Recovery of Lymphocyte Function May Predict Risk of Leukemic Relapse in Pediatric Patients Undergoing Allogeneic Stem Cell Transplant

Delayed immune reconstitution after allogeneic transplant for pediatric acute leukemia has been implicated by some studies as a risk for leukemic relapse.  However, results regarding the specific laboratory parameters of interest have been conflicting.  We initiated a retrospective review of 97 pediatric patients who underwent allogeneic stem cell transplantation for ALL, AML or JMML between the years of 2000 and 2010.  We collected available clinical outcomes data which included lymphocyte subset (CD3, CD4, CD8, CD19, CD16/56) recovery at 90 and 180 days, proliferative response of CD3 T cells to phytohemagglutinin (PHA) at 90 and 180 days, and donor CD3 chimerism at 30 days post-transplant.  Median cutoffs associated with immune reconstitution that were used for data analysis included a CD4 count >200, CD8 count >200, and PHA >30% of lower limit of normal control.  Full donor CD3 chimerism was defined as no evidence of host DNA down to a sensitivity of 1%.  Data for immunophenotype was available for 71 patients; CD3 chimerism was available for 50 patients, and PHA responses were available for 47 patients. 

No significant difference in CD4 or CD8 T cell recovery was detected between relapse and non-relapse patients. However, a higher rate of relapse was observed in patients with a PHA response <30% within the first 180 days (4/7, 5-year RFS 42.8%), compared to those with PHA >30% (5/40, 5-year RFS 84.8%, p=0.02).  In the subset of patients for whom both PHA and chimerism data were available, a higher rate of relapse was observed in patients with either mixed CD3 chimerism or poor PHA response (8/27), compared to those who recovered both full donor CD3 chimerism and CD3 PHA response >30% (0/7, p=0.1). 

Historically, tailoring of immunotherapy post-transplant has focused on the treatment of graft-versus-host disease.  With the availability of clinical tools to better predict leukemic relapse post-transplant, further intervention (such as withdrawal of immunosuppression and/or DLI) may be implemented safely and effectively for those who require it.  This preliminary data indicates that PHA response is a clinically accessible indicator of immune reconstitution that may be an important variable to consider when predicting a patient’s risk for relapse.   Further study is needed to determine the degree to which PHA response might affect specific groups of patients.