How Stem Cell Transplants Work

I haven't listened to Yale Cancer Center Answers recently, so when I visited their web page this week, I saw that one of their shows in June was on Stem Cell Transplants. It's a pretty good introduction to the topic.

(The link above will take you to a pdf of the show's transcript. If you'd like to listen to the show, click here and scroll down to the June 15, 2014 link.)

Yale Cancer Center Answers is a weekly radio show put together by the Smilow Cancer Center at Yale, focusing each week on a different cancer-related topic. There are three hosts, and they interview a cancer specialist from Smilow each week -- usually a researcher, though sometimes a nurse or social worker if the topic calls for it.

For the Stem Cell show, the guest was Dr. Stuart Seropian, a blood cancer specialist; he is interviewed by Dr. Steven Gore, who is Director of Hematological Malignancies at Yale.

As I said, I think the interview does a nice job of laying out the basics of how a Stem Cell Transplant works, the difference between Auto and Allo transplants, as well as some of the issues related to transplants, like Host vs. Graft Disease, and how to become a donor.

While the interview does a great job of laying out the basics of a Stem Cell Transplant, it doesn't get too deep into things like more recent research, I recommend a trip to Lymphomation.org's STC page. Great information, easy to find.

It's interesting to think about the role an STC might play for some of us in the future. It will probably be an option for us for a very long time, though given that it is essentially a chemotherapy procedure, I don't know if some of the procedures being developed -- targeted inhibitors, for example -- will ultimately replace chemotherapy. That will mean a big debate about the goal of Follicular Lymphoam treatment -- to cure? or to control?

Of course, that debate is already happening.

In the meantime, it's good to know all we can about the options available to us.

Men, Women, and Cancer

U.S. News and World Report has an interesting article online called "Cancer: Men Are From Mars, Women Are From Venus." It gets into the differences between men and women when it comes to cancer  -- not so much the physical differences, but the emotional and mental ones that come from a cancer diagnosis and everything that follows.

Women tend to be better communicators when they are faced with a diagnosis. Men tend to retreat to their cave.

Women tend to see things as a process, and look at the big picture. Men just want to get back to their old normal activities.

Women look online for support. Men just want to fix things.

The article struck me because I saw some of myself in it. As I've said here before, after the initial shock of my diagnosis wore off, I went into a pretty heavy depression, thinking about  my family, especially how they would be provided for. (I remember being thrilled when I realized my kids could collect social security until they were 18.) I came out of it because my wife pulled me out of it. I went into the cave; she made me come out and talk. We were kind of a textbook case.

Of course, the article also points out that these trends are sometimes stereotypes, too -- we don't automatically behave certain ways just because we are men or women. Apparently, in a surprise finding to a study, women spend more time online researching their own or a loved one's cancer. Goodness knows I've spent a little time online....

I think it's good to read about things like this, because maybe they give us a chance to stop and think about ourselves. Sometimes we get so caught up in thinking about our cancer that we don't think about ourselves, if that makes sense. We don't think about how we're handling it, if what we are doing is the best thing to be doing, if circumstances have changed -- if our loved ones are handling things OK.

So I like articles like this, that get me to think about myself. Might even end up starting a little discussion.

Even though I'm a guy, I think that might be a good thing.

EZH2 Inhibitor for Follicular Lymphoma?

ASH, the American Society for Hematology, has a summer conference on Lymphoma Biology. It ended a couple of days ago. It's much smaller and more focused than the main ASH conference. They also don't make the abstracts and materials public like they do for the main conference. And it doesn't look like there was much about Follicular Lymphoma discussed there.

But I did find this -- a press release from Epizyme, the company that is partnering in creating and testing EPZ-6438, an EZH2 Inhibitor. The presentation focuses on pre-trial and phase 1 trial results. In other words, it's all very early, and very limited -- they only discuss one Follicular Lymphoma patient -- but I think it's worth looking at, since this class of inhibitors seems like it will be a big part of our futures as Follicular Lymphoma patients.

First off, the whole EZH2 Inhibitor thing. EZH2 is the name of a gene that encodes an enzyme, also called EZH2. When there is too much EZH2, a chain reaction is set off. Too much EZH2 enyzme results in the creation of too much histone methylation, a process that leads to bad things happening to some other genes that suppress tumors. [I just erased a paragraph of science-y stuff that I was having trouble following myself. Let's just say this: EZH2 needs to be controlled, because if it isn't, it will allow cells to live for as long as they want to. Next step = cancer.]

