How did it happen?

Still reeling from the simply unbelievable mistake the doctors made when administering more chemotherapy than necessary, the Yianas family sought to find a reason for the error.  The trust that was once unshakeable is now damaged.  Eleni and Kosta, though terribly disappointed, wanted to be sure that, going forward, they could be able to trust the doctors at the University of Chicago with their son's care and that measures would be taken to prevent another lapse in communication that could put their son in harm’s way.

How did this happen exactly?  Eleni was with Theo during the first three days of his high dose chemotherapy.  Each morning, she documented and watched the medical team hang his two chemo bags that were each infused over a period of 24 hours and the one chemo syringe injection. She asked the name, dosage, and duration of each drug, and she knew that the responses she would get would be the same as the previous day. Nothing was unusual, nor out of the ordinary. The Yianases had a copy of the protocol for the second round of the COG clinical trial specific for a Tandem Transplant. They knew that Carboplatinum, Etoposide and Melphalan were the drugs and the dosages were high. They knew that Theo would be given 3 days of one drug and 4 days of the other two. They knew that their son’s exact dosage was calculated based off his weight and some other factors. They knew there would be side effects that would eventually kick in and linger until his new stem cells could take over.

But, on the third day of chemo, after his medicine was given and the doctors and nurses left Theofanis’ room, Eleni felt nervous and uneasy. She stared at the chemo bags that were adorned with “caution” and “poison” labels. She concentrated, though on the label that captured her son’s name followed by an endless list of numbers and formulas that resembled algebraic calculations. Not fully understanding what she was reading and accepting that pharmacists speak an entirely different language, a feeling came over her. A bad feeling.  As she nervously rummaged through Theo’s Stem Cell Transplant Binder which contained every document pertaining to her son’s treatment, Theofanis noticed her changed demeanor. And when Eleni dragged her 10-lb binder to his IV pole and held it up to his chemo bag, he asked what she was doing. “Just double-checking something, sweetheart.”  She pulled up the protocol and read the pharmaceutical calculation guidelines that Theo was on. She didn’t understand what she was reading. She looked at the chemo bags. She looked at the protocol document. She was looking, but wasn’t sure what she was looking for. Her bad feeling did not go away. Then, Eleni pulled out her laptop, searched her files, and located the 200-page pdf file of the complete Children’s Oncology Group Neuroblastoma Treatment Protocol. She searched for the treatment protocol for children undergoing a Single Stem Cell Transplant. In other words, she searched the protocol that her child was NOT on.  Filtering through the pharmaceutical guidelines for the variable dosing factors (such as adjustments for body mass vs. kidney function loss vs. other possible factors for variance), Eleni found the page of the protocol that she believed her son would be on IF he were only doing one transplant. She held her laptop up to Theo’s IV pole, and she saw every single number jump off of her computer screen and onto the labels of her son’s chemo bags. Every single number on those bags matched the protocol that her son was NOT on. She was punched in the stomach with sickness and stabbed in the heart with panic.  The numbers were all higher.

Eleni called for then nurse and then called Kosta, who was on his way to Comer to “switch” shifts with her. There’s something wrong. There’s something terribly wrong, she told him. Kosta arrived in Theo's room to see Eleni very worried and hurriedly double-checking the protocol worksheets.  A few moments earlier, Eleni was in the pressurized entry way of Theo’s room with the nurse reviewing the formal orders in Comer’s computer system. The nurse insisted Theo was getting the right dose because it was exactly what was written in the orders. Nonetheless, she contacted Reggie, the Pharmacist, who also confirmed he mixed that exact medicine that’s written in the orders. But, when Eleni showed the nurse the COG protocol on her laptop, the nurse stared at the screen, looked at Eleni, and then immediately paged both Dr. Cunningham, Dr. Cohn and the attending, Dr. Uma. “I hope you all think I’m crazy and am freaking out for no reason,” she told the nurse. “I pray to God you all think I’m crazy.” The nurse looked at her, worriedly.

“Get Dr. Cohn, get Dr. Cunningham, get Reggie, get them here now!” she insisted.  “The orders in the computer are wrong! You are overdosing my child!”

Kosta and Eleni demanded that doctors immediately ascertain whether or not the dosage was, in fact, incorrect.  Dr. Cunningham, nor Dr. Cohn were in the building. The other doctors, nurses and pharmacists gathered behind closed doors of a conference room.  Eleni and Kosta sat patiently and calmly in Theo’s room because moments earlier, Theo asked, “What’s going on?” And there was no way they were going to allow their son to worry about anything.  After a short time that felt like an eternity, Reggie came into Theo’s room. Eleni and Kosta stood up, and simply asked, “Is it wrong?” And Reggie looked them in the eyes and said, “Yes, it’s wrong.” He confirmed that Theofanis was overdosed on high dose chemotherapy.

“Then why aren’t you stopping that pump right now?”

“It’s too dangerous to stop it now,” he said.

Here’s the plan…the two drugs that were scheduled for the fourth day will be amended to about half the prescription so that cumulatively he will get the correct total dosage.  However, the Melphalan had already been given in full.  There was no remedy for this.  Theo received about thirty percent more Melphalan than he was supposed to.

As the reality of the erroneous chemotherapy infusion began to be realized, Eleni and Kosta were gripped with fear for their son -- virtually the same feeling they felt when Theofanis was first diagnosed in early May.  How could this happen and why?  Who could have made such a careless error?  But most importantly, what does this mean? What will happen to Theofanis, short-term and long-term?

