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2244 Impact of Typical and Atypical Complex Karyotype Subgroups on Outcome of AML Patients Undergoing Allogeneic Stem Cell Transplantation

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster I
Hematology Disease Topics & Pathways:
Research, Biological therapies, Acute Myeloid Malignancies, AML, adult, Clinical Research, Diseases, Therapies, Myeloid Malignancies, Study Population, Human, Transplantation
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Jule Ussmann1*, Anne Weigert, PhD1*, Lara Bischof1*, Dominic Brauer, MD1*, Donata Backhaus, MD1*, Claudia Diener1*, Maximilian Merz, MD1, Vladan Vucinic, M.D.2*, Klaus H Metzeler, MD3, Uwe Platzbecker, MD4, Sebastian Schwind, MD1* and Madlen Jentzsch1*

1Department for Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University of Leipzig Medical Center, Leipzig, Germany
2Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Leipzig Medical Center, Leipzig, Germany
3Department of Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University Leipzig Medical Center, Leipzig, Germany
4Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, University Medical Center Leipzig, Leipzig, Germany


Acute myeloid leukemia (AML) with a complex karyotype (CKT) confers an adverse prognosis, even within the subgroup of patients (pts) with adverse risk according to European LeukemiaNet 2022 (ELN22) risk stratification. Mrózek et al. further characterized CKT pts according to distinct mechanisms of leukemogenesis into balanced (presence of ≥1 balanced rearrangement), and unbalanced CKT (CKTub, exclusively unbalanced cytogenetic abnormalities). Considering the high incidence of deletions (del) of 5q, 7q, and 17p in CKT, CKTub were further divided in typical CKTub (with latter abnormalities present), and atypical CKTub (with exclusively other abnormalities). In the context of consolidating chemotherapy, typical CKTub was associated with shorter event-free survival (EFS) and overall survival (OS) compared to atypical CKTub. However, we lack data in the context of allogeneic hematopoietic stem cell transplantation (HSCT) which remains the preferred treatment in eligible pts. Here we aimed to investigate this classification in CKT AML pts consolidated by HSCT.


We analyzed 263 pts with AML who were classified as ELN22 adverse risk and underwent an allogeneic HSCT. 105 had a CKT, while 158 fulfilled other ELN22 adverse risk criteria. Of the pts harboring a CKT, median age at HSCT was 61 (range 20 - 76) years. Remission status at HSCT was first complete remission with or without count recovery (CR/CRi, 62%) or refractory AML (38%). Conditioning intensity according to EBMT criteria were myeloablative (19%), reduced intensity (31%) or non-myeloablative (50%). Donors were matched related (16%), haploidentical (2%) or matched (65%) or mismatch unrelated (17%). Cytogenetic analyses at diagnosis were performed using standard techniques of banding and in situ hybridization. Pretreatment genomic DNA was screened for genes recurrently mutated in myeloid malignancies using next generation sequencing. Median follow-up alive was 1.3 years.


Pts with a CKT had a significantly shorter EFS (P<.01) and OS (P<.01) than other ELN22 adverse risk pts. Of all pts harboring a CKT, 17% had a balanced CKT, and 83% a CKTub. Among CKTub, 85% were classified as typical (67% with del(5q), 49% with del(7q), 26% with del(17p), Figure 1). Comparing typical and atypical CKTub, pts with typical CKTub more often had a monosomal karyotype (P<.01), had more cytogenetic abnormalities (in typical CKTub median 8 [range 3-39] vs atypical CKTub median 6 [range 3-9], P=.04), more often TP53 mutations (P=.02), less often RUNX1 mutations (P=.03) and a lower LDH at diagnosis (P=.03). They also had a higher expression of the leukemic stem cell markers CD34+/CD38- (P=.01) and GPR56 (P<.01). However, after allogeneic HSCT, EFS (P=.50) and OS (P=.50) did not differ between pts with typical and atypical CKTub (Figure 2).

Next, we looked for other adverse prognostic factors within CKT pts receiving HSCT, which in univariate analyses were the presence of a del(5q) (EFS P<.01 and OS P=.03), a del(17p) (EFS P=.10 and OS P=.02), the presence of ≥5 vs <5 cytogenetic aberrations (EFS P=.03 and OS P=.06), a concomitant TP53 mutation (EFS P=.01 and OS P=.01), and a higher age at HSCT (≥60 years, EFS P=.04 and OS P=.08). In contrast, neither the presence of a del(7q) nor a monosomal karyotype impacted EFS or OS within pts with a CKT. In multivariate analyses for CKT pts, the presence of ≥ 5 cytogenetic aberrations (Hazard Ratio. [HR] 1.7, 95% Confidence Interval [CI] 1.0-3.0, P=.05), higher age at HSCT (HR 1.6, 95% Ci 1.1-2.5, P=.02), and no CR/CRi at HSCT (HR 1.7, 95% CI 1.1-2.7, P=.01) were adverse factors for EFS, while the presence of a del(17p) (HR 2.0, 95% CI 1.2-3.4, P=.01), higher age at HSCT (HR 1.8, 95% CI 1.1-3.0, P=.02), and no CR/CRi at HSCT (HR 1.8, 95% CI 1.1-2.9, P=.02) were adverse factors for OS.


The presence of a CKT retains its negative prognostic impact after HSCT and differentiates within the ELN22 adverse risk group. However, in contrast to chemotherapy consolidation alone, the subgroup of pts harboring a typical CKTub did not perform worse than pts with an atypical CKTub, indicating a potential immune-mediated beneficial effect of HSCT. Within pts with a CKT receiving HSCT, we identified additional prognostic factors including the presence of ≥5 cytogenetic aberrations. These pts are in urgent need for novel post HSCT approaches.

Disclosures: Ussmann: Sanofi: Other: former travel support. Merz: AMGEN, TAKEDA, BMS, JANSSEN, STEMLINE, ROCHE: Honoraria. Metzeler: BMS: Consultancy, Honoraria; AbbVie: Honoraria, Research Funding; Pfizer: Honoraria; Otsuka: Honoraria; Janssen: Honoraria; Novartis: Consultancy. Platzbecker: Syros: Consultancy, Honoraria, Research Funding; MDS Foundation: Membership on an entity's Board of Directors or advisory committees; Silence Therapeutics: Consultancy, Honoraria, Research Funding; Celgene: Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Fibrogen: Research Funding; Servier: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Merck: Research Funding; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; Curis: Consultancy, Research Funding; Janssen Biotech: Consultancy, Research Funding; Jazz: Consultancy, Honoraria, Research Funding; BeiGene: Research Funding; Geron: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; medical writing support, Research Funding; BMS: Research Funding. Jentzsch: Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Blueprint Medicine: Honoraria; BMS: Honoraria; JAZZ: Honoraria.

*signifies non-member of ASH