Monitoring of residual hematopoiesis after total body irradiation in humans as a model for accidental x-ray exposure: dose-effect and failure of ex vivo expansion of residual stem cells in view of autografting

Abstract

Purpose: To evaluate the residual hematopoiesis at different levels of total body irradiation (TBI) dose in bone marrow (BM) and peripheral blood (PB), and to study the dose-effect relationship on hematopoietic immature and mature progenitors. We also investigated the possibility of expanding ex vivo the residual progenitors exposed to different dose levels of TBI.

Methods and materials: Eight patients treated for AML (n = 3) and myeloma (n = 5) were included. BM and PB samples were harvested before TBI and after doses of: <or=2 Gy, 2.1-5 Gy, and >5 Gy. Mononuclear cells (MNCs) were assayed for burst-forming unit erythroid (BFU-E), granulocyte-forming unit macrophage (CFU-GM), and long-term culture initiating cells (LTC-ICs). Ex vivo expansion: MNCs (after irradiation and controls) were suspended in long-term cultures and expanded with a combination of five cytokines.

Results: CD34+ cells were detectable at 10 Gy. We observed a significant decrease of CFU-GM and BFU-E, respectively, to 13.5% and 8.5% of baseline values for doses <or=2 Gy and to 8.2% and 4.6% for doses ranging between 2.1 and 5 Gy. No dose effect was observed for residual MNCs. LTC-ICs were not detectable after 0.8 Gy. The expansion was not successful after 1.2 Gy.

Conclusion: This study confirms the significant decrease of human mature and immature progenitors in BM and PB immediately after low-dose TBI. In addition, the lack of expansion suggests that autografting using BM or PB residual stem cells collected and expanded in vitro in case of accidental whole body exposure may be impractical.