EZH2 seems to play a role in a bunch of cancers, both solid and liquid, including some types of Follicular Lymphoma. (Remember -- there isn't just one type of FL. About 22% of Follicular Lymphoma patients have the mutation that is related to EZH2.)

So the EPZ-6438 that is being developed and tested is an EZH2 inhibitor -- it's job is to stop EZH2 from allowing cancer cells to grow willy-nilly.

The presentation at ASH focused on pre-clinical results (stuff they found out in the laboratory) and some phase 1 trial results. As I said, the information about Follicular Lymphoma is pretty limited -- they only report results for one patient, who had stable disease as a result of the treatment. Not an overwhelming endorsement, but enough to move forward.

The pre-clinical results were kind of interesting, too. They combined cells with the inhibitor and CHOP, with good results. Then they tried the individual components of CHOP, and found that just Prednisone helped even more, as did Dexamethasone, another steroid. They also found some activity with BCL2 inhibitors.

It's important to remember that the pre-clinical stuff doesn't involve actual patients; it's just an attempt to narrow down possible options for combinations in later trials.

So what do we have here? A whole bunch of possibilities, and not much else.

Which isn't to say possibilities are bad. It's just really early in the process for this particular treatment.

I'm confident, though, that we'll find something, at some point, that works on EZH2. This particular inhibitor isn't the only one being developed that targets EZH2; the results of research on another possibility were discussed about a year and a half ago in the journal Nature.

I'm also confident that all of this research adds to a bigger picture. Even though EZH2 only effects 22% of us FL patients, our broader understanding of the pathways that lead to cancer can only help researchers as they figure out ways to attack other pathways, as they become known.

So for this research -- right now? Meh. In the future? Lots to hopeful about.

Advice for Living with Cancer

I saw an article last week called "Got Cancer? Now What?" written by Lisa Marie Wilson, a cancer survivor, who was also a caretaker for a mother and grandmother who had cancer. It's pretty good advice, especially for someone newly diagnosed.

It's been six and a half years as a cancer patient for me, and reading this brought back some memories.

I like Wilson's advice to be organized early on -- get and save copies of paperwork from each doctor, understand what you'll need to bring to appointments, and make friends with someone from the insurance company. It's been a long time since those hazy first days of diagnosis for me, but I'd also add, bring a friend along who can assist you with all of those things. Another pair of eyes and ears is a big help when your own head is filled with visions of dancing cancer cells. Clarity comes later, when the fog lifts.

She also has some good advice on attitude -- "take the diagnosis as a warning, not a fact." I like the way she put this. Obviously, you need to be realistic, and accept that you have cancer, but you don't need to believe the statistics you read online and take those as a reflection of what your own cancer journey will be. In fact, I'd add something to this list about staying offline for a while, or maybe having that clear-eyed friend read along with you when you go online to make sure you aren't reading the worst.

A couple of other bits of advice on staying positive are helpful, but with some cautions. I absolutely believe in the power of humor, and if you've read some of the very early stuff on this blog from my first year, you know that I'm a great collector of cancer humor. [Which reminds me -- I may need to write a cancer humor post sometime soon. It's been, literally, years since I've done one....] For me, laughing at cancer was a way of facing cancer head-on. And I think it's great advice for people who are equipped for it. For me, I've always been an easy laugh, especially at my own jokes. My wife says I'll always have an audience because I think of myself as so darn funny. But for some people, who may be a little more serious, laughter is going to be forced. And that might just take more energy than you have to spare.

I'm also wary of the "stay positive" advice. Again, I'm a fairly positive person. And I tell my kids, when things are going bad, that the only problem that gets solved by staying in bed is a lack of sleep. Facing the day is the best way to solve a problem. But being positive all the time can be exhausting. There are a few versions out there of responses to the "tyranny of the positive attitude" (I like this one -- less academic). Basically, we're always told that we have to stay positive in the face of something like cancer. And we probably should -- most of the time. But dang it, sometimes we need to just have a crappy day. A day of staying in bed and eating ice cream for lunch and watching Dirty Dancing. And promising ourselves that we'll try to be more positive tomorrow. I think that's a healthy thing to do. We're cancer patients, for crying out loud. We're entitled to a day of cookie dough and Patrick Swayze.

