The "new normal," Part 3

I recently saw the movie Rashomon again. In it, a crime is described by four different participants, each of whom sees it quite differently. The Akira Kurosawa film is considered a masterpiece, in part for what it says about the human experience: We can all see the same thing, yet we can produce substantially different but equally plausible accounts of it.

This is certainly true of doctors and chronic lymphocytic leukemia. My CLL is cause for treatment with Rituxan and fludarabine, according to one doctor. It is cause for Rituxan plus cyclophosphamide, vincristine, and prednisone, according to another. Another expert weighs in with Rituxan plus chlorambucil. Three doctors say it is cause for nothing more than watch and wait, though two of them differ on how to proceed when treatment time comes. If I were to see more doctors, I would probably end up with a laundry list of treatments and no general consensus on whether to treat at all. As in Rashomon, my CLL is experienced differently by everyone who examines it.

But the subjective truth that ultimately matters here is mine. I have come to know my disease better since diagnosis, as I explained in the second part of this series on the “new normal.” And I have gotten to know it even better this year. Part of my “doctor quest” has been to learn more about it, to see it through the eyes of people who are experienced at looking at it, so that I can see it better myself.

What I have learned is that I have what is called “high risk” CLL. The year 2006 brought with it news of clonal evolution, from a “normal” FISH result to deletion 11q. In an IgVH unmutated patient, which I am, this is not good news. Conflicting ZAP-70 tests performed by Quest Diagnostics have been resolved by the lab at UC San Diego, which is considered probably the most reliable place to get your ZAP-70 done: I am ZAP-70 positive.

Beyond that, I have clinical signs of progression: a slowly expanding spleen, slowly expanding lymph nodes, and a booming lymphocyte count. I may feel fine now, my hemoglobin and platelets may be in the normal range, and I may not have any “B” symptoms. But this won’t last. How long it won’t last is a matter of conjecture.

As I explained in the The “new normal,” Part 2, I once thought, with some justification, that my disease might be, if not indolent, at least fairly cooperative. After all, I had likely had it for a decade and was still feeling good, even at Stage 2. Yet, I have now learned that the problems I am having -- acquisition of the 11q, disease progression -- are indeed consistent with having had CLL for a decade, especially in an unmutated patient. In fact, it is a wonder things didn’t get worse sooner. If the statistics are to be believed, and if I were a cat, I would have used up four or five of my nine lives already.

But, as Mark Twain quotes Benjamin Disraeli as saying, "There are three kinds of lies: lies, damned lies, and statistics." I am not giving up. I am looking to refashion my hope in response to this newest “new normal,” to find a realistic path to a better future. If the climb is at a steeper angle, and my heart beats a little faster, then it will only make me stronger.

Afternoon at The James

The last doctor I visited was John Byrd at the James Cancer Center at Ohio State University in Columbus. I have followed Dr. Byrd’s research, and he would be on anyone’s list of the top CLL doctors in the country. More importantly, if doctors were choosing which doctors they respect the most, I believe he would be very high on that list, too. Byrd, a self-described conservative when it comes to treatment, has a reputation for adhering to rigorous scientific and ethical standards in his clinical trials. I could have gone elsewhere, and had I gone a little to the south and west of Ohio, I might even have found an expert who would have promised to “cure” me through chemoimmunotherapy. (And no, I’m not talking about a fly-by-night clinic in Mexico.) But my CLL is hard enough to see -- think Rashomon again -- without adding rose-colored glasses to the equation.

And so, Marilyn and I drove 1806 miles from our house to OSU; the last few hundred yards were the hardest, since we had to find our way from the parking garage to the James, which sits at one side, slightly hidden, of a huge medical complex. It would have helped had they placed bits of cheese in various locations so we could have known if we were heading down the right corridor at any given time. But we did find it, and with half an hour to spare before my appointment was to begin.

It turns out that Dr. Byrd's floor was in mid-renovation, to the point that slips of paper with handwritten numbers tacked to the doors served to identify which exam room was which. The place was phenomenally busy and we were seen phenomenally late. I expected this, of course, and was reminded of the advice offered by a good restaurant I once visited: We take the time to prepare each meal properly, so please be patient.

Eventually my vital signs were taken, and I found that even in the halls of an enormous cancer center, the new normal has its comic moments. We have all heard of a “spit take,” in which a comedian takes a drink of water and, upon hearing something surprising, spits it out. This almost happened to me when I got my temperature taken. After the thermometer was stuck in my snout, I noticed that the nurse’s ID badge was emblazoned with the name “IP Freely.” It took everything I had not to send the thermometer flying across the room.

