The Long and Winding Road Finally Leads to a Path out of the Forest
by Harvey Gould
From July 2000 until November 2013 I lived with PMF, over the years undergoing a wide variety of tests, procedures, and medications, participating in a clinical drug trial, and learning to cope with the numerous ill effects of the disease and, in some instances, of the medications.
Still, there were periods when I was set “free” from returning to the clinic for several months at a time and my wife Karen and I learned to revel in those respites. On the other hand, there also were long stretches when I was at the clinic multiple times weekly for transfusions or other treatments and Karen and I also learned to accept those times—glad in knowing that I was in the care of a doctor who had a true expertise in the treatment of MPNs and BMTs.
In September 2013 my WBCs began rising in an aggressive manner, going as high as 190,000 (10,000 is “high normal”.) Consequently, my daily dose of Hydroxyurea was increased. However, by November my blast level had crossed the 20 “border” and it was determined that my disease had morphed into AML. I was told that if I did nothing, I’d likely be dead in about six months. My doctor and I agreed that my only chance for survival was a stem cell transplant.
A search was launched for a donor. Though the doctor wanted me to start a regimen of chemo quickly, he also understood that life events matter, so he agreed to allow me to wait until after Thanksgiving, (but not through Christmas,) to start treatment.
Starting in mid-December I went on Azacitadine, aka 5AZA, aka Vidaza, a chemo whose purpose was not only to retard progression of the disease, but also to put it into temporary remission during the time for the donor search. However, after I’d finished one full round and was scheduled to start my second in about a week my WBCs had actually jumped—from 190,000 to 235,000. On the very day that that number was determined from a CBC at the clinic (January 2, 2014), I was admitted to the hospital on an emergency basis because, at that number, I was a ticking time bomb for a stroke, a heart attack, or both
Upon admission, the plan was that the first night I’d receive apheresis to get the WBCs down fast and then I’d spend 30 days getting induction chemo with far stronger agents than Vidaza, to “induce” my AML into temporary remission. I’d then be released from the hospital at or around January 30 for a three-week “chemo vacation” to relax, gain my strength, and to get my head in the game; then return to the hospital around February 24 for the transplant. By that time a donor had been found and she agreed to have her stem cells harvested consistent with me going back into the hospital at that time.
Stem cells remain viable for about 72 hours so the time for harvesting must carefully be calculated taking into account the number of days the patient will receive all the advance preparatory drugs plus the “travel time” from where the donor lives to the patient’s location. The cells can be frozen (and apparently all autologous transplanted cells are frozen), but the freezing agent gives off a noxious long-lasting odor that often gets patients quite ill so it is best if they arrive “fresh”. (Besides, we’ve all had a waiter at a restaurant tell us that a particular food is “fresh frozen”. Sorry, it ain’t the same as “fresh.”)
I received my induction chemo, and actually tolerated it reasonably well. The day before I was to start a series of Neupogen injections to boost my counts I had a BMB to confirm that my blasts were then <10%. Unfortunately, life is often sloppy. The BMB confirmed that my blasts still were elevated to the point that I was not yet a candidate for the transplant and it was determined that I required a second round of the induction chemo to “do the trick”. Because of the extended time this process required, however, my hospitalization ended up lasting 44, not 30 days, and I wasn’t released until February 15, not January 30, as originally planned. This also meant that I would not be scheduled to return to the hospital for the transplant on February 24, also as originally planned, but rather that I’d return instead on March 4. Thus, I’d have a shorter time than hoped for to relax and become mentally prepared for the transplant. The donor was contacted and was agreeable to my new admission date.
However, life really can get sloppy. I had my second BMB a few days prior to my release. Several days later and while at the clinic we learned that the results of the second BMB revealed that even the second round of induction chemo had failed to get my blasts to<10%. This was stunning news. I was not a candidate for the transplant. The date for my reentry to the hospital was cancelled.
It had been bad enough requiring a second round of induction chemo to get me “induced,” but idiot that I am it had never even crossed my mind that the second round would also fail to get me ready. I had become depressed with the delayed hospitalization stretching to 44 days, but invigorated at the thought of having a bit of free time before reentering the hospital and having the transplant. Now, we had no idea if I’d ever become a candidate; we knew that I could not go on forever without one; and we had no idea whether, if I were able to become a candidate, the donor would himself or herself still agree to remain “on board.”
