By Paulette Mehta
He wanted to be scooped up in the ocean wave of new discoveries and to ride the wave for as long as he could. Anything, anything to have a chance.
I met Mr. Lemming for the first time in the I.C.U. He had been flown in from Bentonville, a bustling, small town that was home of the national headquarters of Wal-mart in Northwest Arkansas. He had come to the Emergency Room for confusion and blurred vision. Work-up in the local hospital showed that his white blood cell count was more than 15 times normal making his blood thick and possibly causing it to stagnate in his arteries and veins. His referring doctor thought he was having a stroke and sent him to our hospital immediately. Since he had fought bravely in the Vietnam war, had been honorably discharged, and had acquired several conditions presumably because of his service, he was eligible for free medical care in the V.A. system. He was therefore flown to our V.A., the largest such facility in Arkansas.
When I came down to meet him in the I.C.U., I realized that our resident team was giving him blood, antibiotics, and fluids and they were consulting me, the hematologist, to help them figure out why the white blood cell count was so high and what needed to be done.
I took the team aside to find out and asked: “what’s going on?”
The resident answered: “He’s had a diagnosis of chronic myeloid leukemia for 10 years, off and on, and now it’s out of control.”
“When did it start?” I asked.
“This episode started about ten days ago with confusion and headaches. He thought it was from working too hard in the yard in this heat,” referring to the heat wave radiating through the state. The temperature had been over 100 degrees Fahrenheit for the past week, part of the normal Arkansas summer.
“But it kept getting worse and his wife insisted he come. She seems to be in charge. She’s right there in the waiting room if you want to talk to her,” pointing to a tall, thin, 60 -ish year old woman wearing a tailored, plaid dress.
As I entered the waiting room, I saw her sitting alone in a far corner reading The Arkansas Democrat-Gazette with a copy of the New Yorker on the seat beside her.
“Can we talk?” I asked her as I entered the waiting room and escorted her to the conference room. As we walked into the conference room, I asked her permission to take notes.
She started: “Many years ago, he had leukemia, it was low grade, indolent as you doctors say. There was no effective treatment and they told us to go home and let nature take its course. That was in the 1970’s. He was only 22, way too young to let go, but then again, the other young people and even children with cancer were also dying in those days. He was about to go under, to sink under the pressure of his disease; but he was a fighter.”
“Then what happened?” I asked.
“He said no, he was going to fight this disease in whatever way he could. He’d go anyplace, do anything, give himself to science to get a chance. He told me he wanted the chance to live, to swim not sink, to go over the waves not under. More importantly, he wanted his life to mean something, to be used towards research that could help somewhere somehow. He’s a good man.”
“So, what happened then?” I asked.
“He called every place in the country to see if someone could treat him, if there was something somewhere that could help. They were doing a trial at the National Institutes of Health in Washington DC to see if chemotherapy could help and he wanted to go there. We had to get the money to afford the trip, but I worked two jobs, so he could make it there, and they didn’t charge him for the medicines.”
“Someone offered us a chance. They didn’t know if it would work and how long it would work but we could try it. It would be a clinical trial, they would use him like a guinea pig. He was so excited –he wanted to be a guinea pig. He wanted to be scooped up in the ocean wave of new discoveries and to ride the wave for as long as he could. Anything, anything to have a chance.
“The treatment turned out to be chemotherapy which they were using for patients with acute leukemia. He didn’t have acute leukemia, but they were trying it. In low doses. I forgot the names. They were low dose and they made things better for a while, well for about two years. But they made him sick with nausea, vomiting, diarrhea, rashes, and..oh..of course he went bald. He hated it but said it was worth it to be alive. He would ride any wave, any new development, as long as he could live.”
The alarm went off and I went racing into my patient’s room. A whole group of people were hunched over my patient’s bed, compressing his chest, in and out, pumping, pushing, priming. Finally, they stopped, his heart had returned. “Sepsis” the resident murmured to me, “he’s going under; even if he survives he doesn’t have a chance to overcome this storm, let’s get palliative care involved.”
Later in the evening, I went back to be with his wife. “He’s OKfor now. Leave the records with me. I can read about the rest. We can talk later. Stay with him and hold his hand. He’ll know you’re there. I’ll be back tomorrow.”
