HEMATOPOIETIC DEFECT AND DECREASED EXPANSION POTENTIAL OF BONE-MARROWAUTOGRAFTS FROM PATIENTS WITH ACUTE MYELOID-LEUKEMIA IN FIRST REMISSION

Autologous bone marrow (BM) transplantation for acute myeloid leukaemi a (AML) in complete remission (CR) is frequently followed by a slow ha emopoietic recovery. We assessed the haemopoietic capacity of purified BM stem cell (CD34(+)DR(-)) and progenitor cell (CD34(+)DR(+)) popula tions from patients with AML in CR, and compared these data with those of normal BM. The feasibility of ex vivo expansion in stroma-conditio ned medium supplemented with cytokines was also investigated. The numb er of CFU-GM produced by initial patient CD34+DR- cells was decreased compared to normal, whereas these values were similar to normal for CD 34(+)DR(+) cells. BFU-E, HPP-CFC and LTG-IC were reduced for both pati ent CD34(+)DR(-) and CD34(+)DR(+) subpopulations. In contrast to norma l, the patient CD34(+)DR(-) fraction was not enriched in LTC-IC. CFU-G M expansion from patient CD34(+)DR(-) cells was poor and decreased aft er 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 expa nsion culture of CD34(+)DR(-) patient cells, whereas they were variabl y maintained or expanded for normal cells. After expansion culture, cy togenetic and/or FISH analyses did not reveal the anomalies present at diagnosis, regardless of the cell subpopulation analysed. In conclusi on, 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 expans ion could be obtained in culture conditions allowing for a significant expansion from a normal stem cell population.