Change of Course

It's been way too long since my last post.  I think it's because I was feeling low about getting "kicked out" of the RAD001 trial :(.  It was nice to think that I could just take a pill every day, and I'd start to get better.  Unfortunately, it wasn't working that way for me.  At my last visit to DFCI, Dr. Treon decided we should do a bone marrow biopsy to see if the disease was going anywhere.  There was basically no change to the extent of invasion in the marrow.  So even though the blood IgM levels had been going down, the disease load wasn't improving.  Somehow, the RAD001 got the tumor cells to secrete less IgM, but was not reducing the number of evil cells.

So that led to another difficult decision about treatment.  Dr. Treon recommended some form of treatment with Rituxan.  He laid out the pros and cons of 4 different combination therapies:  Velcade/Dexamethasone/Rituxan; Bendamustine/Rituxan; Cytoxan/Dexamethasone/Rituxan; or Pomalidamide/Dexamethasone/Rituxan (in trial at DFCI).  To make a long and tortured story short, I settled on the Cytoxan option.  Velcade has some scary side effects (particularly peripheral neuropathy, a severe tingling and/or pain in feet and hands);  there's very little data on the long-term side effects of Bendamustine therapy; and Pomalidamide has caused low blood counts in some patients.  Cytoxan has its own issues: it can cause genetic mutations, but it has been in use for decades and oncologists have "tuned" the dosage pretty well by now.  All of these can be administered locally, although the Pomalidamide would be started in Boston and would require a monthly trip up there.

My local hematologist also suggested Rituxan alone, but Dr. Treon pointed out that combination therapy has had much better results.

In an earlier post, before going on the trial, I had decided to try Velcade.  I've read a lot more about it since then, hence my decision to go in a different direction.

I also looked into a number of clinical trials - some sound very intriguing - but ultimately decided that since I've tried one experiment, now I'll try the "traditional" treatment.  WM is an indolent disease, and my symptoms haven't been too bad, so if the Rituxan doesn't work, I can try something else after that.

So on October 4, my wife Jodi brought me up to the cancer center at Overlook Hospital to start my infusions.  I'll get infusions every three weeks for six or eight rounds, depending on the response.  I felt fairly optimistic, because the regimen has been in use for many years and is pretty well understood.  As Dr. Treon told me, it's not rocket science.  The infusion lasted about 5 hours, and Jodi hung around for moral support.  There wasn't much to do, really, and she was able to get some work done.

Rituxan is a derived from a mouse antibody.  When your body encounters it, it's not unusual to get a severe allergic reaction as your own antibodies gear up to ward off this intruder.  So they start you off with a big dose of IV benadryl to try to lessen the reaction.  That made me pretty drowsy, and I napped for the first hour or two.  The Rituxan infusion is started at a low rate, and increased every hour or so, again to try to control the allergic reaction.  If there's a reaction, they slow it down or stop it until the sneezing or whatever stops.  I was lucky, I guess - I had no ill effects at all.  At the end of the day, I expected to be able to go to work on Tuesday.

That's when the trouble started.  I woke up Tuesday feeling a little nauseous - a normal reaction to the Cytoxan - so I started taking anti-nausea pills on a four-hour schedule.  Then I was exhausted all day.  I was able to work a few hours from home.  On Wednesday, I managed to get in to work - I really wanted to resume normal life - but I arrived late and had to leave early because I was so fatigued.  I actually was a little worried on the drive home that my reaction time might be slowed down enough to be dangerous.  Thursday was a little better - and that's when I noticed that the pill bottle said "may cause drowsiness."  So I switched over to a different pill that you could take on a 12 hour schedule, and felt much better.  I'm not sure whether it was the pill or the Cytoxan reaction that caused the problem.  I guess I can find out after the next infusion.

The weekend was OK - I was tired, but not like during the week, more like the anemia-related tiredness that I'm pretty used to.

Two steps forward, one step back?

A couple of weeks ago - Friday the 13th, to be exact - I had a blood test that showed the count of a particular type of white blood cell to be 0.7.  The normal range is 2.0 to 7.8.  When I started on the trial, the count was 2.29, I think; it's hard to tell, because each test site (DFCI, local hematologist, and a clinic on Long Island) reports the number under a different name.  The local tests report it as "GRAN".  The first test at DFCI called it "ABS NEUTROPHILS" (I think), but that doesn't show up on subsequent DFCI tests.  The Long Island clinic reported it as NEUT %, which was a percentage rather than an amount.  Anyway, my local hematologist felt that the 0.7 number was too low, and recommended holding the RAD001 for a few days.  The doctors at DFCI concurred, and asked for a re-test on the following Monday, which was when I went to the clinic on LI.  That test showed some improvement in the white blood cells.

I'm a little confused as to why I'm on hold, because the number has been bouncing around between 0.7 and 1.4 for several weeks.  The DFCI team expressed concern about the hemoglobin level as well, which was 7.7.  (Normal is 14-18, although I started the trial at 8.5 and have been below 8 since early July.)

A blood test yesterday showed results almost identical to the test on Friday the 13th, so DFCI is having me continue to hold the drug.  Adding to my confusion is that while the LI test showed improvement in the white blood cells, yesterday's test showed me back down again.  The local tests also report GRAN as a percentage, and if that's the same measure as the NEUT % on the LI test, the measure has gone from 21.0% (8/13), to 44% (LI), and back to 19.3% (yesterday).  How can that make sense, unless the test machines are wildly variable?

