Unusual MDS presentations?

[amkjud]

I posted earlier about my 7-year-old son who has been worked up for suspected MDS. One thing I can't wrap my head around is that he doesn't seem to fit the standard (WHO, FAB) classifications, but doctors insist on pursuing it as possible MDS. Has anyone out there been diagnosed with MDS without WHO/FAB criteria?

Also, are there any younger MDS patients out there with essential hypertenion and/or polycythemia (high hemoglobin) and/or a deletion of chromosome 7q31? I ask specifically about younger patients because the first and third don't generally appear in younger patients (in my understanding).

Also, has anyone experienced an chromosomal abnormality on a bone marrow biopsy that then disappeared (temporarily or permanently)?

I am interested in personal responses as well as any references to the literature. Thank you!

[Neil Cuadra]

Originally Posted by amkjud

Also, has anyone experienced an chromosomal abnormality on a bone marrow biopsy that then disappeared (temporarily or permanently)?

amkjud,

My wife was found to have chromosomal abnormalities, then different chromosomal abnormalities in a subsequent bone marrow biopsy. At the time we thought of it as "unstable marrow" but I think it was more a matter of which defective cells they happened to collect in the bone marrow aspiration. An abnormality that seems to disappear may be one that has affected very few cells and is therefore unlikely to show up in a given BMB.

[Greg H]

Hi amkjud!

As Neil reports, chromosomal abnormalities can definitely come and go from bone marrow reports. And I think he is exactly right that, often, this is matter of what happened in the sampling. It's also important to remember that neither of the common ways for testing chromosomal abnormalities -- karytoype and FISH -- are actually based on a statistically significant sample of cells. So it can be a mistake to put too much weight on the exact percentages in the results.

In my case, I had only a chromosome 1 abnormality when diagnosed, that was joined by Trisomy 8 nine months later, and the Trisomy 8 first expanded, and then pretty much disappeared, after immunosuppressive therapy.

When you say your son doesn't fit the WHO/FAB, do you mean the docs don't agree on whether he is RA, RCMD, or RAEB, etc.?

Those classifications can be a bit of a hard call. My transplant doc diagnosed me as RCMD (dysplasia in all three cell lines in the biopsy) but my doc at the National Institutes of Health said some of that dysplasia was borderline and diagnosed me as having dysplasia in only one line. I think the WHO has a classification that is for hard to pin down variants of MDS.

Hope that helps. Take Care!

Greg

[amkjud]

GREG:

it's not that he has charachteristics that would place him in more that one category of MDS or that he some but not others to place him in one particular category. rather he doesn't seem to have any of the characteristics as defined by WHO/FAB. i've asked about this and they say it is still probably MDS.

i don't understand and need to clarify. is there some undefined category of MDS i missed, or do they mean it will end up as MDS? for example one biopsy showed a slight elevation in megakaryocytes, but his circulating platelets were normal. so is there some type of feeback compensation that the elevated megakayocytes are keeping platelets normal in the meantime but eventually it will catch up and there will be low platelets? also hemoglobin is elevated, but erythropetin, hematocrit, oxygen binding, etc. all normal. are they expecting this to change? it's very confusing.

[amkjud]

GREG and NEIL:

chromosome abnormality (7q31 deletion) showed up on first biopsy but not the second. (will be doing third in december.) i wasn't sure if one of the biopsies involved a lab mixup, if perhaps the second biospy was too small a sample, or if it is possible for the abnormality to disappear. but as i understand you, they don't "disappear," although they may not show up on a particular biopsy? or is neil saying they can be cured with "immunosuppressive therapy"?

[Greg H]

Hi amkjud!

This stuff can be pretty darned confusing. Let's start with the chromosomes. Abnormalities can vary from one bone marrow biopsy to another for several reasons:

1. They really disappeared, either because of some therapy or spontaneously.

2. The second bone marrow sample, which was probably taken from the other hip, may have simply not picked up cells with the same abnormalities. (I gather that the researchers have a lot to learn about what goes on in the marrow, and it might be a mistake to assume that it is uniform throughout -- that what's happening in one area looks exactly like what's happening in another area).

3. Just statistics. The number of cells they look at, in either method of looking at chromosomes, is really too small to give highly reliable statistical results. It would be kind of like trying to predict the outcome of the Presidential election after talking with 20 people.

All of this is multiplied if we are tailing about a small percentage of abnormal cells in the first place. In other words, If your son had 20% abnormal cells in a karotype analysis from BMB 1 and none in BMB 2, it's quite possible that nothing at all has happened.

