Tuesday, February 26, 2008

GvHD Update

The GvHD on the feet and the hands have cleared up quite a bit, but not gone by a long shot, especially on the palms of my hands. My big problem now, though, is GvHD in the mouth, yep, the mouth. So I'm on soft food for now and a steriod mouth wash. The mouth problem set in over the weekend. But, it''s a little better today.

Today was the last of the four days of dexamethasone, but Hosing wants me to start tomorrow on 32 mg of Medrol. I'll do that for two or three days and taper down to 16 mg for a few days and then down to 8 mg and maintain until I see her again the week of the 10th.

So, that's the plan. Oral and topical steroids for awhile and see what happens. Call Dr. Hosing and let her know how it goes. If the GvHD gets worse we'll have to go up on the tacrolimus and maybe the Medrol. I want to keep the oral steroids down to a minimum, although they also help keep the lymph nodes down temporarily. The point is to go into the Sunesis study in pretty good shape with a low tumor load. Ahh, the process.

Saturday, February 23, 2008

Home Again

Yes, we did indeed get home Wednesday afternoon. It is very nice to be home after almost four months.

Dr. Hosing wanted to see me before I went home because she had the same concern as Dr. Tam about a GvHD flare up just after chemo. It didn't take long after the end of the chemo before the GvHD showed up. By Wednesday morning, when I saw Dr. Hosing, it was on the bottoms of my feet and on the palms of my hands. But she let me go home anyway, especially since a second (and last) round of the steroid, dexamethasone (dex for short) was to start on Saturday as the last part of the chemo protocol. Unfortunately, the GvHD got a lot worse very quickly. By Thursday the GvHD was so bad on the bottoms of my feet that I could hardly walk. Friday was worse. But the second round of dexamethasone started this morning. Dr. Hosing's plan Wednesday was to keep applying the topical steroid cream to the affected areas and wait it out until the dex started Saturday. I thought it would take two days worth of dex before it kicked in. Fortunately, it kicked in quickly. So now, Saturday evening, my feet and hands are a lot better.

This second round of dexamethasone lasts four days. So I wonder if the GvHD will flare up again after the dex is over. But Dr. Hosing gave me a plan if that happens. Back to the steroid Medrol, but at a low dose and tapering off quickly. She didn't want to do that this week and interfere with the chemo protocol, so I just had to tough it out.

So, the process continues. But it sure is nice to be home.

Tuesday, February 19, 2008

Chemo Complete

I got done with four days of continuous chemotherapy, Hyper CVAD part A, Sunday night at 9:00. I've been a couch potato ever since. It really wiped out my energy level. Hopefully, I'll get a little energy back tomorrow.

The chemo did shrink the nodes substantially. The big node under my right arm is still somewhat evident, but it's very soft and smaller. I hope that they continue to shrink.

I come back the week of March 10 to start the Sunesis study. We want the nodes to stay down until we can get the Sunesis drug started. I'm going to be in a fourth group of the Phase I study. Usually they just do three groups, or cohorts as they call them. They are already at a therapeutic level, meaning the drug works, with the three cohort groups. And that's with little or no side effects apparently. So what are they going to do? Up the dosage to see if they get any side effects, that's what. I don't know if that makes me feel good or not. But at least I'll get more of the drug and I think more is better.

In the meantime, Dr. Keating says I can go home for a couple of weeks. I'll see Dr. Hosing tomorrow morning. I think she'll let me go home, too. So we plan on being home tomorrow afternoon.

Dr. Tam had some concern that the chemo might stir up some GvHD. Sure enough, he was correct. I've had a little skin GvHD, so I'm applying the topical steroid cream. So far it's under control, but somewhat active. As part of the chemo I get four days of dexamethasone, another steroid, starting Saturday. That will help the GvHD, but I don't know if it will come back when I'm through with the dexamethasone.

So I didn't make it home within the proverbial 100 days, but it's close. 103 days to be exact if we are able to leave Wednesday.

