Question: Hi Doc. I spoke to you back in Feb and gave you info on my low white blood cell count and absolute neutrophil levels. Not dangerously low. WBC running in low 3s and Absolute Neutrophils 1.2. Rest of blood work in normal ranges or right on the cusp of things, so although my PCP was concerned the Hematoligist/Oncologist was not. You suggested PET Scan when we spoke and possibility of Bone Marrow Biopsy. After spoke to you and seeing the Hema/Oncologist again she ordered bloodwork up the whazooo for every type of immune disorder- auto immune, RA, HIV, Hep, you name it... Everything came back normal again other than a 3 WBC, 1.1 Absolute Neutrophils and my IGM level was really low along with the kappa/;lambda light chain urine test showing the lambda as so low it could not even be measured nor could a ratio be given. Because the IGM was low it pointed to only 2 specific forms of Leukemia, Muliple Myeloma or a couple genetic auto immune disorders, so she order the BM Biopsy and FISH tests for MDS and MM...

I did a core bone marrow biopsy since speaking with you, along with FISH tests for MDS, and Myleoma. My FISH tests came back with abnormalities. I was diagnosed with Intermediate De Novo MDS (Myelodysplastic Syndrome) as well as Plasma Cell Neoplasm - but although my Doc says that can only be MGUS, Smoldering Myeloma or MM, I have no M Protein in my urine. She only did one urine test and never ordered a f/u one nor did she order the 24 hour urine test to really do what I feel would be a proper M Protein test. Just my opinion. I'm a Psychologist and not a Oncologist so not my field. Anyway here are specific abnormalities in FISH tests. Plasma Cell Neoplasm Panel showed (32%) 68/215 nuclei revealed abnormal pattern constant with a Trisomy 15 and 11/202 (6%) nuclei revealed abnormal pattern of the two ends of IGH consistent with the translocation involving this gene at 14q32. Additional FISH testing was done for t(4;14(, t(14;16) and t(11;14) and it came back normal. The Doctor and lab concluded a Plasma Cell Neoplasm was present... My Doctor diagnoses it as MGUS... But I had no M protein present or anything else that went with this, so a little confused by the diagnosis...

Now on the FISH test for Myelodysplasia (MDS) The main concern was that I had 16/207 nuclei revealed Abnormal signal pattern consistent with deletion of 7q31. And that Deletion of 7q31 is reported to be an intermediate prognostic factor in de novo MDS. I have not had any chemo or been exposed to a nuclear bomb or any radiation, hence the De Novo MDS not being causative of cancer treatment etc...

So my dilemma is that my Oncologist/hematologist isn't concerned at all by my results. In fact she actually said she thinks it would have been better had we not done the Biopsy so we would not even know that I have MDS and some form of Plasma Cell Neoplasm. She doesn't feel that my fatigue, weakness, low grade fevers that come and go, night sweats, weight loss, and overall feeling like crap have anything to do with any of this. All of which I've been struggling with for several months now. She ordered a PET Scan and apparently asked Radiologist to only look at it for a positive or negative result in regards to Multiple Myeloma. So that came back negative. The radiologist didn't note anything else seen on the scan whatsoever. Not the severe osteoporosis in my bones throughout the left side of spine, hip and leg from the lack of weight bearing throughout all the surgeries from the car accident I advised you of. Which led later to the removal of my forefoot, and fusion of my ankle, and later followed up with my leg being amputated and then later 12cm, and 5cm neuromas removed from my stump as well. So a lot of down time and weak ass bones on that side. The Radiologist also said nothing about the bright lit up area where a mass (complex cyst) is located on my left kidney. Its been watched for 2yrs to see if changing or growing. Every 6 months I have US, CT Scan or MRI to observe it and it went from 9mm x 6mm to 1.2cm x .9mm to 1.4 x 1.2cm to 1.8 x 1.4cm and now is 2.4 cm x 2cm... Again no one is concerned about either saying it's small and just a complex cyst. In the last scan they also observed new changes to my other kidney and are saying its an extra renal pelvis now. It was never there on any other scans till now. That size kidney has grown in size, and previously was remarked as abnormally small, and now is larger than other side and looks like it's protruding out. Anyhoooo I don't know if that has any bearing on the MDS and this Plasma Cell Neoplasm diagnosis or MGUS as she calls that one. Along with my neurogenic bladder issues, and being told they see a 2nd speen in me throughout this too. I have no GB as mentioned to you before. I had cancer in my pharynx 15 yrs ago and full remission. No treatment back then, just removal and all was good.

