Drug-Free Organ Transplants From Unrelated Donors 83
ananyo writes "Researchers have for the first time managed to give patients a complete bone marrow transplant from an unrelated donor. The recipients were also able to accept kidneys from the same donors without the need for immunosuppressive drugs. Normally, such transplants would trigger graft-versus-host disease (GvHD) — an often deadly complication that occurs when immune cells from an unrelated donor attack the transplant recipient's tissue. The researchers report that five of eight people who underwent the treatment were able to stop all immunosuppressive therapy within a year after their kidney and stem-cell transplants, four of which came from unrelated donors (abstract)."
Wish they had this years ago (Score:5, Interesting)
My cousin/sister needed a transplant and it was a bear finding a donor. And even then she had to take all kinds of anti-rejection drugs with really nasty side effects.
Cousin or sister? -Re:Wish they had this years ago (Score:2, Funny)
My cousin/sister needed a transplant and it was a bear finding a donor.
Your sister is also your cousin?
Re:Cousin or sister? -Re:Wish they had this years (Score:5, Funny)
It's his half sister, birthed by his aunt. Interestingly, his cousin is also his wife. They like to keep it in the family, you see.
Re:Cousin or sister? -Re:Wish they had this years (Score:5, Informative)
I'm going to hang this off of your post because it's near the top of the thread:
It's fast, easy and FREE to register as a marrow donor. They ask for an optional $100 donation to cover the cost of the test, but it's not required. The registry test involves swabbing the inside of your mouth, at home. It takes about 40 seconds (4 swabs @ 10 seconds each). It's completely painless and there are no needles or doctors involved.
Join the Marrow Registry - [marrow.org]http://marrow.org/Join/Join_the_Registry.aspx [marrow.org]
Obviously, registering to become a donor is an important and serious decision to make, but they're short on donors of people not of white/European descent. There's a high likelihood chance you'll never be asked to donate, but there's a 1 in 300,000 chance that you could save a life.
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As a liver transplant recipient, I would never discourage ANYONE from volunteering to be a donor. But I would caution you about being a voluntary live donor of anything. In our support group here, one of the live kidney donors talked about the insurance companies that now deny him coverage because of his "preexisting condition".
Utter bullshit if you ask me, but that's our healthcare system for you.
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Naw, that's just an old colloquial Kentucky term for "wife".
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Mother has twin sister. Son X is born. Father divorces mother. Father marries mother's twin. Daughter Z is born. Father's daughter = Z is X's sister. Mother's sister's daughter = Z is X's cousin.
Technically, X and Z are half-siblings, since they only share one parent. But there's no such thing as half cousin.
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Genetically, they're full siblings, since their mothers are genetically identical.
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That depends on how the twinning occurs, and for identical (monozygotic) twins, they usually are genetically identical - mostly. There are differences in gene expression, but such differences are inconsequential in things like genetic relationship tests.
Fraternal (dizygotic) twins are genetically siblings, with a very small chance of having the same profile.
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My brother got a hematopoietic stem cells (HSCs) transplant a couple days ago. They wiped out his then existing immune system with chemo rather than radiation and chemo as in the article; them implanted the stem cells. Right now his WBC is zero where normal is 4,500-10,0000. Anyways getting a bone marrow transplant is a pretty harrowing experience in itself. While the new immune system may not be rejecting the transplanted kidney, there is also the whole rest of the body that may be rejected by the new immu
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I had no idea they had bears doing that now. And we thought H1Bs were a problem.
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Meaning of cousin/sister (Score:3, Informative)
Lifelong immunosupression (Score:2)
I wasn't aware that after a transplant the recipient was put on a lifelong immunosupression treatment. I thought either the organ is rejected or it is accepted and that's it.
Re:Lifelong immunosupression (Score:4, Informative)
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As somebody who had a kidney transplant, I really wish that was the case. I also wish that the immunosuppressants were less expensive (even with insurance).
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I missed a pre-treatment (too complicated to get into) by about a year that would have let me (without much worry) leave off at least one medication, as I see it, for my situation. This pre-treatment has been available in Europe for quite some time (I'm USA). I have the benefit of being a life sciences resea
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According to my Son's transplant surgeon, there are better outcomes on the standard protocol of steroids throughout life than the pre-treatment protocol.
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I wasn't aware that after a transplant the recipient was put on a lifelong immunosupression treatment. I thought either the organ is rejected or it is accepted and that's it.
Common mis-conception, exacerbated by transplant seekers who are desperately seeking to avoid their own death and gloss over how much their post-transplant life is going to suck when pleading for donors.
More medical break throughs please (Score:4, Insightful)
cause I don't want to die.... ever.
Re:More medical break throughs please (Score:4, Interesting)
Hopefully future breakthroughs will be able to use organs from other sources or even artificial organs instead of relying on human donors. After all, we don't want to get into a situation like that Larry Niven short story where the demand for organs to extend peoples lives got so strong they started using convicted criminals as spare parts. And then to satisfy further demand, redefined what constituted a capital crime. Like jaywalking and littering...