After a lengthy interview with Dr. Byrd’s nurse practitioner, Mollie, who knows more about CLL than most doctors I have encountered, we were ushered into an examination room to meet Dr. Byrd himself. The doctor looks a little older in person than he does in photographs, and was dressed in a striped oxford shirt, khakis, and tasseled loafers. Missing were the white coat and that usual doctor neckwear -- a stethoscope thrown jauntily about the shoulders. The one piece of medical equipment that Byrd keeps on his person is a cloth tape measure -- "hardware store issue," he says -- for measuring lymph nodes.

Dr. Byrd was personable and did his best to answer all my questions and address all my concerns. It helped that I came with an open mind for an honest opinion and that I was not shopping for news I wanted to hear. Doctors, even the experts, respond to perceived patient expectations. The more open you are, and the more relaxed -- yeah, I know, that part is not always easy -- the more you will usually get out of a visit. We got a lot accomplished during our hour, and by the time I left, I had several points to ponder:

• Unmutated 11q CLL in a person my age (49) will likely mean a stem cell transplant down the road, in my case from an unrelated donor. It’s a risky therapy, but there is a 50% chance of a cure, or something close to it; a 20% chance of outright failure; and a 30% chance of complications that will eventually lead to, as the doctor put it, “badness.” (For more on transplants, check this article at CLL Topics.) That said, the 11q is not reason in and of itself to jump into transplant mode right now.
  
• It is indeed better, as I have been surmising, to save heavy-duty chemotherapy for a pre-transplant remission and not to burn that bridge now, which would leave me with less chance of effective CLL cell reduction prior to transplant. Such “cytoreduction” is a key element in transplant success.
  
• In the short term, there is no reason not to continue to watch and wait. My nodes, for example, aren’t nearly as big as I thought they were. The NCI Working Group guidelines for node treatment are 10 cm and most of mine are less than half that. I still feel fine, without “B” symptoms, and my platelets and hemoglobin are normal. At the point at which I start feeling fatigue, satiety (fullness) from an enlarged spleen pressing on the stomach, discomfort from nodes, night sweats, low platelets -- the usual CLL stuff -- treatment will be in the offing.
• I might be able to wait six to nine months -- or even a year or more, if the disease plateaus -- before that happens. When it does, there is no reason not to pursue a biologic approach to therapy ("immunotherapy"), either via a clinical trial or through single-agent Rituxan again. Dr. Byrd has done a dosing study of Rituxan, and thinks infusions three times a week for four weeks may be more effective than the once-a-week-for-eight-weeks that I have had. There is no guarantee that this will work, but I have responded pretty well to Rituxan in the past and it may be worth a try. (I have since been reading some Rituxan dosing studies and will post to the blog about them.)
• Dr. Byrd is not a fan of R+HDMP and he has given me pause in that department. I believe the word he used was “vehemently,” as in “vehemently opposed” to my using it. Suffice it to say that a trial at OSU as part of the CLL Research Consortium led to serious problems in five of nine patients and had to be stopped early. Dr. Byrd knows that off-study R+HDMP is popular among patients, but says they are operating with very little data. In my case, were I to pick up a fungal infection from this immunosuppressive regimen, it could rule out a transplant. HDMP is, Byrd wrote in a report to my local oncologist, “associated with significant infectious risks as well as other end-organ toxicities.”
  
• In general, Dr. Byrd is excited about some of the trials going on at OSU, including flavopiridol and Chiron-12.12, a CD 40 antibody. He does think things are progressing nicely in CLL research. “There are a lot of things happening,” he said, “so I think the longer you hold out, the better you are.”

Still, I get the sense from any number of experts that progress is incremental. And, alas, many clinical trials of promising agents are designed for the fludarabine-refractory. There are no silver bullets on the horizon just yet, and my disease is progressing faster than science.

It also remains a difficult case, in which I may have no choice but to take some big risks someday. My predisposition to squamous cell skin cancers makes therapy with fludarabine or Campath -- as well as a transplant -- into higher-risk propositions. (It does little good for the CLL to be knocked back if I develop systemic metastatic squamous cancers in its place.) New information about the Epstein-Barr virus and patients with a past history of full-blown infectious mononucleosis -- that's me -- makes me doubly wary of risking T-cell suppressive therapy. (Richter's Transformation doesn't sound like fun.) Dr. Byrd pointed out that CLL is a journey, and there are no doubt some challenging bridges to cross in mine.

