Watching the Kids Grow Up

Dr. Jean Sanders is the director of Pediatric Clinical Hematopoietic Cell Transplantation at the Seattle Cancer Care Alliance. She is also director of the Bone Marrow Transplantation Service at Children's Hospital and Regional Medical Center; a member of the Clinical Research Division at the Fred Hutchinson Cancer Research Center; and a professor in the Department of Pediatrics at UW Medicine, specializing in pediatric hematology and oncology.

For the past 30 years, Dr. Jean Sanders, pediatric oncologist, has been learning from her young patients.

“We have a unique group of children and former children who are long-term survivors after transplantation who have taught me about the complications experienced after transplantation,” Dr. Sanders says. “I’m lucky to have had this population to learn from.”

Dr. Sanders specializes in the long-term issues faced by people who received bone-marrow transplants as children to treat diseases such as leukemia. To date, she follows more than 700 childhood transplant recipients as they grow and develop through childhood on to maturity.

As a result, Dr. Sanders has learned a great deal about the life-long effects of bone-marrow—and more recently stem-cell—transplants in children. 

“Dr. Sanders is a pioneer in her field who has dedicated herself to helping children,” says Ann Breen, a registered nurse who is the patient and family education coordinator/transition coordinator for transplant patients at SCCA. “She has a wealth of knowledge and experience.”

Dr. Sanders’ children
The children Dr. Sanders has followed include Tamara Stevens, now 49, who received a bone-marrow transplant at age 16 when she was diagnosed with acute myelogenous leukemia.

“I’m one of those miracle kids,” says Stevens, a project manager for The Boeing Co. who power-walks marathons and has been battling a second cancer, metastatic breast cancer, for the past nine years.

“She’s wonderful,” Stevens says of Dr. Sanders. “She did a marathon with me in Honolulu.”

“My personal goal for these kids is to help them to survive and live as normal a life as possible,” says Dr. Sanders. “We can’t prevent them from getting leukemia, but we can offer the best chances of survival and recognize and treat the complications early so that the children will be able to be as near normal as possible.” 

What she’s learned
Children who have been treated with a bone-marrow or stem-cell transplant face post-transplant problems that include chronic graft vs. host disease and growth and development problems. They may also have learning disabilities if they received radiation to the head before a transplant that includes total body irradiation, Dr. Sanders says, “and parents and teachers need to be aware of that.”

Dr. Sanders’ research has focused on these problems and other quality-of-life issues. She has learned that these patients face more health problems as adults than normal control siblings or childhood survivors of non-transplant leukemia therapy, but the former transplant patients are also aware of their good fortune in surviving a serious illness. 

“They will likely need to see the dentist more often than if they had not had a transplant,” Dr. Sanders says. “Also the recipients of total body irradiation often have more cataracts and adult-onset type of diabetes. The transplant recipients also have an increased risk of developing secondary malignancies—or a new second type of cancer.” 

Her patients are a resilient group, however. “They are not depressed,” she adds. “They are happy to be alive.”

But, Dr. Sanders says, young patients and their parents need to understand the realities of life after a transplant. “Many may think or wish that once they are through the transplant they will be all done with seeing physicians and that life will then go on ‘normally,’” she says. “But in fact, they will have life-long health issues.”

It is too much to expect parents and young patients to absorb all of this at the time of diagnosis, when they are trying to cope with a child’s illness and make decisions about treatment, Dr. Sanders says. This is one important reason for follow-up visits. These visits provide a time to review and discuss the details that become more relevant.  

“We need to be attentive to detail, and remind patients and parents at the one-year and subsequent long-term follow-up visits what they can expect in terms of long-term health problems,” she says.

Growth and development
In the early days of bone-marrow transplants, Dr. Sanders says, most doctors were focused primarily on their patients’ survival, not on complications such as stunted growth. “We needed to perfect the details of performing the transplant and have a group of patients who were surviving long-term without leukemia before we could turn our attention to survival issues, such as growth and development in children,” she says.  

From the beginning, Dr. Sanders was interested in her patients’ lives after their transplants. ”Long-term follow-up has always been an interest of mine,”  she says. “I used to keep our young children’s growth charts on the wall in my office.”

In order to prepare the patient to receive the marrow from their family member or unrelated donor, the child receives chemotherapy with or without total body irradiation.  The delayed impact of the transplant preparative regimen are many, only one of which is the impact on the child’s subsequent growth.

Chemotherapy may impact sex hormone production in the mature, adult patient.  In children, the impact of the transplant preparative regimen on the gonads may result in delayed puberty or lack of development of puberty.  Later, these children will require treatment with hormone therapy. 

“We are learning that the effects of different preparative regimens on the developing child are different based on the type of preparative regimen received,” says Dr. Sanders.  “We counsel our patients today based on the knowledge we have gained from our previous patients who have become long-term survivors.”  
About 80 percent of children who receive total-body irradiation before puberty will be shorter than they would have been otherwise because the treatment interferes with the growth hormone production.  

Dr. Sanders wrote one of the first research papers describing some of the late effects observed among children who were long-term survivors after transplantation with or without total-body irradiation. “I looked at the endocrinology (hormone production) and described what’s was observed in these children after they had received a transplant with or without TBI,” she says. “This hadn’t been described previously.  We have subsequently learned that the effects after single dose TBI differ from the effects observed after fractionated TBI.”

She has also done research on giving growth hormone to children who develop growth hormone and growth failure after total body irradiation. “Our results show that children who respond the best are those who were able to receive growth hormone at a young age,” she says. “We begin looking for growth hormone deficiency at the time of the one year post-transplant long-term follow-up visit.” 

Her research also shows that giving growth hormone after a transplant does not appear to harm these children. “Kids do not relapse at higher rates, nor do they have secondary malignancies at higher rates,” she says.

For treatment with sex hormones as well, Dr. Sanders says, the younger the child at the time of transplant, “the greater the chance that the gonads are going to recover.”

Her recommendation is that any child who has had a bone-marrow or stem-cell transplant should also be followed by a pediatric endocrinologist.

Other new research 
Dr. Sanders has also done important research on having a second transplant. Results show that some children who relapse—meaning their original leukemia comes back—after high-dose chemotherapy with or without total body irradiation and a transplant may be able to have a good outcome following a second transplant. 

The best results are obtained when the first transplant preparative regimen was chemotherapy only followed by a second transplant that utilized total body irradiation, she says.  The results were not as good when total body irradiation was included in the first transplant preparative regimen.  “We continue to explore better second transplant preparative regimens for this group of patients,” Dr. Sanders adds. 

Dr. Sanders follows her hundreds of patients on an annual basis, with a letter and questionnaire and, in some cases, by phone. She has completed gathering data on long-term survivors, looking at the quality of their lives in adulthood and also comparing adult survivors of childhood leukemia who were treated with transplants to those who were treated only with chemotherapy.

Always searching for ways to improve children’s treatment, Dr. Sanders is eager to get to work making sense of the new information.  “I’m anxious to analyze the results,” she says. “They will tell us how to design interventions to further improve these patients’ lives.”

 
January 2005

 

 

DEFINITIONS

Graft vs. host disease (GVHD)
Graft vs. host disease is a common side effect of transplants. GVHD occurs when the transplanted or donor cells recognize the patient’s tissues as foreign and attack the tissue. This can cause a variety of problems, including skin rashes, liver-function abnormalities and diarrhea. 

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Total-body irradiation (TBI) Total-body irradiation is radiation therapy to the entire body at the same time. It is done to prepare a patient for a bone-marrow or stem-cell transplant.

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