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Drug-Free Organ Transplants From Unrelated Donors

Soulskill posted more than 2 years ago | from the just-say-no dept.

Medicine 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)."

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Wish they had this years ago (4, Interesting)

elrous0 (869638) | more than 2 years ago | (#39294531)

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 (2, Funny)

Anonymous Coward | more than 2 years ago | (#39294657)

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 (4, Funny)

kimvette (919543) | more than 2 years ago | (#39294705)

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 (0)

Anonymous Coward | more than 2 years ago | (#39295189)

That's nothing. I'm my own grandfather!

Re:Cousin or sister? -Re:Wish they had this years (5, Informative)

Hadlock (143607) | more than 2 years ago | (#39295729)

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.

Re:Cousin or sister? -Re:Wish they had this years (1)

Anonymous Coward | more than 2 years ago | (#39298005)

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.

Re:Cousin or sister? -Re:Wish they had this years (0)

Anonymous Coward | more than 2 years ago | (#39307633)

Please do -- it saved my life!

If you actually get called to donate, it's actually a simple process. Either you donate in pretty much the same way you donate blood or they put you under draw it directly from your bone (trust me, you don't feel a thing) and give you some way-fun pain meds for at home ;)

Depending on your medical system, you may even get a few days off of work.

Re:Cousin or sister? -Re:Wish they had this years (0)

Anonymous Coward | more than 2 years ago | (#39297051)

I've worked with some people from India in years past, and they explained to me that they had in their language (I forget which one), that there was a differentiation between male cousins and female cousins. The direct translation was, I believe, brother-cousin and sister-cousin. I believe the same thing holds true in french: cousin versus cousine?

Re:Cousin or sister? -Re:Wish they had this years (1)

MisterMidi (1119653) | more than 2 years ago | (#39298273)

I think the more direct translations are nephew and niece. Yes, in French they make the distinction between male and female cousins, and in Dutch and German too. English is the only language I know that has a word that doesn't differentiate between male and female. Same goes for "sibling".

Re:Cousin or sister? -Re:Wish they had this years (0)

Anonymous Coward | more than 2 years ago | (#39305951)

Swedish doesn't, either - it's "kusin" for both. It's very close relative does, though (fetter/kusine is male/female).

Re:Cousin or sister? -Re:Wish they had this years (1)

Kyont (145761) | more than 2 years ago | (#39297345)

Naw, that's just an old colloquial Kentucky term for "wife".

Re:Cousin or sister? -Re:Wish they had this years (0)

Anonymous Coward | more than 2 years ago | (#39295179)

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.

Re:Cousin or sister? -Re:Wish they had this years (1)

egamma (572162) | more than 2 years ago | (#39295587)

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.

Re:Cousin or sister? -Re:Wish they had this years (1)

CrimsonAvenger (580665) | more than 2 years ago | (#39296491)

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.

Genetically, they're full siblings, since their mothers are genetically identical.

Re:Cousin or sister? -Re:Wish they had this years (0)

Anonymous Coward | more than 2 years ago | (#39296857)

They are not genetically identical even if they appear identical.

Re:Cousin or sister? -Re:Wish they had this years (1)

Sarten-X (1102295) | more than 2 years ago | (#39300205)

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.

Re:Cousin or sister? -Re:Wish they had this years (0)

Anonymous Coward | more than 2 years ago | (#39295181)

He's from Appalachia. Ask him about Uncle Dad.

Re:Wish they had this years ago (2)

betso.net (950024) | more than 2 years ago | (#39294719)

Even if the results would have been published a year ago, exposure to options like this are preserved only to people participating in studies until the therapy is approved and established. This takes some 3-5 years at least. Also keep in mind that newer things are by far not always better. Btw., here is another interesting article regarding this topic showing that there is a lot of space to work in this direction: http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2012.03992.x/abstract [wiley.com]

Re:Wish they had this years ago (2)

budgenator (254554) | more than 2 years ago | (#39297405)

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 immune system.

Re:Wish they had this years ago (1)

sjames (1099) | more than 2 years ago | (#39294805)

I had no idea they had bears doing that now. And we thought H1Bs were a problem.

Re:Wish they had this years ago (0)

Anonymous Coward | more than 2 years ago | (#39295285)

Ummm, less inbreeding would probably mean less need for doctors.

