Confused about BMB Report
 

I have a history of chronic anemia which has in the last year expanded to include leukopenia and sporadic neutropenia. I have pernicious anemia and I was historically on a B-complex and monthly injections of cyanocobalamin. My numbers were getting worse on this regimen and my GP put me back on loading doses of b12 (every other day injections). I have been taking these for weeks and in September I saw a hematologist because the anemia and leukopenia are not correcting despite the massive doses of B12 and Folic Acid (5mg per day).

The hematologist checked the CBC again and we saw a low reticulocyte count and normal RDW indicating my marrow is not responding to the treatment. We did a BMB a few weeks after that and I reviewed the results with her on Friday. I have been trying to understand the report as I thought were trying to rule out MDS. It appears she did leukemia/lymphoma panel instead? I have been burying myself in research to determine if anything in this report rules out MDS. She says my report is normal - but it looks odd to me based on what little I have been able to find. Any help is appreciated!

Day of CBC:
WBC 3.9K/uL, RBC 3.53M/uL, Hgb11.8 g/dL, Hct 34.3%, MCV 97.1fL, MCH 33.5pg, MCHC 34.5g/dL, RDW 12.7%, plts2 281K/uL, MPV 7.2fL.
Auto diff(%): Segs+bands 51.5, Lymphs 39.4, Monos 7.3, Eos 1.6, Basos 0.2.

Report:
PERIPHERAL BLOOD AND BONE MARROW (ASPIRATION & BIOPSY, ILIAC CREST) DIAGNOSIS:
NORMAL CELLULARITY (50%) With TRILINEAGE HEMATOPOIESIS.
ADEQUATE IRON STORES.
PERIPHERAL BLOOD: MILD NORMOCYTIC ANEMIA AND MILD LEUKOPENIA WITHOUT SPECIFIC CYTOPENIAS (ANC - 2.1K/uL, ALC - 1.4K/ul)

ANCILLARY STUDIES
Cytogenetic Analysis:
Apparently normal female bone marrow chromosome analysis, No clonal numerical or structural abnormalities were observed.

Flow Cytometry - Leukemia/Lymphoma Profile:
No definitive immunophenotypic evidence of high-grade hematopoietic neoplasia, lymphoproliferative disease or a plasma cell neoplasm.
Abnormal bone marrow cells: No immunophenotypic abnormalities detected

MICROSCOPIC DESCRIPTION
Peripheral smear:
Manual differential : Segs+bands 55, Lymphs 37, Monos 7, Eos 1, Basos <1.
WBC: morphologically mature granulocytes, lymphocytes and monocytes; occasional neutrophils with abnormal segmentation
RBC: mild anisopoikilocytosis, minimal polychromasia
Platelets: estimate agrees with the reported count, granulation is normal,
average size is not increased
Marrow aspirate smear/touch prep:
Marrow differential count(% marrow nucleated cells), 500 cells: Blasts 3,
Promyelocytes <1, Myelocytes 7, Metamyelocytes 9, Segs+bands 20, Lymphs 17, Monos 6, Eos 2, Mast cells/basos <1, Plasma cells 4.
Myeloid total 44, RBC precursors 32, M:E ratio 1.4:1
Particles: touch preps are adequate; aspirate smears have scattered cells
Myeloid cells: progressive maturation
Erythroid precursors: normoblastic maturation; minor nuclear contour irregularities
Megakaryocytes: present
Dyspoiesis: minimal dyspoietic changes observed
Lymphocytes: morphologically mature
Plasma cells: morphologically unremarkable
Overall cellularity: 50% (I am 41)

Megakaryocytes: adequate in number; occasional hypolobated nuclei
M/E ratio: estimate agrees with differential count
Granulomas: absent
Lymphoid aggregates: not demonstrated
Infiltrates: absent
Ancillary stain(s) :
Iron stain performed on aspirate smear, aspirate clot and biopsy:
Storage iron: adequate
Ring sideroblasts: none demonstrated
Immunohistochemistry performed on biopsy:
CD34: Highlights scattered immature cells, 3%; also highlights occasional megakaryocytes
CD117: Highlights scattered immature ce1Is, <1%; also highlights rare scattered mast cells
p53: Highlights rare positively staining cells, <1%
CD138: Highlights scattered plasma cells, 5%
CD20: Highlights scattered small B ceI1s, 3-4%

Can anyone interpret? Is this normal? Does anything here rule out MDS?

