Transplant girl's blood type changes!

[The Atheist]

In other words, I'm having trouble understanding the "big deal" in this, as well as the long-term ramifications.

Well orl those dumb ole cheatin' jurnalists and me thank that maybe iffen we can figger out eggsackly wut happened wheel bee abul to repplickeight the cunditions ever sangle time someone gits onna them transplanted thangs.

 

[fls]

Okay, fair enough. I'm still trying to understand what is so special about this case, though.

If you have access to this issue, it would be worthwhile to read Starzl's editorial on the subject.

It is special in that it adds to the information that helps confirm theories about why some people successfully withdraw from immunosuppressive therapy. And it helps give credence to the idea that experimental therapies which duplicate the processes present in this case could lead to the desired outcome.

In autologous BMT (something you probably know more about than I do, Linda), patients own marrow is removed from the body and then otherwise-lethal chemo/XRT is given. The marrow is spun, treated, and given back to the patient. This is, in effect, a re-engraftment of the patient's native erythropoeitic system. I just don't see why this couldn't be accomplished, similarly, with a heterogenous graft.

I think you are referring to the process described in another report in this same issue?

http://content.nejm.org/cgi/content/abstract/358/4/362

In other words, I'm having trouble understanding the "big deal" in this, as well as the long-term ramifications.

I suspect this is because what is hyped in the lay press does not match the reality.

And, I wonder what would/will happen if her system kicks back into extramedullary hematopoeisis.

-Dr. Imago

Then she'd just be back where she started, like everyone else. And there is still the risk of graft-vs-host which is why many people in her situation fail to come off of immunosuppressives.

Linda

 

[fls]

I cannot do anything other than parrot the details provided in the report, since that is all the information I have on this case. I'm not claiming to know what happened.

Finally.

Huh? I at no point implied that I had any personal involvement in this case.

Linda

 

[SteveGrenard]

This may help to better understand the process:

BOSTON (Reuters) - Injecting blood or bone marrow cells into people who have just received a donated kidney can reduce the need for drugs that suppress the immune system, researchers reported on Wednesday.
The stem cells in the blood and bone marrow helped trick the body into tolerating the transplants, two teams of researchers reported in the New England Journal of Medicine.
In one series of experiments, researchers at Massachusetts General Hospital and Harvard Medical School in Boston tested the technique on five volunteers who received a kidney from a relative. Four were eventually weaned off their anti-suppression drugs.
"While we need to study this approach in a larger group of patients before it is ready for broad clinical use, this is the first time that tolerance to a series of mismatched transplants has been intentionally and successfully induced," said Dr. David Sachs, who helped lead the study.
http://www.reuters.com/article/healthNews/idUSN2364870520080124

Dr Ray Weinstein wrote this explanation on another forum to explain what happened in the liver transplant case:

Very interesting report. The donor was O-pos and the recipient was O-neg. When they said they had a different blood type I wrongly assume they were talking about ABO type. It seems that the 2 immune systems fought it out for a while as she developed intractable hemolysis that spontaneously resolved, and when it was all over, the donor bone marrow had petty much taken over. The recipient immune system had developed tolerance to it and treated it as self, just like her own immune cells. This has been accomplished in some experimental laboratory animal models. Apparently she still has some of her own cells too, so she would be referred to as a chimera. There was another article in the same issue (NEJM 1/25) describing a similar case following kidney transplantation.

 

[SteveGrenard]

Then she'd just be back where she started, like everyone else. And there is still the risk of graft-vs-host which is why many people in her situation fail to come off of immunosuppressives.

Linda

In a message dated 1/24/2008 8:08:59 P.M. Eastern Standard Time, kc5arb@ writes:

On the other hand, while the liver was accepted due to the change in blood type, is there any danger to the rest of the organs now being rejected?? I would think not, but it would be a cruel irony. Is the blood stream and particularly the blood type the primary determining factor in the rejection process, or does it have more to do with the composition of the cells of the transplanted organ?

