[back] Leukemia & lymphoma  Vaccinia


From the Los Angeles Times

A Marine's hard fight: leukemia and a smallpox vaccine infection

Odds appeared to be against 20-year-old Lance Cpl. Cory Belken when he was diagnosed with both.
By Jia-Rui Chong

June 7, 2009

Reporting from San Diego First came the stomachaches and low fevers. Then Lance Cpl. Cory Belken broke out in a rash. His temperature shot up to 104.6 degrees.

The young man became delirious, telling his mother, Barbara Skaggs, that he wanted to go to the smoking section even though he had never smoked. His blood pressure dropped.

Belken, a 20-year-old Marine, had been dealing with two potentially life-threatening conditions at once -- a recent onset of acute leukemia and a blooming infection from a smallpox vaccination. He was that unlucky one-in-a-million case, his doctors said, but one they hoped would end well.

Unfortunately, his immune system wasn't regenerating very well after two rounds of chemotherapy.

Belken was crashing.

In doctors' and family members' account of that harrowing night of March 7, hospital staff at Naval Medical Center San Diego scrambled to get Belken to the intensive care unit about 11 p.m. and worked on him for about 12 hours. Doctors pumped five medications called vasopressors into Belken's body at the highest dose, constricting peripheral blood vessels to keep blood pumping to his heart and brain.

Other organs started to fail. His hands and feet turned dusky.

On the afternoon of March 8, Lt. William Danchenko, an oncology nurse practitioner, approached family members in the waiting room. He thought this was it.

"We need you now," Danchenko told them.

Skaggs, 39, rushed to the bedside of her only child. "Come back," she begged.

Bad timing

Belken was the victim of bad timing, said Lt. Cmdr. Edith Lederman, an infectious diseases specialist at the naval hospital.

When a corpsman at the Marine Corps Air Ground Combat Center in Twentynine Palms, Calif., jabbed Belken's arm 15 times to deliver the smallpox vaccine Jan. 13, the young man felt fine.

He was running regularly and lifting weights every day. His family, which hails from the St. Louis area, had no history of leukemia, a cancer of the bone marrow that cripples the immune system.

His answers to a standard set of health questions did not rule him out from getting the standard regimen of vaccines for deploying to Iraq. So Belken got the smallpox shot, which delivers a live form of the virus vaccinia, a milder cousin of the smallpox virus variola.

Had the cancerous cells built up faster, officials would have seen the symptoms of leukemia and exempted him from getting the vaccine, Lederman said. Or, if he had gotten the vaccine several months earlier, she said, his immune system probably could have cleared the vaccinia without much trouble.

"It's a fluke, really," Lederman said.

More than 1.7 million service members have been vaccinated against smallpox since 2002 because of fears of a bioterrorism attack. Most simply develop a tiny blister that scabs over after 14 days. The scab typically falls off by the 21st day, leaving a barely visible circle of new skin on the arm.

But the military knows it is risking potentially fatal side effects to protect service members, who are exposed to diseases most Americans never encounter.

About 200 service members have developed complications associated with the smallpox vaccination that were serious enough to require hospitalization or absence from work, according to Lt. Col. Patrick Garman of the Military Vaccine Agency. Problems included inflammations of the brain and parts of the heart.

Most of these people recovered, but in one case in 2003, two expert panels concluded that a group of standard deployment vaccines, including the one for smallpox, probably contributed to the death of Army Spc. Rachel Lacy.

In 2007, a vaccinia infection also nearly killed a 2-year-old Indiana boy who contracted the virus from his father, a recently vaccinated serviceman. The boy, who was vulnerable because he had the skin condition eczema, developed vaccinia lesions over 50% of his body. He recovered after he received an experimental drug.

This low rate of serious problems is still high enough to keep public health officials from mandating smallpox jabs for the general population, experts said. After all, the disease has been eradicated as a natural infection since 1980.

But because the military still thinks there is a credible threat of bioterrorism with smallpox, one of the deadliest diseases known to man, officials remain committed to inoculating service members, said Dr. Michael Kilpatrick, who directs strategic communications for the Military Health System.

Military officials said that they were doing their best to reduce complications by asking about preexisting conditions, but that they couldn't catch everything.

"The reality is, we're never going to have zero risk on a vaccine," Kilpatrick said. "There's always going to be that individual that has some untoward event that would occur."

Belken was one of the estimated 12,800 Americans a year who develop acute myelogenous leukemia. He just didn't know it when he was vaccinated.

Things started to go awry about a week later.

He had a headache that didn't go away, and he slept straight through a day and a half. A friend took him to an on-base Navy emergency room.

"They drew blood, and they told me that I had half the blood that I should've had," Belken recalled. On Jan. 28, he was admitted to Naval Medical Center San Diego.

Cmdr. Amy Reese, a staff oncologist, thought it best to start chemotherapy immediately, despite the blistering and slightly enlarged size of his vaccination site.