Conclusions

Based on what I have learned from Dr. Byrd and from elsewhere in my travels, I now have some sort of plan, albeit one with some still-open questions:

First, I am going to have my HLA typing done and my local oncologist will do a preliminary search of the National Bone Marrow Donor Program database. (I’ll write more to the blog about this experience, too.) The search results will let me know how many, if any, good matches pop up, and will give me some idea of what to expect in the future: a fairly easy time of finding a donor, or a difficult one. If it were to appear, for example, that finding a well-matched donor is likely to be impossible, I might consider a different approach to disease control.

Not all the doctors I have spoken to are fans of transplants, by the way. One commented frankly that, “in order to get the graft-versus-leukemia effect you have to put up with graft-versus-host disease, and in my experience that can be so bad that you are alive wishing you were dead.”

Point taken. But in a world of hard choices, I think it is probably better to risk being alive wishing you weren’t than the other way around. Not all transplant experiences are bad ones, though they have their share of unbearable moments, and it is worth the gamble to me if I have no other option.

There is, of course, another big "if" for me: My insurance company specifically excludes stem cell transplants from coverage. There are plusses to being self-employed, but finding adequate insurance coverage is not one of them. I will have to cross this bridge somehow, if and when I come to it.

Second, the longer I wait for a transplant, if my disease will allow it, the better. The procedure will only improve with time, as will, presumably, its effectiveness. So a 50% chance of success today may be a 60% chance a few years from now. I am young as these things go, and have a 10-year window before I get to the age where transplants are considered too risky to perform. In the meantime, I need to get in the best shape of my life and avoid comorbidity factors such as diabetes and heart disease that would reduce my chances of transplant success. And in keeping the transplant at bay, I need to be creative, as do my doctors, about treatment. It needs to be strong enough to keep me going, not so strong that it burns bridges I need to save. Finessing this will be tricky, and will be a challenge during the next few years. (So when is that Humax stuff going to get on the market, anyway?)

Third, I will watch and wait for awhile longer. I am unused to this -- letting the disease go further than it has gone before -- but I suppose this is part of my newest “new normal.” And the shark I thought I had jumped -- single-agent Rituxan -- has now re-entered the picture. If the statistics on the more intensive Rituxan dosing schedule hold true, there is a 40% or so chance that I can get a partial remission that might last for 10 months. Hardly sterling, but it’s not like there are many softball choices out there. (I will, of course, keep my eyes pealed for clinical trials of interesting alternatives.)

Beyond Rituxan, there are precious few tools readily available in the low-tox toolbox. There are lower-dose steroids, there’s chlorambucil, and perhaps cyclophosphamide. (As you can see, I am grading on a curve here when I say “low tox.”) If I use some of these now but save fludarabine and Campath for pre-transplant use, will that be enough to get the thorough disease clearance I will need?

Fourth, if the last couple of years have taught me anything, they have taught me this: I need to be ready, at the drop of a hat -- or the fax of a test report -- to adapt to any new “new normal” that may come up. As Roseanne Rosannadanna said, “It’s always something.” For example, while I am grateful to learn that having the 11q deletion does not predispose me to picking up the dreaded 17p, new information indicates that a third of unmutated patients will pick up the 17p on their own, even without treatment.

Finally, I have come to the point where I can own my CLL, all several hundred billion mutant Bucket C lymphocytes of it. There is a tendency, when one feels fine, to ignore bad news, bad test results, unimpressive response to treatment. It is only human to want to believe the best about one’s situation. Coming to grips with my ever-changing new normal has been harder, in many ways, than the mechanics of learning about the disease and consulting with doctors. But being honest with myself and seeing it for what it is as best I can -- Rashomon-like -- is essential to taking the right steps to control and perhaps even conquer it.

Sure, I wish I had better prognostics, or that I had come down with CLL 10 or 20 years from now if I had to come down with it at all. But 50/50 odds on a transplant are a lot better than most people have with most cancers. People have succeeded at far steeper inclines than I will face, against greater and more insidious dangers. Perhaps it is my path to go to the edge and win the hard way. After all, there is a silver lining: a transplant can cure. In this latest “new normal,” I know it is my fate to be free of this disease, one way or the other.

The "new normal," Part 2

My “new normal" began when I was diagnosed with chronic lymphocytic leukemia in the fall of 2003. This new normal has since evolved, or devolved, depending upon how you look at it. Each time I have settled into a comfort zone, things have gotten worse. There’s a reason why my sig line at CLL Forum is a quote from Gilda Radner’s Saturday Night Live character Roseanne Rosannadanna: “It’s always something. If it’s not one thing, it’s another.”