So, overall, I think the article has some very good advice. But, like all advice, I think we need to adapt it in ways that make sense to us. We all deal with cancer differently -- those of us who have it, those of us who care for those who have it, and those of us who aren't sure what to do for someone who has it. The most important things, in my experience, are to communicate with people who can help you, whether they are doctors or caregivers, and to learn as much as you can about your disease, but not so much that you drive yourself crazy.

New Cancer Classifications?

Some exciting news from the well-respected journal Cell a couple of days ago: a large research study of tumor tissues suggests a new way to classify cancers that might help explain why some patients don't do well with certain treatments.

For a very long time, cancers have been classified by their origin. Someone says they have cancer, and they get asked "What kind?" and the answers is "Breast" or "lung" or "colon." The cancer is classified by what part of the body it came from. Lymphomas are the same  -- they are, broadly, "blood" cancers, although most types of cancer also have sub-types (there are differnt types of lung cancer, just as there are different types of blood cancer).

But, for many years, cancers were classified (or sub-typed) mostly by the way they looked under a microscope. Blood cancers could be leukemia, or myeloma, or one of a bunch of different lymphomas, based on what they looked like, at least when they are initially diagnosed.

That has started to change somewhat over the last few years, as the human genome has been mapped, and we are getting a better sense of some of the differences between cancers, and within cancer types: we can see, for example, that not all follicular lymphomas are alike, when one looks at them on a genomic level -- deeper than just a look through a microscope, but looking at how messed up the DNA is, and how that has affected the cells.

The research published in Cell builds on that more recent, deeper way of looking at cancer cells.

The researchers looked at 3527 tumor specimens from 12 different types of cancer. (No lymphomas among the 12 -- the closest we get is a type of leukemia.) What they found was pretty exciting. Certain cancers that had been based on location were actually related to other types of cancer that you wouldn't think of as being related.

For example, bladder cancer could be divided into three types: one that is now recognized; one that is related to lung and head and neck cancers; and one that is related to a different type of lung cancer. Breats cancer is divided into two types, basal and luminal. Other cancers can also be classified by their similarities to other types of cancer.

So the upshot is, unlike in real estate sales, location doesn't necessarily matter. Cell type, based on genomic analysis, is what does.

(There's a joke in there about one of my father's favorite expressions, something about not knowing your ass from your elbow. I'm not going to be the one to make that joke, though.)

Lots of articles online in the last couple of days about what a breakthrough this might be (like this one). I agree that it is absolutely the next step in the evolution of cancer diagnosis. But it's a step. And not an unexpected one, given the type of work that has been done in diagnosis in the last few years. More and more research has suggested this kind of difference between types of cancers. Not all that long ago, you could count the number of types of NHL on two hands; now, because of this kind of genomic analysis, I've heard some people say we have as many as 60 different types. It's not that new types of cancer have developed, just that we've been able to go deep enough to see the differences between them.

The bigger deal is the consideration on how this might change the way we classify them, and that will be important. People get locked into classifications sometimes. "It's DLBCL, so this is what we do." And that can be dangerous. A new or alternate classification system might get doctors to step back a little and think more carefully about how to treat something.

There are dangers, of course. I like a quote from an article about all of this from the LA Times -- a researcher from Dana Farber points out that this new classification would have "grouped two distinct types of breast cancer — one that feeds on estrogen and another on an epidermal growth factor captured by a receptor called HER2 — that require very different treatments into the same category." And that would mean missing out one some very important factor.

My guess is, though, that the danger of that happening -- of this classification system overtaking the current, location-based system -- is slim. More likely is that we see a continuation of the trend, with more and more factors being considered at diagnosis. I could see more of a flow chart approach: 
Did the tissue sample come from the blood? YES.
Does it look like Follicular Lymphoma? YES.
Does it have a 14;18 translocation? NO.
Does it have CD20 cell marker? YES.
CD22? NO.
CD19? YES.
Your treatment should be: IBRUTINIB + RITUXAN, WITH 2 YEARS RITUXAN MAINTENANCE.

Something like that. In other words, we aren't going to rely on a single classification system, but we'll find a whole bunch of factors that distinguish different sub-sub-sub-types of different cancers and determine the best treatment from there.

But that's going to take a lot of work. More research into genomic differences in cells. More development of treatments based on those differences.

And more clinical trials based on that research. And, of course, more volunteers for those trials. Someone has to do it -- right?

