Abstract
Allogeneic stem cell transplantation (alloSCT) is a highly effective treatment for patients (pts) with acute myeloid leukemia (AML). Recently, the presence of a monosomal karyotype was shown to confer to a highly unfavorable prognosis in pts with AML treated with conventional chemotherapy. Therefore, we investigated the prognostic impact of a monosomal karyotype on the outcome of pts with AML following alloSCT. We retrospectively analyzed 153 pts with AML (median age: 45 years, range: 17 – 68 years) who underwent alloSCT in complete remission (CR) at our center between 1994 and 2008. 92 pts (82%) had de novo AML, 27 pts (18%) had therapy-related AML (tAML) or AML evolving from myelodysplastic syndrome. As a stem cell source 131 pts (86%) received peripheral blood stem cells (PBSCs), 22 pts (14%) received bone marrow (BM). Conditioning consisted of standard myeloablative conditioning (MAC) (12 Gy TBI, 2x60mg/kg cyclophosphamide) in 90 pts (59%). 63 pts (41%) received reduced intensity conditioning (RIC) (2x4mg busulfan, 6x30 mg/m2 fludarabine, 4x10mg/kg ATG). 10 pts (7%) had a core-binding factor leukemia (CBF group), 64 pts (41%) were cytogenetically normal (CN group), 19 pts (12%) had an unfavorable risk MK-negative karyotype (MK- group) and 19 pts (12%) had a highly unfavorable MK-positive karyotype (MK+ group) (Breems et al., JCO 26: 4791-4797). After a median follow-up of 58 months (range: 13-176 months) for the surviving pts, 86 pts (56%) are alive and in CR. Causes of death were relapse in 33 pts (22%) or infections/GvHD in 32 pts (22%). At 3 years projected OS was 55%, whereas the probability of relapse or non-relapse mortality (NRM) was 32% or 22% for the whole cohort. At 3 years patients in the MK+ group had a statistically significantly lower overall survival (OS) of 25% as opposed to 49% (MK- group), 66% (CN group), or 67% (CBF-group) (p = 0.01). 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%) (p = 0.001). There was no statistically significant difference in non-relapse mortality between the four groups. Our results indicate that cytogenetics is still one of the most important prognostic factors. In particular, the presence of a monosomal karyotype provides a strong negative prognostic prediction for patients with AML undergoing alloSCT. These patients should be referred to alloSCT in early in CR1.
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