Since my diagnosis, unwelcome new wrinkles have demanded new responses, as well as renewed patience. Required, also, have been constant efforts to find psychic and emotional shelter from a disease that blithely marches on. As I have written here, hope is an active process -- but it is not always an easy one. This is the most challenging year yet, and to understand it, it helps to look back. I have had the disease long enough now to have some perspective on where it has been, and where it may go.

2003

As bad as 2003 was -- I was diagnosed at Stage 2 with swollen lymph nodes and spleen, which threw me directly from the frying pan into the fire -- a few good things came out of it, or seemed to. I learned that I had the inner strength to deal with devastating news and the resourcefulness to learn something about a complicated medical issue. I showed a modicum of wisdom by avoiding the treatment pushed mercilessly by my first oncologist, the fludarabine-happy Dr. Lippencot. I began Googling to save my life, literally, and I discovered that there is a patient community out there full of experienced and knowledgeable people. Largely through their efforts, I found another treatment option, single-agent Rituxan, that would buy me time without burning any big bridges.

In 2003, I also had one good test result -- my CD 38 came back at 12%, or well within the negative range. This was the only prognostic test available to me at that time, and it boded well. And then there was a gray memory that came back into full color: Prior to my diagnosis, my last CBC had been in 1996. I recalled that my white count had been a little high, and that my doctor had told me that it was probably just an infection but that I might want to get my blood retested in a month. His infection comment had struck me as odd, since I didn’t feel as if I had one. But I dismissed his advice, feeling rather immortal. And, of course, I didn’t bother to get a copy of the test report. It no longer exists, since the law requires that these things be kept for only so long, and I stopped seeing this doctor long ago. But what this memory told me was that my disease had not appeared overnight, and that I had likely had it for a long time, during which it had behaved itself for the most part, perhaps slowly building up, as might a more indolent form.

2004

2004 was, in retrospect, a breeze. I began the year with my Rituxan treatment. The progress with which my CLL cells died was so rapid that it created a buzz among the nurses in my oncologist’s office. I left treatment with a normal lymphocyte count, a spleen worthy of an anorexic, and very few visible lymph nodes. I turned my attention to telling my extended family about the disease, and I became involved in reaching out to newbies in the online patient community. Marilyn, Pyewacket, and I even enjoyed a long vacation through the Canadian Maritime provinces.

Upon our return, I underwent a couple of fancy new prognostic tests just made available to my oncologist through Impath Labs in Los Angeles. The first, a FISH test, came out “normal.” This was the second-best FISH result, and it served to confirm my belief that perhaps I had a fairly cooperative case of CLL. After all, my CD 38 was negative, I had evidently had the disease since at least 1996, and while it had slowly built up to Stage 2, it had never sent my red counts or platelets below normal, and I had never had any “B” symptoms. All that, and a mild treatment had appeared to work quite nicely. My lymphocyte count was slowly making its way back up, of course, but that was to be expected with single-agent Rituxan. If my disease could be looked at as a ship -- the SS CLL -- I was standing on the bow and feeling, if not exactly like king of the world, at least that there were no icebergs in sight.

Then the second test result came in: I was ZAP-70 positive. This gave me pause, knowing it was often a surrogate for mutational status. I liked to think then that I had one foot in Chaya’s Bucket A -- the CD 38 and FISH -- and one foot in bucket B -- the ZAP-70 and the fact that the disease had managed to progress to Stage 2. Bucket C was over there somewhere, with flies buzzing around it. And so far, I was avoiding it. At the end of 2004, I joined the board of directors of CLL Topics; there was no reason not to toast the new year with some optimism over a holiday brunch with friends amid the red rocks of Sedona.

2005

2005 sucked, pretty much. If 2004 was punctuated by moments of ease, the year that followed seemed to ratchet up the stress at every opportunity. The new normal shifted from bizarre but comfortable to disquieting. Life with CLL became an unending process of adapting to bad stuff.

The year began with the surgical removal of a squamous cell skin cancer from the top of my head. (“It’s just a pimple,” I had been telling Marilyn. “No, it’s not!” she had insisted. Guys, women know pimples. It’s genetic. Just give in and don’t bother arguing.) I had been reading up on the heightened risk of skin cancer in CLL patients and knew that I was at even higher risk; my skin tone is akin to that of the Pillsbury Doughboy and I have always burned in the sun. In 1999, I had had my first squamous cell growth, a pinkish thing that reminded me of a toadstool, frozen off the side of my face. Now I had a second one, which had implications beyond those of vanity: My CLL-compromised immunity was not stopping the damned things. And treatments that severely impair T cell function -- that’s the thing that keeps those squamous cancers in check -- might be a problem for me. Those treatments include fludarabine and Campath, two of the biggest guns we have.

