Category Archives: Azacitidine
The Typhoon which hit HK overnight was the worst in 13 years, signal 10 went up for a few hours during the night apparently. By morning it was back to signal 8. To get a taxi to take me to the hospital for my check up I had to pay a premium. The taxi had difficulty getting in and out of the apartment buildings as there were 3 trees down! There was a considerable amount of debris along all the roads.
I got to the hospital at 9:30am and went for my blood test and Chest X-ray.Then I went to the RHKYC for a late breakfast but everything was closed. Two huge trees outside the club entrance were down. Those trees have been there since I first joined as an Associate Member in 1985! So sad. I walked to Causeway Bay through the tunnel and got something to eat, by which time Signal 3 was up and the trams started to run again, so I took the tram back to the hospital.
Raymond saw me at 11:30! In all the years he has been looking after me this is, as far as I remember, the first time I have ever seen him before my actual appointment time. The consultation was quite long because we discussed the experimental Azacitidine treatment. He gave me another paper to read which reports on a small scale trial. The upshot of the discussion was that my immunosuppressive drugs need to be tapered off some more before he feels comfortable starting the treatment, so no rush.
After the consultation I headed for the Pharmacy to pick up my 5 weeks supply of drugs. They were unable to fill the ciclosporin prescription. I need 280 10mg tablets and they only had 120. I have to call them tomorrow to see if they have sourced the rest. I have plenty of 25mg tablets left in Manila, so if they can’t fill the prescription I will use those and have a 45:35 dose instead of 40:40.
The good news is that my blood levels are OK, in fact my Haemoglobin is the highest that I have seen it since the transplant. The cyclosporin dose is reduced from 100mg to 80mg per day, the Itraconazole dose is halved (I really don’t like that drug!), and the Prednisolone is reduced from 7.5mg to 5mg but after 2 weeks I am to stop taking it.
I had lunch and dinner with friends and did some packing. Tomorrow is a shopping and seeing friends day.
I’ve had this head cold and non-productive cough for a week now. I guess my system is finding it hard to overcome because of the immune suppression. Hopefully the anti-bacterial co-trimaxazole, which I only take at weekends, will help to kill it off. The nausea has been stronger the past 48 hours, especially at dinner time, which isn’t helping. Maybe the doctor will prescribe some antibiotics for the cold when I see him on Tuesday. My Itraconazole supply is critically low so I have cut down the dose to make it last.
The weather doesn’t help, it’s been raining hard most of the past 2 days. Real, heavy, asian rain. Proper rain; not that pussy stuff they “endure” in Europe. I swear that our apartment was in low cloud when I woke up at 6am yesterday morning. When you can’t see a major city centre about 2km away through the rain, that’s rain! There were a few fools on the golf course when it eased a bit, and the Polo field was well on its way to becoming a boating lake on Saturday morning.
I foresee a long discussion with the doctor next week about this experimental treatment they are thinking of putting me on, Vidaza (Azacitidine) at low doses.
Today has been a good day. Eyes OK, stomach OK, just the swollen feet.
The HK and Singapore doctors are discussing giving me 4 – 5 rounds of Azacitidine, 4 – 5 days per cycle. This is an experimental approach which has shown good results in limited trials so far. You can read the preliminary results abstract on my pages. It turns out that SGH has been trialling this, but did not suggest it for me as I am a tAML patient (MDS transformed to AML). They have approval to start Phase 2 trials now. The discussion has moved from “should we do this?” to the point of “do we wait until after the immunosuppression is stopped, or do we do it now?”
I dropped by my old office this afternoon to say Hi to the people there. It was great to see them all.
Linds took Francesca, Sam and Chia to an Operation Smile mission north of Manila. Operation Smile is a charity which gets medical teams to donate their time to repairing hare lips and cleft palettes in young children. Linds’ Dad was the President of the Philippines branch for many years so she has been before. They talked to the parents and played with the children to keep them calm while they waited for their turn in the operating theatre. Yesterday they went shopping for toys to take with them to give to the kids.
I had a bad start to the day, my eyes were very bad and my stomach was not feeling good even before I took medication, so not surprisingly I found myself vomiting 40 minutes after taking the Itraconazole. I vomited again while I was eating my fruit. The head cold is easing slowly which is good. To cheer myself up I listened to the latest program in the long running BBC Radio 4 Comedy nonsense quiz “I’m Sorry I Haven’t a Clue”. It’s been going for over 40 years and is still as funny as ever.
Someone posted a very interesting article about a new drug treatment for cGvHD which I am including here and as a page. There is also a new page about using Azacitidine (Vidaza) post transplant to improve survival which my haematologist sent to me.
An existing drug dramatically reduced the most serious complications of bone marrow transplants, University of Pennsylvania researchers are reporting
The finding could someday point the way toward an entirely new method of preventing the body from “rejecting” transplanted organs of all kinds in the
future, experts said.
The work demonstrates a possible new approach to transplants of donated bone marrow, said Joseph Antin, a professor of medicine at Harvard, who was
not involved with the study.