See you soon. Actually I can't have much company until my counts come back. The chemo beats down the white counts, so I'm more susceptible to catching bugs, which, of course, can be deadly. Gotta be careful.

Thursday, February 14, 2008

Triple Option Offense

Just seems like an appropriate analogy given Tech's new head football coach and his vaunted triple option.

We are proceeding as expected and as I discussed in my last post.

I have a successful transplant, but the insidious Richter's Transformation form of diffuse large B cell lymphoma (DBCL) has long since escaped the reaches of the new marrow and blood. Eventually, the theory is that the graft would could catch up with it. After all, the lymph system is part of the immune system and goes hand-in-hand with the marrow and blood. But the DBCL is very aggressive and fast growing, so it will stay well ahead of the graft's ability to catch it. There is no known long term or even medium term cure for DBCL using chemotherapy. But it is possible to kill the disease in the nodes for four to six weeks.

So, first of all, we need a short term solution to get the tumor load of the nodes down. Then we need a medium term solution - which could actually become a longer term solution if this next step works out. This medium term solution is the Sunesis drug that I have talked about. It actually doesn't have a name yet, but goes by SNS 032 in the clinical trials. It is not a conventional chemotherapy, but rather is a kinases inhibitor. It attaches to DBCL cells, prevents them from progressing, and causes them to die off as they should (apoptosis). See the following website for a little better description http://www.sunesis.com/science/oncology/MOA032.php

So the plan, which has already started with chemo as of yesterday evening, is to temporarily kill the disease already very active in the lymph nodes. We are doing this with a strong chemo regimen that goes by the cryptic name of Hyper CVAD, part A. I have had this before in the summer of 2006 and it's not too bad. Now part B is a different story; it pretty much kicked my buns and my bone marrow, too, last summer. But we're hoping part A will do the trick and we won't have to go to part B. If this goes to plan the disease will be in temporary remission for four weeks or so.

Then we will start the SNS 032 study. The protocol for this study requires that you be off all chemo and monoclocal antibodies (MAB's) for at least three weeks. So if Hyper CVAD does the trick for four weeks then we can start the SNS 032 study before the DBCL starts to roar back. That timing might be a little tricky because each time you kill back the DBCL you are actually just killing the weaker members of the colony, so each time it comes back it will be with the stronger members of the colony coming back which will just be that much more aggressive.

The SNS 032 protocol is for a six hour once a week infusion for four weeks. Then you wait and see. Seems like we do a lot of that here. The Hyper CVAD/A is a five day continuous regimen so I will be done with that Sunday evening.

I'm not sure what the expected remission time might be with SNS 032. They don't know either. Hence the clinical trials to see just that.

I will be in a late Phase I group or early Phase II group. Either way the maximum tolerated dosage will already be determined. I would hate to be in an early Phase I group because the chances of it doing you any good at the minimum dose would have to be slim.

In the meantime, if we don't damage the graft too badly with the chemo it might acually have a chance to join in the fray. Ultimately we have to depend on the graft to be the permanent solution, but the Sunesis drug might also turn out to be a long term treatment.

Now for a little primer on clinical studies plus a little political commentary. The way clinical trials work is that after the mice, rats, and other varmints are experimented upon, they move to the two legged varmints. Phase I trials are mainly seeking the maximum tolerated dose by humans, the two legged varmints. They are performed on small groups of humans starting with the minimum dose. Then they progress to another group using a larger dose. They repeat several times while increasing the dose each time. At some point they reach the maximum dose and further prove some efficacy of the drug as well. The next step is a Phase II trial where the drug, at the maximum tolerated dose, is given to a much larger group of people to test the percentage and degree of response on a more statistically valid number of people. After that they move to Phase III using an even larger group of people while testing the drug using placebos in some of the participants. After successful Phase III testing it goes to the FDA for approval.

As you might can imagine, development of new drugs is a multiple year process requiring the expenditure of vast resources by the drug companies. So don't complain about the cost of medicine too much. We have the best medical care in the world because it is free market based. Socialized medicine does not support this kind of development. A vote for socialized medicine will be a vote for poorer medical care in the future. There are ways to increase the number of people insured in this country without adopting socialized medicine, so don't be duped by politicians who want to be all things to all people - it can and will blow up on all of us.

