18 replies to this topic

[CMLParent]

For those that have received a transplant could you share your experiences with PCR detection in the first year post transplant and beyond. When if ever did you achieve sustained PCRU?

[Trey]

There are a couple folks who may reply, but not many.  Here is some information while you wait for replies.

 

Under optimal circumstances, a transplant (BMT) should hopefully result in complete removal and re-initiation of the blood making system with the donor cells taking over, and all old blood cells destroyed.  That destruction of the old blood making system is by harsh chemo and radiation, which may or may not completely wipe out the old system since the high level stem cells are very adept at survival.  CML is the most difficult type of leukemia to completely eradicate because it is started and maintained very high in the blood making stem cell hierarchy.  When donor cells are introduced they can sometimes finish the job, as the donor cells will normally attack the old blood cells (especially if not a highly matched donor).  If the blood making system is totally replaced there will never be a positive PCR post-BMT.

 

When there is a positve PCR post-BMT, sometimes a re-infusion of original donor cells called a "donor leukocyte infusion" (DLI) can energize the new blood system to destroy all remaining old blood cells (sort of like a booster shot).  If that happens, the PCR becomes negative and stays negative without TKI drugs. 

 

If the DLI does not work, sometimes there can be a mixed chimerism (both old and new blood making systems working side by side) where the old cells are still partially leukemic, so TKI drugs are needed.  Also, the BMT can sometimes fail, so the old blood making system remains in place, so TKI drugs are needed.  These situations apply to the question you have asked.  There is not a single answer regarding timing of PCR positivity.  For mixed chimerism it mainly depends on the percentages of mixed lineage cells, but a positive PCR could be seen within a year or so for mixed chimerism, but it also could be a couple years.  For a failed BMT, the positive PCR should be seen quickly, probably within months. 

 

So as you can see, there is not an easy answer since it depends on the outcome of the BMT.

[Gail's]

Trey, is it true that even if pcr positive after bmt, the disease may be easier to control with TKI therapy than before bmt?

[Trey]

Neither true nor untrue.  Depends on which cell lines survive.

Edited by Trey, 27 June 2016 - 10:26 AM.

[r06ue1]

With a cure coming in the near future, I would only consider a transplant if I were in blast phase.

[Trey]

The child is in Blast Phase, so BMT is very likely necessary.

[CMLParent]

The child is in Blast Phase, so BMT is very likely necessary.

Hi Trey. He presented in blast crisis almost one year ago and was quickly returned to a second chronic phase during PH+ ALL treatment + imatinib induction. From there he prepped for transplant. Currently his PCR hovers between undetectable and low level. Last recorded PCR was .0002%. He is day +180

[Trey]

So did he already have the transplant?

[CMLParent]

So did he already have the transplant?

Yes. He is day +180

[Trey]

OK then, does he have mixed chimerism?  If so, what percentage?

[CMLParent]

OK then, does he have mixed chimerism? If so, what percentage?

No. All donor to the limits of the test.

[Trey]

There are two possibilities.  One is a false positive PCR.  The other is he actually has mixed chimerism but it is not detected.  I do not believe he could actually be 100% donor blood cells and still have the same CML he previously had.

[CMLParent]

There are two possibilities.  One is a false positive PCR.  The other is he actually has mixed chimerism but it is not detected.  I do not believe he could actually be 100% donor blood cells and still have the same CML he previously had.

Yes the sensitivity of the chimerism (at least at our insitution) is significantly lower than the PCR for BCR ABL so undoubtedly there is a population of host cells. He is just coming off immunosuppressants completely now. Detection is not uncommon post transplant in our population so my hope was to find some adults that have been transplanted and could share their PCR data post transplant. 

 

Trey - What is the predominant PCR sensitivity that you have seen? .001%? or .0001%?

[Trey]

Nearly all PCR equipment and the associated reagents (chemicals) are sensitive to -5 or -6 log (.001% or .0001% using IS conversion).  But at some point the false positives become unacceptable, and it is matter of debate where that occurs.  So various labs cut off PCR positivity reporting anywhere from -4 log to -6 log, with most cutting off at -4.5 log. 

 

There are two types of mixed chimerism.  One occurs as the donor cells are fighting and killing off the remaining host blood cells in the process of going to 100% donor cell blood.  The other type is where the donor cells are unable to kill off all remaining host blood cells and either find a point of mix chimerism which remains stable, or the host blood cells are regaining control and can eventually win out (i.e., the CML is returning).  You are asking what experience people have had to determine which is occurring, and I wish you had some responses but those folks often drop out of the LLS Board.  I would say the PCR status varies by individual, so I would wait and see what the PCR does over time. 

 

Is he taking Gleevec post-transplant?

[gerry]

There is one CMLer on the transplant forum at the moment. Their last update was in April this year. Thread starts with the title 100 days.

[CMLParent]

Nearly all PCR equipment and the associated reagents (chemicals) are sensitive to -5 or -6 log (.001% or .0001% using IS conversion). But at some point the false positives become unacceptable, and it is matter of debate where that occurs. So various labs cut off PCR positivity reporting anywhere from -4 log to -6 log, with most cutting off at -4.5 log.

There are two types of mixed chimerism. One occurs as the donor cells are fighting and killing off the remaining host blood cells in the process of going to 100% donor cell blood. The other type is where the donor cells are unable to kill off all remaining host blood cells and either find a point of mix chimerism which remains stable, or the host blood cells are regaining control and can eventually win out (i.e., the CML is returning). You are asking what experience people have had to determine which is occurring, and I wish you had some responses but those folks often drop out of the LLS Board. I would say the PCR status varies by individual, so I would wait and see what the PCR does over time.

Is he taking Gleevec post-transplant?

Thanks for all your input Trey. He is currently taking Dasatinib.

[Trey]

Recent article on use of TKIs post transplant:

https://www.cml-foun...ln-guidelines-3

[CMLParent]

Thank you Trey. Encouraging data. On the cessation trials what is the criteria to stop TKIs? I wonder if that would be a guideline to think about when we stop TKIs. There isn't a consensus on exactly when to stop post transplant. Our center does 2 years post transplant. But it seems to me it should be more associated with performance much like the cessation trials. BTW we were PCRU at MR 6 on the last test. One data point but pleased it isn't going in the other direction.

[Trey]

You should be very encouraged by the latest PCR.  Very nice news. 

 

Cessation has not been applied to post transplant in any scientific way, so it is all individual decisions.  But I would be inclined to use a hybrid approach such as PCRU plus 1 year minimum, then decrease dosage to half or lower for a couple years, then stop.  There are other possibilities for such a young child that I might be inclined to use, namely switch TKIs every so often to "trade around" side effects on his growing body.  If a certain TKI has growth inhibiting side effects it might be useful to change drugs every few months.  This is entirely an "invention" out of my own head and you would be hard pressed to find an Onc willing to support this approach.  But for a child the TKI drugs can have more of an impact on their fast growing cells, which grow much faster than adults.  TKI drugs target fast growing cells, and a child is nearly 100% fast growers.