After the memorial

The memorial was held as scheduled on Saturday 10 October. I estimate 100-150 people attended. Although I had some hand in the planning and execution, the great majority of the organizational work was done by Huda Akil and her staff at MBNI: Ruth Friedman, Doug Smith and Tom Dixon. We all owe them great thanks and appreciation for all that they did to make the memorial a significant and memorable event.

I have posted new links to an enlarged set of photos of Elizabeth and things she loved as well as some photos of the memorial itself. The latter were taken by my son-in-law Todd McDermott and selected and edited by me.

I want to remind you that anyone who would like to make a contribution in Elizabeth's honor may contribute to the fund created to establish The Elizabeth A. Young Lectureship on Stress and Mood Disorders at the University of Michigan. Donations to the Fund can be sent to MBNI, 205 Zina Pitcher Place, Ann Arbor, MI 48109. Att: R. Freedman.

Memorial Details

The memorial will be held Saturday 10 October from 1-5 PM at the UM Museum of Art. This is located on State Street on Central Campus across from the Michigan Union. There will be a program of 1 and 1/2 to 2 hours followed by a reception. Some speakers will be scheduled, and there will be a period when anyone is welcome to make brief remarks. If you are coming from out of town and need accommodations, see the list of hotels in the previous post. Let me know (pgh@umich.edu) if you need help.

I am planning a slideshow of digital photos of Elizabeth and the things that she loved. If you have photos you would like to contribute to this, please Email me full-resolution versions, since they will be projected on a large screen.

Memorial

We have decided to hold a memorial gathering on Saturday October 10. This will be mainly personal remembrances of family, friends and colleagues with a more formal scientific conference to be organized later, perhaps in the Spring. Everyone is welcome. More details will be announced here as they develop, but I wanted to announce the date as soon as possible for planning.

For those of you from out of town who want to come, we have gathered some hotel information. The first two are in the campus area, the other two at Briarwood, a shopping mall a few miles from campus.

Campus Inn 734-769-2200: Only a few rooms at $184 single and some deluxe rooms at $214. More may open up in a week or so.

Bell Tower 734-769-3010: Only a few rooms available on October 9, more of the 10th. $165 single.

Holiday Inn Express 800-345-8082: $98 with rooms available

Kensington Court 734-761-7800: $119 with availability

An obituary has appeared today in the New York Times and will be repeated on Sunday. It can also be seen online. There is also a notice on the webpage of ISPNE, one of the many professional organizations in which Elizabeth was active

Obituary

Dr. Elizabeth Young, Professor of Psychiatry and Senior Research Professor at the Molecular and Behavioral Neuroscience Institute (MBNI) at the University of Michigan passed away on September 1, 2009 after a yearlong battle with leukemia. She was 59 years old.

Dr. Young was an internationally renowned biological psychiatrist who conducted seminal work on stress biology and its role in severe depression and other mood disorders.

Elizabeth was raised in the Detroit and Chicago area, earned her medical degree from the Ohio State University in 1976, and completed her residency in Psychiatry at the same institution in 1979.

Elizabeth came to the University of Michigan Medical School in July 1979 as a research fellow in the Department of Psychiatry. In 1981 she received a postdoctoral fellowship to work in the laboratories of Drs. Huda Akil and Stanley Watson at the Molecular and Behavioral Neuroscience Institute (MBNI). She went on to join the faculty of the MBNI and Psychiatry where she moved through the ranks to the senior positions she occupied at the time of her death.

Dr. Young was the quintessential translational physician scientist—a role she fashioned for herself before its critical importance was widely appreciated. Early in her career, she conducted fundamental research on the biology of endorphins and on the regulation of the hypothalamo-pituitary-adrenal axis by stress. Simultaneously, she undertook groundbreaking studies on the dysregulation of the stress system in major depression. Elizabeth posited that abnormal responsiveness to stress is not only a consequence of depression but may be part and parcel of the pathophysiology of mood disorders. She was fully aware of the intricacies of the stress system at the molecular, brain circuit, and neuroendocrine levels. Therefore, she realized that there were many points of vulnerability where the system could be disrupted, but also many approaches to resetting its intricate balance. It is because of these unique insights that she spent a significant portion of her career devising novel strategies to challenge the stress system and examine its responses in normal subjects and patients with mood disorders.. She analyzed the stress disruption not only in severe depression but also in related and sometimes co-morbid illnesses, such as anxiety disorders or post-traumatic stress disorder (PTSD). A particular focus of her research was understanding gender differences in mood disorders and uncovering the biological and psychosocial reasons for the increased vulnerability of women to depression and anxiety. Her body of work stands as one of the most systematic and mechanistic analyses of the biology of mood disorders in our field.

