Follicular Sisters

I guess you can label this Good News that Came from Bad News: a bone marrow transplant from one sister to another resulted in the the recipient contracting Follicular NHL from the donor. But it might be leading to some important insights about the disease.

The findings are described in the most recent issue of Oncology Times in an article called "New Insights into Follicular Lymphoma from Sister-to-Sister Transplantation." (Incidentally, I love that oncology has its own twice-a-month newspaper.)

The study described was funded by a grant from Stand Up 2 Cancer, which has lived up to its promise to fund some funky, non-traditional research. Here's what happened: one of the sisters was diagnosed with chronic myeloid leukemia, and received a bone marrow transplant from her sister. In such cases, the recipient is given very aggressive chemo, which destroys the immune system; the donor's bone marrow allows the patient's immune system to recover much sooner. In this case, over the next few years, the recipient received two additional donations from her sister, this time in the form of leukocytes instead of a full BMT. The leukocytes are white blood cells that are able to sniff out and destroy cancer cells in a normal person; the theory is that transplanting them into another person will help the recipient's body to bypass that mechanism that keeps a cancer patient's white blood cells from recognizing their own cancer cells.

So far, so good. But then the donor sister developed Follicular NHL, and six months later, the original cancer patient also developed it. Coincidence? Maybe, but more likely the transplant was the cause.

To find out, some smart people from Dana-Farber in Boston looked very closely at the DNA of the two sisters Follicular cells, and at the leukocytes (some of which remained frozen). The article gives lots of detail about the science behind what they found, but the important thing is this: they could match up a lot of the mutations in the DNA. We already know that a switch occurs between two genes in fNHL cells. But more importantly: they could not match up all of the mutations.

What that suggests is that there might be some "ancestor" cell in fNHL, one that was transplanted from sister to sister. So while chemo might do a great job of wiping out Follicular cells (heck, even Rituxan seems to do a great job for lots of people), the ancestor cell from which they spring, or which causes the mutation, is not affected by the chemo. This might be why Follicular keeps coming back. It might also offer insight into why Follicular behaves so differently in different patients.

Of course, the suggestion that an ancestor cell exists is a lot different from knowing where it is, or what it is, or IF it is, and then somehow sequencing that cell, and ten figuring out how to get rid of it. But it's kind of an exciting first step.

And taking a wider view, the study also has implications for other types of cancer. The method they used to look at the DNA mutation was the real innovation here, and might be helpful in mapping out other cancers that behave differently in different patients.

More baby steps toward a cure.

Cancer Vaccines

All this hype about a "universal cure" had me looking back to something I read earlier this month about cancer vaccines. It's from a sight called "Seeking Alpha," which is not a medical information site, but rather an investment advice site. The article is called "Cancer Vaccine Approaches: A Race for Dominance in the Field," and it lays out some of the different types of cancer vaccines that are out there now, for different types of cancer. (Including NHL, of course; I've been writing about different attempts at a vaccine for a while now.)

It's a pretty good introduction to cancer vaccines, I think. The whole "investment" angle is interesting -- a good investor would, of course, want to gamble on a company that is most likely to have success.

That leads to a caution, of course -- good business isn't always good science (and vice-versa).

Still, pretty interesting reading.

Cure All?

Over the weekend, a bunch of news outlets gave the very exciting news that a "universal vaccine for cancer" might have been found.

All of the excitement came from a report about a vaccine that targets a substance called Mucin 1, a protein found on about 90% of cancer cells. Like most immunotherapies, this vaccine, called ImMucin, stimulates the body's immune system to recognize and attack cancer cells that have this protein. Because so many different cancers have the protein, it is theoretically possible that it could work on 90% of cancers, making it as close to "universal" as anything we have.

There are some cautions, however, before we get too excited about this. Many of them are detailed here.

First, this is still very much in the trail stage. It confirms a study involving mice, but the trial that prompted all of this hype involved just 10 people. And only 3 of the 10 had a complete response (though the others had a "robust and specific immune response" as well). And all 10 had the same cancer, multiple myeloma, a blood cancer.

That hardly adds up to 90% of cancers being cured.