Re:Wish they had this years ago (0)

Anonymous Coward | more than 2 years ago | (#39295545)

I wish they had this years ago too. My wife traded a kidney so that I could get a replacement. Unfortunately, the anti-rejection drugs made me feel terrible. Then, I rejected the kidney anyway. Since this only works with live donors I've blown my chance of trying this.

While it's cool to hear about progress in the field, I'm waiting for them to be able to clone one of my own kidneys or develop something entirely artificial.

Meaning of cousin/sister (3, Informative)

dalias (1978986) | more than 2 years ago | (#39298495)

Yes the incest jokes are mildly amusing, but for those of you unaware, "cousin sister" is Indian English for "female cousin".

Lifelong immunosupression (2)

methamorph (950510) | more than 2 years ago | (#39294597)

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 (4, Informative)

Nittle (1356899) | more than 2 years ago | (#39294905)

My father-in-law lived more than 20 years after a liver transplant and required medication to prevent rejection. I believe the initial anti-rejection drug changed a few years after the implant, but he still was required to take daily medication.

Re:Lifelong immunosupression (0)

Anonymous Coward | more than 2 years ago | (#39296359)

My mother had a Liver transplant in 1986 at The University of Pittsburgh (Dr. Thomas Starzel's team) and it allowed her to live another 18 years. She had to take Cyclosporine everyday for the rest of her life.

Re:Lifelong immunosupression (1)

HAKdragon (193605) | more than 2 years ago | (#39295475)

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).

Re:Lifelong immunosupression (1)

swilde23 (874551) | more than 2 years ago | (#39298085)

I'm a liver transplant (2.5 years now) and I can second all of this. Though my doctors finally allowing me to take generic Prograf has made a huge dent in my monthly drug costs. Also, I'm extremely grateful that I don't have to take Prednisone (as many of the kidney transplant patients do for the the rest of their lives).

Re:Lifelong immunosupression (1)

toomanyhandles (809578) | more than 2 years ago | (#39297049)

I had a kidney transplant close to 6 years ago. I have 3 immunosuppresive meds, 2 of which are fairly targeted, one is good old prednisone. And then 3 more to counteract the effects of these meds.

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 researcher, working in the field of immunology (although not transplant medicine) so I get to geek out a bit more than some over published papers.

The paired-unrelated-donor exchange registries available these days are the neatest advance I have seen, statistically. A HUGE difference in real matches.

These days, blood type match is actually more important than many of the histocompatibility complex match categories, but increased antigen matches can't hurt.

Re:Lifelong immunosupression (1)

modmans2ndcoming (929661) | more than 2 years ago | (#39297441)

According to my Son's transplant surgeon, there are better outcomes on the standard protocol of steroids throughout life than the pre-treatment protocol.

Re:Lifelong immunosupression (1)

91degrees (207121) | more than 2 years ago | (#39299537)

This is one of the reasons why face and hand transplants are a little controversial. The drugs have side effects - mainly the hugely weakened immune system - so when it's about quality of life rather than the difference between life and death it's a lot harder to argue for the operation.

Re:Lifelong immunosupression (1)

JoeMerchant (803320) | more than 2 years ago | (#39299853)

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.

Re:Lifelong immunosupression (0)

Anonymous Coward | more than 2 years ago | (#39301693)

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.

Liver/Kidney transplant, Jan2010. Transplants are a far bigger deal, medically, than they would appear from TV (including medical shows). It is better to think of the transplant as an on-going therapy option than as a fix. For some organs, the choice is transplant or death. For kidneys, transplant may extend your life, but not hugely (dialysis is pretty effective these days). Quality of life is generally agreed to be much better for kidney receipients though.

The drug regimine I am on (to give you an idea of what it really looks like 2y after):
7am - 1.5mg Tacrolimus (no food 2hr prior/1hr after) (2 pills)
8am - 180mg Myfortic (1 pill) (all with food)
                    4mg Prednisone (4 small pills)
                    133mg Mg+protien (1 horsepill) .1mg Florinef (1 small pill)
                      25mg Lopressor (1 pill)
                      60mg Sensipar (1 pill)
                      4000ui Vitamin D (2 pills)
7pm - 1mg Tacrolimus (no food 2hr prior/1hr after) (1 pill)
8pm - 180mg Myfortic (1 pill) (all with food)
                    266mg Mg+protien (2 horsepills) .1mg Florinef (1 small pill)
                      25mg Lopressor (1 pill)
                      60mg Sensipar (1 pill)
                      2000ui Vitamin D (2 pills, could be 1 but i have 1000ui pills to use up)

Additionally, blood work drawn for 2 lab orders (Nephrologist and Hepatologist working independently :-() once per month, must be fasting for that.