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That's actually a pretty good description of the state of the world in his Known Space stuff prior to the Man-Kzin wars. (Though it doesn't help that the world's population is, if memory serves, somewhere around 18 billion at that point as well. It's looking like that particular guess for the population in the 2200s was high by a factor of 2 or more.)
Long ARM of the law (Score:2)
Re:More medical break throughs please (Score:4, Insightful)
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cause I don't want to die.... ever.
Wait until you've lived with sensory deprivation (failing eyesight, hearing, taste, smell, numbness in the extremities), relative dementia (declining ability to learn, remember, reason), reduced mobility, loss of fine motor skills, and chronic pain for a few decades. Also factor in that most of your old friends are suffering similarly, or dead, and if your children are typical, they've left you in the dust long ago.
It comes on slowly, starting around age 20-30, and generally picks up steam around 50-70, ge
in other news... (Score:4, Funny)
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I have to admit, I enjoyed that movie. You forgot the sale of box jellyfish though....
The Fine Print... (Score:2)
It remains unclear whether the secret to Ildstad’s recipe is the facilitating cells or the timing of a certain chemotherapy drug, called cyclophosphamide, that is used to prevent graft rejection and GvHD. “The facilitating cell adds an extra level of complexity that might not be necessary,” Tisdale says. The question is difficult to answer — all of the study subjects received the facilitating cells.
Moreover, much about the cells themselves and the method used to isolate them remain shrouded in a veil of secrecy — Ildstad is seeking a way to commercialize the approach through a company she founded called Regenerex, based in Louisville. “It’s difficult to assess something that doesn’t provide the key methodology,” says Megan Sykes, director of the Columbia Center for Translational Immunology at Columbia University in New York. “Nobody is quite sure what these cells are.”
So the good news is that this will likely be funded right through the trials phase. The bad news is that it'll come out the other end wrapped in IP restrictions and not widely available to the public as a standard procedure.
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since most of the subjects have been children with Sickle Cell and other types of anemia).
Huh. Now that makes a lot of sense as far as recruiting goes. I was wondering how they found people willing to undergo the risk of an partial-match bone-marrow transplant (and how to justify it to an ERB) in addition to their solid organ transplant.
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So the good news is that this will likely be funded right through the trials phase. The bad news is that it'll come out the other end wrapped in IP restrictions and not widely available to the public as a standard procedure.
If there wasn't the potential for obscene profits, nobody would have put up the obscene funding required to do the research.
summary is wrong. (Score:4, Informative)
That's directly from the abstract linked above. How 'bout that "drug free" headline there, eh?
The real news is that a couple of these people were successfully weaned off immunosupressants. And only one of the patients died from the treatment I think (corrections appreciated).
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Re:summary is wrong. (Score:4, Insightful)
By drug free, they are referring to not requiring life-long treatment with immune suppressants. That's a REALLY big deal.
Big Pharma (Score:2)
And a really bad deal for Big Pharma profits, so I'm not expecting this to become ubiqutious anytime soon. No drug dealer likes losing their lifetime customers.
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You got "insightful" for agreeing with me, and I didn't even get "informative" for quoting the relevant part of the summary. /. moderation gets more idiosyncratic every day!
I find this information strange... (Score:5, Interesting)
My Daughter had a bone marrow transplant at the age of 18 months old and has been off immunosuppressants since 30 months of age. (She is currently 7 years of age with no rejection issues and no medications at all -- 100% cured, mild chimerism)
I guess I thought that was common? Her donor was unrelated, but had a 10/10 match on HLA. That might be the magic. This study lists it working for a HLA mismatched recipient.
Of course, I only have the knowledge you get when your daughter is going through the transplant process, not all the unrelated stuff that doesn't pertain to her actual condition.
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IMNAD, but I don't think blood stem cells for transplant are normally engineered before infusion, so that's what's new about this particular procedure.
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I guess I thought that was common? Her donor was unrelated, but had a 10/10 match on HLA. That might be the magic. This study lists it working for a HLA mismatched recipient.
None of the 8 trial participants was a perfect match, ranging from 5/6 down to 1/6 (the article I have access to only lists the */6 system) with 4 organs coming from unrelated donors (the failed transplant case was actually a 3/6 related donor). Also, your daughter's very young age at transplant was a plus.
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Marrow is a little different. It is less about avoiding rejection of the marrow and more about preventing the new immune system from attacking the patient's other tissues and organs (induced auto-immune disease). If she was take off, then that means the marrow was not producing GvHD.
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I'm not sure what the age cutoff is but pre-toddlers haven't developed their immune systems to the point where they would reject organs. There are limitations of course but having an ignorant immune system has its advantages.
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Sounds too good to be true, and no evidence to support it. Recipe for a scam.
