A counterattack against rejection

Elizabeth Rand knew she should go home. Just 13 days earlier she'd had a mastectomy, reconstructive surgery and a breast reduction. The last of five surgical drains had just been removed during a postoperative checkup at HUP - the Hospital of the University of Pennsylvania.

Rand, a senior liver specialist next door at Children's Hospital of Philadelphia, knew her patients were in good hands. She knew that 17-month-old Nadia Kadi would be fine during the last 10 days of Rand's recuperation.

Rand didn't need to check on her.

Her husband, Spencer, reading her mind, had asked her to please come home after her appointment. A colleague had warned her it was too soon to visit CHOP, that she would get sucked in.

But Rand couldn't stay away. Not from those children. Not from their families. Not from Nadia.

It was Thursday, April 26. Rand, 45, slowly walked the one block to CHOP, careful not to pull any of her stitches. Apart from the ridged purple scabs beneath both breasts, she had an abdominal scar stretching from hip to hip where the plastic surgeon had collected the fat tissue for her breast reconstruction.

Nadia's parents, Allison and Joe, would be crazy with worry, Rand thought. The toddler was rejecting her newly transplanted liver.

The first month after a transplant is generally the most dangerous, when the potential loss of the liver is greatest. Forty percent of liver-transplant patients experience some rejection, but doctors can employ an array of drugs to treat and prevent it.

Still, nearly 20 percent of livers transplanted in children across the country fail, leading to second transplants. At CHOP, only 8 percent required another organ.

Rand was going to do everything possible to make sure Nadia didn't join that group.

When she arrived on 8 South, the ward at CHOP where liver patients are treated, Nadia was awake.

The little girl looked up curiously to see who was coming into her room. She offered Rand a coy smile before turning back to hug her father and hide her face in his chest.

She looked good, thought the doctor.

The trick was the meds. Nadia's immune system was attacking the foreign organ. Rand had to find the right mix, the proper alchemy, that would fool Nadia's body into accepting the new liver as its own.

The child was taking 10 different medicines. Two immunosuppressants, tacrolimus and prednisone, to prevent rejection. The rest of the drugs she'd take were to counteract side effects from the first two. Nystatin to prevent fungal infections in her throat and mouth. Bactrim to prevent pneumonia. Ranitidine, an acid blocker, to limit stomach acid. And so on.

Rand's task was to find not just the right balance, but to constantly adjust it as Nadia grew and her body changed.

Joe listened carefully. Allison was home with the couple's 3-week-old baby, Adam - born the same day Nadia got her new liver. He would call her after the doctor left.

Rand was glad she had made the trip to see them.

It was important to be there with her patients and their parents. She didn't believe doctors should build a wall between themselves and those they treated.

Her experience with breast cancer reinforced that approach. She had come to be with Nadia, as she would any patient.

She made especially sure to be there, those two or three times a year, when all her medical know-how failed her and the patient was dying. Some kids were just too sick.

She would stay with them until the end.

That was respectful. To let parents know that she was there, bearing witness. It was the least she could do.

Sometimes, you had to make the best death.

Rand had two young children of her own. Still, she could not imagine the pain of losing a child, even as she stood next to those who did.

Every once in a while, years later, parents would call her. They just wanted to talk to someone who remembered and who was safe. Someone who would not think they were depressed or wallowing in old grief.

Someone to share a memory because they were thinking about their child that day.

Rand filled that role, too. She wanted to do something for those families even though she hadn't been able to save their children.

But she wasn't going there with Nadia.

This little girl was going to be OK.

The trick was in the meds.

Plenty to worry about

After the transplant, Allison stayed home with the new baby while Joe watched over Nadia at CHOP.

The transplant had transformed her. She wasn't yellow. Her belly was firm, not distended by built-up fluid.

But there was still plenty to worry about.

Nadia was now 17 months, but she had yet to crawl, walk, or utter her first words.

Her parents wondered if she would develop normally. Would she catch up to her peers? Would she have a full life? Would she ever be healthy?

It seemed like forever, but Nadia was finally deemed well enough for discharge.

On May 2, nearly a month after her transplant, Allison and Joe took Nadia home.

Dr. Rand returns

Five days later, Allison and Joe rose at dawn to get Nadia to the hospital early. She had an appointment with Rand.

