Identical twins Addisyn and Madisyn Million frolic together now like they have spent every second of their 17 months within an arm’s reach of each other. Addisyn, the younger twin, sometimes sits back and observes her older sister at play. If Madisyn falls down, Addisyn chuckles. It’s a happy laugh borne out of familiarity with one another, which is surprising given the fact that the toddlers spent one-third of their lives separated from each other as a result of severe combined immunodeficiency (SCID). This life-threatening disease is often called “bubble-boy disease” after a famous case in which a boy with the disorder lived for 12 years in a plastic, germ-free bubble.
When she learned she was expecting twins, Emily Million was excited about welcoming tiny additions to her family, but slightly overwhelmed with the thought of the dual responsibilities. She and her husband, Labron, had a 6-year-old daughter, Aliyah, and Emily hoped for two more girls.
“I come from a family of mostly girls, so I was excited to have twin girls,” Emily says.
Although the babies were small and arrived earlier than expected in November 2009, both girls were healthy at first. Babies with SCID usually develop a light cough and some intestinal problems in the first few months of life. They are also slow to put on weight, but Addisyn and Madisyn displayed no excessive symptoms until they were 5 months old.
Emily took the girls to a pediatrician after both twins experienced respiratory problems. When a combination of antibiotics, breathing treatments, allergy medicines and steroids showed limited effect, the pediatrician determined the girls had bronchiolitis, an inflammation of the small air passages of the lungs. During the next few days, Madisyn improved, but Addisyn struggled to breathe, sleep and eat.
As Addisyn’s condition worsened, she was admitted to a local hospital but was soon transferred to the intensive care unit of a nearby children’s hospital. Because she was expending so much energy trying to breathe, Addisyn was put on a respirator to let her body rest while immunologists worked to determine the underlying cause of her symptoms.
“In the ICU, the staff came in every day at 5 a.m. and did X-rays,” Emily says. “Every day the X-rays were a little worse or the same.”
After a negative cystic fibrosis test, an immunologist found that Addisyn had a severe case of pneumonia, known as pneumocystis jiroveci pneumonia (PJP). PJP is a hallmark of babies born with immune deficiencies. Additional tests revealed Addisyn had SCID, a rare disease that is among the most severe of the primary immune deficiency syndromes. Because Addisyn was an identical twin, Madisyn was tested and was also found to have the same immune disorder. Since the only treatment for SCID is a bone marrow transplant, the twins’ immunologist referred the girls to St. Jude Children’s Research Hospital.
Search for a match
SCID is marked by a vulnerability to infectious diseases and the need for strict isolation from the outside world. If not treated early, SCID patients rarely survive past their first birthdays.
“There are several genetic disorders that can cause SCID, but all of them result in a severe defect in the number or function of T cells, the cells that fight viruses and fungi,” explains Mary Ellen Conley, MD, of St. Jude Immunology.
The twins’ admitting physician, St. Jude oncologist Brandon Triplett, MD, vividly recalls their arrival at the hospital.
“Addisyn and Madisyn had no detectable T cells when they got here,” Triplett recalls.
The medical team immediately placed Madisyn in an isolated room in the hospital’s Bone Marrow Transplantation (BMT) unit. Addisyn spent four days in ICU before moving to the BMT unit.
“Addisyn’s condition was extremely fragile when she arrived in the ICU, but she improved quickly,” says Ray Morrison, MD, St. Jude Critical Care division chief.
Physicians found that Addisyn had a mutation in a gene for the receptor for a growth factor called IL7. This novel mutation had never been reported before, says Wing Leung, MD, PhD, director of the St. Jude Bone Marrow Transplantation and Cellular Therapy program. Because the IL7 gene was abnormal, Addisyn’s body could not produce infection-fighting T cells, which are vital to the body’s immune system.
In the two decades before the Millions’ arrival, St. Jude had treated 21 SCID patients, with four receiving bone marrow transplants from siblings. The remaining patients had received transplants from their parents, who are known as “half-matched” donors. The twins’ older sister, Aliyah, was not a match, and no matches were found on the national donor registry. That meant either Emily or Labron must donate stem cells to save their daughters’ lives. The couple mutually decided that Emily would donate to allow Labron to remain at home and continue working.