What's more, the information comes from a press release from the company that makes the vaccine. That's fine, but the results haven't been published yet in a medical journal, where they would be reviewed by other researchers before being accepted.

So while it was a small sample, we can still be hopeful about this. Many cancer experts believe that immunotherapy holds some real keys to the future of cancer treatment, so we can say we'll keep a hopeful eye on this one.

Just hold off for a while on taking up smoking or something.

Hope

This month's edition of Coping magazine (which focuses on coping with cancer) features an article on Hope, written by an oncology nurse. (Oncology nurses are, in general, among the most wonderful people in the world.)

The article is called "Holding on to Hope," and it discusses Hope in the way the poet Emily Dickinson discussed Hope:

Hope is the thing with feathers
That perches in the soul,
And sings the tune without the words,
And never stops at all.

Read that again and think about it.

To me, if Hope is a bird that doesn't stop singing, then there's something about hope that involves never giving up.

Of course, just the idea of never giving up can be exhausting, and as this oncology nurse points out, sometimes Hope exists in opposites -- "sorrow and gratitude, inner strength and weakened abilities, withdrawing and embracing." Hope can still be there even if it's almost silent. As Dickinson's poem says after the opening, the bird of hope is heard "sweetest in the gale," best and strongest when times seem toughest.

It's kind of a heady article, this Coping magazine piece. Hard to get a handle on -- like Hope, sometimes. But the author is good about giving some practical tips for keeping hope alive. My favorite:

"Anticipate survival. Many people have gone before you. Picture yourself among them – after treatment and doing well."

Hard to do sometimes. But you don't need hope when the sun shines, do you? It's in the gale that the song is sweetest, the Hope is most necessary, and our strongest selves shine through.

 

Mike Wallace

Sad news today -- Mike Wallace, the 60 Minutes correspondent, died at 93.

No cancer connection here. Just that I really enjoyed watching him, because it was so much fun to see him make people squirm, as brilliantly parodied on Saturday Night Live.

But mostly the news reminded me of one of my few real brushes with fame -- the time I met him and made him wince in front of a whole bunch of people.

I was working on Martha's Vineyard for the summer, as Coordinator of a month-long writing program for teachers. My job as coordinator was to do pretty much everything asked, from picking up muffins at The Black Dog to unclogging toilets at the homes our students were staying at. I was a month out of grad school, so the "coordinator" title looked great on my resume, but didn't have any of the easy and intellectually fulfilling academic duties that my boss, the Director had.

One nice thing about having a writing program on Martha's Vineyard is that so many writers (and other famous people) live or vacation there in the summer, so an enterprising program Director (as opposed to a toilet-unclogging Coordinator) can often use his connections to get some great guest speakers. I was smart enough to push aside my student workers and assume the duties involved with taking care of the writers who would come to visit. They'd usually speak for a half hour and then take questions from the audience. I got nice autographed copy of a Clifford The Big Red Dog book from Norman Bridwell that way.

So when Mike Wallace came, I was happy to be the one to meet him at his car. He had come straight from a game of tennis, and was still in his tennis whites. (It's all very casual on the Vineyard.) I shook his hand and introduced myself, and asked if there was anything I could get him. "Just some water, please," he said, obviously parched from tennis. The Director took him to the classroom/lecture hall while I ran next door to our program headquarters, a beautiful old sea captain's house.

I grabbed a thermal pitcher from the kitchen, filled it with ice and water, and ran back next door. Mike Wallace had already started his lecture -- a fascinating recollection of some of his interviews, and the writing problems he had faced over the years. I quietly put the thermal pitcher and a cup on the table next to him.

As he spoke, he poured himself a cup of water, paused only slightly to take a sip, twisted his face in thought, and continued on with his lecture.

When he was done taking questions, the director showed him to his car. I started cleaning up, and picked up the pitcher of water and his cup.

The cup was still nearly full. He'd only taken that single sip.

I thought, "I hustled all the way over here with water that you asked for, and you only took one sip?"

Disgusted, I brought the pitcher back to the house, dumping out the cup along the way. When I got there, all that thought of water had made me thirsty, and I poured myself a big cup from the same pitcher. I took a gulp, and spat the water out.