But Elizabeth was much more than a talented physician scientist. She was also a loving wife and stepmother, a caring physician, a wonderful collaborator and mentor, an ardent gardener and appreciator of the best that life has to offer, and a devoted friend. During her ordeal, she and her equally remarkable husband, Dr. Peter Hinman, maintained a blog in which they shared their trials and their triumphs with their countless friends and colleagues. Their courage, love, thoughtfulness and generosity towards their friends were inspiring. In knowing her, those of us who love her learned not only how to live well, but also how to die well.

She is survived by her husband Dr. Peter Hinman, her step-daughter Dr. Mira Hinman and two step-granddaughters Annika and Celia McDermott-Hinman.

A ceremony to honor her memory is planned for early October and a Scientific Symposium in the Spring. A Memorial Fund has been created to establish The Elizabeth A. Young Lectureship on Stress and Mood Disorders at the University of Michigan. Donations to the Fund can be sent to MBNI, 205 Zina Pitcher Place, Ann Arbor, MI 48109. Att: R. Freedman.

A longer version of this is available here

The end

Elizabeth died this morning at 3:41. She was comfortable to the end as far as we could determine. Her breathing rate increased briefly, then simply stopped, so I believe that it was as painless as possible.

The end is near

On Saturday the decision was made between all of the doctors, Mira (my daughter and Elizabeth's step-daughter) and me that Elizabeth's condition is irreversible and that we should focus exclusively on palliative care to make her last time more comfortable and without pain. She had by then lost all cognitive function and was totally unresponsive to any stimuli except pain. Indeed, she seemed at times in terrible agony -- it was horrible for all of us to watch. We disconnected all of the curative IV's and started with periodic injections of morphine and ativan. These would work for a while but quickly wore off and left her again in pain as evaluated by her contorted face and arm motions.

Yesterday afternoon we started a continuous IV drip of morphine, at first at 2 ml/hr gradually increased to 2.7 ml/hr currently. On other advice, we stopped the ativan. During the day today this has been very successful; she has slept peacefully the entire day. Her respiration rate has slowed to 4-5 breaths/hour, which everyone agrees is not due to this relatively small dose of morphine but to a general slowing of bodily function as her body shuts down. We have consulted with the palliative care department and they are alerted if the need for stronger analgesics arises.

No one knows for certain, of course, but expert estimates are that she will die within a few days and possibly within hours. It is a very sad time for us all, but it has been inspiring to see the many of her friends and colleagues that have come to visit and often to stay for long periods. Of course, we are no longer concerned with visitors bringing infection.

According to her wishes (and mine as well) she will be cremated and there will be no funeral. There will probably be a memorial later in the fall that will have both a personal and a professional component, but there are no definite plans as yet.

Continuing Downhill

Elizabeth's condition seems to be getting slowly worse each day. She is now completely immobile in bed and cognitively very impaired. It is not clear that she understands much of what goes on around her and is mainly unresponsive to questions or comments -- occasionally she will answer with a shake or nod of the head. She does object strenuously to the necessary caretaking routines which probably cause her pain and/or anxiety, but we aren't really sure.

No one really understands the causes of this state -- they could be the effect of the leukemia actually entering the brain, but they could also be due to the toxic mix of medications she has been getting, including steroids, chemo, antibiotics, ativan, IV nutrition, etc. Another possibility is that all of the above have put such a strain on her body that it is simply in the process of shutting down.

Although we will be continuing as now for a few days unless things get suddenly worse, it seems quite possible, even likely, that she will die in a relatively short time. We do not intend to apply extraordinary measures to keep her alive unless there is good reason to believe that she has a good chance for a full recovery given a bit more time, something that seems pretty distant as of today.

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.