On top of this, Typhoid Charlene came to visit and gave us colds. I got mine last, and I got over it first -- all of which told me that my immune system was still pretty functional in some respects -- but my lymph nodes ballooned in response. They went back down after a week or two, but provided a visible reminder that my immunity was laboring under a new burden. My immune system was no longer an aerodynamic Prius or a sleek Mustang convertible -- it was, perhaps, starting to look like a clunky and dented 1972 Oldsmobile Cutlass, still making it from point A to point B, but not without some grinding of gears and black smoke coming out the tailpipe.

I received Rituxan again in April and May of 2005; the response, while adequate, wasn’t quite as good as before, and it did not last as long. This implied, of course, that the soft-glove approach might not be effective forever. This wasn't, of course, what I wanted to hear.

And for the first time, prior to starting treatment, I had felt a little pressure in my lower left pelvic region, where lymph nodes had begun to grow. The treatment did not ameliorate it. I was left with an occasional reminder, if I lay flat on my back, that I was sick with something. Slowly, this pressure got worse, until I noticed it when laying on my right side. It is there now, noticeable also when laying on my left side, or when sitting.

Adapting all these things into the new “new normal” took some doing but paled in comparison to the news I would soon get from Quest Diagnostics: my CLL is IgVH unmutated. I still remember the call from my oncologist’s nurse, and I can still see the scrap of paper on which I wrote the single word: “unmutated.” I can also recall the sick feeling I had in the pit of my stomach. “Unmutated” brings with it some “un” implications: “Un-controllable” “Un-stoppable” “Un-likely to have an easy time of it.”

Slowly, as test results had continued to emerge and treatment had became less effective -- renewed Rituxan ending in December fared no better than had April’s doses -- everything I had initially assumed about my CLL started to turn on its head. A newer and meaner new normal was in the offing.

I toasted the arrival of 2006 with trepidation. I told my friends that maybe it would be nice if we could just have a little time without stress, without anything eventful, without something else bad happening. I suppose it was the champagne talking.

This is getting a little long, and so there will be a “The new normal, Part 3," which will bring you up to date on my treatment quest and what the new normal is for me today.

The "new normal," Part 1

The “new normal” is a phrase I run across sometimes in the CLL community. It’s shorthand for what things are like when you are living with the disease. For all of us, the new normal means accepting that we have leukemia, and that this may shorten our lives.

Beyond that, the new normal can vary. Indeed, it is always changing or threatening to change.

For newbies, the new normal may mean coping with shock, traversing the unfamiliar terrain of prognostic testing and blood drawing and busy oncology offices where women with bald heads sit in chairs, their arms linked to bags of fluid on IV poles. The new normal can mean sorting out who your friends really are, who your mate really is, what kind of a work environment you really have -- and that perennial CLL rite of passage, figuring out if your doctor knows his ass from a hole in the ground. It can be stressful and bumpy and yet perhaps strangely exhilarating. After all, when looking mortality in the face, even with a sideways glance, one can sometimes put things in perspective and find ways to live more meaningfully. So, for some, the new normal can be transformative in a good way at the same time that it is fearsome as hell. The new normal is contradictory, and often surreal.

For patients like myself who are past the newbie stage and whose disease is progressing, the new normal can mean arranging your time and finances around visits with experts, who often contradict one another. It can mean serious study about treatment options, none of which is without risk. This new normal means living with a higher level of risk -- risk that the disease could take off even faster if something is not done, or if something particular is done. It means a little more anxiety within the family, an end to the lingering sense of security new patients often enjoy. “Watch and wait” becomes a serious affair and can be akin to sitting in a foxhole not knowing when the first shell will land. In this new normal, time can begin to take on the element of a luxury. For many it is accompanied by symptoms -- fatigue, infections, night sweats, lymph nodes that have grown big enough to hurt, spleens that twinge in the night.

For patients who are at later stages than I, I imagine the new normal can be all-consuming. Heavy-duty treatment, and recovery from that treatment, or complications from that treatment, or the failure of that treatment, all may bring an element of emergency to having CLL that was missing before. Wondering what in God's name is next, searching for something that might work, spending tens of thousands of dollars to find a perfect bone marrow donor, fighting insurance companies, all can be rolled into a ball in which the new normal is little more than a constant state of anxiety -- anxiety carried with you on the proverbial emotional roller coaster with its exhausting ups and downs. For those who have undergone transplants, graft versus host disease is a constant reminder of where the journey has led. And for some, perhaps, the success of a transplant may mean, at long last, the easing of fear, the release of the dragon, a profound relaxation. At any point in the journey, we all enjoy remissions. So successful chemotherapy, too, can restore life almost to its original gait -- until the sword of Damocles returns again from the mist.

