Long-term engraftment failure after marrow ablation and autologous hematopoietic reconstitution: Differences between peripheral blood stem cell and bone marrow recipients

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 longterm engraftment failures, In contrast, there were no long-term engraftment failures among the four low-dose autologous marrow recipients, This difference in longterm 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.