I'll be up in Boston next Tuesday, when they'll test me once again and see if I can get back on the drug.  Meanwhile, I'm worried that the progress I've made (as measured by the IgM levels) will be lost.  I'm also worried that I'll have to go off the trial, which will put me back in the position of having to decide on what treatment to follow next.

Whatever happens with that, I'm going to try to get the DFCI doctors to explain how to compare the white blood count results from the different labs.

Dear Diary

Dear Diary - I've been ignoring you for the past month - shame on me!  I guess I got saturated with WM information, and needed a break.  I switched from reading everything I could about WM to reading mystery stories (Stieg Larsson highly recommended for escapism).

Anyway, I've been on the RAD001 trial for 2 months now, and want to catalog my experience so far.  I started out taking 10 mg/day.  WM is characterized by a proliferation of a particular white blood cell (a kind of "B" cell) in the bone marrow; these B cells secrete an abundance of an antibody called IgM.  IgM is a normal antibody produced by the body, but when you get too much of it, your blood can get thick and viscous, which can cause all kinds of problems.  Think of the thick, viscous tar balls washing up in Louisiana.  Also, the WM-related IgM is not the same as the normal IgM.  Anyway, the IgM level in my blood is improving.  It started at 3190.  After one month, it was 2990, and it is now 2640.  This is a 17% overall drop, which falls into the official definition of "stable disease".  In other words, if this were the end of the trial, the doctors would say it didn't work.   Normal IgM levels are somewhere in the 45 to 250 range.  "Minor response" is defined as a 25%-50% drop in IgM; "partial response" is a sustained drop of 50% or more; and "complete response" requires that the "bad" IgM disappear altogether, and that the bone marrow shows less than 20% of the "bad" B cells.  (I had 95% bad B cells at diagnosis.)  Still, I'm encouraged, since at least the IgM is going in the right direction, and the rate of change is improving.  Measuring the bad B cells involves taking a sample of the bone marrow, which will be done at the 6-month mark.

On the negative side, my anemia has been fluctuating and actually got to a level requiring a transfusion.  The level of anemia is usually characterized by one or both of two numbers that are measured in a blood test called a "Compete Blood Count", or CBC.  These numbers are the hematocrit (HCT) and the hemoglobin (HGB) level.  For adult males, HCT should be in the range 42% to 54%, and HGB should be in the range 14 to 18.  Shortly after diagnosis, my HCT was measured at 24.5% and HGB was 8.5 at the Dana-Farber Cancer Institute (DFCI), where my trial is running.  HCT/HGB were measured as high as 29.8/8.9 at my local hematologist in June, but were measured at 21.4/7.5 at DFCI this past Monday (7/26) - that's when I got the transfusion.  The study doctor had me skip the drug for two days, then resume at 7.5 mg/day.

I've learned that the CBC numbers can vary pretty dramatically between doctor's offices.  At my local doctor, they put a few drops of blood into a machine about the size of a big laser printer, and it prints out a report after a few minutes.  At DFCI, they do something different that involves sending many vials of blood to their lab.

Other side effects have included mouth sores, which are controllable via an oral rinse containing a steroid called dexamethasone.  I've also had more bloody noses than usual (2-3 times per week, as opposed to maybe twice/year before diagnosis), and frequent muscle cramps in my leg and foot at night, although the DFCI team doesn't seem too concerned.  Bananas and Powerade are controlling the cramps.  I've always had eczema that comes and goes on my hands, and it seems to be more persistent right now than usual.  I doubt it's connected, but who knows.

The last few days I've been noticing some tingling and numbness in my hands and fingers.  This can be a side effect of the drug, and can also be a symptom resulting from the raised IgM levels.  I'll need to discuss this with the trial team.

Pernicious - Oh, Dang!

In the midst of all the excitement with the Waldenström Macroglobulinemia, another problem that the hematologist noticed hasn't been addressed fully.  In addition to the unusual proteins in the blood that led to the Waldenström diagnosis, he noticed a vitamin B12 deficiency.  A couple weeks ago, at my weekly blood test, he ordered a test for intrinsic factor.  What's that, I wondered.  Off to Google I went, to learn about it.  It's a protein that needs to be present for proper absorption of the vitamin.  A lack of it, along with a B12 deficiency and low hemoglobin, indicates something called pernicious anemia.  Boy, that doesn't sound very pretty!  It's also characterized by a wide distribution of red blood cell sizes.  Oh dang - my blood test results show that RDW - Red blood cell Distribution Width - is high.  So my red blood counts are low (anemia); the cell sizes are widely distributed; and now we're testing for intrinsic factor.  I spent a week worrying about pernicious anemia.

The following week, when the test came back, the nurses said the test was negative.  "Is 'negative' a good thing, or a bad thing, in this case?" I asked.  They said it was a good thing.  Unfortunately, the hematologist wasn't available to discuss it that morning (last Monday), but I had an appointment to talk to him today.  "So, no pernicious anemia, eh?" I asked him.  He clarified: the test looks for an antibody that destroys intrinsic factor, and the negative result meant that the antibody is not present.  That doesn't mean I do have enough intrinsic factor and that I don't have pernicious anemia.  Oh dang, again.  He said that the next test would be endoscopy, where they stick fiber optics down your throat and look around inside your stomach.  Apparently there is pathology that can be observed to diagnose pernicious anemia.  That would be consistent with the RDW numbers, which I forgot to ask him about.  Meanwhile, he's not particularly worried, especially since I'm taking B supplements every day.  He said let's wait for the WM to settle down a bit, then do the endoscopy.

