A difficult week

Just as her hospital stay was beginning, Elizabeth began to develop new symptoms of gastro-intestinal distress -- first reduced appetite, then nausea and vomiting and finally diarrhea. Although these were similar to the symptoms a couple of months ago that were determined to be GVHD, the docs are still unclear if this is the cause now or something else. Although the nausea/vomiting has pretty much disappeaed, the diarrhea remains and is making life entirely miserable for her. Se is being treated for several possible causes including GVHD (steroids again) and infection (antibiotics). Both the illness and the treatments make her very weak and tired, barely able to get out of bed. To ice the cake, she has now developed a severe hoarseness that makes it hard and eventually painful to talk much. She will get a colonoscopy Monday to take biopsies which will determine definitively whether or not it is GVHD. She is still unable to take more than a clear-liquid diet. In addition to all the meds, she has had several infusions of platelets and is due for some red blood cells; at one time there were 5 IV pumps running at one time.

This is all, of course, a sideshow to the main event of trying to treat the relapsed leukemia. The first part of this proceeded uneventfully -- as expected the anti-survivin drug (which almost universally the staff refer to as "survivin", a logical fallacy painful to my logician soul) had no observable side effects -- well probably not. The troubling point that developed over the period, although it is not thought to be due to the drug, was a big spike in her liver enzymes. There seem to be no good theories what caused this, but it was bad enough yesterday that the planned start of the chemotherapy sequence was put on hold. Fortunately (one of the few bits of good news this week) they were down substantially today and they have as I write started the chemotherapy. We have now to hope that the liver problems stay fixed at least long enough to complete the 3 days of chemo.

Admission

Elizabeth was admitted on Monday afternoon. Her room is 8431 (unit 8B) with phone 734-936-8431.

She is currently undergoing some tests preparatory to the procedure -- some are for her benefit, some for the research study. She is scheduled to get the experimental drug (imaginatively called LY2181308) tomorrow through Friday, then get chemo Friday-Sunday. According to a press release

LY2181308 targets survivin, a molecule that supports the survival of cells that would normally die through programmed cell death or apoptosis. Survivin helps in the abnormal growth of cancer cells, and is abundant in many types of cancers, including colon, brain, lung, skin and others, but nearly nonexistent in normal cells and tissues.

Phase 1 trials have shown that survivin is indeed reduced by the treatment, but these are the first trials that test whether this decrease will really lead to increased effectiveness of the following chemotherapy. Stay tuned.

Another way forward

After consultation with the hematologist Harry Erba that we saw at the beginning of this process, Elizabeth (with my full agreement) has decided to undertake another round of chemotherapy. This will involve two of the same agents she received in the first two rounds, idarubicin and cytarabine, but also a brand new experimental drug. The experimental drug is intended to reduce the ability of the leukemia cells to develop resistance to being killed by the chemo, a common problem in the treatment of recurring leukemia. There is essentially no data on this drug -- this is a phase 2 clinical trial -- but there seems to be little risk and it might do some good. The chemo portion is the standard chemo they would use for relapsed AML. Depending on the outcome of the chemo we will then decide where to go from there. It is still possible that she might get a second transplant preceded by a less rigorous and more survivable conditioning, but the more we read from the literature it seems that there is little evidence that second transplants are successful.

The chemo must be done as an inpatient, so she will probably be admitted to the hospital again early next week. The predicted stay is 3-4 weeks, but of course it all depends on how things go. Because of the presence of the transplanted donor cells, with the accompanying graft-versus-host disease, chemo at this stage is considerably different from the earlier ones and perhaps less predictable. She is already showing quite noticeable effects of graft vs host disease, which means the donor cells should attack the leukemic cells along with the chemotherapy.

Note that I have changed the photo link at the top right -- in place of just a couple of albums, I now have a link to a new gallery with many of my photos from the past several years. If you have some browsing time, have a look.

A Major Setback

We found out on Friday that Elizabeth's leukemia has returned. This was surprising since both the 30 and 100 day tests showed that her marrow cells were 100% donor with none of her old leukemic cells showing up. But somehow there were some of hers left and they have done what they do and multiplied quickly to the point that they now dominate the marrow. This is regarded as very bad with a poor prognosis. We talked with two doctors today and hope to meet with a third in the next couple of days. As we understand it now there are basically two options.

1. Apply palliative care to contain the leukemic cells for a short time (a few months at most) to enable a more comfortable end of life. This might or might not enable us to spend some time away in some interesting and fun place to enjoy our last time together -- it would depend on what the palliative care involved, information we are currently lacking.

2. Give aggressive chemotherapy, stronger than any she has had to date, followed by a second marrow transplant. The original donor cells were roughly double the amount they wanted to infuse for the first transplant, so an equivalent amount was frozen to hold for such an occasion. There is considerable opinion that the chemotherapy itself might be too much for her body to endure -- organ failures are common, especially among people her age and those who have already suffered some organ injury as she has with the liver reactions to massive antibiotics to fight an earlier infection. If she survived the chemo and transplant, it would still be expected that she would have multiple problems over many months, perhaps a year, some of which could kill her then.

Obviously neither option is remotely appealing, but it seems to be where we are now. It is very disappointing, since we were beginning to allow ourselves to think that we were past the worst of the process, but it seems that is still to come. We are still looking for a few more pieces of information, such as the actual data on survival rates for option 2. The doctor reasonably wants us to make a decision over the next week.

Home again

The CMV level did indeed fall below 600 so Elizabeth was discharged and is once again at home. Her main challenge now is recovering muscle strength and tone which hopefully will reduce and eventually eliminate the back pain. Now we start back on a rigorous series of outpatient visits starting with Lab work and a possible platelet transfusion Sunday morning at 8 AM. The doctors aren't quite sure why her platelet level continues to fall after each transfusion but have several theories. To test one they have tentatively scheduled another marrow biopsy for Thursday to see if the CMV has actually lodged in the marrow and is inhibiting platelet production.

A little longer

Sadly, the CMV level came back just above the magic 600 mark so they want to keep Elizabeth in the hospital to continue the double Foscarnet treatment for another few days until the next test on Thursday. We expect that this will mean that she will come home on Friday or (more likely) Saturday. Since there has been no resurgence of the GVHD -- her appetite and digestion have been fine -- they continue to taper the steroids and are terminating one drug (Enbrel) that she has been getting for 6 weeks.

We are coming to understand (at least I am) that the back problems are part of a larger syndrome of general muscle weakening brought on by the high-dose steroid treatments. The physical therapy people she has been seeing believe that the support muscles in the back have been so weakened that they don't support her back properly. Furthermore, she seems very weak all over and this is a standard result of steroid treatment. So the therapy is exercise to build the muscles back up. This will probably take a long time, but at least we have a direction. But it leaves her feeling much less well than she really is otherwise.

Some progress

The reason for this hospitalization was the surge in Elizabeth's CMV levels to over 9000 (whatever the units are). This is now being well-controlled with the drug Foscarnet; CMV levels were down to around 850 at last sampling on Thursday. She should be discharged when they get down to less than 600, which they regard as undetectable, and will continue on a reduced dose of IV Foscarnet at home. The steroids that were introduced to treat the GVHD are being steadily scaled back with no apparent ill effect. This will also help with the CMV control.

So in a sense all is well on the main front. But the back pain is continuing unabated and is really the main current problem. She finally got a CT scan of her back on Wednesday. This showed nothing terribly abnormal in the spine and provided not much in the way of suggestions for how to treat the problem. She gets very stiff and can barely walk. She is doing exercises to stretch and develop the muscles in the back, but it is so far not improving much. There seems not much more to do for the time being.