FAVORABLE PROGNOSIS OF HYPERDIPLOID COMMON ACUTE LYMPHOBLASTIC-LEUKEMIA MAY BE EXPLAINED BY SENSITIVITY TO ANTIMETABOLITES AND OTHER DRUGS - RESULTS OF AN IN-VITRO STUDY

DNA hyperdiploidy is a favorable prognostic factor in childhood acute lymphoblastic leukemia (ALL). The explanation for this prognostic sign ificance is largely unknown. We have studied whether DNA ploidy was re lated to cellular resistance to 12 drugs, assessed with the methyl-thi azol-tetrazolium assay, in samples of 74 children with common (CD10+ p recursor B-cell) ALL, Sixteen patients had hyperdiploid ALL cells and 58 patients had nonhyperdiploid ALL cells. Hyperdiploid ALL cells were more sensitive to mercaptopurine (median, 9.0-fold; P = .000003), to thioguanine (1.4-fold; P = .023), to cytarabine (1.8-fold; P = .016), and to I-asparaginase (19.5-fold; P = .022) than were nonhyperdiploid ALL cells. In contrast, these two ploidy groups did not differ signifi cantly in resistance to prednisolone, dexamethasone, vincristine, vind esine, daunorubicin, doxorubicin, mitoxantrone, and teniposide. The pe rcentage of S-phase cells was higher (P = .05) in the hyperdiploid ALL samples (median, 8.5%) than in the nonhyperdiploid ALL samples (media n. 5.7%). However, the percentage of cells in S-phase was not signific antly related to in vitro drug resistance. We conclude that the favora ble prognosis associated with DNA hyperdiploidy in childhood common AL L may be explained by a relative sensitivity of hyperdiploid common AL L cells to antimetabolites, especially to mercaptopurine and to I-aspa raginase. (C) 1995 by The American Society of Hematology.