Age-Related Differences in Cellular Drug Resistance in Children with Acute Myeloid Leukemia (AML)

Abstract

The prognostic influence of age in childhood acute myeloid leukemia (AML) is less clear as in childhood acute lymphoblastic leukemia (ALL), where infants carry a poor prognosis. Reports on outcome in infant AML have been contradictory, and also the age cut-off point is less well defined as in ALL. We studied differences in cellular drug resistance, using the MTT-assay, between 28 infants (age ≤24 months) versus 122 older children (aged 2–18 years) with de novo AML. We found no differences in drug resistance within the infant AML group, comparing infants <12 months with infants aged 12–24 months. Cells from infants ≤24 months of age were significantly more sensitive to the following drugs, when compared with cells from older children: cytarabine (median 1.8 fold, p=0.02), etoposide (3.2 fold, p=0.003), 6-thioguanine (1.6 fold, p=0.008), doxorubicin (2.9 fold, p=0.02), busulfan (1.5 fold, p=0.01) and ifosfamide (1.1 fold, p=0.03). No significant differences were found for daunorubicin, idarubicin, mitoxantrone, amsacrine, prednisolone, vincristine and L-asparaginase. When children with Down syndrome (DS) were excluded, we found infant AML cells to be significantly more sensitive to etoposide (2.6 fold, p=0.012) and doxorubicin (2.9 fold, p=0.02) only, compared with older children. After excluding FAB M5 cases, infant cells were significantly more sensitive to etoposide (2.3 fold, p=0.016), 6-thioguanine (1.6 fold, p=0.02) and busulfan (1.5 fold, p=0.007). No significant differences were found within FAB M5 AML cases between infants and older children. FAB M4 infant AML cells were significantly more sensitive to ifosfamide only (1.3 fold, p=0.03), when compared with FAB M4 AML cells from older children.In conclusion: As a group, infant AML cells were significantly more sensitive than cells from older children to several drugs regularly used in AML treatment. However, this is caused by a higher frequency of 2 relatively in vitro sensitive subgroups in the infant AML group: children with DS AML and the AML FAB M5 subtype.KeywordsAcute Myeloid LeukemiaAcute Lymphoblastic LeukemiaDown SyndromeAcute Myeloid Leukemia CellInternal Tandem DuplicationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.