Utilization of a human tumor cloning system to monitor for bone marrow involvement in children with non-hodgkin's lymphoma.

The objective of this study was to evaluate the sensitivity of two methods for determining bone marrow involvement with non-Hodgkin's lymphoma. These methods were histologic review of bone marrow aspirates, and clot sections versus in vitro growth of lymphoma colonies on soft agar. Forty-two bone marrow aspirates were studied from 14 children who were without bone marrow involvement at diagnosis. There were seven bone marrow aspirates (from five patients) that had histologic evidence of metastatic lymphoma. Six of these seven specimens formed colonies in vitro. Twenty-nine of 35 histologically negative specimens showed no lymphoma colony growth. However, six histologically negative specimens (from three patients) formed lymphoma colonies. Both the Fisher's exact test and the K statistic were significant, indicating not only an association between histology and in vitro culture results, but also a close agreement. In addition, growth of lymphoma colonies in vitro was associated statistically with both a short duration of complete remission and a short duration of survival.

In vitro sensitivity of normal granulocytic and lymphoma colonies to vinca alkaloids.

Recently, a colony-forming assay was developed in our laboratory for pediatric malignant lymphoid diseases. This assay supports the growth of lymphoma colonies (ML-CFC) as well as normal granulocytic colonies (CFU-C) and thus a direct comparison between the antineoplastic and myelosuppressive effects of a drug can be determined. To test specificity of this in vitro assay to structurally similar drugs, the inhibitory effects of three vinca alkaloids (vincristine, vindesine, vinblastine) on ML-CFC (B-, T-, pre-T-cell types) and CFU-C was determined. Our results demonstrate that all three vinca alkaloids were active agents in vitro and that a direct dose response effect occurred once a threshold dose was reached. Each vinca alkaloid had a different pattern of inhibitory effect on ML-CFC and CFU-C suggesting an inherent difference in drug metabolism by these cells. Also, based on the dose inhibiting 50% of colony formation, vinblastine was 94 times more inhibitory against malignant B-cell ML-CFCs than against granulocytic CFU-C.