title: Long-term engraftment failure after marrow ablation and autologous hematopoietic reconstitution: differences between peripheral blood stem cell and bone marrow recipients.
abstract: We infused peripheral blood stem cells (PBSC) into 51 patients with various malignant disorders, after myeloablative conditioning. Twenty-four patients also received autologous bone marrow (PBSC + BM). In a multivariate analysis, the only statistically significant predictors of neutrophil engraftment were log-dose CFU-GM (P < 0.001) and the number of prior chemotherapy regimens (P = 0.004). The factors predicting RBC and platelet engraftment were log-dose CFU-GM (P = 0.002), PBSC + BM infusion (P = 0.007) and the absence of neoplastic bone marrow involvement (P = 0.009). Seven patients remained platelet and/or red cell transfusion-dependent for 100 days or more post-transplant after good neutrophil recovery. Six of these seven long-term engraftment failures, as well as five additional patients, received < 10(5) CFU-GM/kg. Of the 11 patients who received < 10(5) CFU-GM/kg (low-dose patients), seven were PBSC recipients, of whom six were long-term engraftment failures. In contrast, there were no long-term engraftment failures among the four low-dose autologous marrow recipients. This difference in long-term engraftment failure rate was significant (P = 0.015). The low-dose PBSC patients all had a diagnosis of lymphoma with bone marrow involvement. The low-dose PBSC + BM group was more heterogeneous, but no patient had malignant involvement of the marrow. The low-dose PBSC patients had also received significantly more prior chemotherapy regimens than the low-dose PBSC + BM patients and a significantly higher proportion received total body irradiation (TBI) as part of their conditioning regimen. We conclude that marrow damage resulting from a combination of neoplastic infiltration, chemotherapy and TBI may result not only in low PBSC yields but also in an impaired capacity of the marrow microenvironment to support transplanted stem cells.
authors.affiliation: Department of Pathology, University of North Carolina, Chapel Hill 27514, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Bentley
authors.forename: M E
authors.initials: ME
authors.lastname: Brecher
authors.forename: E
authors.initials: E
authors.lastname: Powell
authors.forename: J S
authors.initials: JS
authors.lastname: Serody
authors.forename: J M
authors.initials: JM
authors.lastname: Wiley
authors.forename: T C
authors.initials: TC
authors.lastname: Shea
mesh_terms: D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D005260:Female; D006084:Graft Rejection; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000628:therapy*; D013997:Time Factors; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous