Nanodiamond production in ambient conditions opens door for flexible electronics, implants and more.


Instead of having to use tons of crushing force and volcanic heat to forge diamonds, researchers at Case Western Reserve University have developed a way to cheaply make nanodiamonds on a lab bench at atmospheric pressure and near room temperature.

The are formed directly from a gas and require no surface to grow on.

The discovery holds promise for many uses in technology and industry, such as coating plastics with ultrafine diamond powder and making flexible electronics, implants, drug-delivery devices and more products that take advantage of diamond’s exceptional properties.

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Their investigation is published today in the scientific journal Nature Communications. The findings build on a tradition of diamond research at Case Western Reserve.

Beyond its applications, the discovery may offer some insight into our universe: an explanation of how nanodiamonds seen in space and found in meteorites may be formed.

“This is not a complex process: ethanol vapor at and pressure is converted to diamond,” said Mohan Sankaran, associate professor of chemical engineering at Case Western Reserve and leader of the project. “We flow the gas through a plasma, add hydrogen and out come diamond nanoparticles. We can put this together and make them in almost any lab.”

The process for making these small “forever stones” won’t melt plastic so it is well suited for certain high-tech applications. Diamond, renowned for being hard, has excellent optical properties and the highest velocity of sound and thermal conductivity of any material.

Unlike the other form of carbon, graphite, diamond is a semiconductor, similar to silicon, which is the dominant material in the electronics industry, and gallium arsenide, which is used in lasers and other optical devices.

While the process is simple, finding the right concentrations and flows—what the researchers call the “sweet spot”—took time.

The other researchers involved were postdoctoral researcher Ajay Kumar, PhD student Pin Ann Lin, and undergraduate student Albert Xue, of Case Western Reserve; and physics professor Yoke Khin Yap and graduate student Boyi Hao, of Michigan Technical University.

Sankaran and John Angus, professor emeritus of chemical engineering, came up with the idea of growing nanodiamonds with no heat or pressure about eight years ago. Angus’ research in the 1960s and 1970s led him and others to devise a way to grow diamond films at low pressure and high temperature, a process known as chemical vapor deposition that is now used to make coatings on computer disks and razor blades. Sankaran’s specialty, meanwhile, is making nanoparticles using cool microplasmas.

It usually requires high pressures and high temperatures to convert graphite to diamond or a combination of hydrogen gas and a heated substrate to grow diamond rather than graphite.

“But at the nanoscale, surface energy makes diamond more stable than graphite,” Sankaran explained. “We thought if we could nucleate carbon clusters in the gas phase that were less than 5 nanometers, they would be diamond instead of graphite even at normal pressure and temperature.”

After several ups and downs with the effort, the process came together when Kumar joined Sankaran’s lab. The engineers produced diamond much like they’d produce carbon soot.

They first create a plasma, which is a state of matter similar to a gas but a portion is becoming charged, or ionized. A spark is an example of a plasma, but it’s hot and uncontrollable.

To get to cooler and safer temperatures, they ionized argon gas as it was pumped out of a tube a hair-width in diameter, creating a microplasma. They pumped ethanol—the source of carbon—through the microplasma, where, similar to burning a fuel, carbon breaks free from other molecules in the , and yields particles of 2 to 3 nanometers, small enough that they turn into diamond.

In less than a microsecond, they add hydrogen. The element removes carbon that hasn’t turned to diamond while simultaneously stabilizing the diamond particle surface.

The diamond formed is not the large perfect crystals used to make jewelry, but is a powder of diamond particles. Sankaran and Kumar are now consistently making high-quality diamonds averaging 2 nanometers in diameter.

The researchers spent about a year of testing to verify they were producing diamonds and that the process could be replicated, Kumar said. The team did different tests themselves and brought in Yap’s lab to analyze the nanoparticles by Raman spectroscopy.