The couple had learned long ago that it was best to avoid the morning commuter traffic into the city. And by getting there early, Nadia could have her blood drawn and the lab results would be ready when they saw Rand and Kate Anderer, the nurse practitioner who coordinated liver transplants at CHOP.

It was Rand's first day back. She was excited to be seeing her patients, to return to her regular Monday morning office hours, to something approaching normalcy.

Her schedule was a little disjointed because of her treatments. She still faced 28 sessions of radiation therapy.

The Kadis were thrilled Rand was back. They had been worried about her. And, feeling a little selfish, they wanted their doctor to be well, to help their daughter get well.

Joe was scheduled to go back to work the next day for the first time in months. He was praying for a quick in-and-out checkup.

Maybe, he hoped, Nadia had made enough progress to start cutting back on some of the many medicines he administered each day.

Sitting next to him in the waiting room, Allison was quiet. She hadn't mentioned it to her husband, but she didn't think Nadia would be going home today.

Over the weekend the Kadis noticed that Nadia's mouth turned a little blue when she slept. Her breathing seemed labored.

Once inside the examining room, Joe pulled out a small package containing 10 syringes - the medical cocktail that was keeping Nadia from rejecting her liver.

The first he squirted directly into Nadia's mouth. While Allison distracted the toddler, Joe flushed the feeding tube with water and started giving her the rest of her meds through the tube.

Sitting on the examining table, Nadia did not complain.

After a short wait, Rand and Anderer appeared. Both noticed Nadia's color was off, but they didn't say anything. Not yet.

Rand's curly blond hair was just starting to grow back.

The doctor and nurse practitioner were a practiced team. Anderer played with Nadia, gently examining her while Rand talked with Allison and Joe.

The first few days at home Nadia did well, Allison told the doctor, but over the weekend things got tougher. Nadia wouldn't drink much formula, and she seemed jealous of her baby brother.

Nadia weighed a little more than 17 pounds and was gaining nicely, the doctor said. It was time to discontinue the overnight feedings that she got through the tube.

Anderer and Rand switched positions. The doctor began her examination.

Allison asked about Nadia's breathing.

She had been fussy in the car seat on the way down. She seemed uncomfortable. And her skin took on a bluish tone when she cried.

"We have been nervous when she lies down and gets in bed," Allison said.

Rand listened. "I'm more curious than concerned," she said. "Her lungs actually sound fantastic."

The doctor sent Anderer to get a pulse oximeter to measure the oxygen in Nadia's blood.

They attached the device to Nadia's finger. Her oxygen was definitely low. When Rand laid the toddler down on the examination table, the levels dropped even further.

The hepatologist began going through a quick checklist in her head, trying to make sure she was considering all the possible problems.

It wasn't likely to be hepatopulmonary syndrome, a condition that prevents the blood flowing through the lungs from picking up enough oxygen. That happened in patients with liver disease, but not after transplant.

Still, she would order an echocardiogram. And a chest X-ray.

Nadia needed to be readmitted.

"We will call for a bed," Rand said.

"How long if everything is OK?" Joe asked.

"I'm hoping it will be brief," Rand replied.

"No surgery or anything?" Allison asked.

No, no more surgery.

Rand sent them down to get an X-ray and then off to 8 South.

Joe called the store to say he wouldn't be coming in the next day.

He was getting tired. He just wanted the doctors to find the problem and solve it so his family could go home again.

Allison called her parents in Doylestown and asked if they would keep Adam overnight. She wasn't as sorry as Joe to be staying at the hospital. Nadia was safest at CHOP.

That scary shade of blue

Waiting for the room to be readied on 8 South, Nadia fell asleep in her father's arms. By the time a young doctor, Dan Leung, saw her, her breath was ragged, and she had turned an alarming shade of blue.

At first, Leung said the child needed to be taken immediately to the ER for oxygen. But Nadia's parents convinced him that they would be better off in 8 South.

The doctor relented.

After some frantic moments getting Nadia hooked up to the oxygen, the little girl took on her normal color. She cheered up.

She had barely touched her bottle all morning, but now she eagerly drank seven ounces of formula.

Rand watched her, pretty sure Nadia had an infection, possibly the beginnings of pneumonia.

They started Nadia on an IV antibiotic.