Dr. Cunningham, who is directly overseeing Theofanis’ care during transplant, arrived shortly thereafter, and told Eleni and Kosta that he took full responsibility for the mistake. But, before confirming that the original chemotherapy orders were wrong, he said, “Theo was not poisoned.” He assured that Theo was going to be ok.  “But, thank goodness you caught the mistake, Mrs. Yianas.” What of the Melphalan, then, Dr. Cunningham?  He proceeded to tell Mom and Dad that Melphalan is highly effective at killing neuroblastoma cells.  It also hits the bone marrow hard and suppresses white blood cell production. So,  Theo's recovery will take longer than expected, and the short-term side effects included more aggravated mucositis.  He said there were no long-term side effects from this drug. Eleni and Kosta listened to Dr. Cunningham, but could no longer trust a word he said.

Yes, trust was gone, and Dr. Cunningham knew it.

“Do you know how we feel right now?” they asked him. Their fear quickly shifted to anger and determination to find answers.   As the Section Chief of Oncology, he took full responsibility.  He admitted that he made the mistake. But, how did this happen?  Who was really responsible? An investigation began, with all the formalities associated when overdosing a child. Root cause needs to be identified, reports need to be written, reviews by committees, etc.  Plus, how does this affect Theo’s status with the Children’s Oncology group now that the protocol was violated? Is he off trial? The one thing though that the Yianas’ knew for a fact was that the “failsafe” system of multiple checkpoints and verification that each chemotherapy order should follow, failed. It supposedly failed for the first time…with their son. “You are a world-class institution. How do you allow this to happen?” Kosta demanded.  No one had a response for him.

Over the next few days, Dr. Cunningham, Dr. Cohn, and Dr. Panigrahi, along with the residents and other fellows received sharp questions and follow-up questions on everything they were doing.  They were reminded that the trust that the Yianas’ had in them had been extensively damaged, and this was not the first time there was a communication issue amongst their ranks.  Yet, this certainly was the most blatant, and was close to being disastrous. As the Yianases continued to experience different emotions, they quickly realized that the most important thing they had to do was not allow Theo to see or sense any mistrust with the hospital, doctors or staff. So, Eleni and Kosta put on happy, optimistic faces each time the doctors came in.

Then, on the Day of Theo’s Stem Cell Rescue, Day Zero, they requested a sit-down meeting with Dr. Cunningham and Dr. Cohn. A meeting where the Yianases asked these doctors if they are willing to work with them on rebuilding trust. The Yianases took the following position:

1. The first step in regaining trust is having access to information. The Yianases asked for full disclosure: the formal investigation report, plus documentation of the medicines Theofanis was given with the dosages he was given.
2. For the remainder of Theo’s treatment, they asked that someone sit down with them and highlight the full COG protocol and identify every area of treatment and dosing, so that they could double-check what every doctor or nurse does.
3. They demanded that no one criticize or complain that they are asking too many questions.  In the past, Eleni and Kosta were told that some folks on the hospital staff thought they asked too many direct questions. Some people didn’t like being watched while they were drawing their son’s blood or while changing their son’s dressing or while changing and cleaning his IV lines. In the past, Eleni and Kosta sensed how some doctors or staff would be annoyed by their redundant questions.  

Dr. Cunningham and Dr. Cohn fully agreed to their requests. And most importantly, they agreed that Theo’s health and recovery is everyone’s top priority.

Then, Eleni asked each of the doctors: “What does your gut tell you about the effects that this mistake will have on Theo?” Dr. Cohn said, “Thank goodness you caught the mistake.” In early clinical trials, children were given the full dosages of the three chemotherapies and it proved to be highly toxic to the children. Then she said something that they heard before: Melphalan is highly effective against Neuroblastoma. That little extra dose may help.  Then, Dr. Cunningham said that he too thinks that the Melphalan will specifically target Neuroblastoma. And he said short-term, Theo’s bone marrow will take longer to recover.

Eleni ended the meeting by telling them that she and Kosta don’t want their relationship or their discussions with them to be argumentative or confrontational. The doctors expressed their appreciation with that. And, she told them both, “I’m kicking myself for not double-checking the protocol on the first day.” Then, Dr. Cohn shook her head and said, “I’m kicking myself.” You see, Dr. Cohn, Theofanis’ primary oncologist and the hospital’s top Neuroblastoma expert, steps away and turns primary care over to Dr. Cunningham and the Stem Cell Transplant team during this phase of treatment. Dr. Cohn did not review the orders. The Yianas’ believe that if she saw the orders, she would have caught the error. And they think she believes the same thing.   

So, what happened? The official investigation summary and report will be complete by end of January. Eleni and Dean were promised copies of it. Apparently, templates for this clinical trial were created and entered into Comer’s computer system a year ago. All current orders are drafted using these templates.  (By the way, these templates were created in order to prevent a mistake like this from ever happening.)  And because Theofanis was the first child at Comer to move forward with two stem cell transplants, the template was used for the first time with him. So, who created the incorrect templates? Dr. Cunningham said he did.

The doctors are sorry.  While at first, it seemed they were frantic and defensive, Kosta and Eleni do know they are sincere in their apologies. What happened was not good for Theo, nor them. Both Dr. Cohn and Dr. Cunningham conveyed that this never happened to either of them before. They had to admit error to the Children’s Oncology Group and to their peers.  Their reputations have been affected. But more so, their patient was placed in harm’s way, and for that, they are very, very sorry.

So, Day Zero of Theo’s second Stem Cell Rescue began with a new understanding of the care and attention the Yianas Family expects their son must receive.  It began with commitment from the oncology team that they will be forthcoming with information. And it began with uncertainty on Theo’s short term recovery. You see, his counts dropped to zero and the signs of side-effects began to surface.