14 replies to this topic

[Chris1579]

Hello - I really need some help understanding my Dad's test results and it was suggested that I post them so that you guys (especially Trey) could put them in some type of language that I could explain to Dad.

If I have not posted something that is needed, Please ask, this reports is pages long and seems all Greek to me (I don't speak Greek) and I am posted what I believe is needed - a million thanks in advance!!

Fish Test -

karyotype

nuc ish (ASS1X1, ABLX2, BCRX2) (ABL1 con BCRX1) [180/200]

CYTOGENETIC FINDINGS:

N/A

IMPRESSION:

Evidence for the BCR/ABL1 gene fusion and deletion of the AAS1

(arginosuccinate synthetase 1 gene at 9q34

BCR/ABL1 QUANTITATIVE ANALYSIS

RESULT; POSITVE FOR BCR/ABL1

% BCR/ABL1; ABL1; 218.683

REFERENCE INTERVAL; NEGATIVE

Bone Marrow Study

Cells Analyzed = 20

Karyotypes = 2

CYTOGENETIC FINDINGS:

Cells 20

Result - 46, XY, t (9;22) (q34, q11.2)

Interpretation - CLone 1

IMPRESSION

Adnormal male karyotype, Philadelphia Chromesome positive

The t (9;22) is consistent with a dx of CML

The results of interphase FISH analysis for the BCR/ABL1 fusion were abnormal

Fluorescense in Situ

KARYOTYPE:

nuc ish (ABL1, BCR) X2 (ABL1 con BCRX1) [192/200]

CYTOGENETIC FINDINGS:

SEE CYTOGENETIC REPORT

IMPRESSION:

Evidence of the BCR1/ABL1 gene fusion with a variant signal pattern

NEUT#.  18.0H

LYMPH#. 1.5

MONO#.  1.0

EOS#. .08H

BASO#. 0.8H

EARLY GRN#. 3.3H

BLAST# 0.0

SEGS% 69

BANDS% 2

LYMPHS% 6L

MONO% 4

EOS% 3

BASO% 3H

META% 6H

MYELO% 7H#

PROGRAN% 0

BLASTS% 0

PLASMA% 0

OTHER% 0

SOD 142

POT 4.1

CHLOR 103

CO2 31

UN 21H

CREAT 1.4H

GLUC 89

CAL 9.4

PROT 6.3

ALB 4.2

AST 38H

ALT 35

ALK 99

TBIL .05

WBC 25.4H

HGB 13.3L

HCT 41

PLT 377

RBC 4.73

MCV 86.7

MCH 28.1

MCHC 32.4

RDW 15.0

MPV 10.8

QUANTITATIVE RESULT;

% BCR/ABL:ABL1 IS 293.057

REF. INTERVAL: NEGATIVE

Bone Marrow

RESULT:  Positive for BCR/ABL1

Quantitive result:

%BCR/ABL1:ABL1 is 119.097

Negative for MPL Mutation

Negative for JAK@ exon 12 mutation

Cell - 200 cell diff

Lymphocte% 12.5L

N eutrophil % 66.5

Metamyelocyte % 5.5H

Myelocyte % 5.5H

Promyelocyte % .05H

Blast % 0.00

Monocyte % 3.5

Eosinophil % 3.0

Basophil % 3.0H

Cell - 500 cell diff

Blast % 1.4

Promyelocytes % 3.0

Other granulocyte precursors 70.6H

Erythroid precursor % 15.4L

Lymphocytes % 2.0L

Easinophils and precursors % 5.6H

Basophils and precursors % 1.2H

Moncytes and precursors % 0.6

Plasma cell % 0.2

M;E Ratio 4.9

Test:  JAK2 Mutation Assay

Result:  Negative for JAK2 V617F Mutation

NEUT# 16.5H

LYMPH# 3.0

MONO# 0.8

EOS# 0.8H

BASO# 0.8H

EARLT GRN #2.8H

SEGS%66

BANDS 2

LYMPHS 12L

MONOS 3

EOS 3

BASO 3H

META 7H

MYELO 4H

PROGRAN 0

BLASTS 0

PLASMA 0

OTHER 0

WBC 25.4H

HGB 13.4L

HCT 40.8

PLT 342

RBC 4.67

MCV 87.4

MCH 28.7

MCHC 32.8

RDW 15.2H

MPV 10.8

SOD 142

POT 4.5

CHLOR 103

CO2 32

UN 25H

CREAT 1.4H

GLUC 99

CAL 9.3

PROT 6.3

ALB 4.1

AST 38H

ALT 3

7H

ALK 95

TBIL 0.6

DBIL 0.2

LDH 295H

NON AFRICAN EGFR 50

[Trey]