Hospital rules

A hospital can sometimes be a bizarre place. As you all know, one of Elizabeth's afflictions is quite debilitating lower back pain. At home her best remedy has been extensive use of an electric heating pad. Of course, we knew instinctively that we would not be permitted to bring such a device into the hospital -- that would be too simple. So immediately upon her arrival on the floor on Monday, E. asked for some source of heat for her back. On Tuesday there arrived in her room a machine about half the size of a large washing machine which works by circulating hot water through a pad. This was duly hooked up. There was some difficulty for the nurse to figure out how to program the machine, but eventually heat began flowing. However, it was soon decided that the pad was the wrong size and it was turned off to wait for a new pad. Then it was decided that the machine was the wrong one and a new one was ordered. Worse, the nurses and even the doctors ordered that this machine could not stay connected -- apparently there was a rule that a patient using this machine had to have vital signs (blood pressure, temperature) checked every 15 minutes to make sure that she was not being adversely affected by the machine. So no heat.

The supply unit then sent up an "new" machine -- identical to the first one! That was sent back and finally there arrived a much smaller machine -- about the size of a toaster. This also works by circulating hot water through the same pad. However, this didn't seem to provide much heat -- there was an adjustment for the temperature, but it needed a special key to adjust. It looked rather like a socket for an Allen wrench, so I took in a set of these, but before I arrived they found a technician who had the official key, and at this point it seems to be working fairly well. But what an effort for a simple thing.

Otherwise, things a proceeding according to plan, but we don't yet know how well the treatment is succeeding in controlling the CMV -- we may get a reading of those levels today. They are continuing to taper the steroid dose,which should also help. Meanwhile, except for the back pain, Elizabeth feels relatively well, although I think she does suffer simply from the large number of medications she is taking -- it's a really terrifying list.

Hospital Round Five

Elizabeth was admitted to the hospital again this evening. Her phone number is 734-936-8117. The proximate cause is a dramatic spike in her CMV (cytomegalo virus) level and the need to treat this more aggressively with higher levels of Foscarnet, which she had already been administering in IV at home for some time. The main reason for doing this in the hospital is so that they can monitor closely her electrolyte (magnesium, potassium, sodium) levels as well as kidney function, which can be depressed by Foscarnet. We are hoping that this can be controlled quickly to the point that she can continue treatment at home, but this is not clear for now.

It is often said of this (and other) diseases that the treatment is as bad as the disease. But the chain of effects we have been seeing is quite amazing. Consider the following analysis.

1. Leukemia develops and is treated with chemotherapy. This destroys the cancerous cells, but also the rest of the bone marrow and along with it its products: red cells, white cells and platelets. These losses require transfusions of red cells and platelets and antibiotics to replace the defensive action of the white cells.

2. A marrow transplant is the permanent solution to the marrow destruction. However, the new marrow sees the rest of the body and "foreign" and thus requires

3. treatment with immuno-suppressive agents, milder at first, but eventually steroids to suppress specific attacks. The new marrow pumps out all three types of cells, but the immuno-suppressants prevent the white cells from acting effectively (which they need to do) and thus permits other infective agents, such as CMV, which is present in most humans, to grow uncontrolled.

4. Anti-viral agents are then used to control the CMV, but these in turn have destructive effects as mentioned above on electrolytes and kidney function and also in suppressing the actual production of all three types of cells.

5. These effects must then be treated in various ways with direct IV administration of electrolytes; the kidney problems have yet to develop, so I don't know what that might entail.

So at this point we are monitoring and treating fifth-order side effects -- how far can this go?

Very positive overall with speed bumps

The very good news is that the 100-day marrow biopsy showed that Elizabeth's marrow is still 100 % donor and there are no detectable leukemic cells. That means, we think, that once she gets through the rigors of the treatment to ward off GVHD, she should have a good prognosis for the future.

Her gut is making a steady recovery with a much improved appetite and the ability to tolerate a steadily growing list of foods. She still has considerable edema from the steroids (which are still being administered at reduced doses). The worst current problem may or may not have much to do with everything else -- she is suffering from quite bad lower back pain, enough to make it hard for her to get around and impossible to get the exercise that she needs to strengthen her leg muscles. One theory is that this was brought on by a brief period just after the hospital stay when she was getting IV nutrition in a 1.5 liter bag that she had to carry around, together with a pump, in a backpack. But since it's a problem she has had before, it may also be coincidence that it is showing up now. She is continuing to get the ECP treatments twice a week, various shots, weekly clinic visits, other tests, and frequent blood draws -- we seem to have some sort of appointment every weekday (often including lengthy stays in waiting rooms) and sometimes more than one. It does occupy a good part of our time.

