8/10 or 9/10 mismatch

[Janire]

I have 2 donors, 9/10 and 8/10. Anybody here with AA has been transplanted with a 8/10 or 9/10 mismatch ?
I dont know already where the mismatch is but I think a 8/10 is a very poor match and I dont know anybody transplanted with 8/10. I know a few with 9/10 and the mayority with 10/10.
What is the difference between a 9/10 and a 10/10??? Is there a big difference?

[Marlene]

Hi Janire,

You may want to follow up with Dr. Brodsky at Johns Hopkins. They have been doing MUD BMT's using cytoxan post BMT to minimize Graft vs Host Disease. I think they've been pretty successful with it. I think there are other centers doing them too but I don't which ones.

It's worth exploring.

Marlene

[evansmom]

My son had a 9/10 mismatched BMT and had zero complications as a result. It is, however, VERY important that the doctor discuss with you WHERE the mismatch is located.
For a simplified example, a mismatch on A,B or C can have much more serious potential complications (graft failure, graft vs. host) than a mismatch on DRB1 or DQB1. To complicate matters, it can also make a difference in terms of whether the mismatch is on the alelle or the antigen.

There has been much research on BMT outcomes as a result of specific mismatches and hopefully your doc can explain the potentials as it relates to your situation.

So having said all of this, it is actually possible that the 8/10 donor BMT may carry less potential risk for unfavourable outcome than the 9/10.

Evan's donor was mismatched on the alelle of DQB1 and was A+, while Evan was O+ and just as predicted in studies, Evan's only issue was slightly prolonged engraftment of the red blood cells.

Hope this helps and best wishes,

[NLJabbari]

Hi Nicole, Yashar had 2 potential 9/10 donors, both males, one in his 30's and the other in his 50's, both A+ (like Yashar) and both (CMV+) Yashar is CMV- I asked the bone marrow doctor we met with at Stanford about the mismatch as I wanted to know at which marker it occurred and she simply told me she didn't have that info :/ I thought that was strange, hmmm...I might have to speak to someone else who might be able to answer these questions

Also, I was concerned with the preconditioning protocol which I believed involved 2 days of Cytoxan and 4 days of full body radiation. The full body radiation seems too extreme to me. Did Evan get full body radiation?

Thanks,
Norma

[squirrellypoo]

Nicole got it spot on - it matters where the mismatch is! I had three possible 9/10 donors and the one they chose for me worked out great. I had minimal GVH before day 100, then pretty much nothing after that, apart from some minor eczema. (I also had the mini transplant, and I had hypo-MDS, which is very similar to AA)

[Janire]

Mmmm....in the forums I read things and my doctor tell me the contrary. I have a 9/10 match and the mismatch in the Hla-A. I asked my doctor for this and he told me that it is the same where the mismatch is so...i am now more confused. Apart from this, for AA a bmt is better and my donor can only donate SCT. I need more opinions.

My Hla-a is 03:01 and my donor hla-a is 30:01.....

[Marlene]

It's always good to get a second or even a third opinion. So don't hesitate.

[Janire]

Originally Posted by evansmom

My son had a 9/10 mismatched BMT and had zero complications as a result. It is, however, VERY important that the doctor discuss with you WHERE the mismatch is located.
For a simplified example, a mismatch on A,B or C can have much more serious potential complications (graft failure, graft vs. host) than a mismatch on DRB1 or DQB1. To complicate matters, it can also make a difference in terms of whether the mismatch is on the alelle or the antigen.

There has been much research on BMT outcomes as a result of specific mismatches and hopefully your doc can explain the potentials as it relates to your situation.

So having said all of this, it is actually possible that the 8/10 donor BMT may carry less potential risk for unfavourable outcome than the 9/10.

Evan's donor was mismatched on the alelle of DQB1 and was A+, while Evan was O+ and just as predicted in studies, Evan's only issue was slightly prolonged engraftment of the red blood cells.

Hope this helps and best wishes,

I have the difference in the HLA-A.

My HLA-A is 03:01 24:02
Donor HLA-A is 30:01 24:02

What is the antigen and the alelle here???

[evansmom]

Originally Posted by NLJabbari

Hi Nicole, Yashar had 2 potential 9/10 donors, both males, one in his 30's and the other in his 50's, both A+ (like Yashar) and both (CMV+) Yashar is CMV- I asked the bone marrow doctor we met with at Stanford about the mismatch as I wanted to know at which marker it occurred and she simply told me she didn't have that info :/ I thought that was strange, hmmm...I might have to speak to someone else who might be able to answer these questions

Also, I was concerned with the preconditioning protocol which I believed involved 2 days of Cytoxan and 4 days of full body radiation. The full body radiation seems too extreme to me. Did Evan get full body radiation?

Thanks,
Norma

Hi Norma,
I am sorry that it has now come to Yashar needing a BMT. How frustrating.
Well, the donors sound quite good so far. Male to male is best, and same blood group is also a helpful feature. I wouldn't worry too much about the donors being CMV+ while Yashar is CMV- as part of his post BMT conditioning while absolutely include acyclovir or another similar anti-viral. Evan's donor was also CMV+, while Evan was CMV-.

You are correct and have every right to seek out and be informed of where the mismatches are. I am pretty sure most pediatric patient's parents and most adult patients themselves do not seek out such detail and I don't really fault them for that because it is a very complicated read, to say the least. Plus, reputable information is not so easy to find.