Count on seeing 4 different doctors, totaling maybe 12 dr appointments per year, assuming nothing weird is happening. Something weird will happen, and you'll get scanned, or extra blood work, or some odd test once or twice a year.

Also, the transplant team is a little paranoid about your care in general. I do not live in the city where I received the transplant, and have now had two Medi-flight trips back to the transplant center because of infections they did not trust the locals to treat properly.

Also note, you need to carry drugs with you, just in case. Tacrolimus and Myfortic are not typically carried by rural health facilities. So, if you wind up in a rural facility, you'll have the arguement where they tell you that you can't bring in your own drugs, "we can provide all the drugs you will need", till an hour later they come back and admit they don't have those two... :-)

More medical break throughs please (3, Insightful)

geekoid (135745) | more than 2 years ago | (#39294613)

cause I don't want to die.... ever.

Re:More medical break throughs please (3, Interesting)

barc0001 (173002) | more than 2 years ago | (#39294755)

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...

Re:More medical break throughs please (2)

mdenham (747985) | more than 2 years ago | (#39294953)

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 (1)

witherstaff (713820) | more than 2 years ago | (#39297199)

Gil The Long ARM of the law [wikipedia.org] was a good Niven character. I know his stories mention a number of organlegging [wikipedia.org] operations - finding reasons to steal organs to sell.

Re:More medical break throughs please (0)

Anonymous Coward | more than 2 years ago | (#39294965)

Hopefully past breakthroughs in public heath will prevent the need to use organs from other sources. Seriously, tobacco smoking, alcohol, and fucking diseased people (i.e. sex) are preventable. Let's work on that first.

Re:More medical break throughs please (4, Insightful)

Anonymous Coward | more than 2 years ago | (#39294985)

Yeah, what a nightmare. Imaging if the prison industry got so big that the government started putting all sorts of people in prison for non-violet crimes. Eventually so much money would be involved that politicians would start trying to outdo each other at being tough on crime and start a never ending cycle of increasing penalties. They might even take away a judge's power to decide what penalty someone faces by creating mandating sentences. Imagine if say 1% of the US population was in prison. 1 out of 100 adults! Science fiction is scary.

Re:More medical break throughs please (0)

Anonymous Coward | more than 2 years ago | (#39300725)

The Chinese already harvest organs from those who get the death penalty. And China sentence a lot of people to death.

Re:More medical break throughs please (1)

JoeMerchant (803320) | more than 2 years ago | (#39299909)

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, generally later in people who don't "live" much in their youth.

I've never met anyone over the age of 95 who wants to live forever.

in other news... (4, Funny)

Eponymous Hero (2090636) | more than 2 years ago | (#39294687)

in other news, the sale of claw-foot bathtubs and bagged ice has seen a dramatic increase

Re:in other news... (1)

Em Adespoton (792954) | more than 2 years ago | (#39295153)

I have to admit, I enjoyed that movie. You forgot the sale of box jellyfish though....

Drug Companies will kill this (0, Interesting)

Anonymous Coward | more than 2 years ago | (#39294971)

Its only a matter of time before one of the large drug companies starts cranking out studies that this kills people. They have to protect their profit margins after all.

ma83 (-1)

Anonymous Coward | more than 2 years ago | (#39295019)

wit4 process and worthwhile. So I We'll be able to My eeforts were invited back again. fear the reaper may disturb other in a head spinning

The Fine Print... (2)

Em Adespoton (792954) | more than 2 years ago | (#39295239)

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.

Re:The Fine Print... (3, Informative)

Anonymous Coward | more than 2 years ago | (#39296991)

If you're curious, facilitator cells are CD4+, CD8+, and make up only a small fraction of the total number of T-cells. (CD4+ are "helper", CD8+ are "killer", and having both on one cell was thought to be impossible.) The processing includes ferromagnetically extracting 85% of the harvested bone marrow cells (collected over four donations per donor, often a parent since 3/6 HLA matches are acceptable, which is a major improvement over traditional technique), retaining the facilitator, progenitor, and hematopoetic stem cells (CD34+), while removing the alpha-beta B & T cells (which contribute to graph vs host), then verifying everything is within acceptable limits by flow cytometry. The facilitator cells also have something done to them, but I'd imagine fewer than ten people in the world know exactly what.