She remained on 8 South for a week. During the stay, her liver-enzyme numbers rose again. Rand bumped up Nadia's steroids to halt the rejection.

It seemed to work.

By May 14, the day Nadia turned 18 months old, she was ready to go home again.

Waiting for their final discharge orders in their room, Allison and Joe played with their baby. Sitting on the sofa, her oxygen tubes still in place, Nadia reached out, grabbed the back of the couch, and pulled herself to her feet.

The parents stared, thunderstruck.

"Oh, my God!" Allison cried. She and Joe cheered, and were rewarded with a huge smile.

They knew most babies accomplished this feat by nine or 10 months. For their daughter, it was a major development. A good omen.

The Kadis were scheduled to come back for blood tests in three days, on May 17.

Rand didn't think she'd even need a full checkup. They could just come in for the blood work to look at Nadia's enzyme levels and 15 other factors, from glucose levels to platelet counts.

Things were looking up. Rand said she'd probably just give them the results right away so they could go home.

Time for the big gun

At 9:45 a.m. on Thursday, May 17, Rand leaned back in her chair in her small office on the third floor of CHOP's Wood Building. How, she wondered, should she break the news to Allison and Joe?

She had studied the numbers carefully.

The last steroid treatment hadn't knocked down Nadia's immune response. The toddler was again rejecting her liver.

Rand had conferred with transplant surgeon Abraham Shaked, and they had agreed: It was time to pull out the big gun, OKT3.

The drug, muromonab-CD3, would obliterate the T-cells leading the attack on Nadia's transplanted liver.

It was not a decision Rand made lightly.

Nadia would need to be hospitalized for the week or two of IV treatment with the drug. Moreover, the long-term side effects of OKT3 could be serious, including an increased risk of cancer. The short-term side effects were no fun, either: fever, nausea, diarrhea.

But the doctor was running out of options. If this didn't work, Nadia could develop chronic rejection.

She could lose her liver. Rand leaned back in her chair and closed her eyes. Nadia needed to be readmitted.

Twenty feet away in the waiting room, Allison and Joe sat with Nadia and her baby brother. They expected to get Nadia's test results and go home.

Rand walked out to meet them, and took them back to the little office. She called up charts on her computer screen. They could see Nadia's liver enzyme levels rising.

"This isn't dangerous in the short term, but obviously it isn't right," Rand explained. The rejection was becoming chronic, and the benefit of steroid therapy had diminished.

Nadia was doing well, but Rand wanted to make sure she stayed that way. She wanted Nadia to have another biopsy to confirm her diagnosis.

She told them the OKT3 treatment would require Nadia to be hospitalized.

Allison and Joe were floored.

Why was this happening? Why did Nadia keep rejecting her liver? When would they stop living in a hospital? When would their little girl be well?

"Yeah, it's getting frustrating," Rand acknowledged. She reassured them. They would get Nadia out of this rut.

Looking over to where Joe held Nadia, Rand saw the little girl sipping on her bottle. The doctor reached over and grabbed it.

No more eating before her biopsy.

Saving Nadia

On the first night, Nadia got the OKT3 at 8 p.m. A nurse checked on her every 15 minutes, then every half-hour, and finally on the hour through the night.

First, Nadia's numbers went down. Then, on the Sunday of Memorial Day weekend, Nadia spiked a fever above 104.

Just before midnight, she and Joe were moved to the pediatric intensive care unit one floor below. Allison and Adam stayed in Nadia's room on 8 South.

Within hours Nadia's fever abated. By noon the next day she was moved back to 8 South.

Her parents were worn out. The incessant cycle of hope and despair - it was excruciating. They wondered how much more of this Nadia's little body could take.

And then, as the days passed, Nadia's numbers stopped surging. Soon, her liver enzyme numbers dropped. She no longer fell sick at the slightest exposure.

Had she turned a corner?

Joe tried not to get his hopes up. He'd kept track of Nadia's ordeal: Since first arriving at CHOP more than a year ago, she'd spent 164 nights. She'd been admitted seven times. She'd had three major operations. She'd been through six liver biopsies.

He'd been by her side throughout.

He'd spent exactly 12 hours with his month-old son.

But Rand was sure. She had been very pleased with Nadia's lab work, and relieved - though not surprised - that the OKT3 had worked.

