Allogeneic Stem Cell Transplantation for Secondary or Therapy-Related Acute Myeloid Leukemia or Myelodysplastic Syndrome with Poor-Risk Cytogenetics.

Allogeneic stem cell transplantation (alloSCT) represents a curative treatment option for the post-remission therapy of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The presence or absence of distinct karyotypic abnormalities has a substantial impact on the risk of relapse and overall outcome. In particular, complex, i.e. ≥3, chromosomal aberrations are associated with a poor outcome.

We retrospectively analyzed 91 patients (47 female, 44 male) with secondary AML or therapy-related AML (n=50; CR1: n=22, CR>1: n=2, no CR: n=24) or MDS (n=41; RA/RCMD: n=14, RAEB-1: n=11, RAEB-2: n=16) who underwent alloSCT at our center between 1995 and 2008. An intermediate-risk karyotype was present in 47 patients, whereas 38 patients had a poor-risk karyotype. Among those, 22 patients had aberrations of chromosome 5 and/or 7. 45 patients were treated with standard myeloablative conditioning (MAC) (12 Gy total body irradiation, 2×60 mg/kg cyclophosphamide) prior to alloSCT, whereas 46 patients received reduced intensity conditioning (RIC) (fludarabine 6×30 mg/m2, busulfan 2×4 mg/kg, anti-thymocyte globulin 4×10 mg/kg). 35 patients had a matched-related donor (MRD) and 37 or 13 patients had a matched-unrelated (MUD) or a mismatched-unrelated (MMUD) donor.

After a median follow-up of 58 (12-170) months, 42/91 patients (46%) are alive and in CR. 20/91 patients (22%) succumbed to relapse and 27/91 patients (30%) died from treatment-related mortality (TRM). Projected OS (DFS) at 1, 3, or 5 years was 60% (55%), 52% (53%), or 50% (48%) and TRM was 27%, 27%, or 31%. Patients with a poor-risk cytogenetic profile had a significantly lower DFS as compared to patients with an intermediate-risk cytogenetics, i.e. 57% versus 36% at 5 years (p=0.04). However, within the group of patients with a poor-risk karyotype, those with aberrations of chromosome 5 and/or 7 had significantly lower OS (30% versus 50% at 5 years; p=0.03), or DFS (26% versus 50%; p=0.01) as compared to patients with complex aberrations. In contrast, the OS of patients with complex chromosomal aberrations excluding those who have chromosome 5 and/or 7 aberrations had a similar OS, DFS, or probability of relapse as compared to patients with an intermediate risk karyotype. Of note, in this subgroup there was no statistically significant difference in OS or DFS between patients conditioned with either standard MAC or RIC. Likewise, there was no statistically significant difference between patients transplanted from a MRD or a MUD.

Taken together, these results indicate that the presence of a poor-risk karyotype has a substantial prognostic impact in patients with secondary AML, therapy-related AML or MDS undergoing alloSCT. In particular, patients with aberrations of chromosome 5 and/or 7 are highest risk of relapse. Nonetheless, a substantial proportion of these patients may achieve durable remissions following either standard or RIC-alloSCT.

No relevant conflicts of interest to declare.