On an outpatient basis I went back on Vidaza, hoping that with all the chemo I’d received while hospitalized, this could now get me to where we needed to be, but things did not go well. At one point, based on the peripheral numbers, my blasts elevated to 67% and I became increasingly convinced that I’d been dealt a losing hand, never would reach the Promised Land of <10%, and that, in essence, I was a dead man walking.
Still, with Karen’s constant reminders that I’d always agreed never to quit the fight as long as there was a glimmer of hope, I hung in there and continued with treatments. However, making matters worse, because of all the chemo I had and was continuing to receive, the “metallic taste” in my mouth remained with me and I had absolutely no appetite. I knew that I was supposed to think of food just as fuel rather than as something to be enjoyed, and that my job was to eat as much “fuel” as possible. Nice concept, but it became virtually impossible for me to eat (and I’m generally a damn good eater). I’d get nauseous at the smell, let alone the taste, of food. If I tried eating anyway, I’d gag and simply had to stop.
By the time I’d left the hospital, I’d already dropped to about 160 pounds (my “normal” weight is about 195). During my continuing outpatient therapy I dropped another ten pounds. I was looking skeletal, and was extraordinarily weak. My joints ached; I had significant trouble walking, standing for more than a minute or so; and found it difficult simply to stand up from a sitting position. I ended up spending virtually all possible time in bed which, of course, made matters worse because I was getting no exercise. While in bed, I’d place a pillow between my knees to avoid a bone on bone rubbing. Meanwhile, I was going to the clinic twice weekly when not receiving my seven consecutive days of chemo, and at least once weekly requiring platelets, RBCs, or both.
Still, my doctor never gave up on me. In early April he decided to try an unusual combination of chemo agents (Decitabine and Zolinza, aka Vorinostat). Zolinza is not cleared by the FDA for use with AML patients, but my doctor found some papers that had been presented at an ASH conference to the effect that, among other things, in some clinical trials primarily focused on patients with other blood cancers, Vorinostat had had a positive effect on a small percentage of AML patients. Still, I was denied the drug twice after which the doctor made his direct pitch and I was cleared for its use.
The doctor and I agreed to be aggressive so that, for example, the protocol for use of Decitabine was to wait three weeks before receiving the next consecutive days of dosing, but we agreed to shorten that waiting period to two weeks. The Vorinostat is an oral medicine, taken for fourteen consecutive days. There is no prescribed protocol for the timing between the use of these drugs so we agreed that I’d take the Decitabine and the Vorinostat on a staggered basis, so that as I’d be completing my round of Decitabine I’d then be starting the Vorinostat. Though this gave me virtually no relief in being away from a chemo, and thus exacerbated my eating problem, we knew that we needed to remain aggressive if we had a chance to get me to the magical “blast” range. I have no idea if this staggered method and shortened period between rounds of Decitabine was critical, but this cocktail combination is what finally got me to the SCT.
Unlike other chemos I’d used, these agents began to have a significant effect on me, including severe night sweats during which I’d change soaked “T” shirts and pillow cases up to seven times a night. (After a while I’d put a towel on my pillow case nightly to minimize the sweat from seeping through.)
The doctor thought that the night sweats might be an indication of tumor lysis, a combination of metabolic disturbances often seen in AML patients after starting cancer treatment. Though the syndrome can lead to potentially lethal complications, e.g., it can cause renal failure and I do have chronic kidney disease, on the other hand it occurs only when large numbers of neoplastic cells are killed rapidly causing metabolic and other byproducts to be released into circulation.
So, it was possible that dead cancer cells literally were being expelled from my body via the night sweats. The doctor followed me closely to assure that I was not exhibiting any dangerous signs if this was tumor lysis. Meanwhile, after two rounds of this new “cocktail”, covering a period of about seven weeks, at least by peripheral analysis it appeared that my blast level actually was <10%. A BMB confirmed that this was so. Holy shit! This actually had worked. My wife and I again were stunned by the news, but this time happily because we both felt so beat up by then that we expected nothing but bad news.
