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Allografting

Factors affecting neutrophil and platelet reconstitution following T cell-depleted bone marrow transplantation: differential effects of growth factor type and role of CD34+ cell dose

Abstract

We have performed univariate and multivariate analysis to determine the factors that affect the kinetics of neutrophil and platelet recovery in 546 recipients of T cell-depleted (TCD) marrow allografts. All patients received marrow depleted of mature CD3+ T cells by complement-mediated lysis using T10B9-1A3 (n = 489) or Muromonab-Orthoclone OKT3 (n = 57) monoclonal antibodies. Neutrophil engraftment to 0.5 × 109/1 and platelet engraftment to 20 × 109/l were assessed as endpoints. Factors significantly affecting neutrophil or platelet engraftment in the univariate analysis included patient age, T cell dose, anti-thymocyte globulin use, gender, diagnosis at transplant, CMV serostatus, HLA mismatch, CD34 cell dose (n = 249), and growth factor use and type. These variables were included in the multivariate Cox proportional hazards regression model. The results showed that a faster rate of neutrophil engraftment was independently associated with CD34+ cell dose 5 × 106/kg and most strongly with growth factor administration. Faster platelet engraftment was associated with transplantation for chronic leukemia, CD34+ cell dose ≥2 × 106/kg, an HLA matched related donor, and the absence of growth factor use. G-CSF had a higher relative risk (RR) of enhancing neutrophil engraftment than GM-CSF and significantly delayed platelet engraftment. The combined use of G-CSF + GM-CSF was similar to G-CSF alone. The enhancing effect of G-CSF for neutrophil recovery was most striking for patients who engrafted to 0.5 × 109/1 at or before day 12 (RR = 9.5, P < 0.0001) compared to patients who received no growth factor. Conversely, the delaying effect of G-CSF on platelet engraftment was strongest for patients engrafting on or before day 25 (RR = 0.4, P = 0.0004). Of the independent variables affecting engraftment kinetics in recipients of TCD marrow allografts only growth factor, and to a limited extent, CD34+ cell dose can be controlled by the clinician. A higher CD34+ cell dose enhances the rate of both neutrophil and platelet engraftment whereas for G-CSF the benefits of myeloid growth factor use in enhancing neutrophil recovery may be partly offset by a delay in platelet engraftment. Bone Marrow Transplantation (2001) 27, 791–800.

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Acknowledgements

We acknowledge the assistance of Claudia Kabler-Babbitt and Diane Bauer, data keepers for the adult and pediatric BMT programs, respectively, for gathering the data needed for this report.

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Keever-Taylor, C., Klein, J., Eastwood, D. et al. Factors affecting neutrophil and platelet reconstitution following T cell-depleted bone marrow transplantation: differential effects of growth factor type and role of CD34+ cell dose. Bone Marrow Transplant 27, 791–800 (2001). https://doi.org/10.1038/sj.bmt.1702872

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