Currently, nanodiamonds are made by detonating an explosive in a reactor vessel to provide heat and pressure. The diamond particles must then be removed and purified from contaminating elements massed around them. The process is quick and cheap but the nanodiamonds aggregate and are of varying size and purity.

The new research offers promising implications. Nanodiamonds, for instance, are being tested to carry drugs to tumors. Because diamond is not recognized as an invader by the immune system, it does not evoke resistance, the main reason why chemotherapy fails.

Sankaran said his nanodiamonds may offer an alternative to diamonds made by detonation methods because they are purer and smaller.

The group’s process produces three kinds of diamonds: about half are cubic, the same structure as gem , a small percentage are a form suspected of having hydrogen trapped inside and about half are lonsdaleite, a hexagonal form found in but rarely found on Earth.

A recent paper in the journal Physical Review Letters suggests that when interstellar dust collides, such high pressure is involved that the graphitic turns into londsdaleite nanodiamonds.

Sankaran and Kumar contend that an alternative with no high requirement, such as their method, should be considered, too.

“Maybe we’re making diamond in the way diamond is sometimes made in outer space,” Sankaran proposed. “Ethanol and plasmas exist in outer space, and our nanodiamonds are similar in size and structure to those found in space.”

The group is now investigating whether it can fine-tune the process to control which form of diamond is made, analyzing the structures and determining if each has different properties. Lonsdaleite, for instance, is harder than cubic diamond.

The researchers have made a kind of nanodiamond spray paint. “We can do this in a single step, by spraying the nanodiamonds as they are produced out of the plasma and purified with hydrogen, to coat a surface,” Kumar said.

And they are working on scaling up the process for industrial use.

“Will they be able to scale up? That’s always a crap shoot,” Angus said. “But I think it can be done, and at very high rates and cheaply. Ultimately, it may take some years to get there, but there is no theoretical reason it can’t be done.”

If the scaled-up process is as simple and cheap as the lab process, industry will find many applications for the product, Sankaran said.

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A Possible Cure for Baldness, in 3D.


 
Set the ball rolling. Human skin cells grown on a flat culture remain dispersed and unable to induce the formation of hair follicles (left). But in a 3D culture, the cells form spheres that can coax new hair follicle growth (right).

Christiano lab, Columbia University

Set the ball rolling. Human skin cells grown on a flat culture remain dispersed and unable to induce the formation of hair follicles (left). But in a 3D culture, the cells form spheres that can coax new hair follicle growth (right).

Scientists have successfully grown new hair follicles from the skin cells of balding men. While the research team hasn’t yet shown whether the structures, which produce strands of hair on our bodies, are fully functional and usable for transplants onto a scalp, experts say the discovery is a significant step toward finding new treatments for hair loss.

“Their work is very elegant and extremely rigorous,” says Radhika Atit, a skin biologist at Case Western Reserve University in Cleveland, Ohio, who was not involved in the new study. “This is a big technical advance.”

Balding occurs when hair follicles stop producing new strands of hair in any area of the body. Now, taking drugs that prevent or slow the hair loss or transplanting hair follicles from one area of the body to another are the only viable treatments. Producing new hair follicles in the lab has not been an option—at least for human patients. In mice, researchers have shown that if they isolate dermal papilla cells, which surround hair follicles in the skin, grow them in petri dishes to produce new cells, and then put the cells back in the mouse, new hair follicles will develop. But when dermal papilla cells from humans are put into dishes in the lab, they lose their ability to induce the formation of new follicles.

Angela Christiano, a skin researcher at Columbia University who has discovered genes related to hair loss, recently brainstormed potential solutions to the problem with her colleagues. They noticed that while the dermal papilla cells from mice naturally formed large clumps in culture, the human cells didn’t. “We began thinking that maybe if we could get the human cells to aggregate like the mouse cells, that might be a step toward getting them to form new follicles,” Christiano says.