By this time it was mid-May. Though the doctor would have liked to have given me two or three weeks “off,” and he did not like that my weight was still low, he was not willing to take the chance that I might possibly lose the benefit of the lowered blasts so he scheduled me to enter the hospital on May 20 for the transplant, giving us only one week for my “chemo vacation.”
A week or so before we received this news I’d lost the metallic taste in my mouth and the doctor had put me on an appetite enhancer that was working. My job was to gain weight fast. I ate copious amounts in the short time before reentering the hospital and managed to regain some of my lost weight.
Meanwhile, the transplant team contacted the donor and extraordinarily we learned that she was still willing to be my donor. I wrote her an anonymous letter (how do you thank a total stranger for offering you the gift of life?) that the transplant coordinating team sends to Minneapolis (the home of the NMDP). In turn that organization “clears” the letter for not providing identity revealing information and it then transmits the letter to the donor. I remain amazed at the dedication of those who are donors since what they endure is not insignificant, involving the taking of some drugs themselves in advance of the harvesting, and the harvesting involving either being under an anesthetic if the stem cells are harvested from the hip, or via the use of apheresis. These people are heroes of the highest magnitude.
And so the next part of my journey began:
Tuesday May 20, 2014
First, Karen and I went to the clinic for my blood draw and a brief meeting with my doctor. He had some information for me about a minor mix-up at “customs” regarding some test results for the donor—the first clue we had that the donor was from out of the country. After we had met with the doctor Karen and I went to lunch before taking the plunge into the hospital. Karen said that with the “customs” hint, she was sure the donor was from Israel since I was a nice Jewish boy. I was admitted early that afternoon. Later in the day I got platelets and very late (starting at about 11:00 pm, one unit of blood.) All in all it was a pretty uneventful day.
The transplant coordinator met us at the hospital. We learned that the donor (we already knew she was a woman,) indeed was from Israel. Karen preened and said, “OK, I’m brilliant, but now we’ve got all bases covered—from my Irish heritage, looking at all the Irish blood you received when you crashed when we were in Ireland in 2006, making you an honorary Irishman, now to knowing that you’re going to get Jewish stem cells, keeping things within your ‘Jewish’ family. We are golden.”
Wednesday May 21, 2014 (D-7)
My allogenic transplant was not with full dose drugs because of my age (69), how much chemo I’d already had, etc. so I’m not sure if the protocol is the same for those receiving a full allo transplant. In my case I received six days of treatment, one day of rest and was transplanted on the eighth day. In the SCT world, days are measured in countdown to the day of the transplant and then in days subsequent to it. So, my first day of treatment was Day-8 (or D-8), then D-7 and so on. Transplant day is D-0; and the first day post-transplant is Day +1, and continuing. On May 21 (D-7) I received my first dose of chemo (Fludarabine). It’s dispensed in about thirty minutes. I had no reaction to it during or after its administration.
Thursday May 22, 2014 (D-6)
I received my second dose of chemo today and my first dose of an immune suppressant drug (AGT) that is dispensed over a seven to eight hour period. It is a rabbit serum and is intended to kill “T” cells. OK. My name is Harvey. For those of you “of an age”, you know “Harvey” was a play and then a movie about a six foot invisible Pookah rabbit who loves Martinis. I’m just shy of six feet and have been a martini drinker for years (though I’m not invisible). Still, it’s pretty funny seeing “rabbit serum” come across the screen of the dispensing apparatus when your name is Harvey. So, if we were golden previously, this added tidbit had to help. We were on the Yellow Brick Road.
At about five hours into the administration of the AGT I spiked a fever, had a small headache and a minor sense of nausea. The nurse paused administration of the drug, gave me an anti-nausea pill and a Tylenol and within 30 minutes or so both the nausea and the headache were better and the fever was lowering. She restarted the dispensing of the AGT; it was finished within a few hours without further incident.
