HELP: Post transplant- prolonged low counts!

[MGirl]

HI-

I'm the Mom of a very young girl who recently underwent a BMT (bone marrow derived) for SAA (diagnosed early 2010) in the setting of Dyskeratosis Congenita (just diagnosed one month before transplant--strangely, nearly a year after her SAA diagnosis: 2x ATG cycles, cyclosporine for the entire year--which didn't work).

She is at day +81, and her counts are still so low, although she herself is very well and hasn't had any fevers. Her most recent counts were: WBC 2.0, ANC 0.26, platelets 5, Hbg low 60s, and a reticulocyte count that is 'abnormally normal' at 50. Her specialist keeps telling us not to worry, "to wait....it will come,...just wait". Another less-experienced doctor who we don't usually see, but was filling in one day, said "oh ya, she isn't doing spectacular, is she...". We feel very confused, but with a bad feeling in our guts on what is going on.

Her unrelated bone marrow donor was apparently "great" and there was a really good cell count in the harvest. They are both CMV neg and pre-BMT screening otherwise was normal. It was a perfect 10/10 HLA match. She had a "reduced intensity" conditioning regimen prior to transplant of Campath, Fludarabine, and 1 day of Melphalan. She was extremely slow to show any engraftment, despite starting GCSF injections on day+7 that continued daily for almost 4 weeks. At that point, her highest WBC was 1.46, and so they discontinued the GCSF after 3 days at this count (around Day+40). Immediately after, and ever since, her ANC has deteriorated and has barely got above 0.2-0.3. Despite those counts, we were sent home to "home-isolation" on day +49 and are going to the out-patient clinic twice per week. The only other complication she had in hospital was that she picked up adenovirus while there at around day +12 (other kids in the unit were in full bloom with it at the time), and was treated with cidovofir with marginal results at the time (per PCR testing of blood, urine, stool), although she was not very symptomatic from that itself.

What are we missing here?
Our BMT 'team' refuses to state that engraftment has failed, as she "still is producing some cells", but we know she is at a very delayed state of blood count recovery at this point in time. We are getting tired of being told "just wait a bit longer" week after week, with nothing happening. She is still fully transfusion-dependent (platelets now once weekly, and RBCs every few weeks). Are we just paranoid parents? Or is our little girl made out of kryptonite and doesn't really even need blood? HELP!

[Marlene]

You may want to look at Grant's caringbridge journal that his mom Wendy kept. Grant had a second infusion of the donor cells. I don't remember the details but if you can spend some time reading through the journal, it may give you some insights.

https://www.caringbridge.org/visit/g...createorsignin

[Neil Cuadra]

MGirl,

Since dyskeratosis congenita, like aplastic anemia, is a rare bone marrow disease, there's probably a fairly small body of knowledge about response rates and timing after transplants, especially with the latest drug combinations.

I hope you find other parents with whom you can compare treatment and recovery time. Although responses can very greatly from person to person I don't blame you for being frustrated and feeling that your patience is running out, especially with your daughter continuing to have a low ANC.

In addition to asking here, you might contact BMT Infonet in case they can give you useful information. You could also talk to the Aplastic Anemia & MDS International Foundation about its Peer Support Network, in case they know another family with a similar transplant experience, even if it's for pediatric aplastic anemia, not dyskeratosis congenita.

Have the doctors indicated that the adenovirus might be partly to blame for your daughter's delayed recovery? If your daughter's recovery continues to be stalled, what do you think your choices are?

[MGirl]

Thanks for the messages--every word of support helps!!!

Our little girl is actually remarkably well, considering her lack of blood counts...
I am wondering if anyone has had any experience with the use of mesenchymal stromal cell infusions as a way to 'rescue' such poor performing post-transplant blood counts....??? Other than that, yes, adenovirus, and its treatment (cidofovir) have among other things been possibly stated as being culprits, but I'm wondering why so still nearly 3 months later? I think I'll have to ask an infectious disease expert about that!

The other concern I have is that her chemo drugs were just simply too 'strong' for her, as they had given her a "reduced intensity/ non-myeloablative" chemo regime, but they also admit now it likely was effectively strong and fully myeloablative of anything she had left. Her lack of hair re-growth is something that makes me feel a bit suspicious of that. I can't find 'typical' doses for campath/ fludaribine/ or melphalan anywhere for pediatric patients. I believe she was simply given the known adult dose as far as my recollection (which may or may not be the same for kids...don't know).

She is on tacrolimus only at this point, and again--is it too strong and immunosuppressive? Her blood levels of this have been the lower end of the range that they want to see...but ?maybe just too strong for her if you don't look at the numbers only.

[squirrellypoo]

Originally Posted by MGirl

Her lack of hair re-growth is something that makes me feel a bit suspicious of that.

Oh, hair takes FOREVER to grow back! I only just had enough for the shortest of pixie cuts at 6 months post-transplant. So really, not having any hair regrowth at <90 days is really very normal (and at nearly two years on, I've only just barely been able to put my hair in a ponytail for the first time this week!).

Is there a BMB planned around Day 100? I would expect them to also do a chimerism check at the same time to determine what percentage of her marrow is donor and what's her original cells. This is routine post-transplant but it might be a good idea to confirm that this is scheduled. That should really show how well the graft has taken and whether the conditioning was enough to kill off her original marrow cells.

I believe Serkan also had a top-up of donor cells after his transplant - you might want to look at his thread here in the Transplants section, too (his username is tsergodan).

Oh, and I had a mini transplant, too, and had fludarabine/campath/busulfan. I could dig out my conditioning sheet and see if it lists my dosages if you really wanted to compare them against what she had. Though with conditioning, they really do a lot of customisation for each and every patient so I'm not sure whether a direct comparison would achieve much anyway?

[Marlene]

On the hair re-growth.....For John, the first thing that came in were his eyebrows. And yes, it takes a while for it to come in on the head.

[MGirl]

Thanks again everyone....we've been in touch with some specialists beyond our own (actually, in another country), just to get any further ideas on what may be happening. They suggested looking for antibodies against the red, white, and platelet cells, and still looking at viral causes. There is a BMB scheduled for day +101! Her chimerism was already 100% donor at day +35ish, but I guess that can revert in rare circumstances..... And thanks for the reassurance about her lack of hair growth still at day 80-90...we wouldn't mind so much, but for a 4 year old who has to be with other kids at school one day we hope, we can't even begin to bear the teasing from children who don't know any better, never mind her self-confidence. I never thought hair would mean so much!