Treatment of patients with AL amyloidosis with high-dose melphalan and autologous peripheral blood stem cells (PBSC) produces hematologic remissions in approximately 40% of evaluable patients, accompanied by improvements in organ disease and quality of life. These patients, who frequently have amyloid deposits in bone marrow blood vessels and interstitium and impaired function of kidneys, liver, spleen, and heart, represent an unusual population for stem cell transplantation, with unique problems. To identify factors influencing engraftment rates after chemotherapy and autologous granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC reinfusion, we studied a group of 225 patients. The median time to neutrophil engraftment was 10 days (range, 8-17 days). In a multivariate analysis, the factors positively affecting the rate of neutrophil engraftment were CD34+ stem cell dose, female gender, and minimal prior alkylator therapy. The median time to platelet engraftment was 13 days (range, 7-52 days). Factors positively affecting platelet engraftment, in addition to CD34+ cell dose, included preserved renal function and the absence of neutropenic fever. The conditioning dose of intravenous melphalan was not found to be an independent predictive factor for hematopoietic recovery. Thus, in this patient population, organ function and host and hematopoietic factors influence engraftment after PBSC rescue.