Haemopoietic defect and decreased expansion potential of bone marrow autografts from patients with acute myeloid leukaemia in first remission.

Abstract

Autologous bone marrow (BM) transplantation for acute myeloid leukaemia (AML) in complete remission (CR) is frequently followed by a slow haemopoietic recovery. We assessed the haemopoietic capacity of purified BM stem cell (CD34+ DR-) and progenitor cell (CD34+ DR+) populations from patients with AML in CR, and compared these data with those of normal BM. The feasibility of ex vivo expansion in stroma-conditioned medium supplemented with cytokines was also investigated. The number of CFU-GM produced by initial patient CD34+ DR- cells was decreased compared to normal, whereas these values were similar to normal for CD34+ DR+ cells. BFU-E, HPP-CFC and LTC-IC were reduced for both patient CD34+ DR- and CD34+ DR+ subpopulations. In contrast to normal, the patient CD34+ DR- fraction was not enriched in LTC-IC. CFU-GM expansion from patient CD34+ DR- cells was poor and decreased after 14 d of culture. No HPP-CFC expansion could be observed for patient cells. LTC-IC were below the level of detection after 14-21 d of expansion culture of CD34+ DR- patient cells, whereas they were variably maintained or expanded for normal cells. After expansion culture, cytogenetic and/or FISH analyses did not reveal the anomalies present at diagnosis, regardless of the cell subpopulation analysed. In conclusion, BM cells of patients with AML in CR show a profound defect at the level of a stem cell enriched population. No meaningful ex vivo expansion could be obtained in culture conditions allowing for a significant expansion from a normal stem cell population.