Her team decided to try a cell-growing approach, called 3D cultures, that’s been successful for other types of cells that need to form complex structures as they grow. The researchers collected dermal papilla cells from seven volunteers who had been diagnosed with male-pattern baldness. Rather than stick the isolated cells on a flat culture dish, they mixed the cells with liquid, then let the mixture hang in tiny droplets from a plastic lid, like condensation on the roof of a container. Because the cells inside the droplets are free-floating, the technique allows them to contact each other in every direction, as they would in the human body, rather than only touch side to side as they do in a flat dish. In the droplets, the cells behaved differently; as they divided to form new cells, they clumped into what the researchers call “spheroids”—balls of about 3000 cells.

To test whether the new spheroids were a better mimic for functional dermal papilla cells than those that had been grown in typical dishes, Christiano and her team determined what genes were turned on and off in different sets of dermal papilla cells. In cells grown on flat culture dishes, the expression of thousands of genes didn’t match up with their normal patterns, explaining why the cells from those dishes had been unable to generate new hair follicles. But in the 3D cultures, 22% of those genes had been restored to their correct on or off state.

The researchers then took 10 to 15 of the spheroids that had formed from each donor and sandwiched them between two layers of human skin that were grafted onto mice. Six weeks later,spheroids from five of the seven donors had coaxed the skin cells around them to start rearranging, forming the telltale shape of a hair follicle, the team reports online today in the Proceedings of the National Academy of Sciences. In two cases, hairs were even seen beginning to extend from the follicles, though the researchers didn’t continue the initial experiment for long enough to test whether the hairs were fully normal in terms of their ability to regrow.

Using one’s own cells to generate new follicles is useful because hair color and thickness will match perfectly with the rest of someone’s head of hair, Christiano notes. And with the new tissue culture technique, clinicians would be able to take just a few dermal papilla cells from a balding patient and expand the number of hair follicles available for transplant, rather than only be able to move follicles around. “Using this technique could change the number of people who would be eligible for hair transplants,” Christiano says.

The success of the approach is exciting, but the real breakthrough for other researchers in the field is the new data on gene expression in dermal papilla cells, says George Cotsarelis, a dermatologist at the University of Pennsylvania. The full readout of what genes are on and off in dermal papilla cells has never been collected before, so researchers now have a new list of thousands of genes to study further that may play key roles in hair follicle development. “It could have implications for not just hair, but treating wounds and scarring,” he says.

The spheroids capable of producing hair follicles could also be used as a new way to test drugs for their ability to restore follicle function, Atit says. “This is a better model system to use for drug testing than a two-dimensional plate.”

The science behind positive thinking your way to success.


Psychology expert RIchard Boyatzis says there is strong evidence to suggest that regular physical or leisure activities throughout the day stokes compassion and creativity at work.

STORY HIGHLIGHTS
  • Activating our parasympathetic systems stokes compassion and creativity, say scientists
  • Positivity increases when workers are given more flexibility in their roles
  • Research shows chronic stress levels hinder professionals and those in leadership positions.

 

Editor’s note: “Thinking Business” focuses on the psychology of getting ahead in the workplace by exploring techniques to boost employee performance, increase creativity and productivity.

 Whether it’s infuriating colleagues, inept management or a lack of appreciation, the modern day workplace can be a positivity free zone.

Sometimes counting to ten or daydreaming of a desert island just won’t purge the everyday monotony of office life and it’s common to become trapped in a spiral of negativity.

But regular coffee breaks, yoga and even praying to a loving god could change all that.

Are we wired to be optimistic?

Leading the doodle revolution

Brain science behind One Direction fans

According to psychology expert Richard Boyatzis, these simple exercises can engage the parasympathetic nervous system — the function responsible for relaxation and slowing the heart rate — resulting in renewed optimism and improvements in working relationships.

Boyatzis, psychology and cognitive science professor at Case Western Reserve University, said there is strong neurological evidence supporting the theory that engaging our parasympathetic systems — through regular physical or leisure activities — stokes compassion and creativity.

