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Association of bone marrow natural killer cell dose with neutrophil recovery and chronic graft-versus-host disease after HLA identical sibling bone marrow transplants.

Larghero J, Rocha V, Porcher R, Filion A, Ternaux B, Lacassagne MN, Robin M, Peffault de Latour R, Devergie A, Biscay N, Ribaud P, Benbunan M, Gluckman E, Marolleau JP, Socié G

Cell Therapy Unit, Assistance Publique-Hôpitaux de Paris, Saint Louis Hospital, Paris, France.

Allogeneic bone marrow (BM) transplant (BMT) outcomes have been correlated with the infused nucleated, CD34(+), and T- cell dose. The potential impact of natural killer (NK) BM infused cell dose has however not been established. We analysed the outcomes of 78 patients receiving an HLA identical BMT. A higher NK cell dose was associated with the speed of neutrophil (P = 0.05) and platelet recovery (P = 0.04). Higher nucleated cells, CD34(+), CD3(+), CD3(+)/4(+), CD3(+)/8(+) and NK cell dose were associated with a lower incidence of chronic GvHD (cGvHD) in univariate analysis. In multivariate analysis, the risk of cGvHD was increased by a lower NK cell dose [hazard ratio (HR) = 2.3 (1.2-4.4) for cell dose <0.9 x 10(6)/kg; P = 0.01] and an older age [HR = 1.4 /10 years (1.1-1.8); P = 0.002]. In addition, a higher CD3(+)/4(+) and NK cell dose were associated with a decreased incidence of viral infections (P = 0.03 and P = 0.06 respectively). No specific cell subpopulation infused dose was associated with survival. In conclusion, a higher BM NK cell dose is associated with an increased speed of neutrophil recovery and a decreased incidence of cGvHD.

Published 8 June 2007 in Br J Haematol, 138(1): 101-9.
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