Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype – retrospective analysis of Polish Adult Leukemia Group (PALG)

Abstract

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK MK and CK MK group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK but not in MK group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK.

Addition of cladribine to the standard induction treatment improves outcomes in a subset of elderly acute myeloid leukemia patients. Results of a randomized Polish Adult Leukemia Group (PALG) phase II trial

“…In the SWOG study MK has been identified in 20% of patients older than 60 but in only 4% of patients aged 30 or younger . Results of PALG retrospective analysis regarding a population of AML patients with a complex karyotype have shown that addition of cladribine to the standard DA regimen improves OS only in MK − but not in MK + cytogenetic group . Other explanation may be the fact that AML in the elderly exhibits several other biological features associated with chemoresistance, including frequent involvement of a more immature leukemic precursor clone or multidrug resistance mediated by MDR1/P‐glycoprotein …”

Impact of pretransplant measurable residual disease on the outcome of allogeneic hematopoietic cell transplantation in adult monosomal karyotype AML

“…8 Numerous studies have subsequently confirmed this association. [9][10][11][12][13][14][15][16][17][18][19][20][21] While results with allogeneic HCT appear better than with non-HCT post-remission therapies, several studies -including one from our institution -have reported poor post-HCT outcomes for adults with MK AML. [10][11][12]14,15,[18][19][20][21][22] Based on these data, it is now generally accepted that having MK AML is an important adverse prognostic factor for patients undergoing allogeneic HCT.…”

Pretreatment platelet count predicts survival outcome of patients with de novo non-M3 acute myeloid leukemia

“…As of today, the molecular and cytogenetic alterations of AML cells are being studied in detail ( Dohner, Weisdorf & Bloomfield, 2015 ; Wierzbowska et al, 2017 ; Zhang et al, 2016 ). According to the national comprehensive cancer network (NCCN) guideline, cytogenetic subgroups are classified as favorable, intermediate, and unfavorable risk ( O’Donnell et al, 2012 ).…”