He has CML.  Although the WBC is not that high (about 25K, which is somewhat lower than most CML diagnosis levels), the two FISH tests shows that over 90% of his white blood cells (WBCs) are leukemic (as shown by the 180/200 and 192/200).  So he is not in some low level state of leukemia.  The cytogenetics shows 2 different "karyotypes" (chromosome analysis of the WBCs).  You do not list exactly what they are, which would be helpful to add.  One karyotype is certainly the Philadelphia Chromosome.  The other could either be a few normal cells, or it could be the ASS1 partial deletion of chromosome 9, which is a variant of the Philadelphia Chromosome (which is  somewhat unusual, but not entirely rare). 

So the fact that over 90% of his WBCs are leukemic should cause him to say to himself: "Self, get off the couch and order the Tasigna and take them".  He is not far from his white blood count skyrocketing.  It is not the cell count, but the percentage of leukemic cells that matters.  He is 90% leukemic blood cells.  Ignore this and the leukemia could get out of control.  After that it really sucks.

He says he likes clarity.  Clear enough?

[Pin]

Hi Christa, I'm glad you posted your Dad's results. Hopefully the more confirmation of the diagnosis the more it will help him to understand it. Let us know how he is going and say hi from us. Almost everyone here has been through a diagnosis too and we really do empathise with him. Xxx.

Hi Trey, good explanation. A question though - it looks as though there are PCR tests in there as well, one on bone, two on blood (if I'm reading it right). They look fairly different though in terms of ratio - is there any significance of the difference between the blood and bone marrow PCR %? Or could it just be testing error?

[Trey]

Pin,

PCRs are not very accurate at high levels of leukemia, as these 3 PCR reports show (218%, 293% and 119%).  That is why more Oncs prefer FISH early on.  PCRs are more useful at the lower levels.

[Judy2]

Trey,

Do you think it is important to know if your lab uses the International scale or not? I say this because it seems that PCR results that come back on the International scale seen higher than those that are not on the International scale. Am I correct in this?

Judy

[GerryL]

Hi Pin,

The leukemic cells are more concentrated in the marrow then the blood stream.

[Chris1579]

Just got off the phone with my Dad -

Trey - Dad said to tell you "yes, it is very clear" - He says you tell it the way it is...

He is ordering his meds tomorrow morning - THANK YOU, THANK YOU!

Pin - Thank you for your support!  You are very sweet

OK - ASS1 - this paperwork is a novel so if I still am not sending you the right thing, just say so - I think this is what you are referring to - (think being the key word)

situ hybridization

Type of Signals          # of cells (%)

1R, 1G, 1F, 1A          180 (90%)

1R, 1G, 1F, 2A          3 (1.5%)

2R, 2G                      17 (8.5%)

total 200

Probes included a spectrumGreen Labeled BCR probe which localizes to 22q11.2 and spectrumOrange-labeled ABL1 and SpectrumAqua-labeled ASS1 probes which localizes to 9q34 (BCR/ABL1 DF, Abbott Molecular; ASS1, Abbott Molecular)  Dual yellow fushion signals (Dual fushion+) are produced by the reciprocal translocation of the BCR and ABL1 genes; however, if deletion of the der (9) t (9;22)involving theASS1 gene occurs, 1 red, 1 green, 1 fusion, and 1 aqua signal will be produced (1R, 1G, 1F, 1A).  A normal cell will have 2 red and 2 green signals (2R, 2G).  A cell containing two intact ASS! genes will have 2aqua (2A) signals.  A cell with a deletion of the ASS1 gene will have 1 aqua (1A) signal.

In the comments it states - The t (9;22) was noted by standard cytogenetic analysis of a pretreatment bone marrow sample 1/20/12, BCR/ABL1 gene fusion with deletion of the ASS1 gene was noted in 97% of the cells by interphase FISH analysis of that sample.

This may be a stupid question but why is his WBC count low when he is 90% leukemic- I understand it is in his bone marrow but that is were the white blood cells come from - what am I not connecting here?