Bayeux Tapestry

Those of you who have visited Elizabeth either at home or in the hospital have no doubt seen stages of this creation. It is an embroidery kit based on a segment of the Bayeux Tapestry -- in this case the very first panel in which Edward sends Harold off to France to tell William that he is to be the next King of England -- check out the Wikipedia entry for more. We bought the kit in 2001 on a visit to Bayeux where there is a marvelous museum housing the tapestry. Elizabeth always thought of it as a retirement project, but it has been ideal for this period when she has a lot of time on her hands. In fact, as she was nearing the completion of this segment, I ordered online two more from the museum; she is already nearly finished with the first of these. This one is about 26 x 17 inches, the others are bigger.

Home again

Elizabeth was discharged from the hospital today. The doctors think that she has made a good start at recovering from the gut GVHD, but she is on a *very* restricted diet for the next few weeks to try to get her gut to repair itself. Between restrictions on fat, fiber, lactose, too much simple carbs and acids; the increased immuno-suppression from the continuing steroids; generally poor and somewhat altered taste and appetite; and the need to build up her protein and weight, it is more than a little tricky to figure out what to feed her. We're working on it.

Amazing treatment

Elizabeth is responding well to steroids and eating very little to rest the gut. But she is also getting a treatment called ECP (Extra-corporeal pheresis). She is getting 3 ECP treatments this week and 3 next week -- they are predicting that she may be released early next week so these may be outpatient. I just witnessed part of today's treatment and find it a fascinating and amazing process. I am obviously no expert and apologize to those who are, but for the rest of you, here is a summary of what happens.

There is a large fully computer-driven machine that is connected to one of her ports. Blood is started flowing to the machine through a series of gates. It first goes into a centrifuge where as much as possible it is separated into three components: red cells, white cells, and plasma including platelets. The white cells are fed into a chamber in a light box and the rest is returned to her body. This cycle is repeated 3-6 times. Then the collected white cells are injected with a chemical extracted from tropical fruits -- I forget the name -- that makes them more light-sensitive and irradiated with ultra-violet light. Finally they also are returned to her body.

I haven't really gotten a good explanation of the process by which this is beneficial, but it seems to be accepted that it is. Somehow the irradiated cells stimulate the production of T-cells that are not so prone as the ones she has, which are in fact being attenuated by the steroids, to attack the gut. It seems contradictory, and the nurse running the treatment agreed, but she was not able to give me a clearer reason. One side effect is that for some 24 hours after each treatment her whole body is more light sensitive, so she has to stay out of the sun (not hard in the hospital!) and wear UV-protecting sun glasses.

Contact info

Elizabeth's phone number is 734-936-8110. She also has a computer in the room and will be checking email regularly.

Back to the hospital

Elizabeth will be readmitted to the hospital this afternoon. Her sigmoid biopsy on Wednesday confirmed what we were increasingly suspecting, that her gastro-intestinal problems are due to GVHD (graft-versus-host-disease) -- essentially the white cells generated by her new marrow are attacking her gut as a "foreign" object. This is apparently a fairly common way for GVHD to show up, so it was not entirely unexpected. In fact, they keep telling us that they want to see some significant expression of GVHD, presumably to ensure that any few remaining leukemic cells will also be obliterated. Treatment will involve high-dose steroids and no food by mouth for a while. Since the steroids have various side-effects, they will be monitoring things closely. In particular, they want to make sure there is no resurgence of CMV. They say she will have to be in the hospital for at least two weeks, but it could be longer. She will be on the BMT unit of University Hospital, 8A (assuming they can find a bed there -- it is currently full). I'll post a phone number as soon as we have one.

Update

I haven't reported for some time, largely because there were no focal events. The upsurge of CMV seems to have been tamed by Valcyte, so this drug has been discontinued for now. The increased gastric and eating problems seemed to intensify about the time Valcyte was started, so we are hoping that these were largely side effects that will now diminish, but it may take some time. These symptoms are currently making Elizabeth rather unhappy some of the time, although there is considerable variation and she does have relatively good days. She has been up to short walks some days, although not all.

Valcyte also depresses blood levels of red and white cells and platelets, so we hope and expect that these will improve in its absence -- reds and platelets are doing reasonably well, but whites have been dropping to the point that she was officially neutropenic (ANC below 1.0) at the end of last week. Also a few shots of Neupogen have been authorized and should boost the neutrophil count. Today is day 81, nearing the watershed day 100. One of the immunosuppressants, CellCept, as already been reduced to 2/3 dose, and we expect that soon also Tacrolimus will be cut back, so perhaps this will also reduce the side effects.