"We know untreated leukemia is 100% fatal," she said.

Doctors weren't sure what the treatments, which wipe out both good and bad cells, would do to the vaccination site. "It's a strange situation to come across," she said.

Doctors said they don't believe his vaccination triggered the leukemia. But his depleted immune system, crippled by the leukemia and chemotherapy, did appear to leave enough of an opening for the vaccinia to take hold.

A colleague asked Lederman to take a look at Belken's lesion because he knew she worked on pox viruses during a fellowship at the federal Centers for Disease Control and Prevention.

When she lifted up the gauze March 2, seven weeks after the shot, she was shocked to see the lesion had grown to nearly 2 inches in diameter.

A rim of blistering tissue surrounded a tan-colored crust. Vaccinia appeared to be actively eating up tissue.

Lederman told Belken and family members who had flown in from Missouri that she was very concerned. She suspected a spreading infection known as progressive vaccinia. She was sending samples to the CDC.

Lederman told the family that it was a rare condition and potentially fatal. In the past, when Americans routinely received smallpox jabs, 15% of patients who developed progressive vaccinia died, despite massive amounts of vaccinia immune globulin, the standard treatment.

In his laid-back, Southern-inflected drawl, Belken asked evenly, "Can it be cured?"

Yes, Lederman told him, but it would probably require some experimental treatments in addition to the standard ones. Because she had worked on the case of the child from Indiana, she knew about a drug called ST-246. The toddler was the first vaccinia patient who had received the drug, and it had worked.

Belken felt encouraged. "All right then," he said.

Lederman secured special approval from the Food and Drug Administration.

Belken got very protective of his arm and didn't want family members to hug too tightly.

"Stay away," he told them. "That stuff's no joke."

Minutes to live

With so many things haywire in Belken's system, doctors hustled to figure out what was causing his crash. The main problem turned out to be a multiple-drug-resistant bacterium called Pseudomonas aeruginosaPseudomonas aeruginosa. It had invaded Belken's bloodstream while his immune system was low.

Tests for vaccinia did not show any in the blood or bone marrow, but Lederman acknowledged that the infection may have had some effect.

"Any time you have an infection or multiple infections going on at the same time, you distract the immune system somewhat," she said.

Doctors gave him minutes to live, his mother recalled.

"And then after those minutes went by, it was hours," she said. "It turned to days, and then it was all right."

One doctor called Belken "Lazarus." Danchenko has never seen such a turnaround.

"He had one foot in the grave and one on a banana peel," he said. "If you have anybody who's an atheist, they should go meet Cory."

The near-death experience left its mark, shriveling some of Belken's toes. Surgeons had to amputate both legs below the knees.

The vaccinia also spawned satellite lesions. Lederman had to add another experimental drug known as CMX-001, which had never been tested on vaccinia patients. About a month later, she had to kill another drug-resistant bacterium that started to grow on Belken's lesion.

The young man required so many doses of vaccinia immune globulin that the CDC has suggested re-evaluating how much we keep in the Strategic National Stockpile. Belken's infection required an amount originally estimated to be enough for 30 people.

In his fifth-floor hospital room one recent morning, Belken patiently crossed his arms and waited for Lederman to apply medicine to his lesion.

His face was gaunt and serious, a contrast with the rosy-cheeked former self smiling back in pictures tacked to the wall.

Lederman was pleased with the scabbing and new purplish-pink skin.

"We haven't got any live virus in over a week," she said with a smile.

Belken still can't believe all of these problems attacked him at once.

"It sucks," he said. "I mean, I did all the training with all my friends and, I mean, we were moments away from going."

Belken and his family wished he didn't have to deal with the vaccinia in addition to the leukemia. They didn't think a smallpox attack was very likely.

"I think it's a big chance they're taking, giving them the shots," Skaggs said.

She was just glad he ended up at a hospital that had enough experience to handle her son's case. "If we wouldn't have tried these experimental drugs, he could've died from it, you know," she said.

Belken has a long road to recovery, but he is making progress.

After a four-month stay at the San Diego hospital, he was transferred to a rehabilitation facility about a week and a half ago. With the help of a front-wheel walker, Belken can now go about 50 feet on his new prosthetic legs without taking a break. He is taking such long, fast strides now that sometimes his physical therapists ask him to pull back because they are worried he might reopen some sores on his amputations.

He was also promoted to corporal last week.

Bone marrow tests lately have shown no evidence of leukemia, and Belken is eagerly preparing for a transplant. Doctors think they have found a pretty close donor match.

Belken's grandmother Judy Weekley said she has heard there is a 20% chance her grandson won't make it through the surgery. But she said the family is holding on to the guarded optimism that has sustained them through this ordeal.

"God's kept him alive through this; he's not going to let him down now," Weekley said. "Cory's a fighter. He wants to live. Real bad."