11 replies to this topic

[SunNsand]

  I've been wondering how someone could match with an unrelated donor and not be related to each other. Is it possible they have a common ancestor or am I understanding this all wrong?

SunNsand

[CallMeLucky]

Here's my understanding, HLA are protein molecules.  I believe there is a finite amount of different HLA molecules that a human can have.  So if you sample enough people who are not related, eventually you will find ones who have the same, or very similar HLA molecules in their body and therefore, they are a good match.

I suppose it is possible that they may have similar ancestry if you go far enough back.  I believe people with similar ethnic backgrounds are better potential matches.  But I don't think it comes down to tracing both individuals back to the point where you find they are related, but then again, who knows?

[PhilB]

Either the a mutation to produce a specific protein happened more than once, or else you share a common ancestor.  That common ancestor may, however, have been at a point when they were still hunting antelope on the African plains or still sitting in a tree peeling fruit with their toes.

[SunNsand]

PhilB - Loved the visual you described, made me laugh. I would like to make a comment regarding the ancestors peeling fruit with their feet but I can't because some of my relatives may be reading this Lol.

SunNsand

[Tedsey]

SunNsand, please forgive me, but did you say once that you were adopted?  I am and I have no siblings.  So, I get anxious thinking about needing a donor.  Anyway, I read that geneticists think that human DNA varies roughly 4%.  I would assume that means if we can find a matching donor, it would be logical to say he/she is probably a "relative".  But like Phil said, it could go as far back as the stoneage.  And although less people of Latino and Asian "origin" get leukemia, it is possible a person of such "descent" could match with one of African or Caucasian, etc. (any human mix is possible for a match).  I read an interesting article by a genetic's prof.  He had his students look at their DNA.  Quite a few students who thought they were of African descent had no "African" genes at all.  Some were more "Caucasian" in their DNA.  So, as far as relatives go, you cannot judge a cousin, grandparent, aunt or uncle, even mother or father by the way they look.

Just thought this was interesting.

Teds   

[GerryL]

Hi Teds,

Not sure this is of any consolation, but my specialist told me you could have 3 siblings and none of them could be a match for you anyway.

Gerry

[SunNsand]

Tedsey, that is interesting. I find genetics and ancestry fascinating. I also agree with you that you can't make a judgment on someone's ancestry just by looking at them. I've long held the belief that we are all pretty much a mix. It would be fun to be able to look at our own DNA and see what surprises we find. 

I wasn't adopted although my older sister used to torment me with the accusation for her entertainment purposes ha. I love her dearly! My maternal side of the family has not escaped cancer for many generations, that is my puzzle of life. I wish I was smart enough to figure this all out and stop it!

SunNsand

[Trey]

There are only two possible perfect donor matches to your white blood cells: one is yourself*, and another is an identical twin (but not always a perfect match).  Every other so-called HLA match is some degree of non-matching, including siblings.  The gold standard HLA match is 10 out of 10, and is often called a "perfect match", but it is not perfect at all.  There are hundreds of alleles, not just 10.  But when matching is done, it assumes that 10 of them are the most important ones for a BMT transplant, and it is not easy to match any more than that.  Even 10 out of 10 matching can result in GVHD, which shows a somewhat significant mis-match has ocurred among secondary alleles.  So it is a matter of "good enough" HLA matching, not an actual match.

As for common ancestry, it plays a part in matching.  Better matching is normally found within racial groups, caucasians tend to match caucasians more often, blacks to blacks, asians to asians, etc.  And the secondary alleles match better and reduce complications.  This is why it is harder to find a match if someone is a member of a racial minority group -- it is a matter of numbers.

If anyone is still reading, a person receives half of their HLA type from each parent.  So when a 10 out of 10 match is discussed, it is 2 sets of 5 alleles, 5 from each parent.  These 5 most important alleles are called A, B, C, DRB1, and DQB1.  So a person has one set of these 5 alleles from their father and one set of the 5 from their mother, making up the 10 alleles whcih should be matched when possible.  Many transplants have been done with less than 10 out of 10 matching.  Sometimes they work, sometimes they do not.  The matching process is an imperfect one.

So back to the overall question: both unrelated donors and related donors do not "match" in the sense S&S asked about.  We would tend to believe that a so-called "perfect match" must indeed be perfect, but it is far from that; it just matches well enough to allow transplantation of tissue in a way that minimizes rejection and hopefully minimizes GVHD.

....and don't even get me started about whether Phil and I might have a common ancestor....

* If you said "Duh" to this, I mean that you can have your own cells taken out and transplanted back later as an "autologous" transplant.  They don't usually cure the patient, but can extend life under some circumstances.

[SunNsand]

Tedsey -

Your pm box is full so I will post here.

  When I mentioned my sister tormenting me about being adopted, we were very young. Hope I didn't offend you. Adoption is a wonderful thing! I have been following the trials you have been through, and you and everyone else on this forum are always in my prayers! When I would read about you taking your small children to appointments and not having a babysitter, I would think, I wish I lived closer so I could help her out!!!

SunNsand

[SunNsand]

Trey -

  Thanks for explaining it in a way that's fairly easy to understand. Now I see the 10 isn't all that perfect after all

SunNsand

[GerryL]

Hi Trey,

Perhaps you and Phil should play "Six Degress of Seperation" http://en.wikipedia....s_of_separation

[PhilB]

I don't know how many have you have been following CherylLynn's postings?  She was dx with CML in Blast Phase and after various discussions on this forum and elsewhere on whether it really was blast phase, she is now playing with the big boys on the Transplant forum.  Because she couldn't find a better than 7 out of 10 match with an unrelated donor she is in a trial for a 'haplo' transplant using her sister's cells.  Her sister is only 5 out of 10 match (ie they both got the same set from one parent, but different sets from the other), but the feeling is that a related 5 out of 10 beats an unrelated 7 out of 10.  They are using an experimental protocol whereby they 'socialise' the donor's t cells with those of the recipient in vitro, perform the transplant with the donor t cells stripped out, and only introduce the 'socialised' donor t cells after engraftment has already taken place.  CherylLynn seems to be doing very well and has even been allowed home already.

If this new protocol works as well as people are hoping it will be a real game changer in terms of sibling matches as whilst you only have a 25% chance of a 10/10 macth per sibling you have a 50% chance of 5/10.

Phil