| ObjectTo describe the prevalence and spectrum of chromosome 1 abnormality in adult patients with primary mylodysplastic syndromes (MDS) and investigate clinical features and prognostic implications of these abnormalities.MethodsClinical and cytogenetic data from 787 primary MDS patients diagnosed between January,2001 and April,2014, for whom complete cytogenetics were available, were retrospectively analyzed. Comparisons between continuous variables were performed using the Mann-Whitney U-test. Comparisons between categorical variables were performed using χ2 tests. Kaplan-Meier method and Log-rank test were used to evaluate factors that influence the prognosis.Results1. Among 428 patients (54%) with karyotypic abnormalities,50 patients displayed chromosome 1 abnormalities, including 2 (4%) with copy number changes alone,29 (58%) with structural abnormalities alone, and 19(38%) with both of these changes. In addition, among the 50 patients with chromosome 1 abnormalities,22 (44%) showed single abnormality,13(26%) showed double abnormalities and 15(30%) showed complex abnormalities (more than two aberrations). The frequency of single abnormality was higher than that in the MDS patients of western countries (19%), on the other hand, the frequency of complex abnormalities was lower than that in western countries (59%). Chromosome 1 abnormality were usually accompanied by other chromosomal abnormalities, among which chromosome 8,7,5,20 and 12 were most common.2. Among 50 patients with chromosome 1 abnormalities, duplication of long arm of chromosome 1 dup (1q) was detected in 13 subjects (26%), unbalanced translocation of long arm of chromosome 1 der(1; var)(q;v)was detected in 12 subjects (24%), balanced translocation of chromosome 1 t(1; var) was detected in 7 subjects (14%), deletion of long arm of chromosome 1 del(1q) was detected in 5 subjects (10%) and other abnormalities of chromosome 1 was detected in 15 subjects (34%) (1 subject showed three different chromosome 1 abnormalities and 2 subjects showed two different chromosome 1 abnormalities at the same). Among 50 patients with chromosome 1 abnormalities, dup(lq) and der(l;var)(q;v) were most frequent, while t(1;var) (28%) was mainly seen in western countries.3. Compared with patients without chromosome 1 abnormalities, patients with chromosome 1 abnormalities were more likely to have complex karyotype (31% vs 11%, P<0.001)and to be higher-risk patients according to the Revised International Prognostic Scoring System(62% vs 38%, P=0.001), however, there was no significant difference in overall survival (Median survival 30 months[95%CI,7.347-52.654 months]vs.48months[95%CI,37.496-58.504 months], P=0.178). The prognosis of MDS patients with chromosome 1 abnormalities was heterogeneous. The patients with del(lq) and der(1;7) 1q whole-arm trisomy had unfavorable prognosis, but patients with non-der(1;7) 1q whole-arm trisomy had better prognosis.ConclusionCompared with MDS patients of western countries, MDS patients with chromosomal 1 abnormalities in our country showed unique cytogenetical features. The prognosis of MDS patients with chromosome 1 abnormalities was heterogeneous. The patients with del(1q) and der(1;7) 1q whole-arm trisomy had poor prognosis, but patients with non-der(1;7) 1q trisomy had better prognosis.Background and objectiveA monosomal karyotype (MK) correlates with poor survival in patients with acute myeloid leukemia (AML), although whether this is also the case in patients with myelodysplastic syndromes (MDS) remains controversial. Some studies report a correlation between a MK and a worse survival, whereas others claim that this correlation arises because of a confounding effect between a MK and a complex karyotype (CK). We aimed to investigate the clinical characteristic and prognostic value of MK in patients with MDS.Methods610 primary MDS patients between January,2001 and December,2012 with evaluable karyotype were retrospectively analyzed. Comparisons between continuous variables were performed using the Mann-Whitney U-test. Comparisons between categorical variables were performed using χ2 tests. Kaplan-Meier method, Log-rank test and COX regression model were used to evaluate factors that influence the prognosis.Results1. A total of 350 patients (57.4%) demonstrated an abnormal karyotype, of which 60 had a MK, representing 9.8% of all patients and 17.1% of patients with an abnormal karyotype. A CK was found in 85 patients, representing 13.9% of all patients and 24.3% of patients with an abnormal karyotype. In addition,55 out of the 60 patients with a MK (91.7%) also had a CK, whereas 55 out of 85 patients with a CK (64.7%) also had a MK.2. Compared with patients without a MK, patients with a MK were significantly older (median age 56 vs 48 y; P=0.007), had lower blood platelet levels (median 43 vs 67×109/L; P=0.010) and higher proportion of bone marrow blasts (median 7 vs 3%;P＜0.001). The distribution of gender (P=0.037), CK (P＜0.001), WHO 2008 subtypes (P＜0.001), IPSS-R risk cohorts (P<0.001) and WPSS risk cohorts (P＜0.001) was also significantly different between subjects with and without aMK.3. To determine the impact of a MK on survival,464 patients who received non-intensive therapies for MDS were analyzed separately. In univariate analyses, patients with a MK demonstrated poorer survival as compared to patients without a MK (median,8 months [95% CI,3-12 months] vs.83 months [95%CI,63-103 months]; P< 0.001). Patients with a CK also demonstrated poorer survival (median, 14 months [95% CI,10-18 months]) than patients without a CK (83 months [95%CI, 65-101 months];P＜0.001). Other significant predictors of survival in univariate analyses were age (P＜0.001), blood neutrophil counts (P＜0.003), proportion of bone marrow blasts (P＜0.001), serum ferritin (P＜0.007), IPSS-R risk cohorts (P＜0.001), and WPSS risk cohorts (P＜0.001). In multivariate analyses, MK (not CK) was an unfavorable prognostic factor independent of IPSS-R and WPSS (HR [hazard ratio] 3.256[95%CI,1.517-6.988]; P=0.002 and 2.92 [95%CI,1.052-8.104]; P=0.040, respectively). This effect was observed predominately in the cohorts of higher-risk patients according to the IPSS-R and WPSS (HR [hazard ratio] 3.94 [95%CI, 1.97-7.89];P＜0.001 and 4.937 [95%CI,2.45-9.94];P＜0.001, respectively) and MK surpassed the impact of a CK in the final survival models.ConclusionMonosomal karyotype was an independent unfavorable prognostic factor adjusted for IPSS-R and WPSS in patients with MDS. The addition of monosomal karyotype as a binary variable could improve the predictive accuracy of current models to estimate the survival of patients with MDS. |
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