Life goes on

Things are pretty stable right now, if not ideal. Elizabeth continues to have problems with energy, appetite and gastro-intestinal cramping, but has periods of being better in all of these respects and able to be more active. She tries to take walks most days, although is only up to quite level terrain. We are down to once-a-week clinic visits, which is a good sign. This is day 62 and our hope/expectation is that by day 100 there will begin to be some tapering of the imunno-suppressive medications and therefore hopefully some reduction in side effects.

On a lighter note, I have added to the blog a link to some photos via Jalbum -- I'll add albums to this periodically, so have a look if you're interested. For now it is mainly photos from our garden and the neighborhood.

Update

Peter was feeling discouraged when posting the last blog. But we would both agree I am doing better now. My energy level is better and I still get out for afternoon walks if the weather cooperates. I am still a long way from my normal high energy self but all things take time. And I am really grateful to be at home, enjoying the glorious spring and watching the spring perennials, and rhododendrons and azaleas bloom in our back yard, which I can see really well from our living room. Our creeping phlox had the best year ever and looks fantastic. Our little wildflower garden has been great and the trillium are still in bloom, and today we have a lady slipper orchid out-it has 9 flowers!!! It is not often I get so much opportunity to enjoy my garden. And I have been able to get out and enjoy the wonderful flowering trees in our neighborhood. So not a bad life-a lady of leisure. Although I keep up with my research staff on grant related issues.
Elizabeth

It's a long haul

While the last post announced good news, the reality since then has been far from easy. Elizabeth has been suffering considerably from tiredness and nausea/loss of appetite. Especially in the mornings, she is hardly able to walk the length of the house without getting elevated pulse rate, exhaustion, and shortness of breath. This seems to lift somewhat in the afternoons, and she has been determinedly getting out for a walk of a mile or so, usually on the most level ground we can find in our hilly neighborhood. The nausea seems to be increasing, and most days she has to struggle to get down enough food to stave off continuing weight loss -- this from a woman who normally really loves good food with a husband who likes to make it for her. Neither we nor the docs can figure out where this is coming from. We can only hope that this is some passing phase.

Great News!

The results of Elizabeth's marrow biopsy show that the current composition of her marrow is 100% from the donor. As far as we understand things that is the best possible result, since it means that her diseased marrow has essentially been completely replaced by the (presumably healthy) marrow of the donor. Of course. we're not out of the woods yet, as there is still plenty of time for graft-versus-host to show itself. Currently she has some rashes that are due to this, but nothing more serious. Otherwise, there is the expected tiredness and lack of appetite, but we are coping well with this. 

Doing better again

Just wanted to update everyone. I am doing better now. I think we found the root of some problems-my blood pressure. Problems started on Norvasc when my blood pressure was too low. This was stopped. I also take hydrochlorothiazide (HCTZ) for hypertension but in the end, even on one pressure med I kept having somewhat low blood pressure and rapid pulse (~100 at rest). When they took my blood pressure lying down, sitting and standing, it became clear I was having significant drops with each. By the time of standing my blood pressure was 75/50.  Plus the HCTZ had caused me lower sodium and potassium. So we stopped this Friday, although I already had taken my daily dose. Saturday was my first day without it and  by Sunday was doing much better in terms of walking etc. Both days I walked 2 miles.
To deal with my quezy stomach  which diminished my appetite they gave me regular Zofran which has helped my appetite now. And most of the “funny taste” with my food is gone.
Elizabeth

Not perfect, but it could be worse

Things are going reasonably well, but there are plenty of reminders that it's far from over. After a few days of relatively good energy and appetite, both have been much reduced the last few days. The culprits are a low level but persistent nausea and rapid resting heart rate. We are told that both of these are standard effects either of the chemotherapy or the transplant, presumably from GHVD (Graft versus host disease). So the docs tell us not to worry, but it's hard not to do so a bit. And it certainly makes life less than pleasant for Elizabeth. Still, we're happy that so far there have been no more severe effects of GVHD. The next major milestone will be a marrow biopsy on 17 April -- my understanding is that this will tell us to what extent the new cells have replaced the old diseased ones.

Home!