And for those less fortunate, for whom the last options have failed, the new normal can mean acceptance that the battle has ended, entry into hospice, precious time spent with loved ones, and then a journey none of us know, but which is likely to be far from anything that seems normal here on Earth.

What is clear from all these stages of the new normal is that once you have entered this world you can never truly go back to the old normal, what life was before diagnosis.

Learning to navigate the new normal can be quite a challenge. Some are alarmed at the first appearance of a pea-sized lymph node, and then they get used to it, and then the lymph node becomes almond-sized. This leads to a bit more anxiety, perhaps a doctor visit, heightened watch-and-wait. Eventually, one can learn that two dozen swollen lymph nodes are the new normal, some as big as a golf ball, some causing pressure or pain. A once-slim neck becomes chunky, the limits of one’s vanity get tested when one is seen in public. The new normal means showing signs that others can see that something is wrong. And yet life goes on, the dog needs walking, the rose bush needs pruning, the bills need paying, the kids or grandkids have birthdays that need celebrating.

In the new normal, time moves both faster and slower. Faster in the sense that there may be less of it than planned, slower in that for many people the adage “be here now” begins to happen, often for the first time. Yet, as much as the new normal can be a place of spiritual growth, or growth by tapping inner resources you didn’t know you had, it can also be a depressing place. For some, this means taking antidepressants, or just dealing with perceived doom through layers of gloom. There are moments, common to us all, when we just sit back and sigh and realize, once again, what a bitch it is to have CLL.

Learning what the new normal is for me has been a challenge, and will no doubt continue to be. As readers may know, I have been searching for the next step in my treatment, and for some broader sense of my long-term treatment plan. I have consulted now with four CLL experts, most recently John Byrd at the James Cancer Center at Ohio State University. In The "new normal," Part 2, I will tell you what I have learned along the way, and what I have concluded -- at least for now, until the new normal changes again.

Hope defined: Groopman's "Anatomy of Hope"

One thing cancer patients do, reflexively, is look for hope. Some turn inward. Some turn to doctors. Some turn to unorthodox treatments. Some turn to God. Some bury their heads in the sand and call it hope.

But what is hope, exactly? And how does it affect the course of disease?

Some answers can be found in a well-written and thoughtful book called The Anatomy of Hope: How People Prevail in the Face of Illness, by Dr. Jerome Groopman. Groopman is a hematologist/oncologist and the chief of experimental medicine at the Beth Israel Deaconess Medical Center in Boston. He has practiced medicine for several decades and for nearly 20 years was a patient himself, suffering from a chronic back condition. Level-headed and science-minded, Groopman provides some insights into what hope is, and what it is not. His search is for the middle ground, “where both truth and hope reside.”

Groopman began his medical career in the 1970s, when doctors were trained to deal with the clinical aspects of disease, not the human ones. There was a tendency to view people as collections of symptoms and test results, passive participants in the medical process. Over time, Groopman realized the limits of his training. He encountered some remarkable patients who taught him a great deal about how human emotions and expectations could affect the clinical outcome of disease, both positively and negatively.

When it came to balancing truth and hope, Groopman as a young doctor went overboard one way, then the other. At first, he avoided telling patients much about their conditions, believing this would foster a sense of hope. When patients became angry and resentful that he had not been honest, Groopman took the opposite tack: telling them the cold, hard facts. This included the now-outdated “you have two years to live” sort of thing, which Groopman abandoned after one patient lived to just the expected two years, after which her family informed him that she had been miserable the whole time, waiting for the clock to run out.

(To be fair, patients do not always agree about what they want to know. In CLL, some patients roll their eyes when they are told they have “the good cancer,” but there are no doubt others who are thrilled to hear it. For some patients, knowledge is power; for others, ignorance is bliss. It is the doctor’s delicate role to finesse each patient’s level of interest and involvement while still insuring that the individual gets a basic overview of the medical facts. This is why the cues you send your doctor -- verbally, emotionally, even in terms of body language -- are so important.)

Eventually, Groopman was to conclude that “omniscience about life and death is not within a physician’s purview. A doctor should never write off a person a priori. At the moment of initial diagnosis, closing off options and denying choices is premature and clinically wrong.”

