Saturday, February 26, 2011

Rituxan, Flu and a Spike in Counts too ...

I've been holding off this post until I had enough new data to share to make it worthwhile, but  I didn't realize I'd get the flu while I was waiting.  Between treatments 6 and 7, I got hit hard with influenza B.  No doubt my youngest brought it home from daycare.  The youngest had a mild fever two days before I came down with it.  Fortunately, everyone (including myself) had been vaccinated earlier in the season, but since I've anihilated my B-cells, there wasn't much benefit left from the vaccine.  I started feeling aches on that Saturday, but it didn't hit hard until Superbowl Sunday.  I got in bed around 10 am, couldn't really move and stopped drinking enough fluids.  Once my fever spiked to 102 around 3 pm, I called the NIH day hospital, and they asked me to come in.

I got to Bethesda around 4:30 pm.  My fever went up and down between 98 and 103 several times while there.  They ran CBC, chemistry and cultures and hooked me up to an IV.  4 hours, 3 bags of saline and a digital X-ray later, I was good to go with Tamiflu and Tylenol in hand.  The next morning at 6 am, I started sweating profusely on my upper body.  At 7 am, I was awake enough to take off my T-shirt, which I could have rung out to get a couple cups of water in a bucket.  I continued to have roller coaster fevers for the remainder of the day, but my temperature finally recovered later that evening, and I was able to go back to NIH the next day (Tuesday) to receive treatment #7.





Needless to say, my counts spiked as shown above. On the plus side, I had a normal WBC for the first time since collecting counts.  Same with the platelets.  I'm hoping the short term boost may have benefited my ADCC response to the Rituxan treatments too. It can't hurt to have all those extra neutrophils and monocytes available to recognize and target the hairy cells...

Lots of HCL patients have anecdotally commented that when they got viral infections, their counts improved for awhile; however, my response was short-lived and only lasted as long as the viral infection.  One exception -- my platelets seem to have gotten a significant and more durable boost, and are at the best level I've ever measured. Hopefully, that's a sign of good things to come.

I've got lots more to add to this post, including another potential treatment that uses a protein known as CD-19L, found on T cells, to kill leukemia cells that express CD19.  Scientists have now bioengineered CD19-L in a solution without T-cells and shown it to kill ALL cells in vitro.  Since hairy cells express CD19 too, I'm hoping CD19-L will bind to and destroy them.  Hopefully, this bioengineered protein will continue to be developed and result in treatments for ALL and possibly HCL too.

I've been studying somatic hypermutation (SHM) associated with the variable heavy-chain region of B-cell immunoglobulins and wondering if the random production of Ig antibody is somehow associated with HCL mutations.  This has led me to postulate some new theories on the cause of HCL.  I think HCL may be caused by RNA cytosine nucleoside exposure to sunlight that results in deamination of cytosine to uracil.  Next thing you know, the alteration causes a protein to fold improperly, chromosomes mix with the wrong crowd, locks get picked with mutated keys and genes start translocating all over the place.  Before you know it, you've got just the right random blend of mishaps and a self-sustaining HCL mutation on your hands.

Dr. John Sutherland, a Professor of Organic Chemistry at the University of Manchester, England has recently shown that RNA may be the starting point for life and that sunlight alone can deaminate cytosine in RNA to uracil.  This was discussed on a recent episode of NOVA Science Now.  I wonder if sunburn inflammation and UVA/UVB exposure as some B-cells divert through capillaries on their way from the marrow to the germinal centers could cause hairy cell leukemia mutations?  Hairy cellers are generally active, outdoor-types and tend to engage in activities that can result in excessive sun exposure.  White males with fair traits have the greatest incidence of classic HCL.  Likewise, HCLers have a higher incidence of basal cell carcinoma (BCC), another disease associated with people with fair traits and excess sun exposure.

      My HCL recipe:
          Ingredients:
               one part genetic disposition (fair trait genes)
                age
                excessive UVA/UVB or sunburn (or maybe high frequency RF since electrical engineers have 8x more incidence than most people)
           Directions:
                 Mix well until random RNA cytosine deamination causes a protein production train wreck and HCL-related gene translocations. 

Perhaps patients that have a durable remission beyond 15 years but then relapse aren't really relapsing, but instead have a new HCL mutation caused again by excessive sun exposure.  Sequencing and comparing the patients' HCL DNA at initial diagnosis and the later onset would determine if the relapse is a clone of the original occurence or derived from a new progenitor.

I wonder if the difficulty in sequencing my hairy cell DNA and generating a PCR primer might be due to an unusually rare cytosine deamination to uracil in my DNA (rather than RNA) that the DNA repair enzyme somehow freakishly failed to catch and repair.  I'm hoping they make some progress soon and can tell me what's different about my sequence.  Regardless, I'm exceedingly grateful for the opportunity to participate in the NIH clinical trial, and all the effort and help Dr. Kreitman and his staff have put into helping me.

Now that I've completed all the treatment provided by this trial, I'm in the watchful waiting stage -- anxiously looking forward to my next bone marrow biopsy and aspiration in June.  Hopefully this time, I'll be negative for hairies on all three tests -- peripheral blood, bone marrow and aspirate.

Wish me luck!

No comments:

Post a Comment