Evan did not have any radiation. When we sat down with the BMT doctor, he explained that Evan would have 3 days of cytoxan and 4 days of rabbit ATG. He stated he was "sitting on the fence" about any radiation. We already knew going into this meeting that we wanted to discuss the possibility of avoiding radiation if at all possible. The doc said that because we are not targeting cancer cells, i.e. leukemia, the need to ensure every last stem cell has been obliterated is not necessary. So he left 'to radiate or not to radiate' with us to think on. I believe he gave us the choice because he knew we were well informed going in and had some opinions formed already. Once home, I began researching BMT conditioning protocols in pediatric AA in more specific detail and learned that a tri-med routine without radiation was not uncommon. I emailed the BMT doc and asked if it would be prudent to add fludarabine to the cytoxin and r-ATG in leiu of radiation and he thought it was a good idea: an extra ounce of prevention for a pound of (hopeful) cure. He said fludarabine is a great chemo agent that will target the stem cells while adding little to the potential side effects Evan would already be getting from the other two meds.

So that's what evan had. 3 days fludarabine, 3 days cytoxan and 4 days r-ATG.

Now Yashar has had AA longer that Evan did and has had, I believe, more treatments with ATG than Evan and has been on cyclosporin longer as well, so these are all things that make no two cases the same.

It would be nice for Yashar to avoid radiation if at all possible. When are his docs thinking of transplant Norma?

[evansmom]

Originally Posted by Janire

Mmmm....in the forums I read things and my doctor tell me the contrary. I have a 9/10 match and the mismatch in the Hla-A. I asked my doctor for this and he told me that it is the same where the mismatch is so...i am now more confused. Apart from this, for AA a bmt is better and my donor can only donate SCT. I need more opinions.

My Hla-a is 03:01 and my donor hla-a is 30:01.....

Hi Janire,
I think your doctor is trying to avoid having you worry about the details but if he told you all mismatches are the same, in other words, have the same outcome, he or she is incorrect.

Bone marrow would be a better source than peripheral stem cells, especially given the A mismatch. Bone marrow engrafts sooner and has a reduced risk of non-engraftment and acute+/-chronic GVH.

Now, having said all of this, there have been and will continue to be many successful and uncomplicated BMT despite HLA mismatches.

[evansmom]

Originally Posted by Janire

I have the difference in the HLA-A.

My HLA-A is 03:01 24:02
Donor HLA-A is 30:01 24:02

What is the antigen and the alelle here???

This is where it gets complicated...I believe these numbers are all alleles. I am used to seeing mismatches such as A*0301 to A*0302. the 03 to 30 seems like a big difference to me. But maybe that is a good thing. I believe I read somewhere that if A has a mismatch, it's better to have more amino acids not matching than only one or two. It's very complicated as you can see.

[SLB]

Hi Janire,

I am a 37 year old that just had an 8 out 10 match SCT on the 6th of March. My story I'd a little different because that was the best match we could even after searching for 10 months and frankly I had run out of time. It was seize this opportunity with all its risks or face 100%certain death. My doctors always said it was a risk balance & once my MDS transformed to AML, we had to go for it. They told me an 8 out 10 was still a good match & that the cost of getting the stem cells from overseas donor alone was $50 000, & they wouldn't be paying for that if not worth it. I had 5 days of fludarabine, 1 day of mephalam then day of rest then stem cells next day. No radiation. On days plus 1,3,6& 11 I had methotextrate. Yesterday I was day +13 and had neutrophils of 0.16, which shows early signs of engraftment. My story is a long way off being over but thought I would tell you anyway. By the way I am not sure when my mismatch was, I didn't really understand & was too tired find out. Thought I was scared enough without knowing & sometimes ignorance is bliss especially when you look at statistics of this disease. Good luck with decision. Sharnie.

[Neil Cuadra]

Originally Posted by SLB

Yesterday I was day +13 and had neutrophils of 0.16, which shows early signs of engraftment.

Sharnie,

I remember waiting day after day when my wife had no white cells, and how we cheered the wonderful news when her count turned to a minuscule positive number. This is a huge step toward success and I'm so glad you told us!

[NLJabbari]

Hi Nicole, Thanks for replying your comments are always so informative. I am very happy that Evan did very well with his BMT and is healthy

Yashar has only had one round of H-ATG. Throughout the years, increasing the dose of CsA is what would increase his counts whenever they dipped. This last drop in counts occurred back in May 2012 right around the time when his Pedi-Hem Dr. retired and Yashar was sent to "Adult Medicine".
What a nightmare as the new Dr seemed to have disregarded or maybe didn't even read his medical record.?? About the only thing she did correctly was to have put him on the transplant list/search through Stanford Hospital. Other than that, we didn't feel like Yashar was getting proper care and since have found a new Dr. that we're very happy with.

The latest BMB showed that Yashar has a 20% PNH Clone, but has no symptoms. His new doctor decided to change his CsA from Sandimmune to Gengraf. He's been on Gengraf for about a month and we've already seen a rise in his counts. His Retic is higher than it's ever been and we're currently just watching to see what happens. He feels great and looks great and all of his labs have been really good. I don't know what this may mean, but it surely does give us time to make better decisions.

As far as transplant is concerned. The first Dr. that initiated the search didn't seem to think the options found through the search were good enough for Yashar. She really didn't say why and instead was recommending another round of ATG.
Yashar's new Dr. however, wants to try this CsA change before deciding to proceed with BMT. It might be because his Platelet count is at around 100K and his WBC is Normal as is his ANC and Neutraphil/Lymphocyte ratio. The only thing lagging are his RBC's which have always been the last line to show an increase. I think she wants to see if this new rise in Retics will show an increase in Peripheral Blood counts.

So, that's where we are once again. I just need to know what to ask at BMT meetings and what pre-conditioning is being done in other centers to compare.

Protocol:
Day -5 Fludarabine
Day -4 Fludarabine, ATG
Day -3 Fludarabine, ATG, Cyclophosphamide
Day -2 Fludarabine, ATG, Cyclophosphamide
Day -1 Total Body Radiation : /

That's pretty much where we're at...