I have tried homeopathic routes to increase my WBC. Shark Liver Oil, COQ10... along with B Complex to help fatigue.

Again my Doc is not concerned with any of this and said she is a chemo doctor and I am not a candidate for chemo and that there is no treatment options avail to me. She says my flow cytometry levels are good. And that the Cytogenic tests were all normal as well. Although they only did the type of cytogenic testing that takes 2-3 days. It's my understanding from research that Cytogenetic testing can take several weeks because the bone marrow cells need time to grow in the lab dishes before they can best be viewed under the microscope. I feel like this testing should be done, along with the 24 hour urine test to better check for M Proteins. I also think a FISH test should have been done for Leukemia since a lot of my symptoms and blood work match up in that area as well. I'm concerned that it's the 7q that is deleting in the MDS findings and not the 5q which has better prognosis. I'm most concerned that my Doc is not concerned at all, and honestly would say it would have been better not to have done the biopsy and just not know about any of this. Isn't early detection supposed to be key? She said she was sending me to the Mayo Clinic in XXXXXXX AZ for a 2nd Opinion and to MD XXXXXXX in AZ to bone marrow/blood disorder specialist. I have been waiting all month for those referrals but nothing yet. I am hoping to arm myself with the best info to attend these appts. And if the referrals don't happen soon, I am going to be switching insurance companies, so that I can call places like the Mayo Clinic and make my appts without the need for referrals and get some real answers and see specialists in all areas since we have urology issues along with hematology / oncology... I don't even know if there are Docs who specialize in genetic testing and if that would be a good route for me as well. My current Oncologist/Hematologst says my numbers (WBC and Absolute Neutrophils) aren't low enough for me to receive treatment, and it's just a watch and wait kinda thing for my MDS and Myeloma. She says she'd need to see my WBC drop to a 1 and my Abs Neut drop to a .500 .... But if my levels were to get that low, then wouldn't doing chemo not be an option either? I have many friends and family members doing chemo for their cancer battles and when their WBC and Abs Neut levels drop low, they have to stop chemo till they raise them up a bit. So it's very confusing. And I don't even want chemo. I just want to know I have some options here. Are stem cells transplants an option if I found a match? What are my treatment options? What more tests should I have done? Are you in agreement with my current Doc that I have nothing to be concerned about and that all my symptoms have nothing to do with my having MDS and whatever the Plasma Cell Neoplasm I have really is?

You say you agree with my current Doctor, but my current Doctor says no treatment plan is available at all to me. She says she thinks we should not have done biopsy and FISH tests and it would be better for me not to even know I have these serious things wrong with me. Her plan is to do nothing. So I don't understand how you agree with that but then you recommended stem cell transplant, and these other treatment options. So that contradicts what she is saying.
I don't feel like you answered any of the questions from my email.

I asked if I should have a 24 hour urine test for M Protein done?

I asked if I should have proper cytogenetics testing done- the type that takes weeks not just a couple days to do, since i have so many different genes coming back abnormal?

I asked if my symptoms could be from the MDS and whatever the plasma cell neoplasm is? Since PET Scan doesnt show myeloma and no m protein shows up and no one tumor somewhere, what other causes would cause me to have translocating and deletion of genes? The IGH3 and IGH5 are splitting and both ends. The 7q31 is deleting. The 14q32 is translocating. These are the main flags. There were other minor ones, but these were of major significance and enough for the specialists that analyzed my biopsy and blood to make the Intermediate de novo MDS Diagnosis and to let my Doctor know that additional a Plamsa Cell Neoplasm is present and to run further tests. But no further tests are being run?