This uncertainty is pretty darned frustrating for us MDS patients and even worse for an MDS parent.

On to the diagnosis . . .

Usually, you get a diagnosis of MDS when the BMB shows abnormal cells in any of the blood lines. MDS is myelo ("bone marrow") dysplasia ("messed up"). So the BMB will say things like "There is megaloblastoid maturation of the erythroid precursors and mild dysmyelopoiesis" or "Mild dyserythropoiesis and dysmegakarypoiesis is seen."

All these "dys" things are cells that should be evolving into normal blood cells, but instead are broken in one way or another. That brokenness -- not the chromosomal abnormality -- is the hallmark of MDS. Lots of MDS people have normal chromosomes, but broken blood factories.

I hope that helps. It's all pretty confusing. If you son doesn't have any of these broken blood cell precursors in his BMB, then I think it would be odd that he's been diagnosed with MDS.

Take care!

Greg

[knstone]

Hi amkjud,
If you havn't already done so it might be good to get a 2nd opinion. Dr. Lewis Silverman in NYC is a leading MDS researcher and would have excellent resources to review your son's BMB slides or do another BMB.
MDS in someone so young is rare, hope you can get some definite answers.

[amkjud]

Originally Posted by Greg H

Hi amkjud!

2. The second bone marrow sample, which was probably taken from the other hip, may have simply not picked up cells with the same abnormalities. (I gather that the researchers have a lot to learn about what goes on in the marrow, and it might be a mistake to assume that it is uniform throughout -- that what's happening in one area looks exactly like what's happening in another area).

Both biopsy/aspirates were from the same hip. One doctor said to bilateral (both hips) next time. Different doctor said this doesn't matter.

[amkjud]

Originally Posted by Greg H

Hi amkjud!

On to the diagnosis . . .

All these "dys" things are cells that should be evolving into normal blood cells, but instead are broken in one way or another. That brokenness -- not the chromosomal abnormality -- is the hallmark of MDS. Lots of MDS people have normal chromosomes, but broken blood factories.

I hope that helps. It's all pretty confusing. If you son doesn't have any of these broken blood cell precursors in his BMB, then I think it would be odd that he's been diagnosed with MDS.

Take care!

Greg

diagnosis is not certain but that's the direction they're going in.
one bmb showed some megakaryocytosis with micromegakaryocytes. also high hemoglobin in circulating blood (which was the original indication for bmb after all other workup negative).
chromosome abnormility is 7q- (7q abnormalities common in MDS and linked to poor prognosis in AML). doctors seem most concerned about this.

[nbullock11]

Hi amkjud,

My son is the 2 year old that was just diagnosed with MDS on 11-4. We just met with our hematologist and I ask about WHO classification as well. I wanted to know what Noah was and the severity of his MDS. I was told that they have a difficult time with the pediatric cases. They usually don't fit into the adult classification system. Most of the kids are put in the refractory cytopenia (RC) of childhood classification.

Here is what happened with Noah and his bone marrow results. His MDS developed over the past 1 ½ years. The last 3 months it shows to be rapidity progressing. Noah has had 3 of them. His first one was 7/10 and for the most part it was normal except for some decrease cellularity. He was at 70%. This is when he was first diagnosed with neutropenia.

A year later 7/11, he had his 2nd one. His cellularity dropped down to 60% with a present of lymphocytosis and dysplastic changes in the myeloid series. There was a population of lymphocytes and paucity of myeloid and erthroid precursors. We were told that it could be a progression to MDS or AA.

His 3rd was on 11-1-11, his marrow was at 50% cellularity. They found trilineages hemotopoietic maturation with numerous lmphoctyes and 4% myeloblast. Dylasisa was present in myloid and erthroid lineages. Also his fetal hemoglobin had elevated to 9.1%. That is when he got the confirmed diagnosis of MSD.

What I was told about the FISH panel is if a chromosomal abnormality shows up then it helps the dr’s confirm the diagnosis sooner. Noah’s FISH panel on all 3 of his biopsies have been negative.

I’m not sure if this information was helpful. We are in the same boat as you. There is very little information on pediatric MDS. I called the MDS Foundation. They recommended a doctor in Florida at All Children’s Hospital, Dr. Gregory A. Hale. He is supposed to be an expert in the pediatric MDS field.

Good luck to you and your family, I hope you get all the information you need to make the best treatment choice for your son. Just know there is at least one other parent out there that is in the same boat as you. I know how overwhelming and frustrating it is …