Association of CD34 cell dose with hematopoietic recovery, infections, and other outcomes after HLA-identical sibling bone marrow transplantation

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Abstract
Although CD34 cell dose is known to influence outcome of peripheral stem cell– and/or T-cell–depleted transplantation, such data on unmanipulated marrow transplantation are scarce. To study the influence of CD34+ cell dose on hematopoietic reconstitution and incidence of infections after bone marrow transplantation, we retrospectively analyzed 212 patients from January 1994 to August 1999 who received a transplant of an unmanipulated graft from an HLA-identical sibling donor. Median age was 31 years; 176 patients had hematologic malignancies. Acute graft-versus-host disease prophylaxis consisted mainly in cyclosporin associated with methotrexate (n = 174). Median number of bone marrow nucleated cells and CD34+ cells infused were 2.4 × 108/kg and 3.7 × 106/kg, respectively. A CD34+ cell dose of 3 × 106/kg or more significantly influenced neutrophil (hazard ratio [HR] = 1.37, P = .04), monocyte (HR = 1.47, P = .02), lymphocyte (HR = 1.70, P = .003), erythrocyte (HR = 1.77, P = .0002), and platelet (HR = 1.98,P = .00008) recoveries. CD34+ cell dose also influenced the incidence of secondary neutropenia (HR = 0.60,P = .05). Bacterial and viral infections were not influenced by CD34 cell dose, whereas it influenced the incidence of fungal infections (HR = 0.41, P = .008). Estimated 180-day transplantation-related mortality (TRM) and 5-year survival were 25% and 56%, respectively, and both were highly affected by CD34+ cell dose (HR = 0.55, P = .006 and HR = 0.54, P = .03, respectively). Five-year survival and 180-day TRM were, respectively, 64% and 19% for patients receiving a CD34+ cell dose of 3 × 106/kg or more and 40% and 37% for the remainders. In conclusion a CD34+ cell dose of 3 × 106/kg or more improved all hematopoietic recoveries, decreased the incidence of fungal infections and TRM, and improved overall survival.

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