Prognostic Impact of a Monosomal Karyotype on the Outcome of Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Stem Cell Transplantation
Authors: Hemmati Philipp G. , Terwey Theis H. , Coutre Philipp D. le , Ziegler Christian , Kofla Grzegorz , Massenkeil Gero , Dörken Bernd , Arnold Renate 
Published: October 2019

Abstract
Abstract 2028

Purpose:
A monosomal karyotype, as defined by the presence of two or more autosomal monosomies or a single autosomal monosomy in the presence of at least one structural chromosomal abnormalities (core binding factor abnormalities excluded), was shown to confer to a highly unfavorable prognosis in patients (patients) with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) treated with conventional chemotherapy. Here, we investigated the prognostic impact of a monosomal karyotype on the outcome of patients with AML or MDS following allogeneic stem cell transplantation (alloSCT).

Patients and Methods:
254 patients who underwent alloSCT at our center between 1994 and 2010 were retrospectively analyzed. 204 patients (80%) had AML (de novo AML: 167 patients, therapy-related AML (tAML), AML evolving from MDS: 37 patients) and were in CR1 (157 patients (77%) or CR>1 (47 patients (23%). 50 patients had MDS (RA/RCMD: 36 patients, RAEB-I: 7 patients, RAEB-II: 9 patients). Median age was 47 years (range: 17–72 years). 223 patients (88%) received peripheral blood stem cells (PBSCs), 31 patients (12%) received bone marrow (BM). Conditioning consisted of standard myeloablative conditioning (MAC) in 134 patients (53%), whereas 120 patients (47%) received reduced intensity conditioning (RIC). 13 patients (5%) had a core-binding factor leukemia (CBF group), 117 patients (46%) were cytogenetically normal (CN group), 79 patients (31%) had an unfavorable risk MK-negative karyotype (MK– group), 26 patients (10%) had a highly unfavorable MK-positive (MK+ group). In 19 patients (8%) the karyotype was unknown/not evaluable.

Results:
After a median follow-up of 51 months (range: 3–191 months) for the surviving patients, 134 patients (53%) are alive and in remission. Causes of death were relapse in 53 patients (21%) or NRM in 58 patients (23%). At 1, 3 or 5 years projected OS (DFS) was 70±6% (66±6%), 57±6% (56±6%) or 54±7% (54±7%). At 3 years patients in the MK+ group had a statistically significantly lower OS (DFS) of 29% (29%) as opposed to 52% (52%) in the MK– group, 68% (66%) in the CN group, or 67% (55%) in the CBF-group (p<0.001). Likewise, the probability or relapse was highest in the MK+ group (72%) as compared to the MK- group (37%), the CN group (24%), or the CBF group (14%) (OS: p=0.001, DFS: p=0.003). There was no statistically significant difference in non-relapse mortality between the four groups.

Conclusions:
These data indicate that karyotypic abnormalities remain the most important prognostic factors predicting the outcome of patients with AML or MDS. In particular, the presence of a monosomal karyotype provides a strong negative prognostic prediction for these patients undergoing alloSCT. Therefore, our data suggest that these patients should be referred to alloSCT in CR (AML) or early stage disease (MDS).

Disclosures:
No relevant conflicts of interest to declare.