(Press-News.org) (WASHINGTON, May 23, 2013) – Treating pediatric leukemia patients with a liposomal formulation of anthracycline-based chemotherapy at a more intense-than-standard dose during initial treatment may result in high survival rates without causing any added heart toxicity, according to the results of a study published online today in Blood, the Journal of the American Society of Hematology (ASH).
Acute myeloid leukemia (AML), the second most common form of leukemia in children, is a blood cancer in which the bone marrow makes a large number of abnormal white blood cells that crowd out other healthy blood cells over time, leading to infection, anemia, or excessive bleeding. Most adults and children with AML receive a first line of treatment (known as induction therapy) soon after diagnosis with a class of chemotherapy drugs called anthracyclines. Standard induction regimens in children typically consist of three days of an anthracycline such as daunorubicin or idarubicin and seven to 10 days of another chemotherapy such as cytarabine. Approximately 60 to 70 percent of children with AML achieve long-term survival with this combination of drugs.
Recent evidence has suggested that increasing the intensity of induction treatment might improve remission rates and perhaps overall survival in AML patients. However, clinicians have used this approach sparingly in pediatric patients because of documented dose-related anthracycline toxicity in children, particularly the significant risk of damage to the developing heart muscle. In an effort to increase the effectiveness of this treatment for children with AML but reduce the cardiac risk profile, researchers are now investigating a liposomal (or lipid-based) formulation of the anthracycline daunorubicin (L-DNR) that allows for more targeted delivery of the drug in the cancerous cells and diffuses at a slower pace in the body which leads to a lower accumulation in the heart. Results from early pre-clinical studies of the lipid-based formulation suggest that L-DNR may be effective at higher-than-standard doses without causing added cardiotoxicity.
"We know that the standard induction treatment regimen is effective in pediatric leukemia patients, but recognize that the toxicities associated with this therapy can be damaging to young patients who are still growing and developing," said lead study author Ursula Creutzig, MD, of the Hannover Medical School in Germany. "This unique formulation of daunorubicin might offer us a way to effectively manage AML in these young patients while reducing their risk of experiencing the acute and long-term toxicities associated with traditional regimens."
To evaluate this hypothesis, Dr. Creutzig and a team of researchers initiated a trial to determine if L-DNR at intensified dosages in child and adolescent patients would improve their outcomes without added treatment-related acute and long-term cardiotoxicity. Between 2004 and 2010, 521 patients under 18 years of age were randomly assigned to treatment with either L-DNR or idarubicin induction therapy. Patients treated with L-DNR received a higher dose (80 mg/m²/day/x3) than the equivalent dose of idarubicin (12 mg/m²/day/x3) during induction. Both groups also received additional treatment with cytarabine and etoposide. High-risk patients (defined roughly as those who were not in the favorable cytogenetic group) also received supplemental treatment with a chemotherapeutic agent (2-CDA) after the induction period. Additional cycles of maintenance treatment were administered to all participants, excluding those who received a stem cell transplant.
After a five-year observational period, researchers noted similar results in both treatment arms (76% overall survival in the L-DNR group vs. 75% in the idarubicin group). The probability of event-free survival (or pEFS) was also similar in the L-DNR (59%) and idarubicin groups (53%), as were pEFS results for standard risk (72% for L-DNR vs. 68% for idarubin) and high-risk patients (51% vs. 46%, respectively).
Overall, treatment with this intensified induction regimen had a similar safety and tolerability profile to the traditional idarubicin dose. Treatment-related mortality was lower in the L-DNR group than in the idarubicin group (2/257 vs. 10/264 patients), and there were no unusual or persistent toxicities seen when compared with previous related trials. The team observed generally low rates of cardiotoxicities across the treatment groups in the study, though fewer events were reported among the L-DNR treated patients than the idarubicin-treated patients. In the L-DNR group, there were four reports of severe acute cardiotoxicities, such as functional impairment, versus five events in the idarubicin group. There was a single patient reported to have late cardiotoxicity during follow-up in the L-DNR group, as compared with three patients in the idarubicin treatment group.
"These findings signal an important step forward in our goal to identify treatments that can give pediatric patients the best chance for long-term survival with minimal toxic side effects, and we believe the approach could have a number of extended applications. For example, this treatment formulation may be appropriate to use in adults or elderly patients to reduce the toxicity profile, or it may be of value for other malignant diseases in both children and adults," said Dr. Creutzig. "We look forward to further investigating L-DNR as the standard anthracycline induction treatment in future studies."
Blood (http://www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (http://www.hematology.org), the world's largest professional society concerned with the causes and treatment of blood disorders.
ASH's mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.
blood® is a registered trademark of the American Society of Hematology.
Improved chemo regimen for childhood leukemia may offer high survival, no added heart toxicity
ELSE PRESS RELEASES FROM THIS DATE:
Adult day services for dementia patients provide stress relief to family caregivers
Family caregivers of older adults with dementia are less stressed and their moods are improved on days when dementia patients receive adult day services (ADS), according to Penn State researchers. "Caregivers who live with and care for someone with dementia can experience extraordinary amounts of stress," said Steven Zarit, professor and head, human development and family studies. "The use of adult day services appears to provide caregivers with a much-needed break that can possibly protect them from the negative health effects caused by chronic stress." The researchers ...
