Still Waiting for Diagnosis: AA or MDS?

[Sheryl C]

My 3 yr old grandson has been riding this roller coaster for almost 4 months. He has had 3 BMB's and is scheduled for his 4th on 9/2/09. Then install port on 9/10 and start ATG therapy. A prelim search found no bm matches and his 8 month old brother is not a match. Does it usually take this long to make a diagnosis?

[Lisa V]

Sheryl, have they said what is causing the difficulty in making a diagnosis?

My husband was diagnosed SAA as soon as they got the results of the first BMB, and started ATG immediately thereafter. A subsequent BMB showed a chromosomal mutation, however, so the diagnosis was changed to hypocellular MDS. His doctor said that those two can be among the most difficult to tell apart. Normally MDS would manifest as a packed marrow and AA as an empty one, but if there is some dysplasia (malformed cells) or abnormal chromosomes along with an empty marrow, it doesn't really fall neatly into either category. Are they saying that is the case with your grandson?

Most MDS is HYPERcellular, and ATG is generally not considered very effective in most cases, but it has a better track record with the HYPOcellular variety. My husband has responded fairly well to it, so we still tend to think of his condition as AA.

[Marlene]

Sheryl,

Have they ruled out genetic anemias like fanconi's and black diamond? These test usually take longer so maybe that's why the delay. I cannot understand why they would treat him if they did not pin down a diagnosis.

Marlene

[squirrellypoo]

Lisa pretty much covered what I was going to say about AA and hypocellular MDS but I just wanted to add that ATG can work really really well so don't get too disenheartened that his brother isn't a match. I had AA in 1984 when I was 5 (and maybe MDS as well, but they didn't really have accurate tests then) and my equine ATG worked beautifully well for 25 years - absolutely normal childhood and adolescence without another thought about "that thing I had as a kid". And who knows what new kinds of treatments will be available when the ATG eventually wears off? In my case, BMTs are certainly less risky now than they were then!

And if it helps you at all, I hardly remember any of the bad things from my time in hospital, but I certainly remember all the fun stuff like new toys and watching Mister Mom in the tv room and visits from clowns and playing Atari. And all those prods gave me a lifelong superpower for needles!

[Hopeful]

Hi Sheryl,

It's been a year since my diagnosis with bone marrow failure, and I still don't have a definitive diagnosis of AA or MDS despite 5 BMB's and consults with 6 different experts.

MDS and AA are overlapping diseases. The good news is that ATG can be effective in cases of hypocellular MDS that behave like AA. A young age is a good prognostic factor.

As Marlene pointed out, be sure he is tested for the genetic diseases.

I am curious why they think he has MDS. Does he have chromosonal abnormalities or significant dysplasia?

[Stephanie]

I am the mother of Dylan. After his third BMB we thought we would have some answers but that wasn't the case. They kept us waiting for two weeks afterwards saying that all of the results were not in. They weren't sure if it was AA or MDS. His doctor believed it looked dysplastic but wasn't sure and had one of her collegues look as well, she also believed it looked like MDS. They sent his slides off to a specialist at Duke University and he said it was AA. So we waited another month and on wednesday we will do his fourth BMB. They have already scheduled him to recieve ATG one week after, which frankly upsets me. I was ready to start treatment after his third biopsy but they wanted to wait to be sure because, "ATG treatment isn't benign." What will it do to my son then? And why schedule BEFORE the results of the fourth biopsy are in? Their answer: they did a preliminary search for an unrelated donor and came back with nothing and his doctor ran his case past some collegues and her mentor from Johns Hopkins who said to treat him with ATG. So NOW we are doing something. I guess I should be happy, it is just frustrating. I want them to know exactly what is going on with my son and FIX IT RIGHT the first time. I know it's never as simple as that, thanks for letting me vent....

[Hopeful]

Stephanie,

I would not delay treatment with ATG if they think your son's disease is immune-mediated, regardless of the label. One of the predictors for a response to ATG is whether it was given within 3-4 weeks of diagnosis. My treatment was also delayed an extra month while awaiting results from yet another inconclusive BMB. It is so frustrating!

Differentiating between AA and MDS in a hypocellular marrow with no chromosonal abnormalities is very difficult. It's hard to estimate dysplasia when there aren't a lot of cells to begin with. Also, a person's marrow can be patchy. For me, some of my BMB's were very hypocellular while others were mildly hypercellular. All of this confuses the diagnosis and ultimately delays the treatment. Meanwhile, the disease is progressing.

Some of my doctors told me that dysplasia meant that I did not have AA. Other's told me that if the dysplasia was not signficant, than it was still likely AA. If the disease is immune-mediated, does the label really matter?

I hope you reach resolution soon. I wish you both the best!

[Lisa V]

Stephanie, the first thing you learn when you or a family member has been diagnosed with a rare disease is that medicine is not an exact science. This goes against our expectations that it will be something like auto mechanics: find the malfunctioning system and repair it and voila! No more problem. In reality, there can be as many different interpretations of symptoms and philosophies of treatment as there are doctors and personalities. That's why it's so important that either the patient of someone close to them educate themselves as much as possible on the condition in question. If you can have reasonably informed discussions with Dylan's doctor, you can have more influence on his course of treatment than you might have imagined, and it will help you overcome your feelings of powerlessness and frustration if you at least understand why they are making the decisions they are. Fortunately the web has made research and interaction with others in the same boat so much easier these days! Just be aware that there is a lot of misinformation out there too, so try not to jump to too many conclusions based on a single piece of evidence.

I have to say I don't quite understand their timing here either. Why do a 4th BMB if it's not going to affect the course of treatment? I agree with Hopeful that if it appears to be autoimmune-related, ATG is his best option, and sooner rather than later. It's true the treatment is not benign, but neither is waiting, so what it comes down to is often a choice between what's in the box or what's behind curtain #2, i.e. a gamble either way. Which option any given doctor will choose will depend on weighing all the factors and a lot depends on their interpretation. As Hopeful has pointed out, there can be varying degrees of what might be considered dysplasia. Most AAers (and perhaps even the rest of us for all I know) have found notes on their CBCs about various oddly-shaped cells, but apparently most of them are not enough to qualify as the kind of "frank dysplasia" that would be a clear indication of MDS.

The issue of determining if a condition is truly immune-mediated can be a tough call too. Most doctors seem to arrive at that conclusion AFTER it responds to immunosuppressive treatment, rather than the other way around. There could be other factors such as shortened telomeres, which may indicate a hereditary condition rather than an acquired autoimmune one, but this is still new research and testing for it is not often done. I suspect the cost and time involved are a big issue, and it also creates a dilemma if there are no other good options available. Better to at least try the thing that has the best track record than to do nothing, at least that's the thinking.

As for what ATG will do to your son, hopefully he'll sail right through it like my husband did, but some people do develop serum sickness from the horse serum. This is why they prescribe prednisone, to counteract that, but prednisone, cyclosporine and ATG are all powerful medications with side effects. Also, any time you have to take something to knock out a portion of your immune system, you're making yourself more vulnerable to infections and other secondary diseases, but the body is remarkable in its ability to compensate and adjust, particularly children and young adults. You'll have to follow certain precautions, but it's only temporary. If he responds well and his counts rebound, he should be off all medications in about 6 months.

I hope none of this scared or discouraged you, I just wanted to shine a light on some of the issues involved. It's a scary time, but you'll get through it. It's what we do.

All the best,