In vitro culture of clonogenic leukaemic cells in acute myeloid leukaemia: growth pattern and drug sensitivity

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Abstract
Bone marrow from 43 of 45 AML [acute myeloid leukemia] patients grew leukemic colonies in culture with a technique using methylcellulose semisolid medium and stimulation with PHA[phytohemagglutinin]-leukocyte conditioned medium. Plating efficiency was significantly greater in M4 FAB [French-American-British] subtypes than in M1 or M2. The presence of Auer rods in cultured cells and the existence of cytogenetic abnormalities in fresh and cultured blast cell in 1 patient confirmed the leukemic origin of these colonies. These clonogenic cells were closely related to the growth fraction, as demonstrated by a high suicide index and a linear correlation between percentage of bone marrow blasts in S phase and plating efficiency. In-vitro CFU-L [lymphocyte colony-forming-unit] sensitivity of cytosine arabinoside (ARA-C) and to adriamycin (ADR) was tested in 22 patients treated with these 2 drugs. In the group sensitive in vitro to ARA-C (10 patients), 70% entered complete remission. In the resistant group (12 patients), only 25% had complete remission while 75% had resistant disease. Of 14 patients sensitive to ADR in vitro, 8 achieved complete remission, while 5 were resistant to chemotherapy. Of 8 patients resistant in vitro, 6 were resistant in vivo. When drug sensitivities to ARA-C and ADR were cumulated, an excellent in vitro-to-in vivo correlation was found when the patient was sensitive or resistant to both drugs in vitro.