It's getting major buzz in the research community since the group presented preliminary results last year. Science magazine (about as legit as it gets) even titled their write-up "The Quest for Transplantation Tolerance: Have We Finally Sipped from the Cup?", as it truly is considered a holy grail of immunology.
Larry Niven's "Organleggers" (Score:2)
(I think the term comes from the word "bootleggers").
Anyway, I wonder if young healthy people will start disappearing off the street. Maybe people will try to GET incurable chronic diseases (like HIV or Hepatitis) and have the fact that they are so infected indicated by a prominent tattoo (to ward off the organleggers. (The scarlet "H"?) Then of course, people will get the tattoos even if they don't have the disease I guess). Finally, maybe the death penalty will be enacted for even the most trivial of c
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Anyway, I wonder if young healthy people will start disappearing off the street.
I've heard stories from decades ago that imply that this has been happening in places like India for a long time. Fortunately there are only a handful of Indians wealthy enough to do this, and with a potential donor pool of over 1B, you've got far better odds of winning a $10M lottery with a single $1 ticket.
StarGate Universe, S2E14 "Hope" (Score:2)
Funny.. I was just re-watching SGU and while encountering The season 2 episode "Hope", one of the secondary characters goes into end-stage renal failure. As part of his treatment, the medic on board describes how they found a kidney transplant procedure in which The Ancients used a bone marrow transplant beforehand to help prevent the donated organ from being rejected.
Without having read the article, I'm going to guess that this was considered possibly feasible long before and the SGU writers picked up on
Anti-Cancer Effects of GVHD (Score:1)
Perhaps more of a trade-off than an all-out win? (Score:1)
Clinical Perspective (Score:4, Informative)
I am a pediatric blood & marrow transplant physician. I have read the article abstract, but I don't subscribe to Science Translational Medicine, so I won't be able to read the article until my hospital library orders & acquires the article. These comments are based only on the abstract.
The Slashdot summary is misleading about what is novel in research. Unrelated donor bone marrow transplants (or hematopoietic stem cell transplants (HSCT), which are a superset) have been done routinely since the 1990's.
Allogeneic (meaning the stem cell source is another person, rather than the patient himself/herself) HSCT patients take immunosupressive medications to try to prevent (or to treat) graft versus host disease (GVHD). If the patient does not develop GVHD, they are usually weaned off the immunosuppressive medications by 6 months after transplant. Patients who do develop GVHD can require years (sometimes 5-10 years) of immunosuppression. In contrast, patients who receive common solid organ transplants (heart, liver, kidney) are usually on immunosuppressive medications for life, although the immunosuppression is typically stronger for the first few months after transplant. The article reports on patients who received simultaneous kidney and HSC transplants from the same donor. Some of these patients could be weaned off of immunosuppression. Although this type of simultaneous transplant is not common, it has been reported before, as well as the finding that patients could come off immunosuppression.
What is novel is the ability to perform unrelated donor transplants using donors who were not good HLA matches (the matching system that is used for HSCT) and not have the recipients develop GVHD. This was accomplished by manipulating the stem cell product after it had been collected from the donor, but before it was infused into the recipient. The majority of HSCT done today are done with unmanipulated stem cell products (I'm not counting processing that often needs to be done when the donor and recipient don't have the same red cell type - which is controlled by a different genetic system than HLA). However, some forms of stem cell product manipulation (T-cell negative selection and CD34+ cell positive selection) have been around for a few decades. They can be successfully used to decrease the risk of GVHD, but at the price of increasing the risk of graft rejection, relapse (for leukemias) and infection. In the end, almost all studies of those methods show that the overall survival or disease-free survival is unchanged.
This article describes a more sophisticated form of stem cell manipulation, in which the graft is enriched in hematopoietic stem cells and tolerogenic graft facilitating cells. There have been past reports of other sophisticated stem cell manipulations giving good results in a study, but these techniques require elaborate facilities to perform, and often when they have been replicated by groups other than the original group, the patient outcomes have not been as good as those in the original report.
So my bottom line is that this result is exciting, but needs at minimum validation in a multicenter study before it starts to look like a game changer.
To address some of the other comments:
1) The concern about graft-versus-leukemia effects is a valid one and it will need to be studied. However, that is not an issue when doing a transplant for a non-malignant disease, so it would be a definite win for those patients. For leukemias, the GVL effect is strongest in CML, then AML, and weakest in ALL (kids don't get CLL, so I don't know much about that disease). Ultimately it would take clinical trials to determine if the benefit from less GVHD outweighs increased relapse risk (if any) from decreased GVL.
2) The article uses reduced-intensity radiation / chemotherapy, which isn't exactly a picnic, but it is less toxic than standard-dose (10-14 Gy) total body irradiation and 120 mg/kg cyclophosphamide (or 4 day busulfan and 120-200 mg/kg cyclophosphamide).