Tuesday, August 01, 2006

Day 0

Hi, this is Michael.

As I write, David is receiving his bone marrow transplant.

The last several days we’ve stood by and watched as our son received what was effectively multiple lethal doses of poison. At this point, he has received a full conditioning regimen. The chemotherapy has killed off his bone marrow, and the Campath has killed of his T-cells. The chemotherapy agents were colorless fluids, innocuous, visually indistinguishable from saline solution or an antibiotic. But google for their chemical names -- [busulfan], [fludarabine], [cyclophosphamide] -- and you’ll find voluminous results detailing their hazardous effects. The Campath came in a bag covered in tinted plastic. This stuff cannot stand the light of day.

David's white blood cell count has dropped to 0, so he is defenseless against the world. It is now up to the donor’s bone marrow -- plus an array of follow up care, to rescue him from certain death.

He had a positive white blood cell count as recently as yesterday, and we were surprised that the staff would actually let us take him out of the room. He had his last stroll in open air yesterday. Now he will remain in isolation from this point forward. He will stay in this room, 15’ wide, 25’ long, with double doors to isolate him from the germs circulating through the ward: Lucile Packard, 2 North.

The marrow arrived by air courier, then was processed to remove most of the red blood cells. The donor is B+ while David is O+, so the red blood cells are incompatible. This filtering need not be 100%: the last traces of red blood cells are not worth the effort of removing, and typically don’t cause any problems. Consequently, the marrow is pinkish-red, becoming more pale as the transfusion progresses. David has received platelets and red blood cell transfusions in the past. The physical details of this transfusion are little different: a simple bag hung on the IV pole.

When they brought it to our room, our doctor and our nurse for this evening went through a painstaking ritual of checking and rechecking the identifiers on the bag, vs. David’s medical chart, vs. his ankle bracelet. This two-person activity had a definite sense of gravity to it, and reminded us the operations one might perform handling nuclear materials. No tolerance for error, here. We heard of one astounding, tragic case a few months back in Texas where a child accidentally received marrow from the wrong donor. The recipient did not survive.

As the bag was prepped, and the staff reviewed the IV machine, materials, and David’s vitals. David was zonked out on Benadryl. We joked, shared experiences, and took photos and posed with the marrow bag in the background. The doctor and nurse were careful to answer all our last minute questions, and we found their experience and familiarity with the range of outcomes reassuring. Has this been T-cell depleted? No, we don’t do that any more. Will he be tested for infection because of the transfusion? Yes periodically, for hepatitis, CMV, and several others. The donor was cleared -- but regular retesting is vital. How long will it take, and what are the side effects?

The transfusion takes about two hours to go in. During that time, an allergic reaction is possible (rash, difficulty breathing), and high blood pressure is a risk. So far, he seems to be handling it without issue. The nurse is in regularly to check vitals, to check for hives, monitor the flow rate (which fluctuates if he rolls over), and so forth. Now, he has had a bit of a run up in blood pressure, to 118/75, and they’ve made adjustments for that.

Fred and Sue, friends who have known me for about sixteen years, and Aimee since she was a child, have spent about two hours with us: praying, talking about friends and family, and sharing stories of past medical challenges. We’ve spent some of this time rehearsing the present situation: we’ve told it often enough that the details go quickly. The hematopoietic stem cells will circulate around his body. Each cell it sensitive to a particular kind of marker, which occurs in bone marrow, a molecular address label. When a stem cell encounters that address, it will stick to the side of the blood vessel, then hoist itself out of the current, then migrate into the spongy material where they will live and go to work.

While embryonic stem cells are able to differentiate into any kind of cell in the body, hematopoietic stem cells are partially specialized. They form the variety of cells which comprise the blood. White blood cells fight infection. Red blood cells carry oxygen, and platelets help the blood to clot. In David’s case, the failure-to-clot caused by Wiskott-Aldrich is the primary reason for us going through this ordeal. We had not seen any evidence that his immune system was defective -- but the literature told us that there was a substantial chance of his immune system worsening over time, having blind-spots to certain kinds of invasive organisms, and possible turning on him in autoimmune disorders. For a while we believed that the risk of the bone marrow transplant was greater than the risk of living with Wiskott-Aldritch. When David had his intracerebral hemorrhage, that was the deciding event. And our doctors and the literature we read were unanimous. So, three months later, here we are.

They say that receiving a BMT is like a second birthday. The immune system gets reset from scratch, any old vaccinations or immunities are lost, and a new life begins. Going forward, David will still be our son, but with two genetic codes. There will a clone of a stranger living in his bloodstream. Pleased to meet you! (I hope he’s kind.)

