17 replies to this topic

[Red Cross Kirk]

I've been meaning to ask this question for a while now.  What's the difference between BCR-ABL testing for minor vs. major?  And when should they be used?

 

The reason I ask is that since I've been going to OHSU, the BCR-ABL portion of my quarterly bill has increased.  When I went to Compass Oncology the bill showed a charge of $177 for BCR/ABL1 Gene Major B (service code 81206).  Now the OHSU bill shows a charge of $287 for BCR-ABL RNA Major B (code 81206) plus $286 for BCR-ABL RNA Minor B (code 81207).

 

Does it make sense to be tested for minor breakpoint after four years of treatment?  Should I ask my doc to have the pathology lab only do one of the tests, instead of both?

[Trey]

PCRs for CML are not all-inclusive.  There is a PCR to test for major breakpoint (P210) and a separate one to test for minor breakpoint (P190).  These are variants of the Philadelphia Chromosome.  Over 95% of CML patients only have the P210 type.  P210 is the e13a2 (b2a2) and/or e14a2 (b2a3) types of Philadelphia Chromosomes, while P190 is the e1a2 type.  A single PCR cannot find both P210 and P190.  FISH testing is not specific for breakpoints, so will find either if they are above CCyR levels, but will not define which types it found.

 

A CML patient should be tested at or near diagnosis for both P210 and P190 variants to identify which breakpoints exist.  If there is no P190 present at diagnosis, then only P210 should be done after that.  If P190 was present at diagnosis, then it should continue to be tested for. 

 

If you never showed positive for P190, your Onc is writing the wrong lab order and you are being overcharged. 

 

Your lab order number is equivalent to Quest Diagnostics:

http://www.questdiag...ction?ntc=91065

Edited by Trey, 24 December 2016 - 04:04 PM.

[Red Cross Kirk]

Thank you Trey!

 

I'll ask my doc if I ever showed positive for p190.  If not, then I can save a little on the medical bills.

[Red Cross Kirk]

I got a reply from OHSU about the PCR testing.  Here's my query:

 

"In an effort to reduce my medical costs, I was reviewing the ongoing charges for my visits with you. I noticed two BCR-ABL tests listed (80003643 HB-LAB BCR-ABL RNA MAJOR B $287.00 & 80003644 HB-LAB BCR-ABL RNA MINOR B $286.00).

I was wondering if at this point in my treatment are both of these tests necessary to determine the BCR-ABL RNA level in my blood?"

 

And here's the reply:

 

"Mr. Tolstrup
I spoke to the lab that runs the test and also to Dr. Heinrich. The two tests that look like they are separate tests (and are billed separately) are really 2 parts to one test. That test is how we monitor your leukemia status and both parts are critical to get the number that we see and that we use to make recommendations as to your treatment. Unfortunately there is not a way to decrease your cost and still do the testing.
You can discuss it further with Dr. Heinrich when you see him on January 9,2017.
If you have other questions or concerns, do not hesitate to contact me.
Florence Seelig, RN, BSN, OCN
Oncology Nurse Coordinator
Oregon Health & Science University"

 

So I guess that I can't save any money if I keep going to OHSU.  Hopefully their profits are being used to fund lots of good research!

[Trey]

Here are the OHSU tests they are talking about:

 

http://www.ohsu.edu/...69C229909F8F5EB

 

The nurse's explanation is not accurate enough to answer your question.  The P210 and P190 tests are two separate PCR tests since they require different reageants, and therefore separate PCR set-up and testing.  So they are two separate PCRs.  More likely it is an OHSU policy to test for both.  You might want to ask Dr Druker.

 

 

Here is what the Mayo lab says, showing the P190 and P210 are different PCR tests entirely:

"This test detects only the e13/a2 and e14/a2 fusion forms, which code for the p210 protein. Other fusion forms are not detected, including those containing the BCR e1 exon, which codes for the p190 protein commonly found in acute lymphoblastic leukemia (ALL). If the patient is known to carry an e1/a2 (p190) fusion form, BA190 / BCR/ABL, p190, mRNA Detection, Reverse Transcription-PCR (RT-PCR), Quantitative, Monitoring Assay should be used for monitoring."

http://www.mayomedic...erpretive/89007

Edited by Trey, 23 December 2016 - 10:10 AM.

[Red Cross Kirk]

Thanks Trey,

 

If I'm reading it correctly, the lab is saying that they are not testing for P190.  Maybe they charge twice so they can justify having two people sign off on the results?  Here's the verbiage that comes from the lab explaining the test:

 

Narrative

Test indication: leukemia monitoring

As per your request, to determine the level of minimal residual leukemia, we have completed a quantitative RT-PCR analysis of BCR-ABL RNA, a marker of the presence and amount of transcriptionally active Philadelphia chromosome positive leukemia cells.

This RT-PCR assay will detect the most common (but not all) BCR-ABL translocation breakpoints within the "major breakpoint cluster region" (encoding the BCR-ABL p210 protein). The common p210 translocation breakpoints that will be detected with this assay include those involving exons 13 or 14 of BCR joined to exon 2 of ABL. Uncommon p210 translocation breakpoints (ie those involving ABL exon 3) will not be detected with this assay. All BCR-ABL minor translocation breakpoints (encoding the p190 protein), such as those often found in ALL, will also not be detected with this assay. These non-detectable "minor breakpoint cluster region" p190-associated breakpoints include translocations involving upstream BCR exon 1. Should an uncommon BCR-ABL translocation breakpoint that is not detectable with this assay be suspected, please contact the lab, as an alternative PCR assay can be utilized.

