5 replies to this topic

[cedespres]

I have a question for Trey or anyone that may be able to give me information on these test results. I recently changed Oncs to a cml expert at 'dana-farber cancer institute in Boston. My BCR-ABL was 0.019 which I am happy about. He is also going to lower my Sprycel to 50mg per day. They put results from a rapid hemo test and I have no idea what they are supposed to tell me. I am going to try and do a cut and paste so that you all can look at them and tell me.

CASE: BL-16-W25752
PATIENT: CHARLES DESPRES






Pathologist: Frank C Kuo, M.D., Ph.D.

CLINICAL DATA:

Clinical History: None given.
Clinical Diagnosis: CML


==== RAPID HEME PANEL ====
RESULT:

Average coverage: 1439X >200X coverage: 90.7% <50X coverage: 3.9%
(A high quality sample/run has >90% of the amplicons with >200X coverage)


Pathogenic Single Nucleotide Variants and Small Insertions/Deletions:

TET2 NM_001127208 c.981delA p.S327fs* - in 3.6% of 2968 reads

Read count analysis shows no significant copy number alteration in the regions
tested.

FLT3-ITD is not detected.

This assay can detect FLT3-ITD with an insert size ranging from 12 to 120 bp.
A negative result therefore does not exclude the presence of small (<12 bp) or
large (>120 bp) FTL3-ITD.

The following recurrently mutated codons have wild type sequences only:

CBL Codon 371 CBL Codon 380-381 CRLF2 Codon 232
CSF3R Codon 615-618 DNMT3A Codon 882 FLT3 Codon 835-842
GNAS Codon 201 IDH1 Codon 132 IDH2 Codon 140
IDH2 Codon 172 JAK2 Codon 539-544 KIT Codon 816-820
KRAS Codon 12-13 MPL Codon 505-515 MYD88 Codon 265
NPM1 Codon 288 NRAS Codon 12-13 PTPN11 Codon 308
PTPN11 Codon 491 PTPN11 Codon 502-503 SETBP1 Codon 868-871
SF3B1 Codon 622 SF3B1 Codon 625 SF3B1 Codon 662
SF3B1 Codon 666 SF3B1 Codon 700 SRSF2 Codon 95
TLR2 Codon 217 U2AF1 Codon 157 U2AF1 Codon 34

The following recurrently mutated codons have inadequate coverage (<50X):

MPL Codon 505 (42X)
PTPN11 Codon 491 (42X)

Other Variants of Unknown Significance (VUS)*:

BCORL1 NM_021946 c.3158A>G p.K1053R - in 99.5% of 210 reads

*Note: Some variants on the VUS list may later found to be pathogenic and some
may be of germline in nature.

INTERPRETATION:

TET2 p.S327fs*
TET2 is a tumor suppressor gene and loss-of-function via mutations, deletion
and IDH1/2 (Isocitrate Dehydrogenase 1 and 2) gene mutations is a common event
in myeloid and lymphoid malignancies and in some otherwise healthy subjects
with clonal hematopoiesis (approximately 5% of elderly individuals in one
study). Mutations in TET2 occur in 50-60% of chronic myelomonocytic leukemias,
20-40% of systemic mastocytosis, 12-32% of patients with acute myeloid
leukemia, 10-20% of patients with primary myelofibrosis, 10-25% of
myelodysplastic syndromes (including refractory anemia with ring sideroblasts
and thrombocytosis) and less than 10% of patients with polycythemia vera,
essential thrombocythemia, chronic myeloid leukemia. TET2 mutations are absent
in juvenile myelomonocytic leukemia and show a low prevalence (less than 5%) in
pediatric AML. Among lymphoid neoplasms, TET2 mutations are reported in
approximately 30% of angioimmunoblastic lymphomas and less than 15 % of other
mature T cell lymphomas and mature B cell lymphomas. Approximately 30% of
blastic plasmacytoid dendritic cell neoplasms also have TET2 mutations.

Regions with less than 50X coverage may contain low frequency variants that are
below the detection threshold. If clinically indicated, additional testing
should be conducted to exclude the presence of low frequency variants in these
areas. A list of these regions is at the end of this report.

Test Information:

The BWH Rapid Heme Panel (RHP) Assay is a next generation sequencing assay
based on the TruSeq Custom Amplicon kit from Illumina. A detailed description
of the assay is available upon request from Center for Advanced Molecular
Diagnostics, Brigham and Women's Hospital.

