Here Comes the Sun…
Spring is my favorite season of the year. After a cold and dank winter, it is wonderful to see the land and creatures blossoming once again under the golden warmth of sunshine. Mind you, spring can be a fickle season. The warm sunlight of today can easily turn into blustery winds chilling the unwary T-shirt wearer to his very bones. But if you are like me, I am sure you take pleasure in the warmth of springtime today, who can tell what tomorrow will bring?
The Dark Days
Harvey had been struggling with daily fevers for several weeks now. We are not talking about the 100.5F fevers for which neutropenic CLL patients are told to go to the hospital. We are talking about mind-bending fevers that reached as high as 104.5 to 105F at their peak. Everyday, the morning would start out mild. No fever, no chills, no problems. By midday, the picture would begin to change. The fever would increase gradually, totally resistant to maximum safe doses of Tylenol and Advil. By mid afternoon it would hit its peak. On some days the fever would break by late evening. On other days it would continue into the night, making it impossible for Harvey or me to get any sleep. Often the fever would be accompanied by bone rattling chills / shivering, followed by drenching sweats that required change of pyjamas and sheets. I have never done so much laundry in my life.
The docs looked for any pathogens that could be causing the fevers. They looked for the common ones, they looked for the uncommon ones, they looked for the downright bizarre tropical ones ones because Harvey had spent a significant chunk of his life in Malaysia and India. With the sole exceptions of HHV6 (reported on earlier) that was soon resolved and a stubborn CMV infection (more on that nasty critter below), they could find no infections in Harvey. Samples from the Hickman port Harvey was fitted with were tested again and again. Nothing. Nada. In desperation, just in case the port was harboring some pathogen that was refusing to come out into the samples collected and tested, the decision was made to pull the Hickman port. I was sorry to see it go, it was working so beautifully and made all the intravenous infusions so much easier for Harvey.
The hope was that if the port was the guilty party, removing it would solve the problem. No such luck. Two days after they yanked out the Hickman, Harvey put on his best fever performance yet, hitting his career high note of 105F. I would be lying if I said I was as cool then as I am now, writing about it after the fact. Fortunately for Harvey and me, an old school friend of ours was visiting and so we had some one to freak out with us. Misery loves company. Oh yes, they did try to culture the removed port itself, to see if any bugs could be encouraged to grow. Once again, the results were a resounding zero.
One of the experts in charge of the protocol decided to do a little experiment. Harvey was given an intravenous dose of 60mg of prednisone, along with the rest of his antibiotic and antiviral medications. Something amazing happened. For the first time in weeks, Harvey had no fever that day. He stayed cool as a cucumber for the whole day, he felt like himself again. We went for a walk, had a relaxed lunch, watched TV, felt human again.
After much back and forth, it finally became clear to me (and most of the attending physicians) that the only agent that controlled Harvey’s fevers was prednisone, carefully calibrated down to 40mg/day. There was some concern about doing this for any length of time, since Harvey still had that pesky CMV infection and it is not safe to prescribe immune suppressive steroidal drugs to patients with live infections. But frankly we were running out of options and I could not see how my friend was going to be able to tolerate these massive fevers any longer.
One Less Thing to Worry About
The CMV infection was the big roadblock in giving Harvey the prednisone dose he needed to control the fevers. Yesterday, for the first time, we saw the CMV viral counts go down. They had been hanging tough at the 2K – 2.7K range ever since CMV was diagnosed several weeks ago. Yesterday the counts went down to 0.2K. Anything less than 0.1K is considered inconsequential. Harvey will stay on intravenous gancyclovir for a week longer, followed by several more weeks of oral version of the same drug (valagancyclovir), just to make sure the CMV is destroyed completely. The fact that the antiviral therapy is proving effective and the viral counts have come down sharply demonstrated that the 40mg prednisone he had been getting for the past 4 days has not gummed up the works.
A Mystery For The Experts
I keep telling Harvey it is OK to be a somewhat boring person at times like this, but he just does not seem to get it. He has become an interesting puzzle for the doctors, as they try to explain what is causing his high fevers. One by one, all the known pathogens have been ruled out, as well as the poor blameless Hickman port. As Sherlock Holmes would say, once you have ruled out all the probable causes, what remains must be the cause, however unlikely it may sound. Among the less likely culprits are (1) drug induced hyper immune reaction (and Harvey has been on drugs enough to sink several good sized boats) (2) Something called an “engraftment syndrome” where the newly minted donor neutrophils go on a rampage, tricking the body into thinking there is an infection of some sort and therefore jacking up the body temperature (3) good old fashioned GVHD. The jury is still out and we do not yet have a consensus on what may have triggered the high temperatures. The fact that Harvey also had a transient but pretty impressive rash on his arms and legs at one point may be a clue.
My money is on some weird and unconventional presentation of GVHD. I have one totally unrelated bit of information for making this bet. Harvey had these “shoddy nodes” along the side of his neck, sort of pebbly nodes I could feel with my fingers, even after going through all the preconditioning and the transplant itself. Over the last couple of weeks these and every other node we could feel all over his body have disappeared. Is this the much longed for graft-versus-leukemia (GVL) effect, clearing his body of the last traces of CLL? If he is experiencing GVL, were the fevers the other side of the coin, the evil twin GVHD? The experts are not convinced. But that is my story and I am sticking to it – for now.
When it rains it pours
Let’s see: we got a handle on how to control Harvey’s fevers with prednisone, CMV viral loads decreased dramatically, Harvey seems to have shaken off the last remaining traces of any unnaturally enlarged lymph nodes – pretty good news you say? Well, you have not heard the last bit yet. Today was got the latest results of molecular studies to check on the status of the two cord blood units Harvey received back on March 26th. As of today, Seattle Slim is 100% in charge and Harvey is fully chimeric and engrafted. There is no trace of the second cord blood unit, or Harvey’s own prior cancerous immune system. Slim is getting pretty good at making red blood cells, platelets and neutrophils (the last need a little coaxing once in a while with a Neupogen shot because of all the immune suppressive drugs Harvey is getting), which means Harvey needs very few transfusions.
Don’t let me get too euphoric. There are still bridges to cross. The experts are still scratching their heads on what caused the fevers in the first place and what would happen if we discontinue the prednisone. Would the fevers return with a vengeance, or would we have succeeded in changing the pattern once and for all? Is the shoe yet to drop on the subject of GVHD? How long will it take Harvey to recover his lost weight and strength? It breaks my heart to see him so scrawny, barely able to keep up with me when we go on our very short walks. But his spirit is doing well, especially since he won his bet with me – contrary to predictions, he managed to keep most of the hair on his head (what there was of it to begin with) as well as his beloved goatee.
It has been a turbulent and oftentimes very scary couple of weeks. Today, I can feel the spring sunshine in my bones, I am holding on to my sense that Harvey has turned the corner and we will soon be heading back home to our beloved Sedona. I can’t wait to get our dog back, our life back. Thanks for keeping the vigil with us, it means a great deal to Harvey and me.