These results suggest than an MMR (Major Molecular Response) has been achieved, indicating a good response to anti-leukemic treatment. The level of minimal residual leukemia is low.

The international scale (IS) of reporting defines a BCR-ABL RNA level of 0.1% as being equivalent to a 3.0 log-reduction from a standardized median pre-treatment baseline value (that is, by definition, equal to 100%). This 0.1% international scale level is, by definition, a "major molecular response" (MMR) as established in the IRIS study (International Randomized Study of Interferon and STI 571). On the International Scale, BCR-ABL IS < 0.1%, 0.01% and 0.0032% are equivalent to MMR (Major Molecular Response), MR4 and MR4.5, respectively. The NCCN guidelines consider early molecular response (EMR; BCR-ABL IS < 10% at 3 months) as a goal of treatment. Achievement of MMR (BCR-ABL IS < 0.10%) at 12 or 18 months post-therapy is also a confirmed good prognostic marker. Although this PCR assay yields quantitative information, please note that the assay precision is such that RNA changes of less than approximately 0.5 log (3.2-fold) should be interpreted cautiously and may not reflect true biological changes in RNA levels, but rather an inherent lab-dependent variability in the quantitation of these transcripts. The low-level analytical sensitivity of this assay is approximately MR4.5 (~0.003% IS, or 4.5 logs below the pre-treatment baseline), such that a negative sample may still have a very low-level BCR-ABL RNA level below that threshold.

This test was developed and its performance characteristics determined by the OHSU Molecular Diagnostics Center. It has not been cleared or approved by the Food and Drug Administration. FDA approval is not required for clinical use of the test, and therefore validation was done as required under the requirements of the Clinical Laboratory Improvement Act of 1988. The OHSU Molecular Diagnostics Center is a fully licensed and/or accredited clinical laboratory under CLIA, CAP, and the State of Oregon.

Reviewed and electronically signed
10/7/2016 3:29 PM


Reviewed and electronically signed
10/7/2016 5:58 PM

[Trey]

Given that, OHSU is simply charging you for testing they are not doing (i.e, the P190 PCR).

[tiredblood]

"Your lab order number is Quest Diagnostics:
http://www.questdiag...ction?ntc=91065

Trey, are you saying that his bcr-ABL testing is a send out to Quest Diagnostics or just used that as an example?

If you are, I always go to Quest Diagnostics site and print my official report. I know once I tested negative for the P190, all my reports from Quest state because the P190 was negative in the past, it was not tested for in subsequent testing. Anyway, FWIW, if they're charging you for it they should be able to produce lab results for it. I know I'm repeating what has probably already been said.

[Trey]

I meant to say it was equivalent since I did not know which lab was being used.  Fixed it in the post above.

[Red Cross Kirk]

Well, today at my appointment I brought up the subject of the PCR tests.  If I understood correctly,  OHSU has a standard procedure of testing for both major and minor breakpoints.  I tallied the cost difference between OHSU and Compass Oncology for my PCR testing, and it's $299 more for OHSU's protocol.

 

I like going to OHSU, but it is more of a hassle.  I think maybe I'll just go there once a year and go to Compass for the other three visits.  Do you think I'll step on any toes if I go that route?

[Trey]

A dumb policy.  I would not care about toe stomping. 

[Red Cross Kirk]

I've asked Dr. Heinrich (OHSU) if he'd be okay with seeing me once a year.  We'll see what he says.  I tried to make an appointment with Dr. Chang (Compass) for my next PCR checkup in April and they told me they'd have to get my records from OHSU so they can schedule the correct labs.  Hopefully it will all work out and there won't be any mashed toes!

[Red Cross Kirk]

OHSU sent me the usual after visit survey, but it didn't really have any questions that pertained to my beef with their PCR testing protocol. So I submitted this to their website contact form:

 

To whom it may concern, I've been coming to OHSU for a couple of years now and just completed a survey about my last visit. I'd like to add some information to my survey. I've recently discovered that one of the tests used to monitor my ongoing treatment has a cost that is about $300 per test higher ($1,200 more per year) than at my previous provider. In order to reduce my healthcare costs I've decided to return to my previous provider. If you would like to dialogue further about this matter, please contact me.

 

I wonder if they will reply?

[Red Cross Kirk]

Here's the generic reply from OHSU:

 

Hello Good Morning,

 

Thanks for contacting OHSU. The best resource is for you to contact billing perhaps by calling our toll free number 888.222.6478.

 

 

Thanks,

Web Team

 

 

It sounds like my concern has fallen on deaf ears.  I've made an appointment with my previous onc for my next CML checkup.  Qué será, será.

[kat73]

Wow, that response is pathetic.  Sounds like OHSU needs a new "Web Team" pronto.

[Red Cross Kirk]

I was curious about my early testing so I asked for copies of those reports.  The first PCR tested positive for both p210 and p190 with results of 88.57% (118.683% IS) and 0.010% (N/A IS) respectively.  The second PCR didn't mention anything about p190.

 

Was the p190 result significant or is it more of a "false-positive" kind of thing?

[Silvertabby]

I had the same thing on my first pcr - p190 was extremely low. Now every three months they test for both, but the p190 has never been detectable since.

[Trey]

Was the p190 result significant or is it more of a "false-positive" kind of thing?

 

Hard to say if false positive.  But given only the initial detection it should not be a long term problem since it obviously responds quickly to TKI drugs.