0000000000150305
AUTHOR
Evelyn Acuña-cruz
Impact of combinations of single-nucleotide polymorphisms of anthracycline transporter genes upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia
Anthracycline uptake could be affected by influx and efflux transporters in acute myeloid leukemia (AML). Combinations of single-nucleotide polymorphisms (SNPs) of wild-type genotype of influx transporters (SLC22A16, SLCO1B1) and homozygous variant genotypes of ABC polymorphisms (ABCB1, ABCC1, ABCC2, ABCG2) were evaluated in 225 adult de novo AML patients. No differences in complete remission were reported, but higher induction death was observed with combinations of SLCO1B1 rs4149056 and ABCB1 (triple variant haplotype, rs1128503), previously associated with ABCB1 and SLCO1B1 SNPs. Several combinations of SLCO1B1 and SLC22A16 with ABCB1 SNPs were associated with higher toxicities, includin…
Evolving patterns of care and outcomes in relapsed/refractory FLT3 mutated acute myeloid leukemia adult patients.
We have analyzed treatment patterns and outcomes of relapsed/refractory(R/R) FLT3mut AML adult patients registered in our institutional data base between 1998 and 2018. Overall, 147 patients were evaluable: 34 from 1998 to 2009, 113 from 2010 to 2018. Salvage treatments were intensive chemotherapy ( n = 25, 74%), and supportive care ( n = 9, 26%) in the 1998-2009 period, and intensive chemotherapy ( n = 63, 56%), hypomethylating agent ( n = 7, 6%), low-dose cytarabine-based ( n = 8, 7%), clinical trial ( n = 16, 14%) and supportive care ( n = 19, 17%) in the 2010-2018 period. Complete remission (CR) or with incomplete recovery (CRi) rate was 44%, 49% among patients treated intensively (vs 3…
Influence of polymorphisms in anthracyclines metabolism genes in the standard induction chemotherapy of acute myeloid leukemia
Objectives Genetic variability in anthracycline metabolism could modify the response and safety of acute myeloid leukemia (AML) induction. Methods Polymorphisms in genes that encodes enzymes of anthracyclines metabolic pathway (CBR3: rs1056892, rs8133052, NQO1: rs1800566, NQO2: rs1143684, NOS3: rs1799983, rs2070744) were evaluated in 225 adult de novo AML patients. Results The variant CBR3 rs8133052 was associated with lower hepatotoxicity (P = 0.028). Wild-type genotype of NQO2 rs1143684 was related to higher complete remission (P = 0.014), and the variant allele with greater gastrointestinal toxicity (P = 0.024). However, the variant genotype of NQO1 rs1800566 was associated with mucositi…