Read more: Don’t get stuck in your own success

“Strain causes a person to be cognitively, perceptually and emotionally impaired,” he said, “if you’re under pressure and stress at work, then you can’t think outside the box because you can’t see the box.”

Boyatzis maintains that chronic stress levels hinder professionals and those in leadership positions from performing to their best. He argues that while we need stress to function and adapt, too much can cause the body to defend itself by closing down.

“You have to engage your parasympathetic nervous system so that you change your hormonal flow,” Boyatzis told CNN, adding that mood and positivity can be “infectious” in the workplace, particularly in positions of leadership.

He added: “If you’re having a horrible marriage, or your teenage kids are dissing you right and left, you get to work and it’s very likely that you are just a bummer.”

Read more: Training the brain to stress less

Evidence shows that positivity increases when workers are given increased flexibility in their roles and more work-life balance, according to a report on well-being and success produced by the World Economic Forum [WEF].

[When] people enter a more positive space they become more willing to take risks and make comments.”
Sarah Lewis, chartered organizational psychologist.

Meanwhile, the report showed bad management and bullying in the workplace can have a damaging effect on employees’ physical and mental health.

Can positivity and happiness lead to success?

A recent study by the University of California entitled ‘Does Happiness Promote Career Success,’ professors concluded that ‘happy people’ are more satisfied with their jobs and report having greater autonomy in their duties.

Additionally, they perform better than their less happy peers and receive more support from coworkers.

Finally, positive individuals are less likely to be unemployed and more likely to be physically healthier and live longer.

And the debate over happiness and work goes way back in history. Ancient Greek philosopher Galen said employment is “nature’s physician, essential to human happiness.”

Read more: ‘Power naps’ may boost right-brain activity

Sarah Lewis, chartered organizational psychologist, told CNN that when people are positive at work it can lead to opportunities because they are more engaged and resilient:

“[When] people enter a more positive space they become more willing to take risks and make comments,” she said “they go into the more difficult conversations and they’re more productive.”

But in a study entitled ‘Benefits of Frequent Positive Affect: Does Happiness Lead to Success?’ the results concluded that positive attitudes can sometimes lead to poor problem solving.

If you want to instigate behavioral change you need to engage the implicit system which operates in the subconscious realm.”
Reut Schwartz-Hebron, founder of the Key Change Institute

The study also stated that the evidence to suggest happy people are more popular and have superior coping abilities is “almost non-existent.”

Reut Schwartz-Hebron, founder of the Key Change Institute — an organization that focuses on workplace behavior — believes that a constant state of positivity in the workplace can be “dangerous.”

“There’s certain things that have to be challenged,” she said, “certain things that have to be improved you can’t just constantly think that everything is going to be fine and positive.”

Schwartz-Hebron — a former Israeli military lieutenant — said to improve working life, it is first necessary “to rewire your brain” by creating new experiences and engaging two different cerebral systems; the explicit and the implicit memory.

The explicit is responsible for storing information and facts while the implicit memory relies on previous experiences to perform a task and is associated with the subconscious.

“If you want to instigate behavioral change you need to engage the implicit system which operates in the subconscious realm,” said Schwartz-Hebron, who runs workshops for Fortune 500 companies.

She added: “We typically work in very, very negative environments because our expertise is actually in difficult change.”

“[The people we work with] don’t see the need for the change; they don’t feel the problem is being defined correctly or they don’t believe that the solution is correct.”

The study by the University of California concludes that while positive emotions are particularly important to encourage optimal success at work, it is important for employees and those in positions of leadership to experience both positive and negative feelings in day to day routine.

New designer compound treats heart failure by targeting cell nucleus.


Cell paper highlights entirely new approach to heart protection, addressing major unmet need

Researchers from Case Western Reserve University School of Medicine and Dana-Farber Cancer Institute have made a fundamental discovery relevant to the understanding and treatment of heart failure – a leading cause of death worldwide. The team discovered a new molecular pathway responsible for causing heart failure and showed that a first-in-class prototype drug, JQ1, blocks this pathway to protect the heart from damage.