“It is the first time that someone has tried to do this, which makes it fascinating in itself,” Antin said. “Now what we need to do is confirm it” and compare how patients fare with and without the drug in a randomized trial.
Antin chairs a committee in the Blood and Marrow Transplantation Clinical Trials Network that will design such a trial that could begin in a year or so.
For decades, transplants of nearly all organs have been possible only with the use of powerful medications that suppress the immune system so that it
doesn’t attack the alien organ. But those immunosuppressant drugs can be toxic to other parts of the body and leave recipients vulnerable to dangerous infections, often for the rest of their lives.
Rather than searching for better immunosuppressant drugs, the Penn researchers asked a different question: “What if we let the immune cells do their job” – attacking cancers and other diseases “and we just tell them where to go and where not to go?” said Ran Reshef, lead author of the paper published Thursday in the New England Journal of Medicine.
It turns out that the traffic signal already exists. It is maraviroc, a drug that has been on the market for five years to treat HIV.
The bone marrow study evaluated only 35 patients, and the first-time finding must be replicated in larger and longer trials. Whether the mechanism would work with transplants of other organs is at this point hypothetical.
Still, several independent researchers said the concept is sound, and the problem it tries to solve – organ rejection – is major.
“Transplant surgeons would love to do two things: to operate during the day” and avoid rejection, said Cataldo Doria, director of transplantation at
Thomas Jefferson University Hospital, who, like others, praised the study as “promising.”
The Penn study tested the HIV drug for prevention of graft-versus-host disease, the most serious complication of donor bone marrow transplants. About 10,000 Americans a year receive these transplants, often after other treatments for leukemia and other cancers have failed.
Because the bone marrow creates immune cells along with blood cells, a transplant imports a new immune system to use against the cancer. To the donated immune system, the recipient’s entire body is alien.
Attacks on organs create graft-versus-host disease in 30 percent to 70 percent of patients.
After the researchers added maraviroc to the standard immune-suppressing regimen for 33 days, they found that just 6 percent of the patients developed a severe form of the disease; typically, 22 percent would have.
After one year, 15 percent of the patients developed severe disease, compared with the normal 29 percent. There were few side effects. The early-phase trial had been intended to test only the safety of the drug. “We didn’t really expect to see any efficacy results,” said Reshef, who said the finding “was amazing even to us.”
If future trials are successful, he and others predicted that maraviroc could become a supplement to standard therapy for donor bone marrow transplants, probably not a replacement.
Maraviroc is made by Pfizer, which won approval of the drug for HIV in 2007. It did not initiate the Penn study but contributed funding, as did the National Institutes of Health, the Leukemia and Lymphoma Society, and other groups. A Pfizer spokeswoman said the company would not speculate about the findings.
The drug treats a specific type of HIV by blocking the path, known as a CCR5 receptor, that the virus uses to enter immune cells.
For graft-versus-host disease, the researchers took advantage of an entirely different mechanism, known as chemotaxis, which controls where and when
cells move around the body.
Just as traffic lights along South Broad Street must be turned on by an electrical current before they can direct cars to, say, Citizens Bank Park, the CCR5 receptors on cell surfaces must receive specific chemical signals called chemokines to direct the immune cells to the liver.
Maraviroc is known as a CCR5 antagonist because it attaches to the same receptors and blocks the chemokines, leaving the cells without direction and
protecting vital organs such as the liver from attack.
Graft-versus-host disease is most severe in the liver and gut; CCR5 is involved with trafficking immune cells to those same organs.
After a donor bone marrow transplant, immunosuppressive drugs typically are tapered off as the new immune system adapts. By contrast, transplants of
“solid” organs, such as the liver, kidney, and heart, require lifelong suppression of the immune system to avoid attacks on the new organs.
The trial did not investigate whether using a drug to block the CCR5 or other receptors would work with those organs, but researchers said the concept would be the same.
“There have been laboratory experiments that suggest that that’s true,” said David L. Porter, a senior author of the Penn paper and director of Penn’s blood and marrow transplantation program. And studies have found that people with a particular deletion in their CCR5 receptor are less likely than others to reject a transplanted kidney, he said.
In an unrelated study published last month, researchers at Jefferson used maraviroc to prevent highly aggressive breast cancer cells from being
trafficked – in this case, metastasizing – to other organs in mice, where they can kill.
Marcel Van den Brink, the head of hematological oncology at Memorial Sloan-Kettering Cancer Center in New York, noted that the concept of “blocking
trafficking” has been pursued since the 1990s but this is the first trial that appears to have had success.
For solid organs, “I think it is possible,” he said, “maybe for the same organs that showed [positive results] here, such as the gut and liver.”
Daniel Weisdorf, director of the adult bone marrow transplantation program at the University of Minnesota Medical Center, said research still needed
to prove that it was the trafficking mechanism rather than something else that caused what he termed “very interesting and promising” findings for
bone marrow transplants.
“If there is directed signaling that tells lymphocytes to go to a kidney and attack a transplanted kidney,” he said, then something like this “might work really well.”