Subcutaneous Rituxan

The United Kingdom's equivalent of the FDA has approved subcutaneous injections of Rituxan (known as MabThera over there). That means a 5 minute shot in the arm, rather than a 4 hour IV.

As someone who sat through 6 treatments of Rituxan, I think that's great news. They estimate it will save about 2.5 million Pounds Sterling (over $4 million), adding up the time and human power it takes to administer by IV. That's not a huge amount (about $2000 per patient), but it all adds up when you consider how many people get Rituxan in the U.S. -- and how much that would save for someone who self-pays.

Of course, the subcutaneous option is not available in the U.S. And as far as I can tell, there isn't a clinical trial in the U.S. that is testing it out, either -- none that I could find in my search. (This one, for example, is recruiting patients in a bunch of other countries -- Algeria, Argentina, Belgium, Brazil, Bulgaria, Canada, Colombia, Finland, France, Greece, Ireland, Israel, Italy, Netherlands, Peru, Poland, Portugal, Russian Federation, Saudi Arabia, Serbia, South Africa, Spain, Thailand, Turkey, Ukraine, United Kingdom, and Venezuela -- but not the U.S.

I'm not sure what the problem is, though I remember reading discussions about this (I think when the results for the trial that led to the UK were reported at ASH is 2012). I think there was still some fear about what would happen if a patient had a reaction; you can slow down a 4 hour infusion, but a subcutaneous injection is over in a few seconds -- no slowing it down.

But that seems like a problem that could be dealt with in trial design. Maybe the first infusion is an IV, and the rest of that course, the next 3 or 5 or 7 treatments, are injections?

I guess it's also possible that, with the patent for Rituxan expiring soon, the manufacturer just doesn't want to put more resources into it?

Whatever the case, cheers to you in the UK who might benefit from this. Bob's your uncle. (And your cancer blogger....)

Yellow Vest, Red Sox, and Cancer

I drove up to Massachusetts yesterday to visit family and watch my brother ride in the Pan-Mass Challenge, the annual bike ride that raises money for cancer research at Dana-Farber Cancer Institute in Boston. My brother is one of about 6000 riders who are working to raise $40 million this weekend.

We met Mike at the Lakeville stop, where he and his teammates stopped for about 15 minutes to rest and fill water bottles. And then he was off again. We knew he was wearing a yellow vest, but he saw us before we saw him. We're proud of him for putting so much work into this every year. He's already more than $1000 over his $5000 fundraising goal, but it's not too late to donate to him.

Thanks again, Mike. Keep up the good work.

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The other bit of cancer-related athletic news over the last few days was Jon Lester getting traded by the Red Sox to the Oakland A's. I'll miss him.

I've told this story before, but I'll tell it again.

Jon Lester is a Non-Hodgkin's Lymphoma survivor. He was diagnosed with Anaplastic Large Cell Lymphoma, an aggressive type, in 2006, his rookie year. He responded well to chemo and came back the next year, pitching well, and winning game 4 of the World Series for the Sox.

I was diagnosed just a few months after the World Series. When we told our kids (who were 10, 8, and 6 at the time), I sat between my sons on the couch with my arms around them. I think the 6 and 8 year olds didn't fully understand what was going on, by my oldest, Peter, certainly knew what cancer was, and knew it was not a good thing. His body stiffened when I said I had NHL, a type of cancer. I said to him, "Peter, you've heard of NHL before." He said he hadn't. "Yes you have," I said. "It's what Jon Lester had."

I felt his whole body relax. Now, Lester had a different kind of NHL than I did, much more aggressive, but that didn't matter. Jon Lester made it back, and made it back big, and that was good enough for us.

A few months later, Lester pitched a no-hitter. I was flipping through channels when I came across the game and saw that he was going into the last inning with the no-no. I ran upstairs and woke Peter up so we could watch together. It was a great moment, and another reason for Peter to feel OK.

And then he won two more games in the 2014 World Series, made 3 All Star games, and has generally been an awesome guy and a great player.

I wore my Lester shirt for all six of my Rituxan treatments. It became a good luck charm. I believe in monoclonal antibodies more than I believe in luck, but I wore the shirt anyway. And I wore it yesterday when I cheered on my brother.

There's a chance Lester will come back to Boston next year, since he's a free agent in October. That would be nice. But even if he moves on to someplace else, he'll always have my appreciation and affection for getting my son through a tough time.

Good luck this year, Mr. Lester.