Amplification method: TruSeq Custom Amplicon Kit, Illumina
Amplicon version: Rapid Heme Panel V2.0
Amplicon Info: Total 1350, average 250 bp, 175 kb total exonic region
Genes: Total 95, hot spot codons for oncogenes, entire coding
regions for tumor suppressors
Sequencing platform: Illumina MiSeq V2.2, 2X150-bp paired-end reads
Raw data processing: Illumina Real-Time Analysis and Somatic Variant Caller
Data File formats: Aligned BAM, VCF
Analysis: Filtering by read count, allele frequency, dbSNP, variant

class and run-normal
Pipeline cutoff: 10 variant reads at any allele frequency or 5-9 variant
reads at >33% allele frequency

The test performed at Brigham and Women's Hospital were developed and their
performance characteristics determined by the Molecular Diagnostic Laboratory
in the Department of Pathology at BWH. They have not been cleared or approved
by the U.S. Food and Drug Administration (FDA). The FDA has determined that
such clearance or approval is not necessary.

Targeted Gene/Exon List (genomic coordinates available upon request):

ABL1 e2-e10 ASXL1 e1-e13 ATM e2-e63 BCL11B e4
BCOR e2-e15 BCORL1 e1-e12 BRAF e15 BRCC3 e3-e11
CALR e9 CBL e7-e8 CBLB e9-e11 CD79B e5-e6
CEBPA e1 CNOT3 e1-e2 CREBBP e2-e21, e23-31 CRLF2 e6
CSF1R e22 CSF3R e14-e18 CTCF e3-e12 CTNNB1 e2-e4
CUX1 e1-e21 CXCR4 e2 DNMT3A e2-e23 DNMT3B e2-e23
EED e1-e12 EGFR e18-e21 EP300 e18-e27 ETV6 e1-e8
FANCL e1-e14 FBXW7 e8-e12 EZH2 e2-e8, e11-e20 FLT3 e14-e16, e20
GATA1 e2-e6 GATA2 e2-e6 GATA3 e4-e6 GNAS e8-e9
GNB1 e5-e6 IDH1 e4 IDH2 e4 IKZF1 e2-e8
IKZF2 e1-e8 IKZF3 e1-e8 IL7R e6 JAK1 e10-e25
JAK2 e12, e14 JAK3 e11-e24 KIT e8-9, e11, e17 KRAS e2-e5
LUC7L2 e3-e11 MAP2K1 e2-e3 MEF2B e3 MPL e10
MYD88 e5 NOTCH1 e24-e28 NOTCH1 e34 NOTCH2 e24-e28
NOTCH2 e34 NOTCH3 e25-e26 NOTCH3 e33 NPM1 e10-e11
NRAS e2-e5 PAX5 e3, e6-e7 NT5C2 e9, e11, e13, e15, e17
PDS5B e3-e35 PHF6 e2-e10 PDGFRA e10-e21, e23 PIGA e2-e6
PIM1 e1-e6 PRPF40B e2-e26 PIK3CA e2, e10, e21 PRPF8 e2-e43
PTEN e1-e9 PTPN11 e1-e15 RAD21 e2-e14 RET e7
RIT1 e1-e6 RPL10 e5 RUNX1 e2-e9 SETBP1 e4
SF3B1 e12-e16 SF1 e1-e10, e13 SF3A1 e1-e2, e5-e16 SETD2 e1-e4, e6-e21
SH2B3 e2-e8 SMC1A e1-e25 SMC3 e2-e29 SRSF2 e1
STAG2 e3-e35 TET2 e3-e11 STAT3 e2-e17, e21-23 TLR2 e1
TP53 e2-e11 U2AF1 e2, e6 U2AF2 e1-e12 WHSC1 e17-e18
WT1 e1-e10 XPO1 e15-e16 ZRSR2 e1-e11

The following regions have insufficient number of sequence reads (<50X) for
evaluation. (In this multiplex, amplicon-based next-generation sequencing
assay, this sample has 52 regions with fewer than 50 read and is considered as
a high quality result.)

