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'Killing an ant with an atomic bomb'

Kip Cleaver

This story involves Dr. Joe Antin, class of ’74, who was Chief, Medical Oncology Stem Cell Transplantation Program at Brigham and Women’s Hospital. I didn’t recognize him as a Williams alum for a few months and then my eyes were drawn across the page in the alumni notes where his name was underlined: someone had seen him riding his bike around a Boston suburb.


He mentored me through my bone marrow transplant for chronic myelogenous leukemia back in 1997. And he did what I consider to be the greatest kind of outside-the-box thinking: that which saves lives. I have told this story to other doctors over the years, and they all say, “If you were my patient, you’d be dead.”


There’s no short version of this story. As long as this is, it’s a bare-bones version.


When I was diagnosed in 1996, everyone I knew who had had leukemia was dead. So it took me a while to believe that if I could find a donor and have a bone marrow transplant, I had a decent chance.


The bone marrow transplant (BMT) has been called the most dangerous and devastating procedure in medicine for a long time. It took the doctors almost an hour to explain to me all the ways I could die. They didn’t tell me I would switch blood types. That was a minor detail compared to what else would be going on.


People like me had about a 50 percent chance of surviving. I don’t think it’s gone up much since then. But, thanks to this test -- the PCR test -- which was new back then, I was one of the first transplant patients to eventually be declared cured. That’s a wonderful but rare word in the cancer world.


With the transplant, which is now called a stem cell transplant, the cure is to wipe out your diseased bone marrow. That’s where your blood cells are made by stem cells. It’s the white cells that are overproducing. The doctors use what’s called "total body radiation" -- a massive dose -- and lots of chemo. They have to come as close to killing you as they can, or they don’t wipe out enough leukemia cells. I had the equivalent of 1200 normal dental X-rays and am here now doing very well. The only drug I am on is one thyroid supplement. One reason I am doing so well is I am a WASP: very common out there so I had a lot of good matches to choose from.


Researchers learned by studying Hiroshima survivors that massive radiation doses, just a little lower than what kills you, can wipe out your bone marrow. They told me the only effect they see from all the radiation is about a ten percent increased risk of developing another cancer earlier than normal. Pretty good deal to get your life back.


The effect of all this is devastating. You can't keep food down so you end up being fed through an IV port, and they do everything they can to minimize the horrible nausea. I went in around 215 lbs. and came out at 160. At 6’4”, that’s skinny.


Sometimes the radiation comes too close to killing you, and patients die right on the radiation table. Some cough up their stomach lining. Dr. Antin calls the BMT “killing an ant with an atomic bomb.” My favorite description is ”a walk through the valley of the shadow…but you get to vomit all over the valley floor,” which is the kind of attitude you need to get through this. My favorite nurse for the almost seven weeks in the hospital told me point blank at the start, “If you give up you will die.”


After basically being killed -- if you don’t get your stem cells you die -- you watch your donor’s stem cells -- your new life -- drip into your arm from a transfusion bag. They call it your second birthday. My donor was from South Carolina and signed up while in the Navy to get on the bone marrow donor registry, because in the Navy if you do that you got the rest of the day off! Go Navy!


My new cells were quite delayed coming in, which worried everyone. They finally tried a new growth factor drug that they had initially resisted because it hadn’t been tested much. It worked, and now results in patients staying in the hospital for far less time.


I finally started making white cells and platelets, but no red cells. The doctors had never seen that.


In Boston, with all the teaching hospitals, lots of doctors want to solve any new problem. My situation would have been a good episode for the Dr. House show. Within a week or two, Joe told me hundreds of doctors had chimed in from around the world. No one had seen this nor had any idea what to do about it.


So I was living on red cell transfusions for several months. I knew that couldn’t go on for too long like that. Finally I got a call from Dr. Antin, who'd gotten an idea while mowing his lawn: I needed to come for a blood test. He later told me he mows his own lawn because it’s the only time he has to really think. I like to think one reason he kept focus on me was because of our Williams link.


His thought process was as follows. First, it’s very rare that a totally new problem comes up in medicine. Second, I took the drug EPO, which always raises red cell production. Apparently not for me, however. Third, I was making two of the three types of blood cells, so my donor's stem cells were at least partially producing. Sometimes the new stem cells don’t work at all, and the patient dies.


Joe finally said to himself, “He’s GOT to be making red cells; what if he IS making red cells?" Pretty bold thought given that even my reticulocyte count -- which are brand new young red cells -- was zero. This was the start of the epiphany. I think a room of his colleagues might have laughed him out for thinking I might be making red cells, with all the data saying I wasn’t.


So he started down that line of thinking. If I was making red cells, something was killing them. Doctors had always been nervous about mismatched blood types, but it had never mattered because the BMT wipes out your blood supply. They match proteins on certain white cells with your donor’s.


But it was the first thing he thought of that could be the problem: If there were antibody cells left in me, they would kill my donor’s new red cells. So I had a blood test and the antibodies were off the scale. So that’s the outside-the-box diagnosis.


So, what to do about it? All they could come up with was plasmapheresis. The antibodies are in the blood plasma. They used the dialysis machine -- a centrifuge -- to exchange my plasma with donor plasma. They had no idea if it would work. And they knew they could only exchange so much plasma at a time.


So I had 16 of these five-hour sessions about a week apart, using the biggest needles available. Every session my antibody level would drop. And now and then this other doctor would stick his head in the door and say, “There are doctors all around the world watching you.” The whole ward where I was treated knew about me too, and knew if this didn’t work, there were few, if any, other options.


At the start of my 16th session, Dr. Antin came in and said this may be the last session. He told me that my veins were a wreck, and they didn’t think they could get the antibody level any lower.


They always did a blood test halfway through the pheresis session. They took the blood and a few minutes later I hear a woman screaming out in the hall and a nurse comes running in, waving the blood test result paper. My red cells had come in! It was quite a scene -- people hugging, cheering, in tears, etc.


Some other patients have had this happen since then, and plasmapheresis worked for them.


(As a side note, I am tired of being a guinea pig. A couple years ago, I had knee surgery to connect a torn hamstring muscle, which resulted in an infection a month later. Even though my knee was red and warm, and I had major chills, the doctor and his assistant talked themselves out of it being infected simply because they’d never seen an infection pop up that long after surgery. So they sent me off. My primary care doctor, however, took one look at my red, very warm knee and ordered a blood test right away -- and there it was. I was lucky it was a “wimpy” bacteria or I might have lost my leg, or life.)


So Dr. Antin forced himself to look at the facts with no preconceptions and realized that things that never mattered might matter. It had never mattered before that a patient was a blood type mismatch. But this time it did, because of too little radiation/chemo.


And I have used this concept-- and the reverse could be true too -- that things that have mattered before might not matter now. What if the problem -- or the answer/opportunity -- is the opposite of what it appears to be, like it was here?


My second wife and I used this type of thinking with her just-out-of-high-school, errant, rebellious son. We asked ourselves, “What’s the last thing in the world we should do with him now?” and came up with some pretty crazy ideas, but one actually helped.


Another conclusion is, if you’ve got a big health problem, find a doctor who mows his or her own lawn.


I am always pushing for more organ/stem cell donors. It is so tragic that thousands of people die every year waiting for an organ, while 42% of Americans who could donate, won’t. I’ve met my donor several times. Talk about the gift that keeps on giving. And you are never too old to donate.

'Killing an ant with an atomic bomb'
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