I asked about Leukemia testing? Isn't translocating of gene 14q32 also present in certain types of leukemia- such as CLL? Along with the IGH showing abnormalities at both ends ?

And what else can be causative of abnormalities of such large percentages 32% of cells being abnormal in regards to Trisomy 15? I wasn't born with any genetic issues and all of this is stuff changing within my body at this time?

I am looking for real answers to the very real questions I presented you with and to better arm myself when I get an appt for a second opinion since my Doc has nothing to offer me, and acts as though none of this is a big deal. I'm ill all the time. I am fatigued all the time. I have no energy to do anything. I went from being someone super active running 5-10 miles a day 5x a week, working out, surfing, hiking, etc... All before and after loosing my leg. There feels like a war is going on inside my body and I'm being told even tho biopsy found all this info that it's not relevant to whatever is causing me to not feel well.

If you could please really read through my first email to you again, and this one, and line by line address the questions I would greatly appreciate it. I can't even afford the fees on her but needed to reach out to someone for another opinion and some real answers. So please can you help me with that? Throwing a couple treatments that I can pull off any MDS website and have already aren't answering my real and very honest questions. I tried to give you a full scope of my health, along with previous surgery info and other things that could be linked to all this or may have no connection at all. I truthfully believe as does my entire family that while my body fought with every ounce of who I am to beat C diff 3 years ago- and no one could properly diagnose me or treat me and let it run ramped in my body for so many months, well I believe it opened the flood gates so to speak to this cancer and MDS crap. I truly believe we all have cancer within us, but our bodies keep in balance and keep it balanced out, but when something happens that lines things up in just the right way or lowers your immunity to much or your body is focusing all it's attention on fighting one thing, it creates open doors that were once shut. And blam get different types of cancers and such...

My Doctor is so focused on the general CBCs and not seeing enough to be concerned with, with the leukopenia and neutropenia that she doesn't feel the results of the Biopsy are concerning at all. This makes NO SENSE to me. We found very real abnormalities and I had the symptoms of MDS and whether it's a form of Leukemia or Myeloma etc, long before i ever knew about these things. 2 years ago is when my first CBC showed lower WBC it went from being in the 8s to being in the 4s... Then as months went on in went into the 3s and sometimes the 2s... But rest of CBC was always fine. Last year the poikilocytosis was noted... I know that is abnormal shaped red blood cells. Again no one was conceded cause RBC levels were fine. Although they are always the exact number on the low side of the normal range, and used to always be right in the middle. No big deal. But now we have done CBCs every 4-6 weeks for 6 months in a row never have they been in normal range. The highest is 3.6 the lowest is 2.1.... My Doc says some people just have lower ranges. Cmon I've had 8s for over 40 years of my life, and always had yearly CBCs for physicals. Always had CBCs when having surgery and I have had over 35 surgeries so there's been a lot of blood work over the years with no flags. How come now it's so low? How come I get sick for weeks every time someone coughs or sneezes in our home? The bruising issues, the bleeding issues... Even when they did the core biopsy the Doc and nurses were very concerned and how much I continued to bleed after the procedure. I've lost 25 pounds of my body weight- and I'm only 105lbs ( and that is if I'm wearing a prosthetic that weighs a few pounds)... So without my leg I'm tittering at 100 lbs. This isn't normal. None of this is. When the biopsy came back I thought, ok I don't like the results but at least now we;re getting some answers and we can figure out how to treat this and get better and do whats needed to cure it if at all possible. Yet she says no treatment, no cure, just don't worry about it cause doesn't want me to develop anxiety or depression over it. I've been a Psychologist for many years, spent a decade earning my PhD and trying to help others. I need help at this time. And I sure don't feel like I'm getting it.

I ask you again, to please take a little extra time from your day and go through the info and questions I've asked of you and shared with you and truly address them all... My husband has thought since the beginning that we are dealing with some form of Leukemia and doesn't understand why she is so focused on it being Myeloma when the M Protein isn't present, and the PET Scan was clear of Myeloma and the additional FISH test for the main 3 genes that show abnormalities in MM were all fine... So could the Plasma Cell Neoplasm abnormalities showing on the Plamsa Cell Neoplasm FISH test be a sign of something else? Such as Leukemia again? The specifics of it being 14q32 and the IGH splitting at both ends... My IGM levels being low aren't only indicative of Myeloma, but also of Leukemia... There are leukemias that only effect the white blood cells and not so much the red correct?

