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.
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.
Keever-Taylor
C A
CA
Bone Marrow Transplant Program, Medical College of Wisconsin, Milwaukee, WI, USA.
Klein
J P
JP
Eastwood
D
D
Bredeson
C
C
Margolis
D A
DA
Burns
W H
WH
Vesole
D H
DH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D018952:Antigens, CD34 / Q000502:physiology; D001782:Blood Donors; D001792:Blood Platelets / Q000166:cytology; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006133:Growth Substances / Q000494:pharmacology; D006402:Hematologic Diseases / Q000401:mortality / Q000628:therapy; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology; D012189:Retrospective Studies; D012307:Risk Factors; D013601:T-Lymphocytes; D013997:Time Factors
D018952:Antigens, CD34; D006133:Growth Substances