Allogeneic peripheral blood stem cell graft composition affects early T‐cell chimaerism and later clinical outcomes after non‐myeloablative conditioning

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Abstract
Summary: We have studied the influence of cell subsets [CD34, CD3, CD4, CD8, CD14, CD20, natural killer (NK; CD3−/CD56+), NKT (CD3+/CD56+), DC1, and DC2 cells] of granulocyte colony‐stimulating factor mobilized peripheral blood stem cells (PBSC) on early T‐cell chimaerism and later clinical outcomes in 125 patients with haematological malignancies who received human leucocyte antigen (HLA)‐matched related grafts after non‐myeloablative conditioning. Conditioning consisted of 2 Gy total body irradiation (TBI) alone (n = 28), or 2 Gy TBI preceded by either 90 mg/m2fludarabine (n = 62) or planned autologous haematopoietic cell transplantation (HCT) (n = 35). Post‐transplant immunosuppression included mycophenolate mofetil and ciclosporin. Multivariate analysis showed that higher numbers of grafted NK cells predicted higher early T‐cell chimaerism (P = 0·03), while higher numbers of B cells were associated with better clinical outcomes and a higher risk for chronic graft‐versus‐host disease (P = 0·05). Higher numbers of CD14+cells were associated with worse overall survival (P = 0·03), while higher numbers of CD34+cells showed better survival (P = 0·03). The addition of fludarabine or autologous HCT predicted higher early T‐cell chimaerism (P = 0·001), while advanced donor age predicted lower chimaerism (P ≤ 0·02). Patients with aggressive diseases were at higher risk for relapse/disease progression, and shorter progression‐free and overall survival (P < 0·01). These results suggest that the dosing of certain cellular subsets of PBSC products can influence important outcomes post‐HCT after non‐myeloablative conditioning.

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