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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 2001 Apr;27(8):791-800

Date

07/31/2001

Pubmed ID

11477435

DOI

10.1038/sj.bmt.1702872

Scopus ID

2-s2.0-0034991285   21 Citations

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 T(10)B(9)-1A3 (n = 489) or Muromonab-Orthoclone OKT3 (n = 57) monoclonal antibodies. Neutrophil engraftment to 0.5 x 10(9)/1 and platelet engraftment to 20 x 10(9)/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 > or = 5 x 10(6)/kg and most strongly with growth factor administration. Faster platelet engraftment was associated with transplantation for chronic leukemia, CD34(+) cell dose > or = 2 x 10(6)/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 x 10(9)/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.

Author List

Keever-Taylor CA, Klein JP, Eastwood D, Bredeson C, Margolis DA, Burns WH, Vesole DH

Author

David A. Margolis MD Interim Chair, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Analysis of Variance
Antigens, CD34
Blood Donors
Blood Platelets
Bone Marrow Transplantation
Child
Child, Preschool
Cohort Studies
Female
Graft Survival
Growth Substances
Hematologic Diseases
Histocompatibility Testing
Humans
Infant
Lymphocyte Depletion
Male
Middle Aged
Neutrophils
Retrospective Studies
Risk Factors
T-Lymphocytes
Time Factors