In contrast to standard therapies for heart failure, JQ1 works directly within the cell’s command center, or nucleus, to prevent damaging stress responses. This groundbreaking research lays the foundation for an entirely new way of treating a diseased heart. The study is published in the August 1 issue of Cell.

“As a practicing cardiologist, it is clear that current heart failure drugs fall alarmingly short for countless patients. Our discovery heralds a brand new class of drugs which work within the cell nucleus and offers promise to millions suffering from this common and lethal disease,” said Saptarsi Haldar, MD, senior author on the paper, assistant professor of medicine at Case Western Reserve and cardiologist at University Hospitals Case Medical Center.

Heart failure occurs when the organ’s pumping capacity cannot meet the body’s needs. Existing drugs, most of which block hormones such as adrenaline at the cell’s outer surface, have improved patient survival. Unfortunately, several clinical studies have demonstrated that heart failure patients taking these hormone-blocking drugs still succumb to high rates of hospitalization and death. Leveraging a new approach, the research team turned their attention from the cell’s periphery to the nucleus – the very place that unleashes sweeping damage-control responses which, if left unchecked, ultimately destroy the heart.

The team found that a new family of genes, called BET bromodomains, cause heart failure because they drive hyperactive stress responses in the nucleus. Prior research linking BET bromodomains to cancer prompted the laboratory of James Bradner, MD, the paper’s senior author and a researcher at Dana-Farber, to develop a direct-acting BET inhibitor, called JQ1. In models of cancer, JQ1 functions to turn off key cancer-causing genes occasionally prompting cancer cells to “forget” they are cancer. In models of heart failure, JQ1 silences genetic actions causing enlargement of and damage to the heart – even in the face of overwhelming stress.

“While it’s been known for many years that the nucleus goes awry in heart failure, potential therapeutic targets residing in this part of the cell are often dubbed as ‘undruggable’ given their lack of pharmacological accessibility,” said Jonathan Brown, MD, cardiologist at Brigham and Women’s Hospital and co-first author on the paper. “Our work with JQ1 in pre-clinical models shows that this can be achieved successfully and safely.”

The team led by principal investigators Haldar and Bradner studied mice who develop classic features of human heart failure, including massively enlarged hearts that are full of scar tissue and have poor pumping function.

For one month, the team administered a single daily dose of JQ1 to the sick mice. The treated mice were protected from precipitous declines in heart function in a matter of days. Animals who received the compound saw a 60 percent improvement, as compared to an untreated control group.

“Remarkably, at the end of the experiment, the hearts of many JQ1 treated mice appeared healthy and vigorous, despite being exposed to persistent and severe stress,” said Priti Anand, a researcher in Haldar’s lab and co-first author on the paper. “We knew we were on to something big the first time we saw this striking response.”

This collaboration started when Haldar read Bradner’s landmark 2010 Nature paper describing the creation of JQ1 and its ability to transform cancer cells into healthy ones. Following an open-source approach to drug development, Bradner elected to make JQ1’s chemical recipe publicly available to accelerate the creation of new treatments for patients. This synergistic approach to discovery opened the door for Haldar to work with Bradner to probe the role of BET bromodomains in the heart.

“So much has been learned from this molecule,” noted Bradner. “The fundamental similarity between the biology of cancer cell growth and heart enlargement following extraordinary stress connects these mature fields of study in new and exciting ways, of immediate relevance to drug development. This study best exemplifies the power of open-source approaches to drug discovery.”

In the coming months, the team will test JQ1 in preclinical models of heart failure and other cardiovascular conditions. With the jumpstart offered by Bradner’s creation of JQ1, the research team hopes to one day move to clinical trials.

Source:DFCI

Mouth bacteria may trigger bowel cancer.


Researchers say they have uncovered how bacteria may set off a chain reaction leading to bowel cancer.

Fusobacteria, commonly found in the mouth, cause overactive immune responses and turn on cancer growth genes, two US studies reveal.