Dr Weinstein replied:

It's tissue HLA types that count for transplants, and blood type is a secondary factor (except in transfusions). The more HLA types the donor and recipient have in common, the more likely a successful transplant. If a recipient rejects an organ, that's called a host vs graft reaction. If it's the bone marrow and immune system that's transplanted then you get a graft vs host reaction (the rest of the organs are rejected).

 

[Ivor the Engineer]

...If it's the bone marrow and immune system that's transplanted then you get a graft vs host reaction (the rest of the organs are rejected).

I was thinking about that. Any idea how likely it is?

 

[SteveGrenard]

I was thinking about that. Any idea how likely it is?

Not very I guess.

How did the recepient wind up with the donor bone marrow if they only transplanted an organ, e.g. liver or a kidney?

The liver contained pleuripotent stem cells that could develop into any other kind of cell. Once released from the liver they went to the bone marrow where they were stimulated to develop into hematopoietic stem cells and then into all the blood cells produced by the marrow (red cells, lymphocytes, monocytes, granulocytes, and probably platelets also). I suspect she still retains here original marrow cells as well.

What's amazing about this case is that she didn't develop a graft vs host reaction where her new immune system rejects the rest of the body. She now has 2 genetically distinct cell lines growing in her body (she's a chimera) and her immune cells (which are probably also chimeric) all recoginze both cell lines as "self" rather than foreign, so they don't attack each other. Ray Weinstein MD

 

[Dr. Imago]

Well orl those dumb ole cheatin' jurnalists and me thank that maybe iffen we can figger out eggsackly wut happened wheel bee abul to repplickeight the cunditions ever sangle time someone gits onna them transplanted thangs.

Yeah, good luck with that. Studying anomalies has historically proven to be incredibly fruitful and widely applicable.

-Dr. Imago

 

[The Atheist]

Yeah, good luck with that. Studying anomalies has historically proven to be incredibly fruitful and widely applicable.

-Dr. Imago

Damn right.

 

[Dr. Imago]

Damn right.

Interesting story. Serendipity and careful scientific observation. And a lot of dumb luck. Are you suggesting that this girl is the next Fleming's accident?

If you are, I'm willing to wager you large money. Spilling some mold on a petri dish is a far cry from understanding the human immune system. Using your analogy, we should've solved cancer in the 1970's when "war" was declared on it. And, how many other countless billions have been spent going down wrong pathways and barking up the wrong tree?

Still, I admire your optimisim. Wish I could share it, actually.

-Dr. Imago

 

[The Atheist]

Interesting story. Serendipity and careful scientific observation. And a lot of dumb luck. Are you suggesting that this girl is the next Fleming's accident?

Certainly not, I was just pointing out that sometimes odd things happen and pay off.

I see you're a betting man! Well, I wouldn't be betting on it being the cure-all for transplant rejection, but every now and then, one of the 1000:1 shots pays off and I think we have to cover all the angles in case this is one of them.

You're quite right - it almost certainly isn't a breakthrough but just another weird thing, like Andrew Stimpson, the bloke who [apparently] cured himself of AIDS. Time will tell.

 

[fls]

Certainly not, I was just pointing out that sometimes odd things happen and pay off.

I see you're a betting man! Well, I wouldn't be betting on it being the cure-all for transplant rejection, but every now and then, one of the 1000:1 shots pays off and I think we have to cover all the angles in case this is one of them.

You're quite right - it almost certainly isn't a breakthrough but just another weird thing, like Andrew Stimpson, the bloke who [apparently] cured himself of AIDS. Time will tell.

The report in the NEJM is the story of discovering what was unique about this case. It didn't turn out to be a breakthrough - it is as though Flemming discovered his mold secreted ethyl alcohol rather than penicillin - but it does at least illustrate that research in this area is on the right track.

Linda

 

[a_unique_person]

Well, if they have no explanation, they sure did an excellent job of hiding it by providing a detailed explanation in the NEJM report.

This is a good example of how the lay press rarely manages to convey the essence of science story.

Linda

Party poopers.