Elizabeth was discharged from the hospital today and is back home. With the help of Neupogen her white counts were at 6.9 this morning. She come home with an unbelievable pharmaceutical regimen and many scheduled blood draws, clinic visits, and possible transfusions, but at least for now she is at home.

Day +10

Things are looking up. My white count was up which they take as a sign of
engraftment. They are talking about discharge early next week. The new
Doctor, John Levine, says there is about a 50% chance I will need
re-hospitalization in the next month but we think this sounds very good.
Better to be home than sitting here
Elizabeth

So far so good

Today is day +9 counting from the transplant day. Elizabeth has been feeling relatively good and suffering few effects most of the time. There have been bouts with nausea, loss of appetite, and currently fairly intense mouth and throat soreness. These are unpleasant but considered entirely normal and expected and are not threatening to her overall health. Blood counts are still low and there have been transfusions of both platelets and red cells. The docs expect/hope that somewhere around days +10-14 grafting of the new marrow will start and lead to fairly rapid production of blood cells. It is possible that she might get sent home towards the end of next week, but that depends of what happens. But they also warn that it is entirely probable that there will be crises of infection or GVHD (graft versus host disease) that will send her back into the hospital over the next few months.

Transplant accomplished

The transplant finally happened about 9 PM yesterday. The cells arrived at Metro airport (we don't know where from) around 5 PM and were taken to the hospital blood unit for various procedures. Among the most interesting things, they do a count of the actual cells. The sending organization reported about 9 million cells, which our docs evaluated as way too many. They were aiming for 4-4.5 million, so initially they divided the sample and gave her one half. Overnight they did their own count, which agreed closely (which apparently doesn't always happen) and now estimate that she got 4.45 million cells. The goal is to have enough cells to initiate just enough GVHD (graft versus host disease, an immune system reaction) to knock out any remaining leukemic cells in her body without triggering destructive GVHD that might attack other organs -- liver, kidney, lung, even brain. The full 9 million would have overwhelmed her body and probably done a lot of damage. They can and do freeze the remaining cells for later use. Since each case is different, it sometimes happens that the initial dose is not enough to kill the leukemic cells, in which case they pump in some more at a later date. All very amazing.

The actual infusion was a bit anticlimactic -- it is just like a blood transfusion, only shorter. It took about 45 minutes, longer than I have heard from others who have done this. The attending on the unit -- Greg Yannik -- did the whole thing, for the most part without even a nurse present. This seemed surprising, since all of the blood and platelet transfusions have been done entirely by nurses. Still, it was an exciting moment, with luck the process that will really cure Elizabeth and get her back to good health.

All is well so far

After two days of chemo, Elizabeth is still in fine shape and spirits. I thought people might be interested in a couple of pictures. You can see how spacious the room is and how good she looks. The hat is one of 10-12 in many colors she made for herself after the original hair loss from the first round of chemo.

Towards the transplant

Elizabeth was readmitted to the hospital today as planned to proceed towards the bone marrow transplant. She has been in very good shape that last week, lots of energy, reasonably good blood counts, and liver enzymes back in the normal range. So she is going into the transplant from a position of strength.

She is again on the 8A unit, which is where all the BMT patients stay whenever possible. Her phone is 734-936-8408, and for now she is happy to get calls, although as usual there are times when she is not in a position to answer the phone. She has a very nice room, one that is set up as a double, but is being used as a single, so there is much more room and it doesn't feel nearly so cramped. We call it her suite.

The chemo regimen starts tomorrow morning and runs Friday-Monday. Tuesday is free and the transplant is scheduled for Wednesday. As far as we know, the actual infusion of stem cells will not be any more taxing than a standard blood transfusion, of which she has had many. Of course, it is expected to have many more effects, both positive and negative, than a transfusion.

More schedule

We now have confirmation that the donor has passed all of his/her tests and is ready to go. Elizabeth will be admitted to the hospital on 12 March. There will be four days of chemotherapy 13-16 March. On 17 March she will have "full-body irradiation" (is this an Irish treatment?) and the transplant will be on 18 March. We'll hope for the best.

The clinical director of the adult BMT unit has once again decided on a change in the chemotherapy protocol. There will be 4 days of Fludarabine but now only 2 of Busulfan. This (FluBu2) is considered a somewhat less gruelling regimen than the one (FluBu4) with also 4 days of Busulfan; the purpose of the irradiation is to reduce the chance that her body will reject the donor marrow.

