Advances in Allogeneic Hematopoietic Stem Cell Transplants in the Pediatric Population

by Steven Kuerbitz, MD
Friday, November 3, 2017

Steven Kuerbitz, MD

Hematopoietic stem cell transplantation (HSCT) has become an accepted and potentially curative therapy for many life-threatening cancers and nonmalignant disorders. Although the approach is not without serious risks, advances in transplants have led to improved patient outcomes, especially in the pediatric population.

Autologous versus Allogeneic HSCT

According to the U.S. Department of Health and Human Services, of the nearly 20,000 bone marrow or umbilical cord blood transplants in the United States in 2014, 11,392 were autologous, while 3,544 were related allogeneic and 4,926 unrelated allogeneic. They report that transplant procedures are continuing to increase. Of the procedures performed in 2016, 19% involved children ages 0 to 18. Anecdotally at Akron Children’s Hospital, we have performed 112 HSCTs since the procedure became available in 2000.

Autologous stem cell transplants (autoHSCT), in which the stem cell graft is derived from the patient’s own bone marrow or peripheral blood, are most often indicated for treatment of solid tumors such as lymphoma, sarcoma, neuroblastoma and brain tumors. Allogeneic stem cell transplants (alloHSCT), in which the graft is donated by a different related or unrelated individual, are generally performed for treatment of leukemia, lymphoma, immune deficiency syndromes, metabolic disorders, hemoglobinopathies, myelodysplastic syndromes, autoimmune disorders and bone marrow failure.

Because allogeneic stem cells almost always come from a genetically nonidentical donor, alloHSCT carries a greater risk of some complications, including Graft-versus-Host Disease (GvHD). A blood relative is the preferred donor, as he or she has the greatest likelihood of a close human leukocyte antigen (HLA) match. For full siblings, the likelihood of an HLA match is about 25%.

Making Better Matches

When a sibling is not available, alternative donor options might include a parent (generally a 50% match) or an HLA-matched, unrelated individual identified from a registry of volunteer donors. Continued advancement in techniques for genetic matching of unrelated grafts has facilitated improved outcomes so that results of related versus unrelated transplants are comparable. Equally important, treatments for GvHD and other transplant-related complications have also improved. That’s not to say there’s no room for improvement. For example, the donor registry includes far more donors of European descent, making it more challenging to find suitable matches for African-Americans and other ethnic minorities. Increasing the numbers of underrepresented populations is a major goal for the registry.

Treatment Considerations for Children

Patients typically spend four to six weeks in the hospital after infusion of the stem cell graft. Close observation is necessary to identify complications such as infection, mucositis, malnutrition, organ dysfunction and GvHD. Infection remains a relatively common problem in hematopoietic stem cell transplant patients due to the disruption of mucosal barriers, such as skin and intestinal mucosal, and because of the immunosuppressive medications necessary to facilitate engraftment and prevent GvHD. To reduce infection risk during engraftment, stem cell transplant units are designed for maximum sterility.

We’ve also found it’s important to address the child’s emotional, social and physical comfort in addition to their medical care.

Future Areas of Study

Research around hematopoietic stem cell transplantation is active and varied, focusing on objectives from the identification of biomarkers predictive for GvHD to augmenting the antitumor activity of the transplanted cells. As HSCT is explored for treatment of new disease categories, such as autoimmune disease, while novel non-transplant therapies are developed for high-risk diseases such as leukemia, the field of hematopoietic stem cell transplantation continues to evolve in an exciting way.


Dr. Steven Kuerbitz is director of Stem Cell Transplantation and Divisional Research at Akron Children’s Hospital’s Center for Childhood Cancer and Blood Disorders. He is board certified in Pediatrics and Pediatric Hematology/Oncology.