The microbes had been linked with colorectal cancer before but it was not known whether they were directly involved in tumour growth.

The early findings are published in the journal Cell Host & Microbe.

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In addition to potential new treatments, the discovery could lead to better early diagnosis and prevention, experts hope.

The first study, carried out by Harvard Medical School researchers, showed that fusobacteria were present in high numbers in adenomas – a benign bowel growth that can become cancerous over time.

The same researchers also did tests in mice showing that the bacteria speeded up the formation of colorectal tumours by attracting special immune cells that invade and set off an inflammatory response which can lead to cancer.

The second study, carried out by researchers at Case Western Reserve University, showed that fusobacteria had a molecule on their surface which enabled them to attach to and invade human colorectal cancer cells.

The molecule – FadA – then switches on cancer growth genes and stimulates inflammatory responses to promote tumour formation.

Higher levels

A synthetic compound which blocked FadA was found to completely halt the process, raising the possibility it could one day be used as a preventive treatment.

The Case Western team also confirmed that FadA levels were much higher in tissues from patients with adenomas and colorectal cancer compared with healthy individuals.

Dr Wendy Garrett, lead author of Harvard study, said: “Fusobacteria may provide not only a new way to group or describe colon cancers but also, more importantly, a new perspective on how to target pathways to halt tumour growth and spread.”

She added that in the future the presence of the bacteria in a tumour may be used to guide treatment decisions.

Prof Yiping Han who carried out the second study added: “We have proven there is an infectious component to colorectal cancer.

“We have shown that FadA is a marker that can be used for the early diagnosis of colorectal cancer and identified potential therapeutic targets to treat or prevent this common and debilitating disease.”

Oliver Childs of Cancer Research UK said: “Our bodies contain many hundreds of microbes, many of which are beneficial and protect us against disease. But some can cause harm and this latest research gives compelling evidence that fusobacteria contribute to the development of certain bowel cancers by helping the cancer cells to grow.

“If larger studies confirm this work, a potential next step will be to develop tests to spot people at higher risk of bowel cancer or drugs that eradicate the effects of the bacteria.”

Source: BBC

 

Studies Cast Doubt on Cancer Drug as Alzheimer’s Treatment.


studies-cast-doubt-cancer-drug-alzheimers_1

Four labs can’t replicate finding that showed large-scale clearance of disease-related plaques. Some hope remains for improving memory

Bexarotene, a cancer drug touted as a potential treatment for Alzheimer’s disease, may not be the blockbuster remedy scientists were hoping for, according to several analyses published in Science on 24 May. Four independent research groups report that they failed to fully replicate striking results published in the journal last year by Gary Landreth, a neuroscientist at Case Western Reserve University School of Medicine in Cleveland, Ohio, and his colleagues.

Landreth’s team reported that the drug bexarotene could lower brain concentrations of the β-amyloid protein that has long been suspected as a key contributor to Alzheimer’s disease, and could even reverse cognitive impairments in diseased mice. But the study garnered particular attention for its claim that the drug could clear 50% of amyloid plaques — sticky clumps of the protein thought to interfere with brain function — in as little as 72 hours.

“That attracted a lot of folks to try to replicate these studies,” says Philip Wong, a neuroscientist at Johns Hopkins University in Baltimore, Maryland. “No drug at the present moment can do things like that.”

None of the follow-up studies published this week replicated the effects of bexarotene on plaques. Two groups did, however, confirm Landreth’s finding that the drug reduced levels of a soluble, free-floating form of β-amyloid, which can aggregate in plaques.

Not all of the papers examined memory in mice, but one group led by Radosveta Koldamova, a neuroscientist at the University of Pittsburgh in Pennsylvania, found that bexarotene treatment led to cognitive improvements.

Sticking points
“It was our expectation other people would be able to repeat this,” says Landreth about the results of the studies. “Turns out that wasn’t the case, and we fundamentally don’t understand that.” He suggests that the other groups might have used different drug preparations that altered the concentration of bexarotene in the brain or even changed its biological activity.

