Allogeneic stem cell transplantation can improve outcome of AML patients without complete cytogenetic response after induction and consolidation treatment

Abstract

Our retrospective analysis was performed on 376 consecutive patients diagnosed with AML. A total of 256 (68%) were treated with standard "7+3" induction and high-dose cytarabine and mitoxantrone containing "4+3" consolidation/ intensification regimens. Our study focused on patients with presumably very poor prognosis -patients, who did not achieve complete cytogenetic remission (CRc). Twenty-five AML patients without CRc were further analysed for clinical and laboratory parameters. Firstly, the subgroups with or without morphologic CR were compared. Similar cytogenetic abnormalities were observed in both with myelodysplasia related changes being the most common. Complex karyotype with deletion of 5q constituted approximately a third of all karyotypes in both subgroups. There were 1 patient with intermediate risk cytogenetics in the subgroup without morphologic CR and 5 patients in the subgroup with morphologic CR. Interestingly, in 4/25 patients subclones were diminished by the chemotherapy treatment, however cytogenetically less advanced clones proliferated. Secondly, transplanted or nontransplanted patients were analysed. Allogeneic stem cell transplantation (allo-SCT) was found to be the only curative treatment for patients without CRc after 7+3 and 4+3 regimens. In our cohort, 40% of the patients, who underwent allo-SCT, are alive. Importantly, 67% of the patients, who died after allo-SCT, died of causes unrelated to progression of AML. Nonrelapse mortality is therefore one of the fields where survival could be further improved.

Chromosome abnormalities at onset of complete remission are associated with worse outcome in patients with acute myeloid leukemia and an abnormal karyotype at diagnosis: CALGB 8461 (Alliance)

“…Another potential mechanism is that the occurrence of non-clonal pre-treatment-unrelated abnormalities could indicate increased predisposition to genomic instability in leukemic blasts, 23 which might increase the likelihood of generation of therapy-resistant clones that lead to relapse and poor outcome. Regardless of the exact mechanism, our findings, if corroborated, suggest that detection of any chromosome abnormality at CR, whether related to the pre-treatment karyotype or not, should be regarded as a sign of increased risk of relapse or death, and that the patients with such cytogenetically abnormal CR samples should be considered as candidates for more intensive therapy, including allogeneic HSCT 14,24 and/or alternative treatment regimens. Whereas both our study and previous ones [10][11][12][13][14] show that cytogenetic analysis of CR samples can identify patients who have an increased risk of relapse or death, the resolution of cytogenetic analysis is relatively low.…”