Two weeks in

I've been in the RAD001 trial for just over 2 weeks now (started Wednesday 6/3).  There have been no serious side effects, although I'm writing down every ache, pain, bruise, sniffle, and other potential symptom.  If any of them evolve into something more serious, I want to be able to say definitively when it started.  I did have a mild nose bleed that recurred every morning for about a week, but I had a blood test today (Friday 6/18) and discussed the platelet count with Dr. Treon.  Neither he nor the local hematologist could see anything in the blood count that would cause unusual bleeding.  There were no bloody clots in my nose this morning, so perhaps it's gone away, and I'm also not bruising or otherwise bleeding abnormally.

And the good news is that my anemia is improving!  At the start of the trial, the hematocrit number was 24.5.  It increased steadily in weekly blood tests, and is now at 29.8.  It's got a way to go, though; normal is 35 to 52.  There are other red blood cell numbers that (it seems to me) should be improving as well, but the improvement isn't quite as clear.  Dr. Treon tends to focus on the hematocrit.

But lest we get too optimistic, my white blood count has been going down.  Neither of the doctors is concerned, but we need to keep an eye on it.  At the start of the trial, the granulocyte count was 2.05 thousand/microliter; it has dropped to .9 (although it held steady at .9 all this week).  I'll have another complete blood count (CBC) test on Wednesday, to be on the safe side, and then it's up to Boston on Monday 6/28.

See-saw

We're used to having a doctor tell us "the answer," and not just put a bunch of options in front of us to let us choose from.  If you have a sinus infection, they don't say you could take amoxicillin or Cipro, and here are the differences; they basically pick one for you, and tell you why.  They write the prescription, and off you go.

The treatment decision for WM wasn't anything like that.  I felt that the doctors would lay out a spectrum of possible treatments, point toward one, and then go to great lengths to push the decision back to me.  At first, it seemed almost like a guessing game: what question should I ask to get him to make a strong recommendation?  Should the first one he pointed to be the one to pick?  I guess it's because much less is known about the disease than is known about sinus infections, and that none of the treatment options is a sure thing.  It's not a sure thing that amoxicillin will knock out your sinus infection either, but it's a pretty good bet, and if it doesn't work, the Cipro is almost sure to work.  (Unless, of course, you've got one of the new "super" bugs.)

So this led to an emotional see-saw ride over the last few weeks.  At first, after consulting with the Bing team at DFCI, I was leaning toward the trial.  A few days later, the nurse-practitioner called with my lab results, and told me that I was well qualified for the trial.  So I decided the trial was the right thing.  But then Dr. Treon called me that same night, and said that I should strongly consider the Velcade/Dex/Rituxan chemotherapy, because of the level of marrow invasion.  I talked to my family doctor, and then to my hematologist, and made up my mind:  the chemotherapy was the right way to go.

Over the next few days, I started reading some scary things about the side effects of the chemo.  I stayed the course, though: it was important to make a decision and move forward.  My hematologist chipped away at my resolve by saying that he would support the trial, but I remained steadfast.

Finally (at least I hope it's final), Dr. Treon called again to ask me to reconsider the trial.  He had some new information that made it sound like it might be a better option after all.  So now I changed my mind again, and am headed for the trial.

Did I say emotional see-saw?  More like a roller coaster.  I told both doctors - Dr. Treon in Boston and my local hematologist - about my feelings.  They said that with cancer, they believe that it needs to be a joint, informed decision.  As more information became available over the last few weeks, the decision parameters changed, and it was up to me to choose the path.  But even though I've learned a lot over the last month, I'm still a neophyte compared to either of the doctors.

Back to Boston

Last Thursday, just over a week ago, I was all set to start the Velcade/dex/Rituxan treatment.  I just wanted to have my local hematologist finalize how he would work with Dr. Treon.  For whatever reason, they weren't able to get in touch right away.  Dr. Treon was away on Thursday, but he always has his cell phone, so it seemed strange that, by Tuesday, they still hadn't talked.  So the hematologist called me on Tuesday to say he hadn't heard anything.  He emphasized that it was important to get some treatment started, whether it was the Velcade or the RAD001 trial.  This was after I had decided, with his concurrence, that the Velcade treatment was probably the best bet.  So now I was confused again: why did he mention the trial option?  But after thinking about it, I decided to stick with my decision.  After all, Dr. Treon, the expert, seemed to be leaning in that direction.

Meanwhile, I started seeing all kinds of scary side-effect reports about Dexamethasone on the IWMF-TALK mailing list.

By Thursday, they still hadn't been able to talk, and then Dr. Treon called me on Thursday afternoon.  He reminded me that he had been leaning away from the RAD001 trial because of the level of invasion in my marrow (95%), the low hemoglobin (8.5), the fact that he had seen hemoglobin (HGB) drop even further in other patients, and that he hadn't yet seen if the RAD001 had an effect on the marrow.  But now, another patient with a similar age and disease profile to mine just passed the 3 month mark, and he found in a bone marrow biopsy that this patient's level of invasion had dropped significantly.  Now he leans more toward enrolling me.  What to do, what to do, what to do?  I told Dr. Treon I thought the trial would be a good idea, but wanted to discuss it with my family and with my doctor.  Thursday night, I left a message at the hematologist's office to please call!


So this morning, Friday, I heard once more from the hematologist.  Finally, he had spoken to Dr. Treon.  He said that he was fine with the trial, and that he would be glad to take care of my local care.  I'll be taking the RAD001 orally, and my blood counts will have to be monitored regularly.  Since the HGB could well drop, I may need transfusions to bring it back up.

