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Predicting Response or Progression of Human Leukemia by Premature Chromosome Condensation of Bone Marrow Cells¹

Department of Developmental Therapeutics, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

The object of this study was to apply the phenomenon of premature chromosome condensation to the prediction of the future course of the disease in leukemic patients during chemotherapy and to the forecasting of relapse if they are in complete remission.

The proliferative potential index (PPI) of bone marrows from leukemic patients was compared with that of solid tumor patients with no bone marrow involvement. This technique involves the fusion of bone marrow cells with mitotic Chinese hamster ovary cells with the use of UV-inactivated Sendal virus. The morphology of the prematurely condensed chromosomes (PCC) of the bone marrow cells reflects their position in the cell cycle, i.e., G₁, S, or G₂. In addition, the G₁ PCC exhibited a wide range of variability in their degree of condensation and were arbitrarily ranked on a scale of 1 to 6. The value of 6 represents the most decondensed and extended G₁ PCC. The PPI of a bone marrow was defined as a percentage of highly extended G₁ PCC (belonging to Classes 4 to 6) among the total number of G₁ PCC scored (Classes 1 to 6). The average PPI values are: 11.7% for solid tumor patients; 27.5% for untreated leukemic patients; 22.0 to 24.5% for leukemic patients responding to chemotherapy; and 39.0% for those not responding to therapy. Among the 13 leukemic patients in complete remission at the time of the bone marrow sample, 4 patients had PPI values greater than 35%, of which 3 relapsed within 6 months. Of the remaining nine patients who exhibited low PPI values, only one relapsed within the same time interval. These data suggest a correlation between the PPI values of the bone marrow cells and the prognosis of the disease. A lower PPI value is indicative of a good prognosis, i.e., impending or continued remission with therapy. A high PPI value during active phase of the disease or during remission, on the other hand, is indicative of continued progression or impending relapse.

¹ Supported in part by Grants CA 16480, CA 14528, and CA 11520 from the National Cancer Institute and by Grant GM 23252 from the National Institute of General Medical Sciences, NIH, Department of Health, Education and Welfare.

Received 7/ 5/77. Accepted 11/ 8/77.