New schedule

Elizabeth's blood counts seem to have stabilized -- they decided she didn't need the normal Friday lab work and there have been no transfusions this week. She is generally functioning well, including going for 2-mile walks, but still gets tired more easily than normal.

It seems that the marrow donor can't fit in to the previous schedule, so it is being moved up a week -- hospital admission is now expected to be around March 11 with the chemo and marrow transfusion coming soon after that. She has a slew of medical appointments over the next ten days all checking out in various ways that she is fit to undergo the transplant procedure. There will be another bone marrow biopsy on March 9 to see what is really going on in there. An unhappy consequence of the new schedule is that we won't have time to go off on our little trip.

We are gastronomically well prepared for the hospital stay -- together we have now prepared quite a stock of dinners that I can relatively easily bring in to replace the horrible hospital food and as I reported earlier the soup supply for lunches is excellent. So to the extent that good food can facilitate her recovery, we are in good shape.

The next few weeks

I haven't posted for a while because there wasn't much new. Elizabeth has been home two weeks. She is slowly recovering from the last round of chemotherapy -- it did a lot more damage than the first one. She is now making white cells, particularly neutrophils, which is good -- there is less danger of infection. But she is still not making either red cells or platelets. This means that she needs transfusions regularly -- she has had several of platelets already and got both on Friday. The docs tell us that this is not unusual -- it can take a long time to recover from the intensive chemo that she had and particularly platelets come back slowest. Her energy level is also recovering slowly -- she works at going up and down down stairs and we go out for walks -- so far a mile is feasible, but tomorrow we hope to try a bit longer one if the footing isn't too bad -- we had about 4 inches of snow today.

We met with the BMT (bone marrow transplant) team on Friday. The original plan was for her to be admitted around now for the transplant, but things haven't been finalized with the donor and in any case they want her to have recovered more thoroughly to be strong going in to the process. On the other hand, they don't want to delay too long to risk that the leukemia might return -- it is considered important that she be in complete remission at the start of the transplant process. So the current thinking is that she will be admitted around March 19 for the transplant. At that point she will be in the hospital for at least a month and in a rather delicate state for the first 100 days after the transplant.

If she can get to a state of not needing transfusions so frequently, we are hoping to be able to get away for a few days in March to someplace warm and fun -- we'll see if it works out.

Home again!

Elizabeth was discharged from the hospital this afternoon. Her temperature has been normal for several days and her white counts finally made it over the magic 1.0 mark. Ongoing problems include relatively severe edema and elevated liver enzymes, but it is expected that these will sort themselves out eventually with a bit of drug help. She is still quite weak, but can get around the house. Given these problems, the transplant will certainly be delayed from the originally scheduled admission on February 18, but it hasn't been determined by how much -- this probably depends on recovery from the above mentioned side effects. For now we will again try to enjoy for a while a simulated normal existence.

New room and phone

Elizabeth has been moved to a different room. Her new phone is 734-936-8109.

Soup alert

Nothing much new to report -- blood counts remain low and the fever/infection persists despite many tests trying to discover its cause. Everyone is stumped for now. They are planning to do a bone marrow biopsy today to try to understand why the counts are not recovering.

Although Elizabeth's appetite is not very good, one thing that still appeals are the soups that I bring most every day for lunch. I expected the backlog from earlier contributions would last through this hospital stay, but with this extension we are close to using them up, so if any of you living locally have time and energy to make another batch of soup, it would be appreciated. The  guidelines remain in force. The main points are using clean chopping boards and cooling it quickly after cooking.

I take them in a thermos that holds 2 cups and serves both of us. We have lots of freezer containers, so feel free to bring a large container for me to divide up. They can be left on our front porch while the weather is still cold. While I am away Wednesday evening-Sunday afternoon my daughter Mira will be in town to be with Elizabeth and can put them away.

More problems

Elizabeth's blood counts are not recovering on the schedule of the first round of chemotherapy -- her white count is still at 0.2-0.3. The doctors had expected it to be up by now, but tell us that it is not too unusual for the second round recovery to be slower. To make things worse, she has again gotten some sort of infection that is giving her fever, so she is back on antibiotics (after a couple of days off) and is rather miserable. Our plan to return to London next week was, of course, dependent on her counts being up so she had enough of an immune system to cope with the world. So she will not be able to go. I will still go to retrieve the many things we left in the flat there, but for a shorter time, leaving Wednesday and returning Sunday.