And now it's back to Boston to get the trial started.  Dr. Treon will be taking a bone marrow biopsy (BMB), both to get a baseline and to put it into a data base he intends to use to investigate whether there is a genetic basis to the disease.  He's got close to a thousand samples in it already.  They'll give me my first month's supply of pills and a diary to keep track of my compliance and any side effects.  I'll also need to find out exactly how often I'll need to get blood work and other lab work done, and what sorts of side effects might constitute an emergency.  I'll take the train up next Wednesday morning, and be back late in the evening.  Easy as pie.

After that, I need to go to Boston once a month for complete blood work, and for a BMB at the end of the third month.  With luck, that will be the next decision point; with more luck, the drug will be working and the decision will be to stay on the trial.

Information Overload

It has been an exciting 3 weeks since my diagnosis.  I've joined the IWMF-TALK mailing list; I've been to see the research team at Dana-Farber; I've had 2 consultations with my local hematologist and several phone calls with my family doctor; I've received a monster info packet from IWMF, and started to digest that data; I've learned about some of the treatment regimens, but can't keep them straight in my head.  I've told my family, some close friends, some co-workers, and my minister that I have incurable but likely non-fatal cancer.  And I need to decide this week what direction to take!  Most likely, it will be Velcade/dexamethasone/Rituxan, and I need to get straight in my head what's involved and also work out how to keep the Dana-Farber gang involved.  I wish I had another 2 or 3 weeks to digest what I've heard and continue the research.  I just found an educational DVD that you can order from the IWMF with presentations by most of the Bing (Dana-Farber) team, and I'd love to be able to watch that before deciding.  I'm going to order it anyway, and just keep plugging away at everything.  Even though I'm pretty certain what path I'll be heading down, there are certain to be plenty more decision points along the way.  The more I know about what's going on, the better my decisions will be (I hope) when I come to those forks in the road.  Right now, I'm not even sure whose woods these are...

Just when I thought it was safe...

Dr. Treon called me tonight to say that with the tumor load in my marrow (95%), it may be better to go with a Rituxan-based treatment.  He hasn't seen tumor load decrease with RAD001 treatment in the short term - that is, at the three month point - in any patients.  He hopes to see it at the six month point, but that data isn't in yet.  At the same time, he said he could support a decision to go ahead with the trial, but that it might require more vigilance and patience on my part.  He wasn't specific about what adverse events might occur if the tumor load doesn't go down, other than likely continuing worsening of the anemia.

He would lean toward Velcade-Dex-Rituxan.  (Dex = dexamethasone, a steroidal anti-inflammatory and immunosuppressant).  Velcade is a biologic drug, so that while it tends to kill tumor cells, it doesn't damage DNA.  This means that there is less likelihood of its causing other cancers later on.

So now I'm confused again.  I have an appointment with my hematologist in the morning, and will see what his perspective is, even though he doesn't have a lot of experience with WM.

Oats Schmoats!

When I was first diagnosed with Atrial Fibrillation (see the "A Prior Adventure" post from May 5), I also found I had high cholesterol.  I went on a strict regimen of exercise and low-fat vegetarian eating, and brought the cholesterol down from 220 to about 150 in just 6 months.  I made myself think of cheese and butter as poison.  One of the key dietary components was raw oats with fresh fruit and soy milk every morning.  Since then, the cholesterol has stayed low, even though I now eat a fair amount of fatty foods (like pizza, buttered bagels, yum) and haven't had the energy for regular exercise - and I had attributed this to my daily oats.  Until this afternoon.  This afternoon, I found out that one of the effects of WM is to lower cholesterol.  So once the disease is under control, I guess I'll have to start being careful about pizza again :(

Harvesting Stem Cells

As I continue to read and learn, I keep running into the idea of harvesting stem cells with the idea of holding them in a freezer for an eventual bone marrow transplant.  The purpose would be to flush out all the diseased cells, and replace them with new, healthy cells.  (Actually, the stem cells will grow into healthy cells.)  The harvesting is done after a course of treatment has diminished the disease.  I asked Dr. Treon about this, and he said they don't recommend it, because there is a 10% mortality rate with an autologous transplantation (meaning you put your own, previously harvested cells back), and a 50% mortality rate if you use someone else's (almost always a very close relative).

Feeling in a RAD mood

I'm pretty sure I'll sign up for the trial.  I don't think there's much of a downside.  I had a few questions that I sent to Dr. Treon and his Nurse Practitioner (Trish Sheehy), but Ms. Sheehy cleared them up on the phone this afternoon.  Here are the questions and answers:


1.  In section B of the consent form, it says that "the purpose of this research study is to determine the safety of RAD001..."  Could you please confirm that the purpose is also to determine the efficacy in treating WM?

- the purpose of the trial is both safety and efficacy

2.  Is the definition of "the drug is working to reduce WM" (page 3, section D, second paragraph of the consent form) a decrease in IgM level, decrease in bone marrow involvement, and resolution or reduction of adenopathy/organomegaly?  In particular, if the IgM decreases and there is decreased bone marrow involvement, but my anemia doesn't improve, would the treatment be deemed successful for the purposes of the trial?

- this is correct: IgM levels, bone marrow involvement, and adenopathy/organomegaly are the indications.

3.  One of the "less likely" risks (page 10, 4th bullet) is anemia.  As I understand it, the reason that near-term therapy (as opposed to "watching & waiting") is recommended for me is my existing anemia.  Is there any reason to think that I'm at additional risk because of my anemia?

- my anemia is likely to worsen, at least initially.  If the HGB level goes below 7, they interrupt the trial and give me hormones to stimulate red blood cell growth or else a transfusion, and resume when the level recovers.  If this happens 3 times, they discontinue me.  Since my HGB is currently 8.5, they will monitor this closely.

