Monosomal Karyotype Predicts Poor Outcome for MDS/sAML Patients with Chromosome 7 Abnormalities After Allogeneic Stem Cell Transplantation for MDS/sAML. A Study of the MDS Subcommittee of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

High-risk MDS/sAML patients have a poor prognosis with conventional therapies. One constant factor predisposing for high risk is the presence of a chromosome 7 abnormality. It is common practice that patients with a chromosome 7 abnormality and other factors that classify them as high-risk are offered allogeneic SCT (alloSCT) as it is believed that this treatment has curative potential. Data on the effect of this approach in these patients are scarce.

The EBMT database was searched for MDS/sAML patients having any chromosome 7 abnormalities and were treated with alloSCT. 278 patients who underwent alloSCT between 1981 and November 2006 were included. Stem cells from related donors were transplanted in 192 patients (177 HLA-identical) while 85 received unrelated grafts. Bone marrow was used as stem cell source in 148 patients while 126 received blood stem cells. Standard conditioning was applied in 222 patients. Sixty-three patients fulfilled the criterion for having complex cytogenetic abnormalities. A monosomal karyotype (MK), defined as at least one monosomy and at least one other chromosomal abnormality (Breems DA et al., JCO 2008;26:4791–7), was present in 63 patients, of whom 23 did not have complex cytogenetic abnormalities.

Median follow-up (FU) of patients alive at last FU was 5 years (range, 0–18 years). Estimate 5–year overall (OS), and relapse-free (RFS) survival was 28±5.5% (see figure) and 26±5.5% respectively. The relapse rate at 3, 12 and 60 months was 9±3%, 29±5% and 39±6% respectively. Non-relapse mortality (NRM) at 3, 12 and 60 months was 21±5%, 36±6% and 40±6% respectively. In multivariate models including age, MK, complex karyotype, blasts at alloSCT, donor type, sex match, conditioning regimen, T-cell depletion and year of alloSCT, a MK highly significantly predicted for extremely poor outcome: the adjusted hazard ratios of MK were for OS 2.4 (95% CI, 1.6 to 3.6), for RFS 2.4 (95% CI, 1.7 to 3.9) and for relapse 3.2 (95% CI, 1.8 to 5.7) (p<0.001 for each endpoint). Five-year OS and RFS for patients with a MK were 0% and 0% compared to 37±7% and 34±7% for patients without MK (p<0.001 for both log rank tests) respectively (see figure). Five-year incidences of relapse and NRM of patients with MK were 52±13% and 48±13% compared to 33±7% and 37±7% for patients without MK (gray tests, p=0.002 and p=0.1).

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This large study of alloSCT for patients with MDS/sAML and any chromosome 7 abnormality shows that long-term survival can be achieved in about 37% of patients without a MK. In contrast, patients with a MK do extremely poor (5-year OS 0%) with standard alloSCT approaches; for these patients new approaches must be explored.

Schetelig:Bayer Schering: Research Funding.