Myeloid Progenitors in Remission Bone Marrow in Patients with Malignant Blood Diseases: Clues for Slow Hematopoietic Regeneration After ABMT?

Abstract

Slow hematopoietic recovery is a well-known feature in patients undergoing autologous bone marrow transplantation (ABMT), and here we demonstrate that compared with patients with other malignant blood diseases, the thrombocytopenia in acute myeloid leukemia (AML) patients stands out, with the median time to recovery of >50 × 10⁹ platelets being 101 days for AML patients and 22–37 days for other patient groups. We have consequently evaluated the content and fate of myeloid progenitor cells (BFU-E, CFU-GM, and CFU-GEMM) in bone marrow preparations from cancer patients in an attempt to uncover factors of importance for their slow hematopoietic recovery after ABMT using three experimental setups. First, we analyzed progenitors in marrow samples from 36 patients [18 AML, 5 acute lymphoblastic leukemia (ALL), and 13 non-Hodgkin's lymphoma (NHL)] exposed to multiple doses of severely myelotoxic cytoreductive regimens and observed that AML patients had suppressed numbers of CFU-GEMM and BFU-E (80% that of normal volunteers) but increased levels of CFU-GM. In contrast, the decrease in ALL patients was more pronounced (50% that of normal volunteers) and demonstrable for all progenitors. NHL patients exhibited normal progenitor frequencies of CFU-GM and CFU-GEMM, whereas their BFU-E counts were found to be increased nearly two-fold. Second, we followed the fate of progenitors through the laboratory manipulations of marrow grafts and found no evidence for selective losses in terms of disease (7 AML, 5 NHL, 1 ALL, and 2 testicular germ cell tumor patients) and progenitor type. Third, we retrospectively evaluated the cell yields of grafts from 121 cases [39 AML, 20 ALL, 22 NHL, 9 Burkitt's lymphoma (BL), 18 Hodgkin's disease (HD), and 13 testicular germ cell tumors] and found those of heavily treated AML, HD, and germinal tumors most affected, with a clear negative correlation in AML patients between age on the one hand and mononuclear cell yield and CFU-GM content on the other. We conclude that the amount of previous chemotherapy and age of patients appear to be among the determining factors on the number of myeloid progenitor cells in cancer patients and that thresholds for acceptability of grafts should take these variables into account.