Pediatric Lymphoma: Zach’s Story

It was September 2010 when John and Pam Witt noticed lumps on their son Zach’s neck.

Worried about the swelling, the Witts took Zach to his pediatrician, who recommended that the family go to a CHOP Specialty Care Center for testing. The family was shocked to learn that Zach had anaplastic large cell lymphoma (ALCL). He was only 5 years old.

Research Study for Anaplastic Large Cell Lymphoma: Zach Witt's Story
John Witt, Father: In October, early October, perhaps late September of 2010, we noticed some lumps one day which very quickly were growing and led us to our pediatrician where, after some testing, diagnosed him with anaplastic large cell lymphoma. And so he started on a conventional chemotherapy and was responding quite well to that. And he was treated until March of last year, 2011, and seemed to be everything seemed to be going great. And then sometime late in March we were seeing things which brought us back again to CHOP where after a week or 10 days of hospital stay and some diagnoses it did confirm that it was a relapse of his lymphoma. Well it's a kind of an overwhelming and somewhat of a helpless feeling because while he's on treatment it came back and so now what, you know.
Richard Aplenc, MD: So I met Zack probably a little over a year ago when he came here with lymphoma that was not responding to standard treatments. We had a trial and still have a trial open here of a new medication that we thought might be effective for him given the kind of genetic changes that have occurred in his lymphoma.
John Witt, Father: When the doctors gave us the option of participating in the study, of course, we had a meeting, and at that point we were considering some more severe standard chemotherapy or this. And we had some apprehension because of being an unknown, but we had a meeting with the doctors and I really sensed, as they were explaining the drug and what they hoped it would do, excitement and hope. And when we came out of that meeting, Pam asked one of them, "If this was your child, what would you do?" And he didn't even hesitate, he said, "I would go on the study."
Richard Aplenc, MD: And so he came here and enrolled on that trial and had a very remarkable response to therapy. Before his lymphoma was resistant to chemotherapy. So we would give him chemotherapy and it would have no impact on the lymphoma. And now on this medication his lymphoma is gone and it's been gone for over a year, which is remarkable.

Yaël P. Mossé, MD: Seven of the eight patients with lymphoma who went onto this trial having had a lot of prior treatment, including more than a year of intensive chemotherapy, and oftentimes when the disease comes back these children also had what we call transplant, which is lethal doses of chemotherapy. Of the eight patients with lymphoma who went on, seven of the eight have had substantial benefit from this drug and their symptoms cleared within days or a couple of weeks of starting this pill.
John Witt, Father: We were very amazed at how quickly he responded to this medication. Really, in two days he was very obviously responding in a dramatic, positive way.
Richard Aplenc, MD: He's been able to go back to school and run around and just be a kid and so that's been really very wonderful to be able to watch and to play a small role in.
Pam Witt, Mother: The second day that he was on the drugs we decided to take a walk down to the playroom, and he literally went out of his room and ran down the hallway. I mean, you couldn't believe it was the same kid that was laying in bed all day. So, it was just a miracle. The drug saved his life.
John Witt, Father: We haven't seen any side effects and I tell people who haven't met him, I tell them I have a son that has lymphoma. I said, "If you saw him here you wouldn't believe me that he has lymphoma," because he runs on high octane all day long and he's doing very well.

Transcript Transcript

Chemotherapy began right away, the conventional approach for children with ALCL. Zach was on treatment through March 2011, and his cancer seemed to be responding well.

But just as his chemotherapy was ending, the Witts noticed cold-like symptoms that quickly developed into frequent fevers. When it was clear that this was more than a cold, he was brought back to CHOP.

After a 10-day hospital stay and multiple tests, doctors confirmed John and Pam’s worst fear — Zach’s lymphoma had relapsed.

“It’s an overwhelming and helpless feeling,” says John. “His cancer came back while he was on treatment, so now what? That’s pretty scary. And it was frightening how quickly everything was happening.”

Candidate for clinical trial of new treatment

The Witts had a meeting with Zack's doctors to discuss the next step in their son's treatment. This was when they learned that their son had a genetic marker that made him a candidate for a Children’s Oncology Group phase 1 clinical trial of a drug called crizotinib. The Children’s Oncology Group is a research consortium that unites scientists from many different hospitals.

The crizotinib study was led by Yael Mossé, MD, a pediatric oncologist and researcher at The Children’s Hospital of Philadelphia.

“Zach's lymphoma is characterized by changes in the ALK gene,” says Richard Aplenc, MD, Zach’s oncologist at CHOP. "It's called an ALK-positive lymphoma or anaplastic large cell lymphoma. The changes in the ALK gene make the lymphoma cells grow out of control. This medication actually targets that change and turns off that driving signal.”

ALK has also recently been found to be important in a form of non-small-cell lung cancer and in a subset of neuroblastomas. The ALK-inhibiting drug crizotinib had already been developed to target the gene directly. For this reason, study leader Mossé and her colleagues were able to quickly move crizotinib into an initial pediatric trial.

The idea of an experimental treatment worried the Witts.

“We were considering more severe standard chemotherapy,” says John. “But we had the meeting with the doctors and I really sensed some excitement as they were explaining what they hoped the drug would do. Pam asked one of them, ‘If this was your child, what would you do?’ He didn't even hesitate. He said ‘I would go on the study.’ That was very reassuring.”

Dramatic change when treatment begins

Zach was enrolled in the phase 1 trial and began treatment in mid-April 2011. Doctors told the Witts that if the drug worked, they would likely see a quick response. In fact, less than 48 hours had passed when they saw a dramatic change in their son.

Pam recalled how weak Zach had been after his relapse.

“He'd wake up in the morning and say ‘Mom, I want to go to the playroom.’ But he just didn't have any energy to get there,” she says. “The second day that he was on the drug, we decided to take a walk down to the playroom. He literally ran down the hallway. I mean, you just couldn't believe it was the same kid that was lying in bed all day. It was just a miracle.”

The new treatment gave Zach more than an energy boost. It gave his family hope that their son will live a long, healthy life.

Looking to the future

In Zach’s first year on the drug, scans have shown no evidence of lymphoma. He’s living the normal, happy, high-energy life of a 6-year-old and experiencing no side effects from his treatment, which he’ll continue for the foreseeable future.

“Zach's case is an outstanding example of the kind of therapy that we would like to have for every child with cancer,” says Aplenc. “We want to get to the point where we understand why the leukemia or the lymphoma happened, and then give medicines that specifically target what went wrong without affecting the normal cells.

"It's been so satisfying to play a small role in making a difference in Zach’s life," Aplenc says. "He's been able to go back to school and run around and just be a kid. That's been very wonderful to watch.

"We’re working very hard to be able to do this for all children with cancer.”

Originally posted: May 2012