China NMPA approves LENVIMA for treatment of unresectable hepatocellular carcinoma
September 24, 2018 - A new approach for finding Alzheimer’s treatments
September 24, 2018 - USC research uncovers previously unknown genetic risk factor for dementia
September 24, 2018 - Study examining mental health among students finds significant disparities in treatment across race
September 24, 2018 - Breakthrough discovery paves way for future test to identify drowsy drivers
Neurocognitive risk may begin before treatment for young leukemia patients

Neurocognitive risk may begin before treatment for young leukemia patients

image_pdfDownload PDFimage_print
First author Yin Ting Cheung, Ph.D., formerly of St. Jude, pictured with corresponding author Kevin Krull, Ph.D., a member of the St. Jude Department of Epidemiology and Cancer Control. Credit: Seth Dixon/St. Jude Children’s Research Hospital

Leukemia itself, not just side effects related to its treatment, may increase the risk for long-term problems with attention, organization and related neurocognitive skills in survivors of the most common childhood cancer, according to research from St. Jude Children’s Research Hospital. The study appears today in the journal JAMA Oncology.

Researchers analyzed the cerebrospinal fluid (CSF) of 235 St. Jude pediatric acute lymphoblastic leukemia patients treated with chemotherapy alone. The group included 138 long-term survivors who participated in the study. Even before treatment began, some patients had proteins in their CSF that suggested injury to cells that make up the white matter in the brain. These are glial cells that help the brain function efficiently by insulating and supporting the neurons.

“This was a surprise. Until now, we had not suspected that leukemia, by itself, or the inflammatory response to the disease, may lead to changes that leave ALL survivors at risk for problems with executive functioning and processing speed later,” said corresponding author Kevin Krull, Ph.D., a member of the St. Jude Department of Epidemiology and Cancer Control.

Thirty to 40 percent of childhood leukemia survivors treated with chemotherapy alone develop neurocognitive problems. Researchers had assumed the problems were a side effect of therapy, particularly treatment with the chemotherapy agent methotrexate. So finding elevated biomarkers in the CSF of some patients during methotrexate treatment was not unexpected, but previously, little was known about the neurotoxic mechanism involved. The biomarkers identified were indicative of injury to neurons, axons and glial cells.

Researchers also found evidence that genetic variation may influence patients’ vulnerability to such treatment-related neurocognitive problems.

“Taken together, the results suggest that survivors’ neurocognitive deficits are multifactorial and reflect a complex interaction among genetics, treatment intensity and other factors,” Krull said. “Monitoring CSF biomarkers and screening for genetic mediators of brain injury may help identify and intervene with survivors at risk for neurocognitive problems.”

For this study, Krull and his colleagues analyzed CSF that had been collected from 235 patients at five times before and during treatment. The CSF was originally collected to monitor patients’ response to treatment and check for relapse.

The patients were enrolled in the Total XV St. Jude clinical trial. Their CSF was collected between 2000 and 2010. The analysis included neurocognitive testing and brain imaging of 138 survivors who were at least 8 years old and five years from their cancer diagnosis.

The researchers checked patients’ CSF for five proteins and other biomarkers of brain cell damage related to treatment with either high-dose intravenous methotrexate or methotrexate delivered into

the spinal fluid (intrathecal delivery). The biomarkers were present early in therapy, but changed and varied throughout treatment. For example, biomarkers of demyelination were present in some patients newly diagnosed with ALL and then decreased during treatment. Others, including biomarkers of inflammation and neuronal damage, were detected and increased as treatment progressed.

Overall, methotrexate treatment was associated with biomarkers that signaled as much as a 70 percent increased risk for reduced neurocognitive functioning as long-term survivors.

Researchers also checked for evidence that genetic variation may influence the susceptibility of pediatric ALL patients to methotrexate injury. Investigators checked patients’ DNA for 42 different gene variants known to influence drug metabolism, neurodevelopment and oxidative stress, which can damage cells.

The analysis identified a variant of the COMT gene that was associated with higher biomarker levels following methotrexate treatment. The gene encodes instructions for a protein involved in processing the neurotransmitter dopamine in the frontal regions of the brain.

“Dopamine is the primary neurotransmitter in executive functioning,” Krull said. “This suggests that two independent processes might be coming together in some patients that influence their risk for diminished executive functioning.”


Explore further:
Methotrexate exposure impacts cognitive processes cancer survivors need to multitask

More information:
JAMA Oncology (2018). DOI: 10.1001/jamaoncol.2018.0089

Journal reference:
JAMA Oncology

Provided by:
St. Jude Children’s Research Hospital

Tagged with:

About author

Related Articles