At 3 months of age, Charlie Rein is the second person in the U.S. — and the fifth in the world –to be diagnosed with a particular kind of cancer.
Known as Anaplastic lymphoma kinase positive histiocytosis, the cancer causes an enlarged liver and spleen and a drastically low platelet count.
“ALK+ histiocytosis is rare, even by rare standards,” said Dr. Michael Kelly, Charlie’s doctor and the cancer program director at Children’s Wisconsin.
Mysteriously enough, the only other child in the country with ALK+ histiocytosis was also treated at Children’s. Kelly has no theory or explanation of how that came to be.
Doctors first became aware that something was medically wrong with Charlie two days after he was born on Aug. 3 at Ministry Saint Clare’s Hospital in Weston, Wisconsin. After noticing he appeared jaundiced, doctors did a blood test and discovered his platelet count was 18,000, significantly lower than the average count of 150,000.
Charlie was transferred by Flight for Life to Ministry Saint Joseph’s Children’s Wisconsin 50 miles away in Marshfield just after midnight on Aug. 6. His platelets at that point had dropped to 14,000, and he underwent his first of many platelet transfusions.
Over the next several weeks, doctors performed every test imaginable on Charlie, according to his mother, Bethany Rein of Mosinee, Wisconsin. Yet, doctors could not determine what was behind his low platelet count, liver dysfunction, anemia and inflammation.
“I had the perfect pregnancy,” Bethany said. “I had no idea that anything could be wrong.”
Bethany and her husband, Shannon, eventually decided to transfer Charlie, their only child, to Children’s Wisconsin, where he arrived on Sept. 15. He underwent liver and bone marrow biopsies, a spinal tap, numerous blood and urine tests, and biopsy slides.
Initially, Kelly said conditions like congenital infections, metabolic problems or genetic disorders were thought to be the problem.
In the end, doctors diagnosed Charlie with something unexpected: the life-threatening cancer ALK+ histiocytosis.
According to Kelly, ALK+histiocytosis causes connective tissue cells called histiocytes, which get produced in the bone marrow, to get stuck in the spleen and liver instead of migrating to the blood and organs as they should. The spleen and liver subsequently become dangerously enlarged. In Charlie’s case, they are five to six times the size they should be.
Doctors have known about Histiocytosis for a hundred years, but ALK+ histiocytosis has only presented itself in the last 10 years, Kelly said. The cause is not known, yet doctors do know that it is not genetic.
“For eight weeks, we didn’t know what he had. We prayed for an answer, but it wasn’t the answer we wanted,” Bethany said. “Then once they knew what it was, they didn’t know how to treat it or what drug to treat it with. It took two weeks to figure out the next step.”
Like Charlie, the four other patients with ALK+ histiocytosis were in the first couple months of life at the time of diagnosis. They, too, had enlarged livers and spleens, had fluid in the belly, needed transfusions and struggled with feeding. None had a fever and all were otherwise clinically well.
“All of them got better, and all of them got better over the course of months to about a year,” Kelly said.
Complicating matters, however, was that none of the previous four patients underwent the same course of treatment. In fact, one was not treated at all. So, with no medical consensus, the question became, how to treat Charlie.
“There’s an open question as to ‘Does this need to be treated?’ and the second issue is ‘If you’re going to treat it, what are you going to treat it with?’” Kelly said. “With only four cases reported, and Charlie the fifth, there’s really no obvious standard of care for this particular disease.”
In Charlie’s case, Kelly and Charlie’s parents elected to treat him because his enlarged liver and spleen were interfering with his ability to eat and gain weight. In addition, the abnormal functioning of his liver required many supplements, and the large spleen required blood transfusions daily or every other day.
Kelly did not want to follow the same treatment plans as the previous patients because he believed some of the chemotherapy drugs and steroids used had many short- and long-term side effects, including everything from infections, weight gain and bone health problems to secondary cancers later in life.
Furthermore, the international experts on Histiocytosis were split on treating Charlie with the chemotherapy drugs Cladribine or Clofarabine. Kelly, however, said those can result in toxicities and side effects like low blood counts and infections during and after chemotherapy.
Kelly and Charlie’s parents ultimately opted to use Cytarabine, which is a contemporary chemotherapy drug for Histiocytosis.
“The reason Cytarabine is a good choice is because it’s effective in a wide number of Histiocytosis disorders, and there are limited short-term or long-term side effects,” he said. “And in a setting where it’s not clear the disease needs to be treated to begin with, side effects are the major concern.”
Children in Charlie’s age group are more prone to side effects, according to Kelly, because their organs and cells are growing, and the chemotherapy has the capability to interfere with those processes.
Charlie recently began his third round of chemotherapy. Each round consists of five consecutive days followed by a three-week break to allow Charlie’s body to recover from any potential side effects.
The plan is to continue that chemotherapy regime until measurable results in the spleen, liver and platelet count are obtained. If Charlie’s condition worsens, Kelly said he will reassess and consider more aggressive chemotherapy.
Since Charlie began treatment at Children’s MACC Fund Center, however, his platelet count has increased to 20,000 and his spleen is smaller. His transfusions have also been spaced out from three times a week to less than once a week.
“It’s good for him that he doesn’t know what’s going on, and he won’t remember any of this. But it’s sad he can’t experience the other things a 3-month-old experiences,” Bethany said. “I’m confident that Children’s will be able to treat him and cure him, though.”
“We expect to cure Charlie,” Kelly echoed. “The goal is to minimize potential problems during and after therapy, and my hope is to get him home in the new few months.”
Kelly is quick to point out, though, that a large team of providers have been responsible — and will continue to be responsible — for Charlie’s care at Children’s.
For instance, Charlie stayed in the Neonatal Intensive Care Unit before moving to the cancer unit. Gastroenterology, hematology, genetics and pathology were other areas that played a role in his diagnosis and care.
“It really highlights the tertiary care necessary to take of kids like Charlie,” Kelly said. “Also being in a medical academic center allows us to explore possibilities outside of our own experiences. We engage others across the country and the globe who have experience in these disorders to give the best therapy to Charlie.”