From there, the recipient takes some chemotherapy drugs to reduce (but not eliminate, an important difference!) their own bone marrow. The goal is mixed chimerism, where both the donor's and recipient's bone marrow work together without killing each other so you have two populations of blood cells. The first advantage is that, if the graph fails, the recipient still has their original immune system. The second is, as the summary states, they don't have to be on immunosupressants for the rest of their life (which is hoped to be long, since most of the subjects have been children with Sickle Cell and other types of anemia).

The researchers are highly secretive about the processing. They know that this discovery is likely to make someone rich, and perhaps Nobel-worthy if it is as successful as they hope (so they absolutely want to be the first to do it, even if the lack of collaboration makes things slower). Bone marrow transplant currently is the only cure for a great many disease, but has ~50% five-year mortality, whereas this technique seems to be much safer. I personally find such secrecy in research to be highly distasteful, so I distanced myself from the project and outright left when non-disclosure agreements were mentioned. It is absolutely groundbreaking though.

Re:The Fine Print... (1)

Guppy (12314) | more than 2 years ago | (#39311367)

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.

Re:The Fine Print... (1)

JoeMerchant (803320) | more than 2 years ago | (#39299933)

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.

Re:The Fine Print... (0)

Anonymous Coward | more than 2 years ago | (#39311481)

If there wasn't the potential for obscene profits, nobody would have put up the obscene funding required to do the research.

The funding isn't obscene. More money is spent on advertising (to maximize profits :-)

summary is wrong. (3, Informative)

Medievalist (16032) | more than 2 years ago | (#39295281)

Eight recipients of human leukocyte antigen (HLA) mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200-centigray total body irradiation, and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus and mycophenolate mofetil.

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).

Re:summary is wrong. (1)

Dyinobal (1427207) | more than 2 years ago | (#39295317)

Yep even if the headline is miss leading this is a big deal. Assuming these people remain rejection free.

Re:summary is wrong. (3, Insightful)

sjames (1099) | more than 2 years ago | (#39295383)

By drug free, they are referring to not requiring life-long treatment with immune suppressants. That's a REALLY big deal.

Big Pharma (1)

ThatsNotPudding (1045640) | more than 2 years ago | (#39299689)

By drug free, they are referring to not requiring life-long treatment with immune suppressants. That's a REALLY big deal.

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.

Re:summary is wrong. (1)

Medievalist (16032) | more than 2 years ago | (#39300513)

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... (4, Interesting)

Binestar (28861) | more than 2 years ago | (#39295327)

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.

Re:I find this information strange... (1)

macaran (766186) | more than 2 years ago | (#39295593)

I'm not sure this is actually true, but I believe bone marrow regenerates. So she probably doesn't have any of the donors bone marrow in her anymore. The suppression drugs are more for people who have actual organs transplanted, which will always have cells that are not from your body inside you.

Re:I find this information strange... (2)

Binestar (28861) | more than 2 years ago | (#39296281)

Oh, she still has the bone marrow in her. That is the point of the transplant. She had a condition called "Kostman's Syndrome" which to put short, meant her bone marrow had a genetic defect that she was unable to produce the white blood cells that fight bacteria. Not only is her bone marrow someone else's, if she were to take a DNA test on her blood she would show up as male, as the donor was a male. WIthout the donor's marrow, hers would go back to not producing neutrophils.

Re:I find this information strange... (0)

Anonymous Coward | more than 2 years ago | (#39296691)

I'm just really glad to hear your daughter made a 100% recovery :)
-AC

Re:I find this information strange... (1)

macaran (766186) | more than 2 years ago | (#39297523)

That's pretty awesome binestar! I'm glad modern medicine worked out for your family!

Re:I find this information strange... (1)

TheLink (130905) | more than 2 years ago | (#39298717)

The thing I'm wondering about this new treatment is why wouldn't immune cells from the donated marrow start attacking the host?

Re:I find this information strange... (1)

epp_b (944299) | more than 2 years ago | (#39307689)

From the abstract:

We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells

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.

Re:I find this information strange... (1)

Guppy (12314) | more than 2 years ago | (#39296843)

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.

Re:I find this information strange... (2)

modmans2ndcoming (929661) | more than 2 years ago | (#39297465)

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.

Re:I find this information strange... (1)

Riskable (19437) | more than 2 years ago | (#39299827)

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.

Re:I find this information strange... (1)

Binestar (28861) | more than 2 years ago | (#39306645)

Interestingly enough, after her transplant she needed to have her titers checked to see where she was on her vaccination schedule. There were a few vaccinations she needed to get that she had already had, but due to the transplant she was now immune to Chicken Pox, having never received the vaccine nor had Chicken Pox, it was determined she inherited the immunity through the donor.