Exceptions to the rule

Groopman reached that conclusion because he discovered that there are some people’s diseases that “did not seem to read the textbook.” He talked of one patient who “didn’t surrender from the start, and not surrendering has sustained her life.” Another, a fellow physician named George, beat stomach cancer, where the odds were 99% in favor of fatality, through sheer will and excruciating chemotherapy and surgery.

“The mustering of the will to engage the foe and the strength to sustain the battle, in themselves, became a form of victory,” Groopman writes. Later, he adds: “To hope under the most extreme circumstances is an act of defiance that, as George explained, permits a person to live his life on his own terms. It is part of the human spirit to endure and give a miracle a chance to happen.”

These miracles, Groopman takes pain to emphasize, are medical ones, and they are rare. Sometimes hope cannot put off the inevitable, but it can make the road to the end easier. As such, hope can take many forms.

One patient, Barbara, fought her cancer with equanimity and good humor. Groopman detected none of the seesaw of emotions that we associate with such a battle.

“Barbara Wilson’s unique calm and acceptance were present from the outset -- not surrender, but steady realism; she set the parameters on her care with a clear-eyed vision of what was possible, what made sense to her, how she wanted to live, when it was time to die. . . . Barbara did not cling to a desperate belief that I would arrive at the bedside with a cure from the laboratory just in the nick of time, though I deeply wish such a moment had occurred . . .

“Barbara’s hope was real and undying . . . it reflected the fact that she had found purpose and created meaning in her life through relationships with her loved ones, and with her God. Barbara did not dwell on the ineffable questions “Why me?” and “Why now?” She saw death as a natural part of life. It is not necessary to be a person of profound faith to hold this view and to act on it. I sensed that my father had the same approach to life and death. Personal philosophy and experience, rather than faith, seemingly prepared him to acknowledge the reality of his mortality.”

Hope, then, can be seen both in will, and in acceptance. This may seem contradictory, but it isn’t. Hope is what gets us through the experience of our disease. Depending upon our personalities and our medical conditions, it may take different forms.

Searching for the mind-body connection

The mind-body connection comes under scrutiny in the book as Groopman searches for a “biology of hope,” science-based evidence to support the improvements and cures that he has seen defy the odds.

Through Groopman’s interviews with some leading researchers in this nascent field, we learn that some aspects of this biology are coming into focus, though we are far from understanding exactly how it works.

Dr. Bruce Cohen, a professor at Harvard Medical School, talked about mind, body, and soul. Our emotions, thoughts, perceptions, and desires appear to be a product of “mind,” and therefore somehow disembodied, “hovering in an ether several inches above our heads.”

“Of course,” Groopman quotes Cohen as saying, “this is not the case. ‘Mind’ is a manifestation of brain. What we view as products of the mind -- thoughts, feelings, and emotions -- are a mighty mix of chemicals and electrical circuits that have evolved over the millennia, and still are changing. So, too, is consciousness -- our memory of the past, awareness of the present, and anticipation of the future. ‘Body’ includes brain, and thus mind, so that the construct ‘body-mind connection’ only emphasizes the artificiality of how we have traditionally divided them.”

(“Soul,” Cohen added, is something else again, “a fundamentally metaphysical and religious concept where the divine spark resides.” The soul is not the product of “cerebral chemicals and neuronal circuits.” There is no way for scientists to “experimentally locate or characterize such a metaphysical entity. It was beyond science; it was a matter of faith.”)

Cohen recommended that Groopman study the placebo effect, and Groopman details accounts where it has been found to be real. The placebo effect can change the autonomic nervous system, help control asthma, speed recovery from a heart attack, reduce joint pain, and help release dopamine from “untapped” areas of the brain, which is an aid to those with Parkinson’s Disease. Hope can, in actual practice, release chemicals in the brain that make one feel better.

“Within our brains are chemicals akin to opiates,” Groopman writes. “These chemicals are called ‘endorphins’ and ‘enkephalins.’ Belief and expectation, cardinal components of hope, can block pain by releasing the brain’s endorphins and enkephalins, thereby mimicking the effect of morphine.”

There is a flip side. Groopman points out that physical pain and deterioration can feed our anxieties and confirm our worst fears. This has the effect of reducing the outflow of the brain’s “good” chemicals, and perhaps heightening those, such as cholecystokinin, or CCK, which can amplify the pain circuitry.

“This is a vicious cycle,” Groopman writes. “When we feel pain from our physical debility, that pain emphasizes our sense of hopelessness; the less hopeful we feel, the fewer endorphins and enkephalins and the more CCK we release. The more pain we experience due to these neurochemicals, the less able we are to feel hope.”