And lastly the MDS- myelodyplasia I understand the amount of cells being deleted isn't very high, but the fact that they are being deleted at all, and that the Doctor who performed these tests and specialists diagnosed me with Intermediate De NoVo MDS.... So why is my Doctor not concerned about this at all, and so adamant that it's not a big deal at all. I was diagnosed low low risk... or low risk. Or intermediate 1, I was told it was intermediate 2. Which leaves only high risk and very high risk above me in levels to go... Wouldn't it be better to get it controlled and treated now before I move up in levels?

All the things going on- would it not be better to be doing something to try and raise my WBC and neutrophils? To do something to bring my IGM levels up to normal ranges? To even biopsy the complex cyst or whatever the mass is the lit up like Christmas on Pet Scan, enough that the technician running it even said, they really need to biopsy that and get it out of you either way before you loose that kidney. Maybe my body fighting that in addition to all else is an added source of whats wearing me down. I wish there were Doctors that truly looked at the whole picture of a human being. And tied everything together. And what doesn't link to other things or makes sense, then do what's needed to heal one thing at a time. Everyone wants to send you to someone else. Everyone else wants to minimize findings.

You say stem cell transplant. But my Doc says no treatment at all. Says she is a chemo doctor and I'm not a candidate for chemo or any other treatment. I'm not sick enough or my numbers aren't low enough to offer me treatment. Says we need to wait till I go below .500 on neutrophils and below a 1 on WBC. Why can't it be treated before I'm even sicker than I am now? Can a stem cell transplant be done without chemo being done first? Is that even an option?

I'm sorry I know I've asked a lot. But I have a complicated case with a lot going on clearly. I'm hoping by next week to have appts for second opinions and it would help to know as much as I can, and from another doctor who specializes in this stuff. I can google just fine and find tons of info. I have done so to many times. I just want honest answers. If you were my Physician, I was your patient and you had these tests results and me sitting before you weak, fatigued, unexplained fevers of unknown origins, all low grade, bruising and bleeding issues etc... what would you be recommending to me? Nothing? Something? Pls just be honest. And one last time, please re look through everything so you can see the full picture. And please try and address each of my questions and concerns if you can. I just don't feel like that took place with my questions to you last night. You are only saying you agree with my doctor who recommends doing nothing and yet your mentioning stem cell transplants and other treatment options which would not coincide with my doc here. So please clarify. Thank you so much.

Thank you for your reply. Like I researched 14q32 not only show translocation in Multiple Myelomas but also in Chronic Lymphocytic Leukemia (CLL) just as you have now explained as well. Might I ask along with MDS doesn’t Chromosome 7q31.1 show as a deletion in acute myeloid leukemia?

It seems like a lot of the things that are showing up as abnormalities in both the FISH panels for MDS and for Plasma Cell Neoplasm could be related to Leukemia and not necessary MGUS or MM as Doc keeps referring to… Again this isn’t my specialty. That is why we come to Docs like you guys so we can get things figured out… I just research as much as possible and look for things that make sense. If I had M Protein in my urine, then I would understand us being on this MGUS or MM path. But nothing else shows up that points to it all except the Plasma Cell Neoplasm FISH test. A FISH test wasn’t down for any form of Leukemia so perhaps that would have given us more info. This is why I wanted confirmation of my thoughts as well that a 24 hour urine test should be done, since only one normal urine test has been done throughout this to check for m protein and I was told NONE was found. I would think in MGUS even a small amount would be found.

