Abstract
Abstract 2028
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).
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.
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.
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).
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
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