Hi Bandit224,

I am not an expert at bone marrow biopsies, but from what I see, MDS doesn't seem to fit as a diagnosis, primarily due to the presence of plasma cells and mast cells, as these are normally absent in MDS. Also, although not all MDS patients have cytogenetic changes, it is pretty common, and you do not have any. Also, there isn't any mention of dysplasia in any of your blood cells, which is the defining feature of MDS.

Unfortunately, I think that you will need to ask the doctor about the potential implications of this report.

I wish you well through this period of uncertainty.

Dan

Thanks Dan. As with most who end up here, I'm trying to read data that is well beyond my expertise. So are hyperblated nuclei in the megakaryocytes, abnormally segmented neutrophils, and irregular nuclear contours not dysplastic changes? Any insight on the low m:e ratio or presence of cd34 positive blasts? I know no one hear is a doctor but I'm learning as much as I can.

Hi bandit224,

I agree with DanL, in my non-expert opinion, your BMB doesn't seem to indicate MDS. Although you have dysplasia in some of your cell lines, it is only mentioned as "minor, minimal, or mild". With MDS, the report would indicate significant dysplasia involving over 10% of the cells.

Also, your MCV is normal. I think this number is usually elevated if your marrow is under stress.

Obviously, something else is going on given your worsening symptoms and low M:E ratio. Have you had any exposures to drugs or chemicals? Are you taking any supplements? Do you have bleeding or GI issues?

If you haven't already, check out this pernicious anemia forum for other possibilities as to why the shots aren't working.
https://healthunlocked.com/pasoc/posts

Good luck in your search!

Thanks Hopeful. I am on that forum and a member of the PA society. I am on (And have been for a while) B12 injections (every other day), and folate, magnesium, iron, and vitamin D supplements as all were low at one point. The fact that I am worsening despite these supplements is what has everyone confused and this was the reason for the BMB. My marrow is still not responding despite months of supplementing. I do not have any GI bleeds (had upper and lower endoscopies) and no chemical exposure that I am aware of. The search continues. I appreciate both of you having a look and your support!

Just a quick update...
 

No new diagnosis, but I know sometimes folks read these forums, see someone similar, and wonder what happened to them.

Since my last post I have continued to have unexplained anemia, leukopenia, and downward trending platelets. My hematologist and gynecologist recommended jointly that I have an endometrial ablation (in case heavy periods were causing the problem) with monthly CBCs + LDH to monitor for improvements. I have had 6 months of monitoring post the ablation, and while it seems to have been a resounding success in terms of completely stopping my periods, this has had no effect on my bloodwork. All my vitamin deficiencies are monitored and all have been corrected where necessary via supplementation and injections (Vitamin D, Iron, B12, Folate, Vitamin C, Zinc, and Magnesium levels are all good). Still no change (in fact the bloodwork seems to indicate minor shifts downward for RBCs, WBC, and Platelets). Most recently I had a moderate elevation in LDH which has historically been normal.

Current Levels are below and still not emergency levels but enough to leave me tired and exhausted. Other than the change in LDH (has been hovering in the mid 100s), everything else has been consistently similar with slight trend down over the last few years.

WBC 3.9K/uL, RBC 3.37M/uL, Hgb10.4 g/dL, Hct 32.1%, MCV 95.3fL, MCH 32pg, MCHC 33.6g/dL, RDW 12.5%, plts 234K/uL, MPV 8.4fL LDH 344 (range 81-234)

The hematologist is back on the idea that there is some sort of marrow damage and is re-testing everything again next month and then depending on that outcome, wants to discuss a repeat bone marrow biopsy.

So no answers but wanted others with unexplained low blood levels to know they are not alone and I will update if we ever get to the bottom of my mystery. As of now the anemia has been ongoing for over a decade, the leukopenia for over 6 years, and platelets have been all over the place but mostly normal with downard trend (only occasional low results).