In a response published alongside the comment articles, Landreth emphasizes that some of the studies affirm two key conclusions of the original paper: the lowering of soluble β-amyloid levels and the reversal of cognitive deficits. He says that the interest in plaques may even be irrelevant to Alzheimer’s disease. In the past ten years, some neuroscientists have begun to question whether it is plaques or soluble β-amyloid proteins that are most dangerous to brain health.

As the debate over plaques continues, Koldamova says that the cognitive improvement she and Landreth observed suggests that bexarotene is still very promising. “Patients don’t go to the doctor because they have plaques. They go because they have memory decline,” she says.

Ethical dilemma
Other researchers say the contradictory results suggest that much more basic research is needed before bexarotene is used to treat Alzheimer’s. “The mechanism of action behind bexarotene has not been proven,” says Kevin Felsenstein, a neuroscientist at the University of Florida College of Medicine in Gainesville, and a co-author of one of the dissenting papers. Felsenstein’s group found no evidence that bexarotene lowered levels of soluble or plaque forms of β-amyloid protein.

Felsenstein worries that interest in Landreth’s original results could lead to misuse of the drug because, unlike many experimental treatments, it is already on the market. The US Food and Drug Administration has approved bexarotene to treat skin cancer.

In August 2012, The New England Journal of Medicine published an article anticipating growing demand for unauthorized prescriptions of bexarotene as an Alzheimer’s treatment and urging physicians to wait for evidence from human clinical trials.

Physicians and researchers may get some answers soon: Landreth’s group has begun an early clinical trial to test the drug in healthy participants.

Source: scientificamerican.com

 

Therapeutic vs. Prophylactic Platelet Transfusions


Prophylactic platelet transfusions might not be needed for thrombocytopenic patients undergoing stem-cell transplantation, but are indicated for those receiving chemotherapy for acute myeloid leukemia.

Current practice is to give platelet transfusions to patients with hematologic malignancies when platelet counts decline to 10,000/µL. However, fewer platelet transfusions might be required if they were limited to thrombocytopenic patients with clinically important bleeding (WHO grade 2), regardless of the platelet count.

To determine the feasibility and safety of this approach, German investigators conducted a prospective, open-label, multicenter study involving 391 patients receiving chemotherapy for acute myeloid leukemia (AML) or undergoing stem-cell transplantation (SCT) for hematological cancers. Patients were randomized to receive platelet infusions when their morning platelet counts were 10,000/µL (prophylactic group) or only when they experienced grade 2 or higher bleeding (therapeutic group). Patients were assessed twice daily and all new bleeding, headaches, or other cerebral symptoms were investigated. Results were as follows:

  • The therapeutic group required fewer transfusions than the prophylactic group (mean, 1.63 vs. 2.44; P<0.0001), but experienced a higher rate of bleeding (42% vs. 19%; P<0.0001), including more grade 4 bleeding (5% vs. 1%; P=0.02).
  • AML patients experienced more bleeding than SCT patients (37% vs. 18%; P<0.0001); only AML patients experienced grade 4 bleeding, including two episodes of fatal cerebral hemorrhages in the therapeutic group.
  • The therapeutic and prophylactic groups experienced similar overall survival, number of red blood cell transfusions, duration of thrombocytopenia, and number of days in the hospital.

Comment: The indications for platelet transfusions require continued review, and pegging their use to a specific platelet count might not always be appropriate (JW Oncol Hematol Feb 17 2010). As this study shows, thrombocytopenic SCT patients infrequently experienced major hemorrhages, so therapeutic platelet transfusion might be more appropriate for this population. In contrast, predicting bleeding does not seem possible in thrombocytopenic AML patients, even with careful monitoring. So platelet transfusions only for bleeding might be more appropriate for these patients.

Source: Journal Watch Oncology and Hematology