Re:I find this information strange... (0)

Anonymous Coward | more than 2 years ago | (#39299497)

Part of that may be to due with her age: I remember hearing about an infant in Canada who was given a heart transplant that wasn't even close to matching, but there was no rejection. Last I heard, they still didn't know for sure what mechanism allowed this (there were some theories about the higher number of stem cells still in babies' systems), but they've had repeated good results with very young patients integrating foreign tissue without the compliations you see in adults.

My bet (0)

Anonymous Coward | more than 2 years ago | (#39295707)

Sounds too good to be true, and no evidence to support it. Recipe for a scam.

Re:My bet (1)

Guppy (12314) | more than 2 years ago | (#39297027)

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" (1)

wisebabo (638845) | more than 2 years ago | (#39296647)

(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 crimes (like parking tickets) with the executed having their organs freshly harvested.

More likely is if the government enacts a policy whereby if you sign up for a post-humous organ donation program (and presumably are enrolled in it for at least a year), you are put on the priority list for organ(s) shoud you need them. I understand this has already been proposed and maybe even put into place in some areas (at least for blood transfusions). It would make me more likely to participate, that's for sure.

So yeah, if this pans out, there are some interesting implications.

Re:Larry Niven's "Organleggers" (1)

dalias (1978986) | more than 2 years ago | (#39298517)

This all sounds pretty far-fetched, considering that we're probably at most a decade or two away from making organ transplants completely obsolete (replaced by growing the patient's own replacement organ with their own DNA or slightly modified to correct for the genetic disease that caused the original organ to fail).

Re:Larry Niven's "Organleggers" (1)

JoeMerchant (803320) | more than 2 years ago | (#39299961)

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.

Shhh it's a secret (0)

Anonymous Coward | more than 2 years ago | (#39297225)

Anybody else really dejected by the bit at the end of the article that basically said, "it's being commercialized -- so we can't tell you exactly how we do what we do!" If this was NIH supported, then I'm a pissed off tax payer. Moreover, how did they do the procedure without releasing the details on the method -- wouldn't 45 CFR 46 basically require release of the information?

StarGate Universe, S2E14 "Hope" (1)

QuasiSteve (2042606) | more than 2 years ago | (#39299751)

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 that, but I still thought it neat that something that might otherwise be considered science fiction is, in fact, quite possible today.

Re:StarGate Universe, S2E14 "Hope" (0)

Anonymous Coward | more than 2 years ago | (#39301773)

You are correct. Liver/Kidney receipient, 2010, listed for kidney in 1998. Been following the research for a while. I thought Stanford had been doing this already for a number of years. Either that, or I know one of those people in the study.

Oh, come on! (0)

Anonymous Coward | more than 2 years ago | (#39301655)

Would it kill you to even briefly explain how they were able to do this in TFS?

Mild GVHD is beneficial as an anti-cancer effect (0)

Anonymous Coward | more than 2 years ago | (#39302103)

I had a stem cell transplant, SCT, (commonly referred to as a bone marrow transplant) 10 years ago to treat a bone marrow failure disease called Myelodysplasia (MDS). My older brother was the donor with a 5 out of 6 HLA match. About 3 months post transplant I started to experience GVHD (affecting liver, skin, eyes, lungs) which was controlled using a combination of immunosuppressants, cyclosporine and prednisone (a steroid). GVHD tends to have a more pronounced effect on the large, high surface area organs such as the skin, liver and lungs. High doses of the two drugs would be administered initially and then the dosage gradually reduced until evidence (monitoring of the liver enzymes) of GVHD returning. If the GVHD had returned the drug dosage would be returned to it's high level and the gradual weaning process started again. I went through 3 such cycles over the course of 2 years before the GVHD "burned" itself out. I have been off the immunosuppressants for about 8 years now. Long term use of cyclosporine causes kidney damage and prednisone has a host of side effects including water retention, calcium loss, glaucoma, voracious appetite and weight gain, insomnia and extreme mood changes. Very nasty side effects but they are wonder drugs at controlling the potentially life threatening GVHD.

It is common knowledge that some mild GVHD is beneficial as an "anti-cancer" effect. The donor immune response, GVHD, as well as attacking the host tissues also destroys residual cancer cells remaining after the transplant process. Studies done removing donor T-cells prior to stem cell transplantation showed reduced incidence and severity of GVHD but this was accompanied by a marked increase in morbidity due to disease relapse. I am curious as to how the procedure described in the article impacts the "anti-cancer" effect of GVHD and possibility of disease relapse?