Friday May 23, 2014 (D-5)
I received my third dose of chemo today and my second dose of AGT (at double yesterday’s dosage.) l learned that I would continue to receive Fludarabine and AGT through D-3 and that the dosage for the AGT would be increased each remaining day. Meanwhile, even with the continued delivery of the Fludarabine and the continued and increased dosage of the AGT I had no additional reactions to either med.
I am also receiving a steroid via IV. Unfortunately, one of its possible effects is to increase blood sugar and it is doing so in spades with me. I am a diabetic, but at home, easily control my diabetes with two pills daily—no insulin. With the steroid, my blood sugars have been high (into the 300s and 400s) so I received some large doses (over 30 units) of insulin. I am scheduled to receive my last dose of the steroid on D-3 and hopefully, with the end of me taking that drug, I will return to a more normal cycle and get away from receiving the large insulin injections.
Saturday May 24 (D-4)
At about 2:00 a.m. I received my first administration of Busulfan, a chemo drug to kill cancer cells in the bone marrow and thus provide additional help in preparation for a BMT. This takes about two hours to administer. (From that time through Sunday (D-3) I received Busulfan every six hours.)
At 10:00 a.m. I received my next dose of Fludarabine and after that, my next increased dose of AGT. During my stay I also have received a number of antibiotics. Today I needed two units of blood. Tomorrow I will additionally receive some platelets. My WBCs are now 0.2 and Neutrophils are 0.15. No surprise there. These drugs will draw those down to 0 so that the donor’s stem cells (hopefully) will start growing healthy cells, but first we’ve got to clear the deck. On that score, as all of you probably know the transplant itself is simply the transfusion of the donor’s stem cells—a short term process. If you think about it, it’s a pretty anti-climactic event after all that any transplant patient endures to get to “transplant”, and we all also know that this “anti-climactic event can have dire consequences afterward.
Sunday May 25 (D-3)
Today I received my ending doses of Fludarabine, Busulfan, AGT and the pesky blood sugar sky-rocket-raising steroid, but I continued to receive anti-immune suppressants and antibiotics and was told that I will be on yet another steroid that will have some blood sugar raising effect. My sugar levels remain in the 200s and 300s. The transplant is getting close and the reality that it will happen is both scary and exhilarating. I feel strong both mentally and physically for the upcoming fight with whatever the transplant will throw at me though my weight still is light by 30 pounds or so.
Monday May 26 (D-2)
Today I started Tacrolimus, an anti-rejection drug. My blood sugars remain high and I continue to receive fairly whopping doses of insulin, but I have been most fortunate that I have not been sick from these drugs and pretty much have sailed through it. (I know I shouldn’t have written that because I’ll pay for it in spades in the aftermath of the transplant.)
Tuesday May 27 (D-1)
This is designated as a “day of rest”, so I have dubbed it my “Transplant Shabbos” and indeed I did some of what you’re supposed to do on the Sabbath, including plenty of rest and saying a few prayers, in one, praying for the souls of my parents and telling them that I hope to join them one day, but am fighting to put it off a bit. They said that I should be sure to take my time.
For the last day or so I’ve been asking if they know the time when the transplant will occur. No one could provide an answer except to say, “We’ll let you know early on the day of the transplant.” Though Karen is with me every day, she and I wanted to know so that if it was going to be particularly early she could still be sure to be here at that time.
Wednesday May 28 (D0)
The day has actually come! God, it seems like I’ve been through a thousand journeys during the last fourteen years, sometimes taking detours and heading down dead ends and into a dark forest from which escape seemed impossible. Exactly what am I now facing? Will it actually cure me or am I headed to one final disappointment? Is it possible that Karen and I truly will be able to share many more years together doing what we want rather than being shackled to a clinic? These and a million other thoughts were swirling through my head when my nurse came into the room to tell me the transplant would be at 11:30 that morning. Perfect. I called Karen who arrived at about 10:00 saying she didn’t want to take any chances.
Not long after 11:00 two nurses came into the room, one carrying a small cooling case. They then went through the regular routine used for hanging platelets blood, or any number of IV meds, one reading my name, hospital ID number and date of birth from my wrist band, then reading and double-checking the statistics for what was about to be transfused. After they finished, one took a soft plastic bag out of the container. It contained a smaller amount than you’d see in a bag of RBCs and was a red to pinkish color and I thought, “Holy shit! Is that enough or did someone screw up?”
