Lymphocyte recovery in related and unrelated stem cell transplant recipients generally falls into three patterns that are significantly associated with survival, according to findings from a phase 2 clinical trial published in Biology of Blood & Marrow Transplantation (2015; 21:1237-1245).
This first-of-its-kind research continues the efforts of principal investigator Amir Toor, MD, of the Virginia Commonwealth University Massey Cancer Center in Richmond, to understand the immune system as a dynamical system that can be modeled to improve stem cell transplantation.
“We began considering lymphocyte reconstitution following stem cell transplantation as similar to population growth models. So, we graphed the lymphocyte counts of our patients at various times following their transplant as a logistic function and observed distinct patterns that correlated with clinical outcomes,” said Toor.
“Our goal is to use this data to develop models that can predict complications from stem cell transplantation. Then, we may be able to intervene at key points in times with appropriate clinical treatments that will make the most positive impact on patients’ outcomes.”
The study retrospectively examined lymphocyte recovery and clinical outcome data from a recent phase II clinical trial (Clinical trials.gov identifier NCT00709592) in which 41 patients received a stem cell transplant from related or unrelated donors.
As part of the clinical trial protocol, the patients underwent low-dose radiation therapy and received one of two different doses of antithymocyte globulin (ATG), an immune-modulating drug given before transplantation to guard against graft-versus-host-disease (GVHD). GVHD is a condition that occurs when immune cells from the donor attack the recipient’s body.
Following transplantation, the researchers observed that the patients’ lymphocytes recovered in one of three general patterns that correlated significantly with survival, relapse, GVHD, and the need for further donor immune cell infusions to treat the cancer.
Group A experienced fast, early lymphoid expansion, culminating in a high absolute lymphoid count (ALC) within 2 months of transplantation. Group B experienced a slower, but steady lymphoid expansion that peaked much later than group A with a lower ALC. Group C experienced very poor lymphocyte recovery that demonstrated an early, but brief lymphoid expansion with a very low ALC.
Group B had the best clinical outcomes with a survival rate of 86%, followed by group A with a survival rate of 67% and group C with 30% survival. Relapse rates between groups A and B were similar at 33% and 29%, respectively, while group C experienced a 90% relapse rate.
GVHD occurred in 67% of patients in group A, 43% of patients in group B, and 10% of patients in group C. Finally, adoptive immunotherapy with donor cell infusions was required for 13% of patients in group A, 21% in group B, and 70% in group C.
“We’ve uncovered order in the structure of the immune system, we’ve found new variables influencing GVHD and we’ve now shown patterns in lymphocyte reconstitution that identify at-risk patients,” said Toor. “Now, we are working to put it all together and develop a model of immune system reconstruction following stem cell transplantation that will allow physicians to make more informed treatment decisions.”