Sometimes treatment of physical symptoms can help restore a patient’s sense of hope and well-being, presumably with a resulting chemical cascade in the brain.

Take fatigue, for example. This is a common complaint among CLLers, and Groopman uses as an example the case of a depressed CLL patient. Her anemia was gradually worsening, and so was her sense of despair, Upping her dose of erythropoietin, to boost red blood cell production, changed her attitude.

The patient told Groopman she felt better. “I’m still tired,” she said. “But not like I was, so fatigued that I didn’t want to move out of bed in the morning.” Groopman writes: “It was as if the relentless signals from her tissues, demanding hemoglobin and the gift of oxygen, had crowded every corner of her mind and allowed no room for hope.”

Hope deconstructed

It is in his interview with Wisconsin Professor Richard Davidson, an experimental psychologist and expert on positive emotions, that Groopman “deconstructs” hope, getting at its essence.

Hope, Davidson posits, is “an emotion made up of two parts: a cognitive part and an affective part. When we hope for something, we employ to some degree our cognition, marshaling information and data relevant to a future desired event.” A cancer patient, for example, has to generate a different vision of his or her condition. “That picture is painted,” Davidson explains, “in part by assimilating information about the disease and its potential treatments.”

But hope also involves a second component, what Davidson calls “affective forecasting – that is, the comforting, energizing, elevating feeling that you experience when you project in your mind a positive future.”

Together, these components “interweave and modify each other.”

Dr. Antonio Damasio, a professor of neurology at the University of Iowa, argues that emotions are “cognitive guides, fostering the process of logic rather than retarding it.”

Hope and other emotions, Groopman writes, can “powerfully influence cognition and other deliberative feeling. They impact the machinery of perception, the circuits that are used to take in and process data and make decisions.”

In other words, as one of my CLL heroes -- the late David Covell -- once put it, hope is an active process. And an essential one for any cancer patient to get a handle on.

Even before reading Groopman’s book, I had the intuitive sense that hope was more than just an emotion. After reading the book, I think it can be seen as the synthesis of emotion and rational thought into a realistic plan for a better future. Creating this vision allows the patient to be proactive and intelligently involved in medical care. Hope is, perhaps, the difference between wanting to do something, and having to.

As time goes on, new information and circumstances can cause us to adjust the vision that arises from our hope, but as a rule hope stands the test of tough times. Once firmly established, it is hard to uproot.

True and false hope

In his final chapters, Groopman looks at hope as a tool for coping with disease.

“While it is a convenient construct to divide hope into a cognitive and an affective component, the two are tightly coupled. Feelings and emotions mold logical feelings and deliberate decision making . . . True hope, then, is not initiated and sustained by completely erasing the emotions, like fear and anxiety, that are often its greatest obstacles. An equilibrium needs to be established, integrating the genuine threats and dangers that exist into the proposed strategies to subsume them. So when a person tells me that he doesn’t want to know about the problems and risks, that he believes ignorance is necessary for bliss, I acknowledge that yes, unbridled fear can shatter a fragile sense of hope. But I assert that he still needs to know a minimum amount of information about his diagnosis and the course of his problem; otherwise, his hope is false, and false hope is an insubstantial foundation upon which to stand and weather the vicissitudes of difficult circumstances. It is only true hope that carries its companions, courage and resilience, through. False hope causes them to ultimately fall by the wayside as reality intervenes and overpowers illusion.”

I would argue that, in CLL, the bar of “knowing a minimum amount of information” about our diagnosis and its course is far higher than in most cancers. This is simply because, as has been well-established, the disease is idiosyncratic, treatments are all over the map if one treats at all, and even the experts disagree on what to do. Therefore, the cognitive element of hope -- the process of marshaling information and data -- is more complex, but no less essential.

What is clear from The Anatomy of Hope is that we patients cannot sit back and expect hope to happen to us. It is an active process, something we must create, and recreate when necessary. Part of this is learning, part of it is intuiting, all of it is essential if we want to live longer.

Hope is a mechanism that optimizes our ability to function. Groopman calls hope “as vital to our lives as the very oxygen we breathe.” As a doctor he searches for it whenever he sees a new patient.

We patients, too, must search within ourselves for it.

As Groopman concludes:

“Patients are awash in a sea of statements about their emotions and their maladies. For years I diverted or dismissed their inquiries because I did not know how to answer. Now my response is formed by the lessons taught to me by my patients and the stirrings of serious science. I recount some of the narratives here, and say we are just beginning to appreciate hope’s reach and have not defined its limits. I see hope as the very heart of healing. For those who have hope, it may help some to live longer, and it will help all to live better.”