Human myeloma in vitro colony growth: interrelationships between drug sensitivity, cell kinetics, and patient survival duration

Ninety-seven patients with multiple myeloma evaluated serially had both a tritiated thymidine labeling index of bone marrow plasma cells (LI%) and in vitro myeloma stem cell culture performed. Thirty-three patients with myeloma colony growth had in vitro drug sensitivity testing carried out, 18 having in addition in vitro thymidine suicide determinations. The LI% and the likelihood of in vitro myeloma colony growth were highly correlated: the higher the LI%, the more likely was colony or cluster growth (p less than 0.001). The tritiated thymidine suicide of myeloma stem cells was usually very high. There was excellent correlation between in vitro and in vivo drug sensitivity. Both pretreatment drug resistance and selective sensitivity (e.g., interferon, bisantrene, methotrexate, vinblastine) at the time of relapse were accurately detected and correlated well with survival duration (p = 0.01 Wilcoxan). Although LI% and in vitro sensitivity were clearly independent variables, a high LI% (greater than 3%) plus in vitro resistance were associated with a subsequent survival duration of less than 6 mo. The studies allowed dissection of the complex interrelationship between cell kinetics and drug sensitivity.