Codon Codon
Gene Exon From To # reads Gene Exon From To # reads
ATM e57 2848 2906 0 BCL11B e4 541 603 10
BCL11B e4 603 691 1 BCORL1 e7 1425 1490 11
BRCC3 e5 119 200 7 CEBPA e1 1 66 47
CEBPA e1 66 134 4 CEBPA e1 134 207 8
CEBPA e1 207 280 0 CREBBP e28 1439 1512 3
CREBBP e30 1665 1733 0 CREBBP e31 1816 1875 46
CREBBP e31 1875 1936 29 CREBBP e31 1936 1996 2
CUX1 e4 52 141 14 CUX1 e24 1398 1473 14
CUX1 e24 1473 1537 9 GATA1 e6 282 356 37
GATA2 e3 162 211 11 GATA2 e5 306 396 21
IKZF3 e1 1 11 42 JAK3 e13 514 606 4
JAK3 e17 721 792 45 JAK3 e17 791 862 45
JAK3 e21 854 912 22 JAK3 e21 945 1003 22
JAK3 e22 963 1040 13 JAK3 e23 1001 1077 3
KIT e14 653 736 6 NOTCH1 e26 1260 1329 7
NOTCH1 e26 1329 1397 7 NOTCH3 e33 2131 2185 8
NT5C2 e15 344 434 40 PDS5B e24 707 761 0
PTPN11 e8 308 375 1 PTPN11 e8 350 417 1
RAD21 e8 239 323 10 RUNX1 e3 1 42 0
RUNX1 e8 430 504 36 SETD2 e1 1 38 3
SETD2 e12 1729 1802 0 SF1 e10 243 292 2
SF1 e10 330 379 2 SF1 e10 383 457 47
SF1 e10 470 544 47 SF1 e13 518 605 1
SH2B3 e3 658 706 9 STAG2 e7 116 196 2
STAG2 e14 389 480 10 STAG2 e21 636 681 49
STAG2 e21 743 788 49 STAT3 e22 676 762 20
WT1 e1 1 41 0 WT1 e1 41 99 39
WT1 e1 99 159 45



Final Diagnosis by Frank C Kuo M.D., Ph.D., Electronically signed on
Thursday July 07, 2016 at 07:51:41AM

Component Results

There is no component information for this result.

General Information

Collected:

06/29/2016 12:00 AM

Resulted:

07/07/2016 7:52 AM

Ordered By:

Richard Maury Stone, MD

Result Status:

[Buzzm1]

cedespres, congrats on the 0.019; I've forgotten your CML history; could you please summarize it ... tia ...

 

PS... glad your new Onc is proactive in lowering your Sprycel dosage to 50mg ... 

[cedespres]

Hi Buzz,

I was dx in July of 2014 while in the hospital for other things. My white cell was around 120,000 and I started on gleevec by August. I began to develop retinopathy  just after starting the med. Had many eye surg and ended up legally blind. Both my eye doctor and my onc concluded it was a rare side effect of g (in fact there was only 1 other case reported in the literature they examined) I was changed to Sprycel 100 and developed PE and CHF very quickly and was back in the hospital. Reduced to 70mg but continued to have fluid and breathing problems. I had a problem with paying my co-pay and had to go on 70mg every other day for a few months. I I then went on 70mg one day and 50mg. My onc was still saying our goal was to get back to 100mg so I went to Dana-Farber in Boston and saw a CML specialist and he decided I should be on 50mg at most with a goal to go lower if my bcr-anl numbers stay good. I would like to stay on sprecel if low dose gets rid of the PE issue,as it is working and I am able to handel the regular side effects so. I never got test results that were so detailed in the past and was wondering what it all means. I would put my history in my sig but don't know how.Thank you

Charles Despres

[Buzzm1]

To add your CML history into your Signature:

upper right, next to your forum name, there is a drop-down menu activated by clicking on it

Select "My Settings"

on the left, Select "Signature"

scroll down and add as much info as desired

when  finished "Save Changes" at the bottom

the information in Signature can be edited, or added to, as often as needed

[Trey]

Interesting, but useless to you.  Dana Farber B&W invented this test, so I suppose they are trying to recoup their investment by doing it on all leukemia patients, even when it is not needed.  Since you are MMR and close to 4 log reduction despite your issues with drug breaks and such, the test was unnecessary for you and for 99% of CML patients. 

 

Here is the Dana Farber Onc discussing the test and why it is used.  It is mainly for those with difficult variants of AML or ALL leukemias, or patients with MDS and other hard to diagnose blood cancers (I do not recommend others watch this unless they are really, really bored and have already captured all their Pokemon critters for the day):

https://www.youtube.com/watch?v=o5MJR_turmI

 

As for your individual results, they show you have a TET 2 mutation, which is found in about 10% of CML patients and is of unknown significance (meaning likely not significant at all):

http://www.ncbi.nlm....arch&term=54790

 

I don't see anything else on there.  The rest is just saying you are human and have human genetics. 

 

If you want to have some fun ask your Onc to explain the results.  I doubt he can except to say there is nothing there to be concerned about.

[cedespres]

Thank you guys very much. It is so nice to have things simplified when dealing with cml.

Buzz, thanks for your support! I am doing very well considering all of my health issues and I am just thankful this happened to me after the advent of TKI drugs. I am still alive and plan to stay that way for awhile.

 

Trey, Thanks again for the info. I could not help getting a good laugh about the B&G test and your suggestion about asking my onc to explain these results. It is wonderful to have a good laugh now and then.

Thanks again,

Charlie