I came home with a briefcase filled with paperwork. My husband peered at me and said “another all-nighter? You’re an attending now, give up being an intern! ” I wanted to, but I couldn’t. Who was this man in my I.C.U. and why was he holding on so tight?
“What’s for dinner anyway?” my husband called out to me.
“Whatever you cook or whatever you call out for,” I answered. “OK, it’s pizza tonight, again, the fourth time this week.”
The wife had gotten all the details right. He had been diagnosed with chronic myeloid leukemia, in chronic phase and he had been treated with low dose cytosine arabinoside. His blood counts had partially normalized but were still too high. His liver, spleen and lymph nodes were enlarged but had receded with treatment.
Then two years later he relapsed despite still taking the chemotherapy. His treating physician suggested hospice, but he refused. He knew the storm was returning but he wasn’t ready to drown under the waves. He wanted to surf the waves again and ride over, not under, them. He had weathered the last storm, could he do it again? He had resisted calls to give up, to go to palliative care, to go to hospice, or to “let nature take its course.” He would resist again. But what would he do?
His wife called every cancer doctor in the city and no one had a better treatment. That’s when she called the research nurse at M.D. Anderson again and begged for another trial. Did they have anything, anything at all which could help? Was there a wave of discovery he could ride again?
“Why, yes, we do have trials and we could discuss options with you,” the research nurse had responded. “We’re experimenting with interferon and some patients have already done well with it.” Interferon was a drug that stimulated the immune system, and the immune system in some people could fight the leukemia. But the inflammatory response was very robust, and most people developed high fever, chills, shakes and felt sick for the whole day. The drug was given by self-injection into the abdomen three times a week. Most of the time my patient felt really sick on it. He had however gone into complete remission for eight months. He rode this wave very successfully as he had ridden the past one. He was riding high over the wave, not under.
Until he wasn’t.
That was when he relapsed, again. The disease was literally stalking him. The waves were about to take him under again. What should he do? After two types of different treatments, there was very little likelihood that cancer would respond to still another treatment. Therefore, his treating doctors had suggested, again, to consider palliative re and hospice support for comfort care only.
That’s when he and his wife wondered if another type of treatment should be considered. That’s also when they started calling around again, to the same places they had called earlier. Maybe just maybe something had changed. She wanted him to stay above water, to float over the waves for as long as he could.
Some of the cancer doctors from M.D. Anderson had moved upstate from Texas into Arkansas and had developed a stem cell transplant program at the University of Arkansas for Medical Sciences (UAMS) hospital. It was quickly becoming the biggest stem cell transplant center in the world focusing mostly on treating patients with multiple myeloma. But the program accepted any patient needing a stem cell transplant, regardless of diagnosis. The team had a well-greased machine and was led by a giant in the field who had assembled an amazing group of doctors from around the world.
The wife hesitated to call at first. Would they accept him? Would they give him a chance? Would they do a transplant event though his heart wasn’t working well anymore? What would the charge? Could they afford it? But most importantly could her husband stand it? Would he drown in the recurrence of his disease or stay afloat with this new discovery again?
“Come as soon as you can,” the voice on the phone told her when she finally got the courage to call. “We can take care of him. We can take care of anyone.” This would be another wave of discovery. He could again ride the waves and get some more time.
She continued talking to me: “He was in relapse when he showed up in the stem cell transplant clinic. His counts were sky high with a white blood cell count ten times normal, and with low red blood cells and platelets. They gave him treatment and he started to improve.
“Transplant had just developed as a possibility for chronic myeloid leukemia. Would it work? Would he survive it? He had trembled while thinking of it, but his wife said it could save his life and he should ride the wave of this new discovery now. She wasn’t ready to be a widow. He wasn’t ready to die. He didn’t want to drown. He wanted to ride this wave for as long as it would possibly hold him.
The wife continued, “I had shouted at him: ‘If you can’t do it for yourself, do it for me! Hold on and ride this wave for as long as it lasts! Do it for me!’
“He agreed, for me.”
“Months later after he finally went into remission with the chemotherapy, he underwent transplant and it worked like a charm. All of the blood counts normalized quickly. He felt better. He could get around better. His mood improved. Our marriage was better.”
