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Tuesday, March 6, 2012

Molecular Tests for MM

Since coming back from DFCI on Friday with a boat load of medicines, I spent the weekend mostly sleeping.  I couldn't figure out why I was so tired, but I thought perhaps the Ativan pills might be the culprit.  I started skipping some doses and found I had more energy, without experiencing any nausea.  I have been fortunate that I haven't been nauseous at all since getting the Cytoxan on Friday.  Today I am feeling more energetic.  I thought I was supposed to start feeling crappy this week from the Cytoxan, but so far I'm feeling pretty good.  I'll keep my fingers crossed.

Starting on Sunday, Gretchen has been doing her Florence Nightingale routine by stabbing, I mean injecting my stomach with two doses of Neupogen to stimulate stem cell growth.  She's really good at it, so it's no big deal.  We have to continue this every day until I go in for my stem cell harvest on March 13.

I am now onto a new research project.  Now that I have achieved a Complete Response (CR) to my treatment protocol (for which I am very grateful), I am curious about how to further classify my response in order to better understand my prospects for a long-term remission.  Since the blood and urine tests now show no evidence of the MM, the next level of testing is to look at the molecular level.
Increasingly sensitive analytic techniques are now available to define more stringent degrees of CR or elimination of minimal residual disease (MRD), including multiparameter flow cytometry and polymerase chain reaction (PCR).  Demonstrating eradication of MRD by these techniques has already been shown to predict for improved outcomes.

I asked Dr. Richardson last Friday about the PCR approach, and he said they don't use that method at DFCI, but rather rely on flow cytometry.  Flow cytometry is accurate to one part in ten thousand (one-hundredth of one percent), so that even very low levels of residual MM cells can be detected this way. This technique is particularly useful in prognosis after stem cell transplants.  Patients without MRD three months after the SCT have a much better long-term prognosis than those where MRD is detectable.

Without trying to get too technical about flow cytometry, the bone marrow biopsy aspirate samples are treated with several types of antigen molecules, denoted by their cell differential (CD) designations.  For MM, the cell-marker molecules CD19, CD38, CD45, CD56, and CD138 are often used.  These molecules will either adhere to healthy cells (positive) and not adhere to MM plasma cells (negative) or vice versa.  The treated bone marrow aspirate is then passed through the flow cytometer, which illuminates the flow with a laser, and the light-scattering characteristics are measured.  The resulting scatter diagrams can determine if there is any MRD.  MM cells will test positive for CD38 and CD56 and negative for CD19 and CD138.

I know that this analysis is useful for prognosis after ASCT, but I'm curious about what it might mean for me now.  My recent bone marrow biopsy pathology report had the following comments:  "Flow cytometric analysis of this bone marrow aspirate reveals a small population of plasma cells (positive for CD38 and CD56; negative for CD138 and CD19) that shows cytoplasmic kappa light chain excess."  The report concludes with the note: "Definitive features of involvement by a plasma cell neoplasm are not seen in the biopsy specimen, while the flow and aspirate findings raise the possibility of minimal persistent involvement."

OK, so I guess I may still have a little trace of MM left in my system.  My question is whether or not these trace cells will contaminate my stem cell collection, which might affect the efficacy of my ASCT.  I don't know why I'm asking you. I should be asking this of Dr. Richardson, but he's not here right now.  Anyway, it's probably useless to speculate.

By the way, I'm still not nauseous, although I suspect most of you are after having read the foregoing.

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