Anti-Cancer Effects of GVHD (1)

stainless416 (1886770) | more than 2 years ago | (#39302235)

I had a stem cell transplant, SCT, (commonly referred to as a bone marrow transplant) 10 years ago to treat a bone marrow failure disease called Myelodysplasia (MDS). My older brother was the donor with a 5 out of 6 HLA match. About 3 months post transplant I started to experience GVHD (affecting liver, skin, eyes, lungs) which was controlled using a combination of immunosuppressants, cyclosporine and prednisone (a steroid). GVHD tends to have a more pronounced effect on the large, high surface area organs such as the skin, liver and lungs. High doses of the two drugs would be administered initially and then the dosage gradually reduced until evidence (monitoring of the liver enzymes) of GVHD returning. If the GVHD had returned the drug dosage would be returned to it's high level and the gradual weaning process started again. I went through 3 such cycles over the course of 2 years before the GVHD "burned" itself out. I have been off the immunosuppressants for about 8 years now. Long term use of cyclosporine causes kidney damage and prednisone has a host of side effects including water retention, calcium loss, glaucoma, voracious appetite and weight gain, insomnia and extreme mood changes. Very nasty side effects but they are wonder drugs at controlling the potentially life threatening GVHD. It is common knowledge that some mild GVHD is beneficial as an "anti-cancer" effect. The donor immune response, GVHD, as well as attacking the host tissues also destroys residual cancer cells remaining after the transplant process. Studies done removing donor T-cells prior to stem cell transplantation showed reduced incidence and severity of GVHD but this was accompanied by a marked increase in morbidity due to disease relapse. I am curious as to how the procedure described in the article impacts the "anti-cancer" effect of GVHD and possibility of disease relapse?

Perhaps more of a trade-off than an all-out win? (1)

morsedl (1812320) | more than 2 years ago | (#39302277)

As a 43-year-old male who has had a matched unrelated donor transplant (MUD) for acute mylogenous leukemia (AML, subtype M6) at age 35, I can tell you that having total body irradiation (TBI) and ablative chemotherapy is no walk in the park, and my chances of acquiring seconary cancers later in life is dramatically increased. So, for those requiring solid organ transplant, this approach is perhaps a win relative to the toxicity and other effects of lifelong immuneosuppression, I suspect it is far from a panacea. In addition, I think its worth noting that these findings were NOT based on fully-ablative bone marrow transplantation, as chimerism resulted (and indeed, was sought). Thus, the promise of no chronic graft-vs-host disease does NOT apply to those needing fully-ablative transplants (e.g., leukemias and other blood-based cancers or disorders requiring complete destruction of the host bone marrow).

Clinical Perspective (3, Informative)

UltraOne (79272) | more than 2 years ago | (#39303999)

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).

The summary confuses me... (0)

Anonymous Coward | more than 2 years ago | (#39307515)

Probably because it's wrong. Actually, it's incomplete.

From TFA (emphasis mine):

Now, researchers have for the first time managed to completely replace peopleâ(TM)s bone-marrow-derived stem cells with those from unrelated donors without causing GvHD

The emboldened bit is the important part, here, and the summary is misleading in this respect. It's already known that using mobilized blood stem cells (as opposed to stem cells directly from bone marrow) reduces that occurrence of GvHD to about 10-20%. Given that the sample size in this study was eight, it's very possible that these patients were outside of that static.

While interesting, using a bone marrow transplant as a solution to mismatched organ donors and recipients seems overkill to me.

Consider this excerpt from the abstract:

Eight recipients of human leukocyte antigen (HLA)â"mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200-centigray total body irradiation, and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus and mycophenolate mofetil.

You see all those scary-sounding drugs and treatments? I've had all but one of them (among many others not mentioned that are just as rough or worse) for my bone marrow transplant. The pain and discomfort involved is more severe than that of major surgery and it goes on for weeks on end while using the maximum safe dose of powerful analgesics.

This is no panacea. Bone marrow transplantation is a long, painful and risky process and generally only used as a last resort for people with otherwise terminal conditions. It's the kind of thing doctors only consider as a cancer treatment after trying standard chemotherapy regimens.

I guess the question is: how does success rate and longevity compare to that of organ transplant with immunosuppression?

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