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Drug-Free Organ Transplants From Unrelated Donors
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)."
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.
SJW: Someone who has run out of real oppression, and has to fake it.
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.
cause I don't want to die.... ever.
The Kruger Dunning explains most post on
My cousin/sister needed a transplant and it was a bear finding a donor.
Your sister is also your cousin?
in other news, the sale of claw-foot bathtubs and bagged ice has seen a dramatic increase
insensitive clod overlords obligatory xkcd car analogy russian reversals whoosh pedant fanbois ftfy in 3...2...1..PROFIT
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.
The Christian Right is Neither (Christian nor right). See: Matthew 23, Matthew 25, Ezekiel 16:48-50
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.
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.
He's from Appalachia. Ask him about Uncle Dad.
That's nothing. I'm my own grandfather!
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.
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).
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.
Do you Gentoo!?
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.
Battlemaster--Game with friends in medival realms
Sounds too good to be true, and no evidence to support it. Recipe for a scam.
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 - http://marrow.org/Join/Join_the_Registry.aspx
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.
moox. for a new generation.
Genetically, they're full siblings, since their mothers are genetically identical.
"I do not agree with what you say, but I will defend to the death your right to say it"
(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.
They are not genetically identical even if they appear identical.
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?
Gil The Long ARM of the law was a good Niven character. I know his stories mention a number of organlegging operations - finding reasons to steal organs to sell.
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?
Naw, that's just an old colloquial Kentucky term for "wife".
You shall see a cow on the roof of a cotton house.
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.
Also, it appears there was legislation to try and fix this... but it never went anywhere:
http://www.govtrack.us/congress/bill.xpd?bill=h111-1558
http://www.govtrack.us/congress/bill.xpd?bill=s111-623
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".
Yes the incest jokes are mildly amusing, but for those of you unaware, "cousin sister" is Indian English for "female cousin".
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.
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.
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.
You do not have a moral or legal right to do absolutely anything you want.
Would it kill you to even briefly explain how they were able to do this in TFS?
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?
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?
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).
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).
Swedish doesn't, either - it's "kusin" for both. It's very close relative does, though (fetter/kusine is male/female).
From TFA (emphasis mine):
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:
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?
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.