Friday, December 4, 2009

Tough Stuff Part 4, the last part for now

Maybe I am trying to read the tea leaves and what I am looking into is a mug with leftover coffee grains.

Not sure this makes all any sense. Last glance backward to put it all together for the future plan.

I developed ITP the first time when I had a significant tumor load. When the combination of cyclosporine A (CsA), an killer immunosuppressive drug, mostly used to prevent transplant rejection, and occasionally to calm down an over zealous immune system, and rituximab, a monoclonal antibody, Vitamin R, used for everything from CLL to rheumatoid arthritis and ITP, worked their magic and sent my platelets skyward, my celebration had just begun. The combo offered a surprise bonus no-one expected when it had a profound anti-leukemic effect, shrinking all my palpable nodes, and reducing the CLL in my marrow from 90% to 3%. Went on to transplant and the rest is history.

I am focusing on the ITP here. These two drugs work well on ITP for people who don't have leukemia, so it is completely logical, but far from certain, that the reduction of my tumor load was not the issue in controlling my ITP.

Here's where it gets tricky. True, my ITP was gone when my tumor burden was only 3%, but it was also gone when it had climbed to 25% after 4 months off the R, though still on CsA.

I was on CsA and IVig until just before the transplant.

With the heavy conditioning chemo (FCR) for the transplant, my tumor burden dropped even more, to MRD negative in the marrow with shrunken gut nodes. Eventually, the CLL creeped back, slowly and last August, when my platelets started to fall again, a bone marrow biopsy showed it had snuck back like a terrorist cells in the Swat valley, claiming 2.8% of the niches of my marrow. The nodes were growing slowly too.

So here's the way I see the relationship between my CLL and my ITP. A weakness of this analysis is that it only assesses the bone marrow and not the nodes, and the nodes have always taken the lead in my CLL dance.

1 year of CLL growth = no ITP

High tumor load (90%) = 1st episode of ITP

Reduced load (3%) = ITP controlled w CsA+R

Increased load (25%) = ITP still controlled w CsA and IVIG

Greatly reduced load (MRD-) = ITP still controlled post transplant & heavy FCR

Slight increase (2.8%) =ITP back gentler & controlled sorta with IVIG

The relationship is hardly lock stepped. Immune dysfunction does increase with the time with the disease, so the ITP may recur with less and less CLL induced immune chaos.

Dr Hamblin says if steroids fail, I should move to control the underlying disease that drives it. My concern is that I need to get a MRD neg,. remission, (and possibly shrink all the nodes, including the more provocative ones in the gut) to control the ITP. I worry that a simple PR ( partial remission) or even an old school CR (complete remission) will not accomplish the mission.

R+HDMP gives me an over 90% chance of a response , but the odds of a CR are much lower. and the odds of a CR, MRD negative without adding campath are even smaller.

Will that solve my ITP? A dear friend developed ITP after R+HDMP did a great job on her blood, nodes and marrow. She developed ITP, like me, with a very low tumor burden too.

The effects that are caused by all these drugs on the CD200+ and Tregs and who knows what else that play a vital role in self tolerance and thus prevention of ITP is beyond my understanding. I think it is fair to worry that not only might R+HDMP not get me over the finish line to MRD negative and thus control of the ITP, but could make matters worse.

Might it make my platelets situation critical and refractory again? Not likely.

Might it make things more difficult to move to the next more myelo-suppressive step? Quite possibly.

It still might be worth the risk to avoid the more toxic path of FRC and transplant, but I need to prepare for the Sabbath, and lay my burdens down for next 25 hours.



Blogger Unknown said...

Thoughts from the other side of the looking glass


I started to follow your blog after you announced your pending transplant in the comment section of PC’s transplant diary. I had just completed six cycles of CFAR and my extensive mesentery nodal mass had already started to grow again after just three months. Although there was still a lot of work to be done before I could consider transplant, I knew it would be my only chance for long-term survival. I wanted to get a look at what was likely to be in my future and to see what life might be like after transplant.

I am now about 250 days post-transplant. I was on an outpatient protocol and the first 100 days were fairly benign. I was never hospitalized. My first sign of GHVD was asymptomatic oral changes that started on day 80. I had a related donor. My cyclosporine taper was due to finish on day 140. The last week of the taper I developed GVHD of the skin and liver. In addition, my oral GVHD became symptomatic to the point where it was difficult to maintain my weight. The thought of eating was very unpleasant. Topical steroid cream and a steroid mouth rinse were not very effective. Fortunately, a gradual increase in the cyclosporine was able to control the symptoms. Just about the time I was ready to consider starting oral steroids, things started to turn around.

I have also had some difficulty tolerating the prophylactic antibiotics. Bactrium continues to wipe out my ANC. The second line combination of dapsone and penicillin has also wiped out my ANC. My ANC has now returned to an acceptable level so we will be trying a new combination over the next few weeks. With all this going on, as well as the recent peak in N1H1 activity, my exposure to other people has been very limited.

My point is that the majority of transplant patients require immune suppression for two years or even longer. As long as we are immune suppressed, it is difficult to fully develop a new immune system. On top of that, full immune reconstitution is questionable after age 50 due to involution of the thymus gland.

I was able to maintain my practice and was fairly free to travel during my watch and wait period (30 months) and my chemo period (21 months). So far I have been very lucky to have a mild post-transplant period with only a few bumps along the way. During my first 140 days post-transplant I envisioned a quick return to my past life. The last 110 days have shown me that it won’t be as easy as I once hoped. Although N1H1 is the current threat in the news, there are plenty of other pathogens that are just as harmful to a weak immune system.

I am thankful that I was able to get my nodal mass down to a manageable size so that the odds of a successful transplant were shifted more in my favor. I am also glad that I had enough fludarabine exposure (10 cycles) so that I had no question of graft rejection. In a way, I guess, I was lucky. My back was up against the wall and I had no other choice except transplant. I do not envy your position – being able to choose but only having a vague idea of what might be the best option. If it would help, I would be glad to share my carepages site to fill you in on the details of my clinical course. Also, I would be happy to listen, if it would help you sort things out. You can contact me via e-mail if it you think it might help.

Best wishes,
Steven Karan

December 4, 2009 at 10:25 PM  
Blogger Unknown said...

The question of R+HDMP obtaining a CR+MRD seems central to your current thoughts. So could you not quantify this particular number more? For example if this has proven an infrequent outcome then the value of this approach may not be there (based on the analysis) and you then have a simpler decision to undertake the myelo - suppressive treatment option leading to the transplant. Put another way trust the central theme of your analysis and get expert opinions on specific points.


December 4, 2009 at 10:25 PM  
Blogger Brian Koffman said...

Steven Karan,

I would very much like to connect and share war stories, but I have no way to contact you other than here, but you can email me at Look forward to it.

Often hear the complaint after a transplant that you are trading one disease for another, and this is not what was bargained for. Tragically true for some, mild and annoying for others. Drop me an email.

Be well



The published data from Castro showed a 1 in 3 chance of a CR and a 1/3 chance that would be MRD negative. Only 3 patients had 11q del and 1 got a CR, MRD + I assume. I have other issues with HDMP+R as I mentioned. Do stay in touch, good to hear from a fellow Canadian raw foodie.

Raw food and neutropenia is a no go combo, and so you may need to be flexible,

Be well


December 4, 2009 at 11:27 PM  

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