title: Analysis of factors predicting speed of hematologic recovery after transplantation with 4-hydroperoxycyclophosphamide-purged autologous bone marrow grafts.
abstract: We previously described the predictive value of graft colony-forming units granulocyte macrophage (CFU-GM) content after 4-hydroperoxycyclophosphamide (4-HC) purging for the duration of aplasia after autologous bone marrow transplantation. Despite the uniform 4-HC concentration, we observed heterogeneity in CFU-GM survival and the kinetics of engraftment. We have now analysed patient and graft characteristics for 154 patients undergoing autologous transplantation with 4-HC purged grafts to further define this heterogeneity. Patients transplanted for the treatment of malignant lymphoma reached a peripheral blood granulocyte count of greater than 0.5 x 10(9)/l (median, 20 versus 40 days; p less than 0.001) and platelet transfusion independence (median, 30 versus 70 days; p less than 0.001) significantly faster than patients transplanted for acute non-lymphoblastic leukemia. Other diagnostic groups were intermediate. These differences were independent of graft CFU-GM content. Multiple other patient and graft factors including patient age, peripheral blood counts on day of harvest, and amounts of other hematopoietic progenitors also predicted the kinetics of engraftment in univariate and multivariate analysis. Cytomegalovirus infection during the aplastic period predicted a delay in granulocyte (p = 0.024) but not platelet recovery (p = 0.174). This analysis demonstrates that multiple patient, graft, and post-transplant factors predict the engraftment capacity of autografts, and the kinetics of engraftment with 4-HC purged grafts. The multiple predictive factors explain a significant portion of the variability in engraftment kinetics observed after transplantation with 4-HC purged autografts.
authors.affiliation: Johns Hopkins Oncology Center, Baltimore, Maryland 21205.
authors.forename: S D
authors.initials: SD
authors.lastname: Rowley
authors.forename: S
authors.initials: S
authors.lastname: Piantadosi
authors.forename: D C
authors.initials: DC
authors.lastname: Marcellus
authors.forename: R J
authors.initials: RJ
authors.lastname: Jones
authors.forename: N E
authors.initials: NE
authors.lastname: Davidson
authors.forename: J M
authors.initials: JM
authors.lastname: Davis
authors.forename: J
authors.initials: J
authors.lastname: Kennedy
authors.forename: J M
authors.initials: JM
authors.lastname: Wiley
authors.forename: J R
authors.initials: JR
authors.lastname: Wingard
authors.forename: A M
authors.initials: AM
authors.lastname: Yeager
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000166:cytology; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000379:methods / Q000473:pathology*; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007223:Infant; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000473:pathology / Q000601:surgery; D014182:Transplantation, Autologous
chemical_list: D003520:Cyclophosphamide; C011272:perfosfamide