4.  My family doctor had the concern that if I go on the trial, and it doesn't help, then I'll have lost some time on the more traditional therapy.  On the other hand, it's my understanding that the Rituxan-based therapy might fail as well.  My feeling is that since there's a risk of no-response either way, perhaps this isn't an important consideration.  Does this sound like a reasonable point of view?

- NP Sheehy considers this a reasonable point of view.  Either treatment could fail, and the alternative can be started.

And related to the disease in general rather than the trial specifically:

5.  What are the likely negative outcomes if the disease is left untreated?

- The anemia will likely get worse, and eventually start to damage organs including the heart.  The malignancy can also spread.

6.  What is the expected survival rate?  Much of the literature says 5-7 years, but at the same time some of it says that with therapy, the symptoms can be managed and the disease is not likely to be fatal.  What is the Bing Institute's view on this?

- At the Bing Institute (the WM research center at Dana-Farber), they currently view the survival rate as 12-19 years.  They can't say more than 19 years only because they haven't been studying it that long.  It sounds like, for all intents and purposes, the treatments can manage the disease.  NP Sheehy believes that the 5-7 numbers that are all over the Web haven't changed because the organizations that post them (e.g. American Cancer Society or National Cancer Institute) just haven't kept up with the latest research, because they're busy with the more common cancers like lung cancer and breast cancer.

Anxiety unwarranted

The visit with Dr. Treon was by any measure a big success.  The facility is world-class: several of Boston's biggest and most prestigious hospitals (Beth Israel Deaconess; Brigham & Women's; The Children's Hospital) are all located within a few blocks of each other, and the whole complex seems to be closely related to the Harvard Medical School.  There's a branch of the Harvard Coop (basically the Harvard University bookstore) right across the street from the Dana-Farber institute.  The whole area is bustling with doctors, nurses, students, clinicians, and other health-care workers.

Dr. Treon's research center - the Bing Center for Waldenström's Macroglobulinemia - has two full-time physicians (Dr. Treon and Dr. Irene Ghobrial) and a staff of nurse-practitioners, administrators, and other support staff.  It's supported by all the labs and research centers that make up the Harvard research facility.  Dr. Treon said that he gets help from the best geneticists in the world when he needs it.

My visit started with registration, a quick review of vital signs (blood pressure etc), and then 40+ minutes with Patricia Sheehy, Dr. Treon's nurse-practitioner.  She reviewed my symptoms, confirmed that I have WM, and discussed several treatment options with me.  She also patiently (very patiently) answered all my questions about the disease mechanisms, the definition of various terms, and some symptoms that I thought might be related (ringing in the ears; blurry vision).  The tinnitus (ringing) might be related, but the blurry vision is probably not, because rubbing my eyes can make it go away.

Tricia invited me to join a statistical trial where they're tracking about 1000 patients.  This will help them try to identify causes of WM and keep track of which treatment regimens are effective.  I signed right up for that one.

She also described a trial of a drug called everolimus.  Everolimus has been approved in transplantation medicine (as Zortress in the US and Certican in Europe), and for cancer of the kidney in the US (as Afinitor). It has also been approved for second-line treatment of WM, i.e. for treatment of WM if Rituxan therapies proved ineffective.  (To use some of my growing vocabulary of jargon, for treatment of patients who are "refractory" to Rituxan therapy.)  Dr. Treon is working on a trial of everolimus as a first-line treatment, and they invited me to join that trial as well.

After Tricia provided all that information, she left us to read the info about the everolimus trial while she brought Dr. Treon up to speed on my situation.  Dr. Treon came in, and gave me a brief physical exam, including probing the lymph nodes in my neck, stomach, and groin, and looking at my hands and feet for evidence of cryoglobulins (I think).  After that, he spoke with me for 30 minutes or more about the treatment options.  There are several variations of Rituxan treatment, all of which involve Rituxan in combination with chemotherapy and a steroid.  The steroid just seems to make everything work better.  The chemotherapy options are Cytoxan, Velcade, Cyclophosphamide, and Bendamustine.  Each has its pros and cons.  They are what are known as alkylating agents, and they basically stop cells from dividing and cause them, ultimately, to die.  It's not clear to me how they target the correct cells.  He did say that the course of these drugs is limited, because aggressive treatment with them can, in the long term, result in other malignancies.  He didn't indicate how the particular set of drugs is chosen.

My impression had been that with Rituxan therapy, one can expect to go into remission, more-or-less, and enter a phase called "watching and waiting."  In this phase, most of the symptoms have gone away, and your blood levels and bone marrow are monitored.  If the indications (IgM, bone marrow invasion) come back, you go on the therapy again.  Dr. Treon said this level of remission is relatively rare, and that it is much more often the case that after the initial course that a maintenance course is necessary.  The initial course is an infusion of the Rituxan cocktail every three weeks, for 18 weeks (six treatments).  The maintenance is an additional infusion every three months.  An infusion pretty much takes all day, with constant monitoring of your vitals and any effects you may feel (chills, unusual tastes in the mouth, ...).  Also, the chemotherapy can cause hair loss and other "classic" chemotherapy side effects.

Everolimus is a pill.  You take one a day.  For the trial, they require a visit to DFCI (Dana-Farber Cancer Institute) every 4 weeks for the first 3 months, then another visit every three months after that.  The trial lasts 48 months, or until the drug isn't helping your symptoms.  If it's not helping, you can go to the traditional therapy (Rituxan etc).  At the end of the 48 months, either the drug will be approved, and you can stay on it with insurance paying for it, or you can buy it yourself, or you can go to Rituxan.

