No impact of total or myeloid Cd34+ cell numbers on neutrophil engraftment and transplantation-related mortality after allogeneic pediatric bone marrow transplantation.
Although the influence of transplanted bone marrow (BM) CD34+ cells on neutrophil engraftment (NE) and transplantation outcomes has been discussed controversially, thresholds between 2 and 4 × 10(6)/kg CD34+ cells are commonly accepted. This has substantial consequences for a donor in terms of BM volume to be collected, which frequently covers up to 15 to 20 mL/kg. As the BM CD34+ compartment contains varying fractions of CD34+/CD19+ B lymphoid progenitors, we tested the hypothesis that the infused CD34+/CD45dim/CD19-/CD10- myeloid stem cells might reliably predict NE in 94 children who received BM from 37 HLA-identical sibling donors (MSD) and 57 matched unrelated donors after myeloablative conditioning. The grafts contained a median of 3.6 × 10(6)/kg total CD34+ cells, which consisted of a median of 73% myeloid CD34+ cells and 27% B lymphoid progenitors. Grafts from donors <15 years old yielded significantly lower myeloid fractions compared with grafts from older donors (P < .001). All patients achieved sustained NE after median 20 (range, 11 to 40) days. By multivariate analysis, neither the number of total CD34+ cells (P = .605) nor of myeloid CD34+ cells (P = .981) correlated with NE, whereas transplantation from MSD (hazard ratio [HR] 3.51; P = .019) and the administration of granulocyte colony-stimulating factor (HR 2.24; P = .002) remained independent factors associated with earlier NE. Furthermore, neither total nor myeloid CD34+ cell quantities were associated with incidences of severe infections before NE (P = .271 and P = .132) or transplantation-related mortality (TRM) at day +100 (P = .294 and P = .490). Taking into account that the number of transplanted total CD34+ or myeloid CD34+ cells does not seem to have a relevant impact on time to NE, sepsis rates, or TRM, the need of certain threshold cell numbers should be revisited, at least for pediatric MSD.
Pediatric Hematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Austria.
Herbert
H
Pichler
Pediatric Hematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Austria.
Volker
V
Witt
Pediatric Hematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Austria.
Elisabeth
E
Winter
Pediatric Hematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Austria.
Heidrun
H
Boztug
Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria.
Evgenia
E
Glogova
Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria.
Ulrike
U
Pötschger
Pediatric Hematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Austria.
Susanne
S
Matthes-Martin
Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria. Electronic address: gerhard.fritsch@ccri.at.
Gerhard
G
Fritsch
D000293:Adolescent; D018952:Antigens, CD34 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D018655:Lymphocyte Count; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D011446:Prospective Studies; D035781:Siblings; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
D018952:Antigens, CD34; D019653:Myeloablative Agonists
CD34+ cell dose; Graft composition; Hematopoietic recovery; Pediatric stem cell transplantation