About half, I guess, of the doctors at MD are not from the U.S. As Dr. Keating said, he would rather live in his native Australia but he can't pursue his work there. Google Michael Keating and you will find that he is arguably the best CLL doctor in the world and could practice anywhere he wanted. Dr. Tam, his very sharp Aussie assistant, has just moved back to Australia because his visa expired and our tightened immigration laws don't allow for exceptions anymore. My bone marrow doctor is Indian. This is very real. We are benefiting from our system that attracts the best talent in the world. Adopt socialized medicine and much of this talent won't stay here. A word to the wise from someone who is in the thick of it.

Thursday, February 07, 2008

Day 90

Thanks for all the comments. I love reading them. Anna, do you really think I could be an Austin resident? I would love to and I've never been there before.

Anna's husband, John, is going through a difficult time right now and is back on G11 for treatment of pneumonia and a fungal (maybe) infection in the brain. Anna is, of course, going through it with him, and I'm sure it is rough on her too. John and Anna are real troopers and have been an inspiration to me. So please add them to your prayer list.

A friend of mine from my old TEC group is here having undergone treatment and surgery for a rare GI tumor. Then this afternoon they called him in for a thyroid biopsy and found he has thryroid cancer, too. Fortunately, the prognosis is good for both.

So I'm not alone on my roller coaster ride.

I saw Dr. Hosing today in clinic. She said I could go home after scans next week as far as the transplant department is concerned. We still have the problem with the nodes, though. But we're working on getting on the Sunesis study. I have to talk with Dr. Tam tomorrow. I might have to have some chemo to shrink the nodes real quick. We have to keep the tumor load down so that the graft has a chance to work its GvL magic on the disease. Dr. Hosing said that the graft can still defeat the disease but we have to keep the tumor load down, otherwise the lymphoma will grow faster than the graft can work.

Hopefully, I can get on the Sunesis study and the "drug" will be effective. Theoretically, it could cure the disease by itself. That's still something of a long shot given the experimental nature of the study. But I'm looking forward to trying it.

More later after I talk to Tam or Keating.

Monday, February 04, 2008

Well That Didn't Take Long

In my last post I said that we would see how the nodes did when the Medrol was reduced and the Rituxan wore off. Well the nodes are back. The big one under my right arm popped up Sunday morning.

We saw Dr. Tam in the leukemia department this morning. We had already plotted our plans B & C, so we explored those at more length this morning.

We are going to start on a drug by Sunesis Pharmaceuticals. It doesn't even have a name yet, just a number, SNS 032. I thought I would be in one of the phase I studies where they are just trying to determine what dosage might work - pretty experimental. But we found out this morning that they have now moved into Phase II studies. That is good news because it means that they know the effective dose. Phase II studies test the efficacy of the drug on a larger sample of guinea pigs, er, I mean people.

This drug is different than what I've had before. It blocks the pathway for the development of more disease and increases the death rate (called apoptosis) of the diseased cells. So it's not just more of the same old stuff that never worked for me anyway.

I have a successful transplant. But the problem is that the transformed disease is already in the lymph nodes. Given enough time the graft would probably act on the lymph nodes, but we may not have the luxury of that much time. Plus we have muzzled the graft cells after we induced GvHD. Now we are slowly taking the muzzle off again while trying to find the right level of Tacrolimus (anti rejection drug and muzzle) and taper off the Medrol. We want to be completely off the steroid Medrol and maintain the Tacro level right on the line between having GvHD and not having it. We're still a few weeks away from finding just that right place. Dr. Tam would like for us to tolerate some GvHD in order to get more GvL, but a rip roaring case of GvHD can be deadlier a lot quicker than the lymphoma.

So here we sit, betwixt and between. It will be three more weeks before we can start the Sunesis study. I'm really ready to get home. The transplant doctor has okayed me to go home at the end of next week but that all depends.