I'm leaning towards joining the everolimus trial.  I've still got a few questions about it, and they also had to take some blood to make sure I'm eligible.  I went into the blood lab, and they drew 21 separate vials of blood!  I asked them if they could get both arms going at once to make it go faster.  I'll post separately on my thoughts on joining the trial.

Anxious over Boston Trip

Tonight we're driving up to Boston for a 9AM Monday morning appointment with Dr. Treon.  I haven't let myself get upset over having WM, but now I feel like tomorrow will be a day of reckoning.  First of all, I've found out that my hematologist hasn't positively diagnosed WM, but that is his initial thought.  I heard this from my family doctor, who got a letter from him.  I worried that perhaps it's jumping the gun to go see Treon, but she assured me that it's an appropriate step at this point to get a second opinion.

So now I have to worry about what if it's something else?  It's pretty clearly a bone marrow disease, but there are lots of those.  I'be been reading the IWMF-TALK mailing list pretty regularly, and there are so many other things it could be.  I need to just stay calm and see what tomorrow brings.

The IWMF-TALK list is full of information about different treatment protocols, the disease mechanism, support group meetings, recent research and clinical trials, and personal experiences.  I've thought of a whole bunch of questions for Treon, and need to write them down.

So I expect to clear a lot of things up, but probably generate some new uncertainties tomorrow.  That's what I mean by a "day of reckoning."

Latest Treatment

I signed up for a mailing list for WM sufferers.  It's delivering 10-20 messages a day.  It's going to be difficult to wade through all of it, but I did find a gem in one of the threads: a link to the latest treatment protocols by Steven Treon.  It's from July 2009, so it's pretty up-to-date.  I'll be reading it before my next appointment with my local hematologist and before I go up to Boston to see Treon.

Talking to the Family

How do you tell your family about this?  I talked to the minister at the church we belong to about it to see what insights he might have.  He suggested just staying calm and sticking to the facts.  That's easy for me, being a factoid freak.  It also makes sense.  I'm not real upset about the situation at present, so there's no anxiety to pass on to others.

My wife has known about the diagnosis as long as I have.  She was with me when I got the good news (it's not multiple myeloma)/bad news (it's an incurable but usually manageable blood disorder) from the hematologist.  We talk about how we feel about it, and she subscribes to the blog to get my logical analyses and descriptions of the situation.  She seems to be about in the same emotional place as I am right now:  this is a serious state of affairs, but not something to get panicked about.  It needs to be treated, but it's not an emergency.

My high-school son saw me looking at the huge package from the IWMF (see previous post) the other day, and asked me what it was all about.  I had previously told him about the anemia, so he was curious about what's been diagnosed.  I told him it's an incurable but treatable disease and that I'll be going to Boston to see a world-class expert.  He took it fairly well.

My daughter called this evening, and I took the opportunity to tell her about it.  I was going to wait until she visits this weekend and tell her in person, but the time just seemed right.  Since there are no good guidelines about how to do this, I just opened up.  Like everything else about being a parent, there's no clear-cut way to handle this situation.  The conversation went well, although it tends to get tricky when the words "incurable" and "cancer" come up.  She was upset with the news - we all are - but seems to understand why we're relatively calm.  She had lots of questions, and I told her we're continuing to learn about the disease.  She'll be reading this blog to follow what I learn and to follow my emotional progress as the adventure moves forward.

Boston Bound

I've got an appointment with Steven Treon at the Dana-Farber Cancer Institute for the 17th, but I'm going to move it to the 24th.  They want medical records a week in advance, and there's no way I'll get the records to them by Monday.  I'm excited about this: as mentioned in previous posts, he's The Man when it comes to WM.

A package arrived from Dana-Farber today.  It's got a list of places to stay near the center.  There's a wide variety of options, from the YMCA at about $40/night to fancy hotels @ > $200/night.  There is also a network of volunteers who let patients stay for free in their homes.  Sort of couch-surfing for cancer patients.  There are some reasonable options for under $100/night.  I'll probably pick one of those; I'm not interested in a 4 star hotel, and don't want to mess with the volunteer network on my first visit.  If I end up making lots of trips (don't consider that likely at this point) I may look into it.  My plan is to go up on Sunday for a Monday appointment and return home that same day.

IWMF

The IWMF - International Waldenström's Macroglobulinemia Foundation - sent me a giant package of information about the disease.  In addition to a welcome letter with phone numbers for support groups and people with information about various aspects of the disease, the package includes 6 glossy five-by-eight booklets:

• Review of Therapy, discussing various therapies and the scientific literature on their outcomes;
• Treatment Options, which appears to cover much of the same material but from the point of view of the patient rather than as a review of science;
• Medical Tests, discussing the various tests to diagnose the disease and the reasons for performing them;
• Basic Immunology in Waldenström's Macroglobulinemia, describing the relationship between the disease and the immune system;
• Healthy Living, which recommends healthy lifestyle choices which are intended to make it easier to live with the disease (nutrition, exercise, the usual suspects); and
• Questions and Answers, a basic FAQ list (Frequently Asked Questions, for non-geeks out there) on the disease and treatment.