Because my Flow Cytometry all looks normal again there is no concern for much of anything. This is what my Doctor said... Me, well I am more concerned that although we may not see what sends off much flags to a Doctor based on CBCs that when we go inside, ie/: core biopsy and FISH tests we get way more answers. And I think although a lot is normal on my CBC, that there are still enough flags to show something is going on, or like my insurance company said they never would authorize such expensive tests like PET Scans and Core Biopsies and FISH tests etc… So the combination of a low WBC, Low Abs Neutrophils, Low IGM levels, Poikilocytosis, these all equate to something, as does the deletion, transplication and splitting of my cells, my DNA…. My Doctor only cares about not seeing blasts, not seeing clones, not seeing issues with platelets…. Meanwhile all we are seeing is disregarded…

chronic myeloid leukemia- low white blood cell counts (leukopenia) and neutropenia very common. The translocation of chromosomes and deletions of the types found abnormal in my FISH tests could also be linked to some of these leukemias- is that not correct?

When they ran all my tests they did Cytognetic testing and it all came back normal. This test was done over a 2-3 day time span. That is why I inquired with you on doing the several week cytogenetic testing which you concur with as well. Thank you... Again according to my doctor even though I had so many abnormalities on the FISH panels, showing transolocations, deletions and trisomy 15, and cells split at both ends (IGH) my cytogenetic tests were fine, so again no concern. Every ounce of research I have done says that proper cytogenetic testing takes several weeks. In order for me to have the type done that takes weeks would I need another bone marrow biopsy to to do so?

And you mentioned doing Immunophenotype testing and FISH tests, so this could be done if I had another bone marrow biopsy done yes? My Bone Marrow biopsy was a few weeks ago, would they allow me to do another or is there some waiting period needed? Can FISH or immunophenotype be done in other methods or are they both only done through bone marrow biopsy? Which FISH panels would you recommend as I've done the MDS and the Plasma Cell Neoplasm and the Myeloma already? Would you recommend FISH for the CLL or also even the AML? Or what specifically?

The only thing I can’t find a great deal of info on is Trisomy 15. I find a lot of medical information on it, but mostly all linked to babies in the womb with it being found or after born and it causing birth defects and even death to fetus etc. I can’t find much linked to someone my age. Can you explain Trisomy 15 to me more based on the findings that 32% of the nuclei looked at in my FISH test showed abonrmaties consistent with Trimsomy 15? This was the most alarming one to me because it was 32% of the cells. That seems like a lot, am I wrong? Thank you again for being more clear and really helping me understand more of this. And thank you for the info on raising white blood cell counts. My Doctor feels I need no treatment at all. She doesn't think it being at 3 or my Abs Neut being at 1.1 is that low. Nor does she think my symptoms are related to any of this. I strongly disagree.

Ahhh I see the Immunophenotype was the Flow Cytometry report that I had. You are saying to do a fresh one and the FISH and allow 3 weeks in-between those 2 tests? Or allow 3 weeks since my last one? Lost me there... On the Flow Cytometry Report she said the findings were normal. I would like to share it with you, in case you see anything she did not.
Immunophenotype
Cell Type %
Total Lymphocytes 34
B Lymphocytes 7
CD20+ 8
T Lymphocytes 84
NK Lymphocytes 18
____________________
Granulocytes 57
Monocytes 7
CD34+ Blasts 1
Plasma Cells 0


Analysis of bone marrow reveals no specific diagnostic abnormality. 34% of the cells are in the analyzed Lymphocyte region. Membrane marker analysis reveals up to 84% phenotypically normal T Cells with a smaller percentage of polyclonal B cells. There is an inversion of the CD4/CD8 ratio (0.82) which is a non specific finding and can be seen in a viral and reactive processes. The remaining elements consist of 57% maturing myeloid precursors, 7% monocytes and 1% CD34+ blasts. There is no evidence of B cell monoclonality. AN increased blast population is not identified. Correlation with the histologic findings is recommended.

The trisomy 15 abnormality was not noted on mds panel at all. It was noted on the myeloma panel entitled plasma cell neoplasm panel. It was 32 percent of the nuclei tested that were abnormal. My doctor gave nonexplation of this and i cant find much online that isnt tied to this being at birth or while women are pregrnsnt. Can you pla explain wht trisomy 15 is and why its not on my mds panel but on the plasma cell neoplasm panel and something doctor wasnt concerned with.