IN-VITRO GROWTH IN ACUTE MYELOBLASTIC-LEUKEMIA - RELATIONSHIP WITH OTHER CLINICO-BIOLOGICAL CHARACTERISTICS OF THE DISEASE

The in vitro growth characteristics of a large series of acute myeloid leukaemia (AML) patients and their relationship with other clinical a nd biological disease characteristics were analysed. Patients with AML were studied, 181 with ne novo AML and 45 with secondary AML (24 myel odysplastic syndrome, sAML-MDS, 21 myeloproliferative disorder, sAML-M PD). Leukaemic colony forming units (L-CFU) were assayed by plating pe ripheral blood (PB) blast cells in methyl-cellulose and using LCM-PHA as stimulant, In each case parallel cultures were made with and withou t stimulating factors, Plating efficiency (PE) was defined as the numb er of clusters plus colonies/10(5) cells plated. Autonomous growth (AG ) was the number of colonies plus clusters growing without stimulant. The autonomous proliferative index (API) was calculated as the number of clusters + colonies without stimulating factor divided by the numbe r of clusters + colonies with stimulating factor. No significant diffe rences in the PE between tie novo and secondary AML were found. Autono mous growth was significantly higher in sAML-MPD. The FAB subtype M3 l eukaemias displayed a significantly greater PE and a significantly low er API when compared with the other FAB subgroups (P = 0.0002). Upon a nalysing the relationship with the immunophenotype, only CD33 expressi on showed a significant relationship with the in vitro growth pattern; CD33(+) cases displayed a higher PE (P = 0.0002) and AG (P = 0.0003) than CD33(-) cases. When patients were grouped according to the level of rh123 efflux (MDR1) it was observed that cases with >30% eliminatio n showed a higher AG and API than those with <30% (P = 0.03). Finally we found that patients with higher API (>0.05) displayed a significant ly shorter overall survival as compared with patients with API <0.05 ( P = 0.04). The in vitro study properties of clonogenic cells produces relevant clinical information of leukaemic cell biology in AML patient s.