The long wait

A week since the last post and not much change -- white counts have been stuck at a very depressing 0.2 for 5-6 days. There have been several infusions of platelets since these levels also fall after each one. The one bright spot is that hemoglobin levels have stayed in the 9-10 range for most of the time since the last transfusion about 10 days ago, but even these are down today and she may need another transfusion tomorrow. We are still very much hoping that this week will bring enough of a recovery to allow us to make our planned brief trip to London 1-8 February.

We have talked more with the marrow transplant people -- physician and coordinator. The best available  match is still 9/10 and it looks as if we will have to go with this one. The admission date for the transplant has been tentatively scheduled for February 18, but this will depend on the timely availability of the donor. At that point she will get a stronger regimen of chemotherapy for a few days, then the transplant. The hospital stay is expected to be at least 4 weeks, possibly longer. It's a very risky process and things could go badly in many different ways, but everybody agrees that it is her only chance for a real cure.

Steady state

The infection now seems under control with just the first antibiotic and there has been no fever for the past day or more. But it still seems that they will keep her in the hospital until the blood counts recover to near-normal levels -- at this point the white count is at 0.1. She got two units of blood and one of platelets yesterday, so these levels are a bit higher. We are fondly hoping that she will start making white cells is a week or less, but it's hard to guess when she will get out.

The combination of blood and no fever has put her back at a higher energy level to the point that she is now ready to talk to people on the phone -- her room number is 734-936-8418. She may also be accessible by email and Skype, although Skype is as always uncertain because of the unreliability of the hospital wireless network and her ability to reach the computer.

a setback

Elizabeth has been checking her temperature regularly. This afternoon she had a reading of 101.8. After this continued for a while, she called the clinic and was told to report to the hospital emergency room. After more tests, they decided she should go back in the hospital, probably for the remainder of the time that she is neutropenic, around 2 weeks. They haven't figured out what sort of nasty organism is causing the fever, but they have started her on antibiotics to try to control it. As I write she is still in Emergency waiting for a bed on the unit -- they are very full and she has to have a private room. So we are back to the hospital routine.

the return of neutropenia

As scheduled, Elizabeth had her second round of chemo last week Tuesday-Thursday. It all went well with no immediate side effects and through Monday she was feeling pretty normal with enough energy to take walks of several miles. Then yesterday she was very tired  and felt constantly cold. Since the Monday red count had been only a bit below normal --- 9.6, not low enough to trigger a transfusion --- we thought it must have dropped suddenly. But today's count was only slightly lower, so we don't have a good answer. But the doctors ordered transfusions anyway -- 2 units of red and one of platelets -- and we spent the day in the infusion unit. We'll have to see if this does the trick. But the white count has gone back down to the very low level (0.2) that it was for 10 days or so during the last round and she is officially neutropenic again. Now the goal is keeping her infection-free until that recovers. 

Long-term outlook

After discussions with the doctors yesterday, we begin to understand their treatment plan. The prevailing view (at least here) is that for the particular subtype of leukemia that Elizabeth has, no amount of chemotherapy will reliably provide a permanent cure -- the only hope for that is a bone marrow transplant. Her blood and marrow may look clean, but there will always be bad cells lurking that with time will take over again. The transplant group is a separate one and they are reported to be searching for an appropriate donor. We hear that there has been one found that matches 9 of the 10 markers and that there is a possible lead to a 10 of 10 match. It will take time, in the range of months, to find, and verify any match and then collect the marrow.

Meanwhile it is important to make sure that Elizabeth remains in remission, and for this there will be continuing chemotherapy at a slightly lower level than the first series -- 3 days instead of 4. The idea is that she should have 3 days of infusions every four weeks given as an outpatient. Each time this will depress her red, white and platelet counts and require transfusions for the red and platelets and extreme care to avoid infection because of low white counts. Any infection will lead to hospital admission. So this is what is now starting -- today was the first in this series.

A bright spot is that they agreed that it would be safe to postpone the next series from 2 February to 9 February and for us to take this week -- a time when her counts will have temporarily recovered -- to go to London to have a few days of fun and clean out our remaining possessions in our flat there. From the plan outlined above it seems certain that we will not be able to return to London for a longer stay this year. Indeed, the doctors are saying that after the transplant she may not be able to go back to work for up to a year, although knowing Elizabeth I really doubt she will be anything like that slow. But we will just have to take it as it comes.