Question about DLI for graft failure

[carrieridge]

I havent' posted in a while, but I read through periodically. Hubby has treatement related MDS from years and years of treatment for lymphoma. He had a allo on 11/24/14 using his brothers stem cells. Did great at first, about 4 months after was back in hospital with severe gvhd in gut. About 3 months ago, chimerism kept going down, down, last one was 4% donor only. Bm biopsy shows trisomy 8 back and MDS no blasts however. Prepping to do DLI, but a few things happened, 1) insurance change, 2) salmonella poisoning 3) shingles outbreak 4) stomach flu. BM biopsy of 2 weeks ago showes 8% blasts. So his diagnosis changed a little to read: "Variably cellular marrow with erythroid preponderance and scattered multilineage dysplasia, consistent with myleodysplastic syndrome/refractory anemia with excess blasts (MDS/RAEB-1) - Immunostains confirm increased blasts - Flow cytometric studies demonstrate abnormal myeloblasts with aberrant expression of CD7 and CD56.

They said they need to do the DLI sooner rather than later (I was hoping to let my husband "heal" a little from all the crap thats been thrown at him. I believe they are worried about 1) his lymphoma coming back aggressive and 2) his MDS moving to AML - as it seems it's on some kind of path already - I don't know nearly enough about MDS - I immersed myself in learding all about lymphoma, but MDS has been a hard one for me to understand. They want to do his DLI but give him fludarabine and some sort of antibody (I can't remember the acronym for it but they said it was derived from horses).

Any insight and expereince in MDS transforming to AML - is it a slow process? fast?

[carrieridge]

I read this on a CD report on the Beacon:

MDS blasts frequently produce the surface marker CD34. Increased CD34 production is associated with poor prognosis and an increased risk of progression to acute myeloid leukemia. However, not all blasts produce CD34. The researchers pointed out that in those cases, CD117 may be used as an alternative surface marker. MDS blasts may also be identified by the absence of surface markers CD11b and CD66b.

Clarification please: My husbands BM report, the flow portion says: HLA-DR with aberrant CD56 and CD7. then it has a list of markers, that says Blast Gate, then underneath that it says MARKER, % of total, result and intensity. for CD34 it says 5, positive, bright.

So does that indicate and higher chance for him to progress to AML?

I'm sorry for all the questions, my hubby has to doctors at UCLA, his lymphoma doctor and Dr. Paquette. While I love Dr. Paquette he's not saying things "straight out" to me (like mikes other oncologist does) and I know he cant predict the future he just says when I ask him we we can hold off on the DLI 'we should do it sooner rather than later". I'm just worried that my hubby won't be able to take the chemo - he's very very weak and I'd like for him to get stronger before we undertake more chemo

[Whizbang]

HI, Carrie. I only check this site occasionally to see how my hubbys friends are doing. He passed on 12/17/14. He had MDS, received a transplant from his brothers cells. Was doing amazing with no GVHD for 8 months. Then we received the devastating diagnosis July 3rd, 2014 of Erthroid Leukemia. Docs were planning a 2nd transplant, but 2 rounds of inpatient chemo did not bring down the blasts enough for that. We were also planning DLI in conjunction with a clinical trial. We started the clinical trial 10/14. His counts improved a little but nothing significant. He ended up not feeling well 12/5. Went to hospital where he got pneumonia and major organ failure. So my advice do the DLI ASAP. Don't mean to scare you, but hope this helps.

[carrieridge]

Wife of Wizbang - I tried joing this forum about a year ago but didn't get much response, so I thought I'd try again. It seems to be a private club, so maybe it's just not open to anybody. I'm so sorry about your husband - I feel like mine is slipping away myself and i"m so ignorant about MDS (ask me about lymphoma and I can hang with you). oh well, I hope you and your kids are holding up okay. Again, I appreciate you responding to my post.

[DanL]

I am sorry to hear about your husband's relapse. It looks like your physicians are considering something that looks like a lower intensity conditioning regimen with a DLI. Basically this would work on depleting some of the MDS cancer cells, and give the existing graft a bit of a booster shot, while minimizing the damage from transplant.

the antibody that would be going with the fludarabine is usually ATG (anti-thymocyte globuulin). The syrum comes from either a horse or a rabbit. It is a powerful immune suppressant that helps reduce graft rejection. ATG can be a rough ride for the couple of days that you take it, but it is mostly flu-like symptoms - fever, chills, body aches. I had 3 days of ATG prior to my transplant and really the first day was the hard one.

As for timing - if the doctor is saying sooner than later, he believes that the risk of waiting is worse than the risk of administering the chemo and DLI. there is a "magic number" of about 12-14% blasts that you want to be below prior to transplant, so if they feel like the disease is progressing or is likely to progress quickly, this may be the big driver. Very rarely do blasts decrease on their own.

It has been a hard lesson for me because I am analytical and want all of the answers before going in, but the key is that if you like the team of doctors that you have, ask the questions, but trust the doctor's guidance on timing.

Best of luck for you husband and you.

[carrieridge]

We go to see his lymphoma oncologist today - and i'll discuss things with her. She's pretty awesome and works with Mikes other doctor, Dr. Paquette who coordinated Mike transplant last November. We had an insurance change as of oct 1, so they have to resubmit all of the authorization. Mikes bone marrow showed the MDS was back along with the trisomy 8 but no blasts 3 months ago, now there's 8%, so i guess that's my worry. I know they'll repeat the bm just prior to the DLI, to see if he's had blast increases. I guess i should just be thankful that his lymphoma is behaving, but sometimes I think it was easier to deal with than the MDS. Is there a huge difference between treatment related MDS and denovo MDS?

[DanL]

Historically speaking, it was believed that t-mds was harder to treat than de-novo mds, and I haven't seen a whole lot of research in the recent years to support or debunk the observation. Because transplant is the only potential cure for MDS, It appears that doctors are using more objective measures like the updated IPSS-R, which basically takes a snapshot in time and applies a risk rating. Secondary or therapy related MDS is not one of the factors included in any of the ratings.

There have been more studies done that focus on current treatments and whether or not the patient has t-mds or not.

From what I see, it really comes down to the patient's condition at time of transplant - what is the transfusion dependency, how many blasts, what chromosome damage is there, and how deep is the damage - does it affect 25% of cells or 95% of cells. Multiple chromosomal abnormalities is usually considered higher risk, more transfusions is higher risk, and of course, higher blast cell counts are higher risk.

Taking that into account, t-mds patients tend to have more chromosome damage, which would explain the harder to treat concept. As with any transplant scenario, the cleaner your blood work is when you go in for the transplant, the better the outcome typically.