I am about to appeal a denied cost for genetic testing as part of a bone marrow biopsy. Specifically, the insurance company says that 75 Gene Heme NGS panel (procedure code 81455- if that means anything to anyone) is not a covered cost. In writing this appeal letter, I'm trying to understand some things better.
I was diagnosed in December 2020 with PV. However, I am negative for the predominant v617f mutation but positive for one of the rarer exon 12 mutations. This same genetic panel was used to diagnose me with PV exon 12 on a 2 week earlier blood sample - also initially denied but accepted upon appeal. As part of the BMB, a sample of the aspirate was tested for this 75 gene panel. Both the blood and the aspirate samples showed the JAK2 exon 12 mutation and a TET2 mutation and no other mutations. However, for exon 12 the Variant Allele Frequency (VAF) was 5% for blood while 35.3% for aspirate and for TET2 the VAF was 2.8% for blood while 1.3% for aspirate.
So in justifying this testing (not cheap) I am wondering if the aspirate sample is necessary and typical. Should it be the same as the blood sample? Is the VAF more accurate in the bone marrow than blood? Is there some standard of care for bone marrow biopsy procedures?
Experience people have in this is appreciated. Thanks so much for your input.
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gvibes
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That is a very large difference in the bone marrow vs blood for the JAKexon12 VAF. Others on the forum have made reference to there bein a difference in VAF from bone morrow and blood, but I have never seen any research on this topic. Since it is in the marrow that most blood is being made it would make sense that these levels might be higher. Not really sure about the data on this.
Successfully appealing the non-payment for the second round of NGS testing will depend on the plan rules for your insurance program. You will need to know these rules and apply the doctor's rationale for retesting to them. I have mounted multiple successful appeals using this approach.
Thanks hunter. I will look closer at the insurance rules- while every blood cell has genetic material, they must count multiple cells to get the percent mutated. I guess you could get a bias sample. I will look deeper.
Some companies have the plan rules posted on their website. With others you have to request them. Typically your doc can file the appeal(s) or you can. I have gone both ways, but sometimes find that i have more time to do the research to file a successful appeal.
My intention is that this comes from the docs letterhead - my guys a hematologist - non MPN and time constrained and obviously difficult to go to deep in this. Yeah I am better off doing the research (I'm retired) and get him to review and sign it.
Most of the time it does not matter whether it comes from the doc or from you. What matters is following the plan rules in filing the appeal. Most docs have a nurse or medical assistant write the appeals. They do not always have the time to research the rules, particularly if it is a more unusual situation. I have done it both ways, filing it myself and writing it for the doc's office.
Agree with Hunter on the large difference. Some reports have BM very close to PB (Peripheral Blood), others like this one comparing MPNs show BM giving higher results. I had Jak2 5 points higher on BMB.
<<JAK2 V617F for ET (21.71% for PB and 24.95% for BM) was significantly lower than that for PV (56.88% for PB...72.66% for BM), and PMF (56.16% for PB... 59.04%for BM...)
But your result for Jak2 has an extreme difference. This alone should be a good Ins Co justification for the extra testing. You want to have good data at Dx for reference in your future treatments.
It's also great you got nexgen, 75 genes is a lot, I had 54. This info is likely esp useful for future reference as knowledge increasingly can act on it.
Thanks EP Guy, I read the referenced paper. Techniques a little different for preparation of PB vs Bone marrow, not that I understood it very well. Were you able to gather what they theorize is the cause of the difference in their PB vs BMP results? Anything you've read portrays either allele burden of PB or BMB samples as more representative of real conditions?thanks for the help!
This is not your question, but related, in this old study, Exon 12 requires special methods to get good info.
<<the molecular diagnosis of mutations in exon 12 of the JAK2 gene is complicated by heterogeneity (too many different types) of the mutations and low allelic load.>>
<<More than 10 different sequence variations have been found in exon 12 of the JAK2 gene>>
This text in a newer study suggests there are many ways to measure allele, but is directed to the more common Exon 14
<<Recent molecular methods including ARMS PCR, PCR–RFLP and HRM are highly sensitive and have been used for detection of JAK2 exon 14 (V617F) mutation.>>
Most reports on this area are old, suggesting the science is relatively mature. There is a member here who has worked in this field, maybe we'll get more detailed comments. But my take is that: the place the sample comes from may matter less than how it is tested. And Exon 12 requires special attention for accurate results. So you will want the best qualified labs to get reliable results for your mutations.
Thanks. All interesting and it helps. One thing I didnt know was that low allele frequencies are common for exon 12 and apparently produce detectable disease - seems different than v617f. Always interesting to go a little deeper...
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