Half and half
Before the transplants, the twins received individually designed chemotherapy to prevent their immune systems from rejecting their mother’s stem cells and to encourage the engraftment process. A week before the transplants, Emily arrived in the hospital’s Medicine Room to begin the first of six consecutive days of granulocyte-colony stimulating factor (G-CSF) injections to stimulate her bone marrow into producing more white blood cells. Emily experienced the shot’s common side effects of flu-like symptoms. On the fifth day, she sat in a chair in the hospital’s Blood Donor Room to prepare for the five-hour extraction of her blood stem cells.
“I was honored to donate,” Emily says. “You can’t move at all, but when you think of why you are sitting there and what you are doing it for, it’s not that bad. ‘Children go down there and donate to themselves all the time,’ I thought, so that made it a lot easier.”
Nurses inserted an intravenous needle into each of Emily’s arms; blood was then withdrawn from one arm, passed through a machine designed to trap the white blood cells and infused back into the other arm. On the sixth day, Emily underwent the same process for five more hours.
“She had to donate to two patients, so we had to split the cells,” Leung explains. “We had never done that before at St. Jude.”
Research technicians split the 20 million cells in half, with each twin receiving a total of 10 million cells during their two infusions. The technicians also removed the T cells from Emily that might create rejection problems and left behind cells known as natural killer, or NK cells, to encourage the engraftment process.
A solitary split
While the donor cells grew, the twins recovered in isolated rooms on opposite ends of the hospital’s BMT unit. Because the girls were identical, had the same last name and were enrolled on the same protocol, staff members took extraordinary precautions to avoid confusion. Each twin had a separate nursing team so that when medicine arrived from the Pharmacy or blood from the blood bank, it was given to the right patient.
“Madisyn and Addisyn’s situation was unique,” says Jenn Wallace, Madisyn’s primary nurse practitioner. “We had to be careful to focus on our individual patient and to ensure the details of her medical course were handled properly.”
When entering the babies’ rooms, each family and staff member wore a gown, mask and gloves to protect the girls’ developing immune systems. Emily credits Labron’s mother and stepmother for coming to Memphis and helping during the two-month period when both girls were in the transplant unit.
“It was strict isolation,” Emily says. “We couldn’t pull down our masks to give them a kiss or to show them who Mommy is—that was kind of tough. The nurses were really nice about stepping in and giving us a break when we needed one.”
The twins’ inpatient stay in isolation ended in July 2010, just 19 days after their transplants—the fastest on St. Jude record.
“Because the chemotherapy we prescribed was gentle but very good to help engraftment, the twins recovered their blood counts quickly with no side effects requiring a long hospital stay,” Leung explained.
After discharge, each child was housed in a separate apartment in the hospital’s patient housing facility, Target House, to minimize cross infections. Although the girls were not in strict isolation, they still could not be near each other. Visitors were also limited. During the day, Emily divided her time between the girls, but at night, she usually slept with Addisyn. The babies visited the hospital twice a week, each on separate days.
In mid-October, Addisyn’s nurse practitioner, Ken Burnette, delivered the news that the Millions had waited 120 days to hear: “Dr. Leung says you can go home,” Burnette said.
“It was kind of like a dream, and I thought I didn’t hear him right,” Emily recalls. “I made him write it down on a piece of paper.” The girls also set the record for leaving Memphis the earliest after a transplant for SCID.
The twins traveled to St. Jude for biweekly check-ups until January of this year. It took a few months for them to become reacquainted after so much time apart. At first, the girls treated each other like strangers with no special bond.
“Being identical twins, everybody thought they wouldn’t forget each other, but I think they did,” Emily says. “It might have been because they were so young and didn’t get to know each other before.
“I thank God for working a miracle in my girls,” Emily continues. “I can’t thank St. Jude staff members enough for what they do—not only for my girls, but for every patient who walks through the doors.”
Emily says the girls play together now like they were never separated, and each one has a curious interest in the other. They return to St. Jude for monthly check-ups and, since their immune systems are now normal, for vaccinations. The St. Jude visits will be yearly after the first anniversary of the transplant in May.
Now cured of SCID, the girls should have no restrictions and should be able to handle infections and function like any other children.
“I think these girls really exemplified how collaborations between families and the St. Jude staff can turn a deadly disease into a disease that can be cured,” Leung says.
“One day you have no hope; the next day, someone is telling you it can be fixed—and fixed quickly.”