Rand discharged Nadia on Tuesday, June 5. Allison and Joe prayed it would be the last time.

A week later, they drove back for a clinic visit.

Nadia's enzyme numbers looked so good this time she didn't have to come back for two weeks.

Another milestone passed.

Allison and Joe smiled at each other. They had worried that Nadia would be readmitted yet again. Joe hadn't slept the night before.

Rand looked at the couple. She knew she couldn't give them a happy ending, just a new beginning.

The relief on their faces was obvious, but they were still afraid. It would take time. The transition to living with a transplant was hard, especially for the parents.

Nadia would bear the physical scars of her treatment forever, but she had the same potential for a fulfilling, happy life as any other 19-month-old.

Allison and Joe's scars were still raw. The trauma of Nadia's illness had left them in an almost constant state of fear. Yes, their lives were forever changed. But this was a gutsy set of parents. They had, after all, decided to have a second child despite what had happened to the first.

Medicine can get you only so far, and Rand could do only so much. It wasn't her job to heal these two, but she needed to give them a push.

For Nadia's sake, and for theirs, Allison and Joe needed to craft a different kind of life, a good life, one where they accepted that some things were beyond their control.

Where is Nadia sleeping? Rand asked.

Nadia still slept in her parents' bed. Rand wanted Nadia in her own room.

Allison and Joe weren't sure they were ready.

What if something happened? They woke at the slightest sound or cough. They checked on her obsessively.

That's a problem, Rand said. It's time for Nadia to sleep alone. Let her cry.

Allison and Joe weren't about to disagree with the doctor. But there was no way.

Still, two weeks later, Nadia's biopsy results were the best yet.

The cycle was broken.

A prescription for life

Rand was satisfied. Nadia's numbers weren't perfect, but they were steady. Rand and, more important, Nadia, could live with them.

Nadia had passed the most dangerous period. Now it was a matter of living as a transplant recipient. But as Nadia grew, and as her body changed, Rand would have to adjust her mix of medicines.

All told, CHOP was paid $528,092 for Nadia's care from her first arrival April 24, 2006, through her transplant and her subsequent hospital readmissions. Nadia was covered under Joe's health insurance. And because of her condition, Nadia qualified for Medicaid. The program paid the costs not picked up by their primary insurer.

On June 29, Rand went for her last radiation treatment. It had been eight months since her diagnosis of breast cancer. She was in remission.

But the cancer had left its marks on her.

She could see them in her mirror. Her hair was short. Her breasts were smaller and no longer quite matched. Her belly button was slightly off center, making her feel strangely asymmetrical.

Rand knew a recurrence, it if happened, was most likely between two and seven years. She hadn't wanted to get the odds, because in the end it would either happen, or it wouldn't.

Certainly, she hoped to see her kids graduate from high school and college, go to their weddings, and hold her grandchildren.

But it was best not to dwell on the possibility the cancer would return. Best not to go there.

She often told her patients and their parents that even in the face of serious illness, it was really important to focus on the moment, to truly live.

Rand looked ahead with optimism.

That weekend she went shopping with a friend while her children and husband went to a baseball game. She drove to the King of Prussia mall intent on reclaiming some control over her body. She stopped at the Piercing Pagoda and walked out with with two more earrings - clear rhinestone studs - in her left ear.

A little asymmetry of her own.

Nadia's next steps

On July 1, as Allison straightened Nadia's room, she looked up to see her daughter stretching backward to the rocking chair for balance. Suddenly, the child launched herself forward toward the bed.

Allison rushed over - not to grab her, but to protect against a fall as Nadia walked across the four feet of carpet to grab hold of the crib.

"Joe!" Allison called out to her husband. He rushed in.

Nadia demonstrated her newfound talent, walking the three feet between her excited parents, who held out their arms even as they wept.

They hovered as they watched their little girl haltingly take her first steps. This was what they had been waiting for, yet they could not bring themselves to let down their guard.

They stood over her, ready to catch her if she fell.

Epilogue

Nadia, who will be 2 years old on Nov. 14, is doing well. On Sept. 7, nearly five months after her transplant, the family drove to Children's Hospital for a scheduled checkup. As Nadia scampered about, the visit was captured on video.

She still sleeps with her parents.