Prognostic Impact Of a Newly Defined Structurally Complex Karyotype In Patients With AML and MDS After Allogeneic Stem Cell Transplantation
Authors: Dobbelstein Christiane E , Dammann Elke , Weissinger Eva M , Stadler Michael , Eder Matthias , Schlegelberger Brigitte , Ganser Arnold , Gohring Gudrun 
Published: October 2019

Abstract

Background
Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, relapsed disease is a major cause of treatment failure and death after SCT which is dependent on several pretransplantation variables, including cytogenetics. A diagnostic karyotype is a key determinant of outcome and has emerged as one of the most significant prognostic factors and provides the framework for current risk-stratified approaches. Monosomal karyotype (MK) defined by at least two autosomal monosomies, or one autosomal monosomy associated with at least one structural abnormality, is a rather new cytogenetic entity first described in AML by Breems et al., identifying a subset of patients with a dismal prognosis. A structurally complex karyotype has recently been defined as more than or equal to 3 chromosomal aberrations, including at least one structural aberration (Gohring G et al. Blood. 2010;116 (19):3766-3769). A structural aberration is defined as an altered chromosomal structure which can appear as a deletion, duplication, translocation, insertion, inversion, ring chromosome or isochromosome. Here, the presence of a structurally complex karyotype was a better predictor of a very unfavorable prognosis in children with MDS than a monosomal karyotype.

Aims
The objective of the present study was to determine whether a structurally complex karyotype has a similar adverse prognostic effect in the setting of allogeneic transplantation for adult patients receiving an SCT at Hannover Medical School for AML and MDS.

Methods
All patients with the diagnosis of AML and MDS who received an SCT from 2006-2011 at our center were retrospectively evaluated. Excluded were patients with ≥ 2 SCT, extramedullary AML as sole manifestation and haplo-identical SCT.

Results
248 evaluable patients could be identified, 106 with a normal karyotype, 8 with a core-binding factor (CBF) AML and 134 with an aberrant karyotype. In these 134 patients, a structurally complex karyotype did not allow a better prognostic distinction compared to a monosomal karyotype. As expected, most patients with an aberrant karyotype were transplanted without a prior remission, and only 48 patients (36%) were transplanted in 1st or 2nd complete remission (CR). For all patients who were transplanted in CR the differentiation between a structurally complex karyotype was a better prognostic marker than a monosomal karyotype in terms of relapse and overall survival. When evaluating the subgroup of patients with an aberrant karyotype, patients with a structurally complex karyotype had a significant higher relapse rate compared to patients without a structurally complex karyotype (53% vs. 14%, p<0.01). Also, overall survival was far better without a structurally complex karyotype (29 months vs. 11 months, p<0.01). There was no significant difference in relapse incidence for patients with and without a monosomal karyotype, also OS did not reach statistical significance, though it was better in the cohort without a monosomal karyotype. However, subgroups are small and a further discrimination between a monosomal but not structurally complex karyotype and vice versa could not be performed.

Conclusion
Patients with a monosomal or structurally complex karyotype had a poor prognosis. Notably, a structurally complex karyotype was associated with a shorter overall survival, even for patients transplanted in complete remission. The presence of a structurally complex karyotype had a stronger prognostic impact on survival after allogeneic transplantation than a monosomal karyotype. Our data strongly suggest further studies to determine the prognostic impact of this newly defined karyotype.

Disclosures:
No relevant conflicts of interest to declare.