Impact of conditioning regimen on peripheral blood hematopoietic cell transplant

AIM To investigate infused hematopoietic cell doses and their interaction with conditioning regimen intensity +/-total body irradiation(TBI) on outcomes after peripheral blood hematopoietic cell transplant(PBHCT).METHODS Our retrospective cohort included 247 patients receiving a first, T-replete, human leukocyte antigen-matched allogeneic PBHCT and treated between 2001 and2012. Correlations were calculated using the Pearson product-moment correlation coefficient. Overall survival and progression free survival curves were generated using the Kaplan-Meier method and compared using the log-rank test.RESULTS Neutrophil engraftment was significantly faster after reduced intensity TBI based conditioning [reduced intensity conditioning(RIC) + TBI] and > 4 × 10~6 CD34+cells/kg infused. A higher total nucleated cell dose led to a higher incidence of grade II-IV acute graft-versus-host disease in the myeloablative + TBI regimen group(P = 0.03), but no significant difference in grade III-IV graft-versus-host disease. A higher total nucleated cell dose was also associated with increased incidence of moderate/severe chronic graft-versus-host disease, regardless ofconditioning regimen. Overall and progression-free survival were significantly better in patients with a RIC + TBI regimen and total nucleated cell dose > 8 ×10~8/kg(3 years, overall survival: 70% vs 38%, P = 0.02, 3 years, progression free survival: 64% vs 38%, P = 0.02).CONCLUSION TBI and conditioning intensity may alter the relationship between infused cell doses and outcomes after PBHCT. Immune cell subsets may predict improved survival after unmanipulated PBHCT.

T cell metabolism in graft-versus-host disease

Graft-versus-host disease(GVHD)is a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplant(allo-HSCT),one of the most effective approaches to treat hematopoietic malignancies.1 However,current prophylaxis regimens and treatments that reduce the detrimental effect of acute GVHD can be offset by increased incidence in opportunistic infections and relapse of the primary malignancy.2 In addition,the majority of the approaches that inhibit T cell responses are non-specific,resulting in the inhibition of both alloreactive T cells and protective T cells from the donor.Therefore,there is an increase in the demand to develop novel approaches that selectively target alloreactive T cells.One potential means to address this issue is to take advantage of the unique metabolic profile of activated T cells.