The plan is to plow through all of these.  So far, I'm about 20 pages (out of about 60) into the first one above.  It's heavy going - lots of references to scientific literature, and discussion of outcomes both in terms of remission of symptoms and life expectancy.  I'm still struggling a bit with this life expectancy thing; I kind of think that this booklet focuses on it in the discussion of various studies because the disease is a cancer, and that's a standard measure of effectiveness.  My current point of view is that it's not likely to be fatal ("It is more likely that you will die with WM than from it"), but that one could die from it, just as one could die from a cold, or from the flu, or the measles, or just walking down the street.  This is one of the things I intend to discuss both with my hematologist and with Steven Treon when I see him in Boston.

Anyway, that's getting away from a discussion of the IWMF.  Besides all the material they sent, their Web site has all kinds of good information.  Among other things, there's a discussion group that I intend to join.  According to the Web site, the group has about 20 messages per day.  I'll see how that works out, and post something about it..

There are no support groups listed for NJ, although there is one for NYC.  I've emailed the named contact for that group (last week), but haven't heard anything back yet.  In the package the IWMF mailed to me, there is a support contact in NJ for Rituxan treatment; he's in area code 201, so it's not too far from here, and I'll get in touch with him soon.

A prior adventure

About 10 years ago, I started noticing irregular heartbeats.  The episodes would usually last no more than a few minutes, but occasionally would last an hour or so.  It got to the point where running up a set of stairs could wear me out, if it was during an episode.  So I went to the doctor one morning when I noticed the symptom.  He gave me an EKG, and told me to get someone to rush me to the hospital - my heart was in atrial fibrillation.  I told him it would likely go away in half an hour or so, but he was adamant.  So I went back home, got a toothbrush and a paperback, and headed to the emergency room.  The toothbrush was in case they checked me in (which I doubted), and the paperback was because there's always a long wait in the ER.  I didn't even bother to call my wife, because I was sure I'd be heading home soon.

Sure enough, when they hooked me up to the EKG at the hospital, no a-fib.  The cardiologist initially thought my family practitioner must have been mistaken; but when I mentioned his name, he said he knew him and doubted he had mis-diagnosed me.  So he asked me to schedule an appointment at his office for a more complete evaluation.  After lots of testing, and assurances that the risk of a complication was low, they put me on a blood thinner and an anti-arrhythmic drug called Fleicanide.  This took care of the condition for about 8 years, although I had to cut way back on caffeine and alcohol.  I only drank decaf coffee, no caffeinated sodas, and just a few glasses of wine a week tops.

Then the arrhythmia started to return.  Eventually, it turned out that the Fleicanide can become ineffective after long usage, and can actually aggravate the arrhythmia.  I had to stop taking it, and took a beta blocker instead - which was not nearly as effective as the Fleicanide had been.  So for the next two years the arrhythmia, while not a big danger, interfered with my active lifestyle.  The next step was radio frequency ablation.  This is an invasive procedure where an electrophysiologist - a cardiologist with a sub-specialty in arrhythmia - uses catheters to zap small areas of heart muscle with microwaves to change the electrical conduction patterns in the heart.  They're not sure why, but this can more-or-less cure a-fib.

The first try, in the Fall of 2008, didn't do the trick.  He tried again in April of 2009, and that seemed to work.  But while I was in the hospital - the procedure takes several hours, and recovery takes 1-3 days - the doctor noticed that I was anemic.  He gave me a transfusion, and told me to follow up with my family doctor.  And that's what led me to the current diagnosis.

So for the last two years I haven't been exercising nearly as regularly as I used to.  I feel that I've got to get this started again, because I want to be in good physical condition for whatever treatment is in store for me next.

Local care and support

As mentioned in the previous post, Chris Patterson on Dr. Treon's staff sent a reference to a doctor at the Hackensack Medical Center - Dr. David Siegel.  Looking over his CV, he seems to be more focussed on multiple myeloma, although he is a member of the WMCTG (Waldenström's Macroglobulinemia Clinical Trials Group).  He doesn't have any trials underway at present, as far as I can tell.

There seems to be very little activity at Sloan-Kettering, and a smattering at Weill-Cornell, both in NYC.  It's notable that Chris Patterson (previous post) didn't refer anyone from either of those places.

The IWMF has a link for support groups.  There isn't one listed for NJ (which makes me all the more eager to get consultation from someone out of the area), but I emailed the contact for a group in NYC yesterday.  So far, no response...

The Bing Center

Dr. Treon's center is called the Bing Center for Waldenström's Macroglobulinemia.  Last Friday, I got an email from the Administrative Director of the center, Christopher Patterson.  He's also the "organizing secretariat" of the last two international workshops.  Here's what he had to say:

I called Karin Anderson's number today.  She wasn't available, but someone named Jake took all my information and promised that she'd be back to me within a day to schedule a consult.  They take my insurance, yay!  My local hematologist wants me to have a CAT scan to rule out lymphoma - scheduled for Friday - so I'll set up to go to Boston after those results are in.  I'm excited that Treon may be able to work with my local doctor regarding my treatment.  I'll have to remember to ask him if he just sets initial direction, or if he stays involved during the progression of the treatment and disease.

Thank you very much for your email. In terms of a second opinion, Dr Treon is accepting new consults and can work with your local oncologist in terms of direction of treatment and diagnosis. To speak with our new consult administration, please contact Karin Anderson at 617.632.3823.

If you wish to look for a second opinion within your area, Dr David Siegel at the Hackensack University Medical Center, Hackensack, NJ. The link for his information:

http://www.wmctg.org/biopage_Siegel.html


Attached, please find the Bing Center for WM's April newsletter. Should you have any questions, please feel free to contact me.

All the best-

Chris

The Bing Center April newsletter wasn't real informative; it was just an announcement for a meeting of a support group (already passed).  But it's good to learn that there is a support group up in Boston, and it will be worth keeping an eye on what they're presenting there.