Type of Signals               # of cells

1R, 1G, 1F, 1A               194 (97%)

1R, 1G, 1F, 2A               0

2R, 2G                              6 (3%)

total                                   200

type of signals                   # of cells

1R, 1G, 2F                              0

1R, 1G, 1F                              192 (96%)

2R, 2G                                   8 (4%)

Does that mean the 9 broke off?  If so, what in the heck does that mean?

what does "clinicpathologic correlations are recommended" mean?

what does "moderately hypercellular bone marrow with panmyelosis" mean?

what does full spectrum of maturation.  Slight basophilia mean?

And lastly what is megakaryocytes - slightly increased in number with some small forms with nuclear hypolobation mean?

Many thanks for all the help and support!  It means so much!

After reading this medical report - me not feeling too smart - LOL

[Pin]

Christa! I can't tell you how glad I am to read this! Very good news indeed - wonderful!

Trey - thanks, I figured as much, always appreciate your knowledge and input!

Gerry - thanks! Yes, this does make logical sense but I do wonder if there are individual differences with this kind of thing too.

Pin xxx.

[Trey]

The additional information confirms that his variant of the Philadelphia Chromosome is missing pieces of the chromosome 9 (aka "der 9" or -9q deletion), which occurs in about 10% of CML cases.  When the CML process starts, pieces of the 9 and 22 chromosomes break off and swap places.  Usually it is the entire piece that has broken off from 9 re-attaches in the wrong place (on 22).  In some cases, including his, some of the broken off piece of the 9 chromosome was lost while floating around before it re-attached at the chromosome 22 location.  So only part of the chromosome 9 re-attached, and the remainder was lost.  Prior to TKI drug therapy this was a poor indicator.  But the TKI drugs overcome this issue most of the time.  So it is mainly an academic exercise at this point as long as he takes the drug.

You asked why his WBC is low.  It is not low, since it is about 4 times higher than the average mid-range WBC.  But it is relatively lower than many of us at diagnosis.  But within a couple months it would be over 100K.  So the percentage being 90% leukemic is the real indicator. 

Your other questions were:

"what does "clinicpathologic correlations are recommended" mean?"

It means the lab should cross check test results -- standard verbiage

"what does "moderately hypercellular bone marrow with panmyelosis" mean?

He has too many blood cells in the marrow and they are mainly WBCs

"what does full spectrum of maturation.  Slight basophilia mean?

Blood cells are maturing properly (good).  But basophils are somewhat high (expected).

"And lastly what is megakaryocytes - slightly increased in number with some small forms with nuclear hypolobation mean?

Megakaryocytes are cells that break apart into fragments to form platelets.  Some are mis-shapen (expected in CML).

Here are some of my papers explaining various aspects of CML:

http://community.lls...ttype[document]

[Judy2]

Hi Christa,

I am so glad your dad is ordering his meds. Please let us know when he starts them, I'll feel better once I know he has taken his first pill. Good job for keeping after him and getting him all the info.

xo,

Judy

[NotJack?]

Hey Christa,

I am so glad that your dad is going forward.  I felt so sorry for you and your family that he was killing himself for no reason.   I take my Tasigna first thing in the am, so that I don't have to schedule two fasts.  Some prefer 10 and 10 so that it is between traditional feedings.  You can always change down the road, as your window is ideally 12 hour between, but in a pinch, after 8 hours and before 14. This is based on the half life of the drug as stated by Dr Druker. There are other threads about this.  You take care, and thumbs up to your dad,  Jack

[mabdou2005]

Hi trey

Can i ask you why the doctor ask in this case JAK2 V617F Mutation is this test belong only the ET case  or it can be with CMl?

 

M abdou

[Trey]

The JAK2 mutation is not directly related to CML.  If both the Philadelphia Chromosome and JAK2 are present, it is assumed that there are two separate diseases.  The second disease could be several different ones.

http://en.wikipedia....erative_disease

[Chris1579]

Thank you very much!  Dad's meds should be in by Monday, I will keep you posted and naturally, if Dad has more questions I will ask.  Thank you for helping me to save his life!

God Bless

xo

Christa

[Susan61]

Hi Christa:  So glad your Dad is going to take his meds.  Please keep us posted, and will pray we see a great response for him.

God Bless you and Dad.

Susan