A nurse hung the bag, hooked me up, and let us know that the transplant was beginning. Karen and I held hands and looked into each other’s eyes as my donor’s stem cells began to enter my body, both of us thinking, “Let this be the beginning of a new life.”
The transfusion took all of half an hour. They then “rinsed” the bag twice and transfused that residue to make sure I received all possible stem cells.
That afternoon, five nurses came into my room to sing “Happy Birthday” and to deliver a few birthday cupcakes.
I had no reaction during the transfusion, but that night got chills, a fever, nausea, and had some vomiting, but what the hell, I was on my way. This was just proof that my new tough Israeli stem cells were fighters!
Thursday May 29 (D+1)
I was weak but feeling better. All the symptoms of the previous night were gone.
The actual event of the transplant is so anticlimactic that it is hard for me to absorb the enormity of what had happened and what it had taken to get to the point that I was able to undergo the process. I’m not an idiot. I know that I’m still facing major challenges, but I also know that without the chance I’d been given, my life was over. I closed my eyes and flashed on much of what had happened during the last fourteen years, how Karen’s and my life had been upended—treatments, a clinical trial, BMBs, exhaustion, night sweats, more exhaustion, splenectomy, too many transfusions to count, relentless night spasms, seemingly half our life in clinic, deeper exhaustion, chemo, chemo, and more chemo, “tinny mouth”, rapid weight loss and so much more.
I cried, thinking that now, for the first time, I had a chance of leaving all the nightmares behind me; no, leaving all the nightmares behind us. The truth is that without Karen’s love and support I’d never have made it to the transplant. It was only because I so desperately wanted for the two of us to have the chance to continue to build memories and live the life we wanted to live that I was willing to endure what was required to make it to transplant. Otherwise, I know that I’d have given up along the long and winding road.
Friday May 30 (D+2)
An uneventful day. I continue to receive a myriad of different IV drugs and oral meds—immune suppressants (anti-rejection drugs), antibiotics, anti-fungal, and God knows what else. I feel good—weak, but without any nasty symptoms.
Saturday May 31 (D+3)
Ditto re D+4. I’m slated to begin Neupogen injections on D+7, protein injections intended to aid the body’s recovery of its counts. As is, my WBCs and ANCs are zeroed out and I need platelets about every other day (my baseline for a transfusion is 10) and blood perhaps twice weekly (my baseline is 8). Of course, without guarantee, the “expected” date when my numbers might begin to recover is between D+12 and D+14. I’ve been told not to obsess about my “numbers” though they are posted daily on a board in the room. Good luck with that.
Sunday June 1 (D+4)
The meds just keep on coming, both oral and IV. I am receiving three doses of Methotrexate and I know that I will receive three doses of a med via spinal puncture. I’ve developed a bloating sensation in the stomach and feel filled before starting to eat. The doctors say this is not unusual and that the chemos run riot with the GI tract. Other than that, I have no major complaints.
Monday June 2 (D+5)
More of the same as D+4. I am not eating well, but doing the best I can. Karen has brought in some frozen dinners, but they don’t help much. I am not losing weight, possibly from bloat, but the doctors do not appear worried.
Tuesday June 3 (D+6)
Again, a day similar to yesterday. The good news is that I continue not to have any major disturbing symptoms and the doctors appear quite pleased about that. Tomorrow is another big day when I’ll receive the first of my Neupogen injections, then start the waiting game for the numbers to rise.
Wednesday June 4 (D+7)
Things continue to go well. No mouth sores or rashes, no fevers, no pain, and the bloating has slacked off. The big event for today is my first Neupogen injection. My stomach is pretty black and blue from all the insulin injections (though my blood sugar numbers are now far more in control), but the nurse iced a portion of my stomach and warmed the Neupogen just by rolling the tube in her hand before injecting it, and it was fine. The consensus remains that it should take between five to seven days of Neupogen injections before seeing numbers rise. I’ll report at some later date how all goes from here and though I am still on the long and winding road, now I see a hopeful way out of the dark and foreboding forest.
Take me back to the Contents
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