The thermal pitcher, it turned out, was the same one I'd been using for the coffee we'd been serving every morning with our Black Dog muffins. And in my haste, I hadn't bothered to clean it out. Mike Wallace had taken a single sip from the most bitter, disgusting water I had ever tasted. That twisted face he had made hadn't been from deep thought -- he had been trying not to throw up.

No one  noticed the real reason for the twisted face. It really did look like he was in deep thought. But he was ever the professional -- kept right on going, despite a parched mouth from a mid-summer tennis game and an accidental near-poisoning.

So, I was sad to hear about Mike Wallace today. But very appreciative that he never said anything about it to my boss the Director.

Reflection

No work tomorrow, and no school for the kids. It's a state holiday, officially a "Day of Reflection."

I'll do more reflecting tomorrow, but I'll start today.

I saw a colleague yesterday at work, someone I haven't really had much chance to talk to lately. He mad some smart-ass comment to me, as he usually does, as I was unlocking my office door. I don't remember what it was. I responded in kind. He made some other comment -- a reference to my health. I laughed, because it was funny, and went into my office.

A minute later, he came in. More serious this time.

"How is your health?" he asked.

As I said, I hadn't had much chance to talk to him in a while.

So I gave him an update. My health, overall, is pretty good. No treatment for well over two years, while the median for Rituxan is 12 to 18 months. My physical went well. Bloodwork looked good. EKG, PSA, HDL -- all fine. Asthma is under control. Ran 5 miles on Saturday.

He was glad to hear all of this.

Later in the day, I chatted with another colleague -- this one a cancer survivor. He has a scan coming up on Tuesday. He's starting to get that nervous, pre-scan feeling. He feels great, and knows in his bones (and relevant internal organs) that he's OK. But he can't shake that feeling. I told him we call it "scanxiety" in my support group. He liked that.

So that's what I've been reflecting on: things are good now. My wife and I are too busy to say more than hello to each other, but it's "good busy," and the kids are happy and healthy and doing well. Can't complain.

Friend #2 knows the scan will be fine, but he doesn't want to jinx it by talking about it. I understand that, but I'm willing to take the risk.

Friend #1 knows that what I have is slow-growing but incurable, and knows that I deal with that, emotionally, every day. He's pretty sure he wouldn't be able to handle it if it was him.

Ah, but he would. Because, really, what other choice would he have?

I've never been a "carpe-diem, sieze-the-day, go-sky-diving-because-you-just-never-know" kind of cancer patient, and I doubt I ever will be. But it's nice to stop and reflect every once in a while, and realize that, despite being dealt what some people would call an unlucky hand,I'm a lucky guy, and today is a pretty good day.

CD 47

Fascinating cancer news that came out last week concerning an anti-CD47 antibody. Apparently, it works on all kinds of cancers, not just on NHL.

As regular readers know, antibodies have been created that target proteins on cancer cells. Rituxan, for example, seeks out the CD20 protein. CD47 is also present on some stem cells -- immature cells waiting to grow into the various blood cells. On a normal, immature cell, the CD47 is a protection. When the immature cell is approached by an immune-system cell called a macrophage, which patrols the blood and eats invaders, the CD47 signals the macrophage that it's got the wrong dude, and the immature cell is released. It's like the body's Obi-wan Kenobi ["These aren't the cells you are looking for"].

Cancer cells, the Darth Vaders of the body (sorry -- had to extend the metaphor), have figured out that they can express CD47 on their own surfaces as a way of keeping themselves alive. The macrophage encounters the cancer cell, finds the CD47, and leaves it alone. Tricky.

That's where the anti-CD47 antibody comes in. It basically masks the CD47, so macrophages encounter the cell, see no "leave me alone" signal, and do their job of cleaning up the invaders.

So far, the antibody has been tested only in mice, but it seems to work on a whole bunch of different cancer types -- breast, ovarian, colon, bladder, brain, liver and prostate (not to mention lymphoma).

Anti-CD47 has already been shown to possibly be effective when combined with Rituxan for NHL patients.

So now we may have anti-CD47 to use for more than just NHL.

Of course, for all of these cancers, NHL included, we still have lots of testing to do. But given the reduced side effects compared to chemo, this looks like another small victory for immunotherapy.

Fingers crossed.