“Thanks, you’ve been a great historian, let’s get together tomorrow and talk more,” I said, knowing I needed to move on and finish my day’s work. This evening my husband and I had committed to going to a potluck dinner and I needed to make chicken curry for the evening meal. We were part of a potluck group that met weekly on Wednesdays and we never missed a date. It was our home away from home with people who knew us better than any of our colleagues or even our families all so far away.
After the potluck, I kicked off my shoes, put on my PJ’s and continued reading.
The stem cells he received were from a matched unrelated donor, nicknamed a “MUD transplant” for the acronym. The donor was unrelated to him, matched perfectly with him, and would save his life. He would never know the identity of this kind stranger who had donated so many stem cells out of the goodness of his heart to someone he didn’t know and never would know. The cells from the other person “homed” to his bone marrow and fully engrafted after 30 days, as expected.
Then something strange happened. The stem cells from the donor—that is, the graft—turned against him in a condition known as graft-versus-host. First the donor stem cells (graft) invaded the skin, then liver, then the intestines. There was intense inflammation, pain, fevers, rashes, bruising, bleeding. The blood counts dropped. It was controlled with steroids, very potent anti-inflammatory drugs. The storm was raging again, and he was fighting above the waves, or at least he was afloat. Or at least alive.
Gradually the acute graft-versus-host disease abated, but later a chronic form erupted. The chronic form of graft-versus-host disease involved mostly the joints causing stiff painful arthritis. It also involved the esophagus and stomach making it hard to swallow and to tolerate eating.
In effect, he had traded one disease for another, leukemia for graft-versus-host disease. It was a good trade: he had traded his leukemia for chronic graft-versus-host; the former was fatal, the latter was not.
Now here he was with us in the V.A. hospital and in the I.C.U. The graft versus-host-disease had resolved, but the leukemia had come back. Perhaps the graft-versus-host-disease had been treated too well, preventing the donor cells from fighting his normal but also his leukemia cells. He was very sick with active rampant disease. The storm had become a tsunami, the water was devastating, the waves overwhelming. He would never get out of the I.C.U.until his leukemia abated. And if it didn’t abate, he would die.
But there was still no effective chemotherapy and another stem cell transplant was out of the question while he was so sick. I couldn’t figure out anything to do to get him to ride another wave of discovery. I did not imagine he could ride over this wave, rather I saw him sinking deeper and deeper to the bottom of the ocean. His time had come, I thought.
That’s when one of the medicals students asked me: “why can’t we try STI 1571? It worked in other patients with this disease and some of those patients are still alive. I read about it in an abstract that was presenting a few months ago at the American Society of Hematology.”
“Really?” I asked, not admitting that I didn’t know anything about it.
The drug was so new that it didn’t have a name yet. But people were talking about it. A young doctor at Oregon State Hospital had figured out that this safe, oral, daily drug could stop the oncogene driving this disease and cure the leukemia. Initial trials were unbelievable with 90% of patients achieving a complete response within 4-6 weeks, even if they had previously not 6responded to other treatments. Later when it proved itself indeed to be a miracle drug, it was approved by the FDA under the name “Gleevec” and became the gold standard for initial treatment for all patients with chronic myeloid leukemia, eliminating the need for most hematopoietic stem cell transplants to control this disease.
But this was before FDA approval and I wondered how I would get it. It didn’t have a name. It was not FDA approved. It was not sold over the internet.
My medical student interrupted my thoughts with her comment: “I’ll call the company and see if we can get it by compassionate use. I’ll beg them for the drug, I’ll explain that this man needs it, that he can’t live without it, that it means the world to him, his wife, and….to us.”
Then she continued, “I already spoke to his wife, she’s the next of kin, and she said yes, she was so afraid he was finally drowning but this new drug could save him from the waves that would otherwise overwhelm him. He could ride this wave too, a new wave of discovery which he could surf for as long as it took him. She would make sure that he agreed, if not for himself than for her. She needed him.”
“Let’s get it,” I said, awed at his luck in riding so many waves of discovery, each of which kept him alive one wave at a time.
Paulette Mehta, M.D. M.P.H., is a professor in the Department of Internal Medicine Division of Hematology/Oncology at UAMS.