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 va rious malignant disorders, after myeloablative conditioning, Twenty-fo ur patients also received autologous bone marrow (PBSC + BM), In a mul tivariate analysis, the only statistically significant predictors of n eutrophil 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 involve ment (P = 0.009), Seven patients remained platelet and/or red cell tra nsfusion-dependent for 100 days or more post-transplant after good neu trophil recovery, Six of these seven long-term engraftment failures, a s 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 f our low-dose autologous marrow recipients, This difference in longterm engraftment failure rate was significant (P = 0.015), The low-dose PB SC patients all had a diagnosis of lymphoma with bone marrow involveme nt, The low-dose PBSC + BM group was more heterogeneous, but no patien t 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 re gimen, We conclude that marrow damage resulting from a combination of neoplastic infiltration, chemotherapy and TBI may result not only in l ow PBSC yields but also in an impaired capacity of the marrow microenv ironment to support transplanted stem cells.