Link between war support and PTSD, time it late in negotiations and courtship by narcissists
Public level of support for war influences soldier PTSD Soldiers returning home from combat may be at a heightened risk for developing post-traumatic stress disorder if public support for a war effort is low, according to recent research. Social validation or invalidation shapes the level of distress soldiers feel from the act of killing, the researchers say. The study involved two experiments that asked participants to exterminate woodlice in a modified coffee grinder – in one, having an actor show either interest or disgust for the act and in another, asking participants ...
Schools should provide students with daily physical activity, IOM recommends
HOUSTON – (May 23, 2013) – A new report from the Institute of Medicine says schools should be responsible for helping pupils engage in at least 60 minutes of vigorous or moderate intensity activity during each school day. No more than half of American youth meet current evidence-based guidelines of at least an hour of vigorous or moderate intensity physical activity daily, according to the report, which was released today. "Because children are in school for nearly half of their waking hours, the committee recommends a Whole-of-School approach to strengthening physical ...
Researchers find common childhood asthma unconnected to allergens or inflammation
NEW YORK (May 23, 2013) -- Little is known about why asthma develops, how it constricts the airway or why response to treatments varies between patients. Now, a team of researchers at Weill Cornell Medical College, Columbia University Medical Center and SUNY Downstate Medical Center has revealed the roots of a common type of childhood asthma, showing that it is very different from other asthma cases. Their report, in Science Translational Medicine, reveals that an over-active gene linked in 20 to 30 percent of patients with childhood asthma interrupts the synthesis of ...
Depression common among children with temporal lobe epilepsy
A new study determined that children and adolescents with seizures involving the temporal lobe are likely to have clinically significant behavioral problems and psychiatric illness, especially depression. Findings published in Epilepsia, a journal published by Wiley on behalf of the International League Against Epilepsy (ILAE), highlight the importance of routine psychiatric evaluation for pediatric epilepsy patients—particularly for those who do not respond to anti-seizure medications and require epilepsy surgery. Current medical evidence indicates that mental illness ...
OSA is associated with less visceral fat accumulation in women than men
ATS 2013, PHILADELPHIA ─ A new study from researchers in Japan indicates that obstructive sleep apnea (OSA) is independently associated with visceral (abdominal) fat accumulation only in men, perhaps explaining gender differences in the impact of OSA on cardiovascular disease and mortality. "Visceral fat accumulation, which is a risk factor for cardiovascular disease, is also associated with OSA, and gender differences in mortality related to sleep apnea have been reported in some studies. Accordingly, we examined if the relationship between OSA and visceral fat ...
Migraine and depression together may be linked with brain size
MINNEAPOLIS – Older people with a history of migraines and depression may have smaller brain tissue volumes than people with only one or neither of the conditions, according to a new study in the May 22, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology. "Studies show that people with migraine have double the risk of depression compared to people without migraine," said study author Larus S. Gudmundsson, PhD, with the National Institute on Aging and the Uniformed Services University of the Health Sciences, in Bethesda, Md. Gudmundsson ...
Ants and carnivorous plants conspire for mutualistic feeding
An insect-eating pitcher plant teams up with ants to prevent mosquito larvae from stealing its nutrients, according to research published May 22 in the open access journal PLOS ONE by Mathias Scharmann and colleagues from the University of Cambridge and the University Brunei Darussalam. The unusual relationship between insect-eating pitcher plants and ants that live exclusively on them has long puzzled scientists. The Camponotus schmitzi ants live only on one species of Bornean pitcher plants (Nepenthes bicalcarata), where they walk across slippery pitcher traps, swim ...
Captive-bred wallabies may carry antibiotic resistant bacteria into wild populations
Endangered brush-tail rock wallabies raised in captive breeding programs carry antibiotic resistance genes in their gut bacteria and may be able to transmit these genes into wild populations, according to research published May 22 in the open access journal PLOS ONE by Michelle Power and colleagues from Macquarie University in New South Wales, Australia. Brush-tail rock wallabies are currently being raised in species recovery programs and restored to the wild to bolster populations of this endangered species. Here, researchers found that nearly half of fecal samples ...
New cave-dwelling arachnids discovered in Brazil
Two new species of cave-dwelling short-tailed whipscorpions have been discovered in northeastern Brazil, and are described in research published May 22 in the open access journal PLOS ONE by Adalberto Santos, from the Federal University of Minas Gerais (Brazil) and colleagues. The reddish-brown short-tailed whipscorpions inhabit cool, humid limestone caves in an otherwise arid region. Both new species, Rowlandius ubajara and Rowlandius potiguara, were found deep within the limestone caves, which are also home to bats. Bat guano and seed deposits harbor springtails and ...