Network works

My friend Annie came through - her brother was able to find out that Dr. Treon is indeed the leading expert on Waldenström's Macroglobulinemia.  He (the brother) is no longer at Dana-Farber, but has many contacts there.

This prompted me to do some more googling (never binging!).  There have been 6 international workshops on the disease, and Treon has been a presenter or organizer for most of them.  So he should know as much as anyone about what to expect.

Networking

A few years ago, I did some software consulting with Novartis Oncology.  A colleague from my company, who became a good friend, has subsequently taken a job at Novartis.  Coincidentally, she also has a brother who is an oncologist at Dana Farber Cancer Institute.  I asked her if she'd see if her brother has any insights into the disease, and also if he could find out who some of the experts are.  In particular, he may have information about Steven Treon (mentioned in previous posts), who's also at Dana Farber.


She also made the excellent suggestion that I search the Novartis web sites for information about the disease.  So far, I've found about a dozen pages under novartisoncology.com - more on those later when I have a chance to browse through them.  I'll do the same kinds of searches at other pharmas to see what info they have, and to get more clues about who the experts are.

That was quick!

As previously posted, it looks like Steven Treon might be one of the "top" specialists in Waldenström's Macroglobulinemia.  (It's starting to get easier to type that word - some "muscle memory" is developing.)  He already responded to the email I sent him last night; here's what he said:

We see folks from NJ all the time, so happy to see you. Best for you to call our new patient admin, Karin Anderson (617 632 3823) to arrange for an appointment.  I will cc: her on here too.

With best regards,

Steve Treon

I want to do a little more research first, and need to understand the insurance situation, but I'm pretty sure I'll go visit him.  It's about 4 1/2 hours away, but we're dealing with an incurable disease.

Ongoing question list

I'm going to use this post to collect questions for the hematologist.  First, here's a list from the American Cancer Society:

• Do you recommend starting treatment now or waiting until later on?
• What options do I have for treatment of my Waldenstrom macroglobulinemia?
• What options do I have for reducing symptoms of my Waldenstrom macroglobulinemia?
• Which chemotherapy drugs do you recommend? Would you compare their effectiveness and side effects to others?
• Are biologic therapies or stem cell transplantation an option in my situation?
• What side effects can I expect from my treatment?
• What should I do to be ready for treatment?
• Should I get a second opinion?
• How long will it take me to recover from treatment?
• When can I go back to work or resume other activities after treatment?
• What are the chances that my cancer will recur?
• How long do you think I'll survive?

Now, here is my (growing) list:

• Who are the experts on this disease?
• Is Rituxan a "biologic therapy"?
• Should I consider taking part in a clinical trial?
• There seems to be some research indicating that apoptosis (cell self-death) therapies exist.  What can you tell me about them?
• What are the "important" blood numbers?  In particular, what are my Immunoglobulin-M (IgM) and red blood cell count (RBC)?  What's the difference between the hemoglobin (HGB) measure and RBC count?

Getting Diagnosed

Well, I was found anemic while in the hospital about a year ago for a heart procedure. Over the last year, I've had various blood tests and a colonoscopy to try to figure out where those red blood cells are going. Finally, about a month ago, my primary care physician noticed some abnormal protein levels in my blood. She sent me to a hematologist.

The hematologist ordered a bone scan, a bone density evaluation, a bone marrow biopsy, and more blood work, and ultimately diagnosed Waldenström's Macroglobulinemia. This was, in a way, good news; the initial indications could have meant multiple myeloma, which is an incurable blood cancer that killed my mother. What he didn't say was that it's a form of cancer. He told me that treatment would include an agent called Rituxan as well as chemotherapy, but he didn't use the "C" word.

Subsequent research on the Internet (cancer.gov, cancer.org, wikipedia) revealed that it's a very rare cancer - only about 1500 cases diagnosed per year in the US. Yikes, it's cancer. Incurable cancer. Average age of diagnosis is 63 years old, and average survival is 5-7 years. That sure scared me - but then I also read at iwmf.com (International Waldenström's Macroglobulinemia Foundation) that one is more likely to die WITH the disease than OF the disease. I'm still not sure what all this means. I'll be seeing the hematologist again in a few weeks, and will have a lot of questions for him.

Fortunately, it's a slow-moving (indolent) disease, and one doesn't have to jump right into treatment. This gives me some time to research it, understand it better, and prepare my questions for the next visit.

Meanwhile, given the rarity of the disease, I'm going to get a second opinion, and from someone who has as much experience as possible with it. My hematologist said that he sees a case about every six months, but I've got my doubts. If there are only 1500 per year in the country, that's about 30 per state, and he sees 2 of them? I guess it's possible, but it seems like more than his share. In any case, if he does see only 2 per year, he can't be that much of an expert on it.

The first place I looked for an expert was Memorial Sloan Kettering ("the best cancer care anywhere"). Surprisingly, they had only one doctor who listed it as a specialty. Eventually, I found Dr. Richard Furman, who heads a research center at Weill-Cornell Medical Center, and Dr. Steven Treon, at Dana Farber Cancer Institute in Boston. Treon is the Director of the Bing Center for Waldenström’s Research and an attending physician for medical oncology, at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, in Boston, Massachusetts. He's got his own web site with the banner "Dedicated to the Discovery of the Cause and Cure of Waldenström’s Macroglobulinemia". I sent him an email (through a "Contact Me" link on his site) asking if he could recommend a specialist in my area, or if he could perhaps supervise my care from afar.