They say that it will take about two weeks before they can detect the graft having any effect. For now, his white blood cell count is 0, and it will stay 0 until about two weeks out when they expect to see a bump. His numbers should climb 4-6 weeks past today -- Day 0 -- but they say it takes about four months for an engrafted immune system to start to respond at about the same level you might see in a newborn baby. What will be happening in the short run is an extraordinary process of conflict and adaptation. What remnants of the old immune system remain will fight the donor cells. What donor cells survive the doses of Campath in the next two days, will fight the remnants of David’s immune system. Plus, those surviving donor T-cells, educated in another body, will identify much of what they see as foreign. They will go on a potentially deadly rampage: acute graft-vs.-host disease (GVHD). The primary goal is to get a full engraftment; an important secondary goal of the conditioning regimen and the treatment in the coming weeks to is prevent or minimize GVHD. T-cells are tricky: they have memory, they learn, they can battle an astounding array of invaders, but they can cause a host of problems if they fail or misfire.

Aside from GVHD, there are potential risks from the chemotherapy toxicity. There are risks from mucositis. The cells of the digestive tract have an important trait in common with both stem cells and cancer cells -- they divide rapidly and have short life cycles -- replacing the population in 5-7 days. So the chemotherapy drugs have a side effect of causing mass deaths in intestinal lining, which is painful, makes eating impossible, and raises the risk of infection and bleeding.

We’ve been pleased that David has made it so far without major problems. Of course, he hates taking his oral meds, and the first day of chemotherapy was rough -- but otherwise it has been smooth sailing so far. The next few weeks we expect to be rougher. But, we’ve heard of a number of WAS kids who have made it through. It’s easier when the patient is younger. Kids are more resilient than adults. They don’t suffer the same neurotic fears. He didn’t have preexisting illnesses -- no malignancies. He has been eating well. He didn’t go through the massive doses of chemo that cancer patients need, and he thankfully hasn’t had radiation. Our doctors have crafted a customized drug protocol which is tailored to his particular case. Since WAS is a rare disease, they don’t always have data to conclusively decide between one treatment and another -- so devising the treatment program remains a bit of an art, an immature science. Specifically in David’s case, he has received about half of the Cytoxan specified by the “normal” regimen, and he isn’t receiving ATG or steroids. The other chemotherapy agents were Busulfan and Fludarabine, which have less toxicity and milder side effects than Cytoxan. They’re still deadly to bone marrow, and have a host of risks -- but its all a matter of degree. The Campath is a monoclonal antibody, and destroys T-cells. The Campath given before today wiped his T-cells, and the Campath he will get in the next two days will knock out the donor T-cells. It takes the place of the ATG, and the steroids remain deferred -- in case GVHD crops up later.

Well, we are just about done. The bag is empty, and have just the rest of the cells in the line to go in. Our nurse is a veteran who has been doing BMTs for about twenty years, and she’s happy with David’s progress tonight. She has some war-stories to tell: having started with SCIDs babies -- children with 0 T-cells from birth, and having seen the gamut of outcomes. It’s all very individual, she says. She’s seen patients with poor HLA matches sail through without problems, and patients with perfect matches do terribly. It’s impossible to predict. But David’s doing well, considering. We look at the donor’s bag, and the blood type says “B+.” Be positive.


Anonymous said...

Dear Aimee and Michael

I am checking these posts multiple times a day and forwarding updates to praying friends. As always my prayers are with David and you. I look forward to a happy, playful child that can romp without fears of slight accidents causing great grief.

Be positive. Right on.

Love, Mom

Anonymous said...

Hi, Michael and Aimee!

Just updated myself, and hoping to see you today. I'll call when we're there. (Ethan'a appt. is at 11:30, and we'll have some waiting time for labs.)

So glad to hear things are going well so far!

Andrea Marley

Anonymous said...

Dear Michael and Aimee,

Just read your update. Thank you for keeping us informed. My heart, mind, prayers are with David and all of you. Much love, Luanna

Anonymous said...

Dear Aimee and Michael ~ Yes! Be positive! Danny and I and your Grandmother send you all our deepest, most heartfelt wishes for David's "new life" to be a joyful, active one. Thank you, Michael, for your excellent update to the blog. It cleared up some questions I've had. Hope to see you all very soon. Love you, vicki & danny

Anonymous said...

Hi Aimee and Michael,

We got your blog address from our friend Marion Snyder with whom we used to UCG in L.A. We now attend at UCG in St. Petersburg, FL. Just wanted to let you know we'll be praying for little David for a quick recovery.
We have a 14 month old son. It must be hard to see your baby in the hospital. I'm certain God will heal him and you'll soon have him doing cartwheels in your front yard!
Keep the sunny side up!
Take care,
The Huitema Family

Anonymous said...

Thanks, Michael, for sharing these details. My awe for God's creation is over the top. I am humbled at how God is allowing modern science to help us get a glimpse into the intricacies of what makes our bodies work. As David said in Psa 139:14 "we are fearfully and wonderfully made." Thanks again, Mike. Love, Mel