Patients with leukemia and other hematologic malignancies who do not respond to chemotherapy often require hematopoietic cell transplantation (bone marrow or stem cell transplantation). This treatment involves destroying the patient's bone marrow cells and transplanting new ones from a matched donor.
A phase II clinical trial has explored a novel approach to reduce the risks associated with hematopoietic cell transplantation, predominantly graft-versus-host disease. The trial's findings, published in the Journal of Hematology & Oncology, suggest that this modified strategy can boost the anti-cancer effect of the transplant while minimizing immune-related complications.
Disentangling Immune Issues
Matching patients with a donor involves comparing human leukocyte antigen (HLA) genes. According to Brandon Triplett, MD, St. Jude Department of Bone Marrow Transplantation & Cellular Therapy, "There are hundreds of different variations on each gene, and we try to match at 12 genes, so, the number of combinations of immune type is innumerable."
A perfect match for hematopoietic cell transplantation is very difficult to find. Often, this type of procedure can lead T cells (immune cells produced in bone marrow) to treat their new ‘host’ environment as a foreign pathogen, triggering graft-versus-host disease. “This disease is the opposite of organ transplant rejection,” Triplett explained. “If a kidney is transplanted, the immune system sees that as different and will attack the kidney. With graft-versus-host disease, the new organ is now the immune system. The patient is what is different.”
New Transplant Strategies
The trial (NCT01807611) launched in 2013, hypothesized that by only removing naïve T cells, they could leave mature memory T cells in place. This would spare the patient from graft-versus-host disease while also exploiting a strong anti-cancer phenomenon called the graft-versus-leukemia effect.
“We showed that you can give large doses of these cells and have a robust and diverse immune system very early after transplant,” Triplett said. “And it was associated with a very low risk of relapse in these patients.”
More Firepower to Combat Cancer Cells
The clinical trial tested another innovation in bone marrow transplantation by adding natural killer cells to the treatment. These cells further boosted the anti-cancer effects of the transplant. “Natural killer cells are alerted by the absence of molecules that T cells look for,” explained Triplett. “So, the type of cells that are evading T cells are the type of cells targeted by natural killer cells.”
According to Swati Naik, MD, Department of Bone Marrow Transplantation & Cellular Therapy, “The patients in remission did extremely well, and the patients who had refractory disease also did well considering that they had no other options, and most transplant centers refrain from taking refractory patients to transplant.”
The findings, which both increase the chance of survival and lower the risk of complications, offer hope for patients with the highest-risk disease.
“We're figuring out the right combination of cells that are going to help the patient be successful in that early phase after transplantation and lead to even better long-term outcomes,” Triplett said.
