Li B

[CSF3R, ASXL1,SETBP1, JAK2 V617F and CALR mutations in chronic neutrophilic leukemia].

OBJECTIVEnTo observe the CSF3R, ASXL1, SETBP1, JAK2 V617F and CALR mutations in patients with chronic neutrophilic leukemia (CNL).nnnMETHODSnTwelve suspected CNL patients were retrospectively reviewed according the WHO criteria (2008). CSF3R,ASXL1,SETBP1 and CALR mutations were sequenced, and JAK2 V617F was tested by allele specific (AS)-PCR.nnnRESULTSn6 of 12 cases were diagnosed as CML, and all of the 6 carried. 4 of 6 patients also had ASXL1 and SETBP1 mutations and one had a CALR mutation (c.1154-1155insTTGTC). Two patients with monoclonal gammopathy with uncertain significance (MGUS) combined with CNL-like symptoms had no CSF3R, ASXL1, SETBP1, JAK2 V617F or CALR mutation. The same results were also seen in other 4 cases with secondary neutrophilic leukocytosis.nnnCONCLUSIONnCSF3R, ASXL1 and SETBP1 mutations differential diagnosis of CNL, and should be included in the diagnostic protocol so as to improve diagnostic accuracy for CNL.

Prognostic evaluation of comorbidities in patients with myelodysplastic syndrome

目的 探讨合并疾病对骨髓增生异常综合征（MDS）患者预后的影响。 方法 回顾性分析676例连续入组有详细合并疾病评估的MDS患者临床资料并进行统计学分析。 结果 676例患者中395例（58.4%）伴有合并疾病（合并疾病组），281例（41.6%）不伴合并疾病（无合并疾病组）。两组患者≥60岁比例（32.4%对18.5%）、骨髓原始细胞比例中位数[0.035（0~0.190）对0.025（0~0.190）]、染色体核型异常比例（37.5%对35.9%）、分型诊断构成比和修正版国际预后积分系统（IPSS-R）分组比较，差异均有统计学意义（P值均<0.05）。多因素COX分析证实合并疾病为影响患者总生存（OS）的独立预后因素（HR=3.051，95%CI 2.018~4.612，P<0.001）。按MDS特异性合并疾病指数（MDS-CI）评分模型对伴有合并疾病的MDS患者进行危险度分组，低、中、高危患者中位OS时间分别为32（1~153）、19（2~85）、13（1~37）个月，而不伴有合并疾病的患者中位OS时间为96（1~166）个月，差异有统计学意义（P<0.001）。IPSS-R低危、中危及高危组患者根据MDS-CI模型进行再分组，各组患者OS时间比较差异均有统计学意义（P值均<0.01）。 结论 合并疾病是MDS患者独立于IPSS-R之外的预后影响因素。OBJECTIVEnTo discuss the impact of comorbidities on the outcomes of patients with MDS.nnnMETHODSnThe clinical characteristics of 676 MDS patients with detailed comorbidities evaluations was analyzed retrospectively.nnnRESULTSnThere were 395/676 cases (58.4%) with comorbidities (group 1), 281/676 cases (41.6%) without (group 2). Significant differences were seen in the distribution of age (≥ 60 y), bone marrow blasts, abnormal karyotype, WHO 2008 subtypes and IPSS-R risk cohorts (P<0.05) between the two groups. While gender, HGB concentrations, WBC levels, platelet levels and serum ferritin were not significantly different (P>0.05). Independent prognostic significance of comorbidities was seen in both uni-variate and multi-variate analyses (P<0.001). According to MDS-specific comorbidity index (MDS-CI), the median survival were 32(1-153) months, 19(2-85) months and 13(1-37) months in the low-risk, intermediate-risk and high-risk cohorts respectively, while 96(1-166) months in cohorts without any comorbidities, of which significant differences were seen (P<0.001). The MDS-CI allowed further stratification in the IPSS-R low-risk, intermediate-risk and high-risk cohorts (P<0.001).nnnCONCLUSIONnComorbidities provides prognostic stratification independently of IPSS-R for MDS patients.

[Long- term outcome of thalidomide and cyclosporine in patients with IPSS low/intermediate- 1 myelodysplastic syndromes].

OBJECTIVEnTo investigate the long- term outcome of cyclosporin A (CsA) combined with thalidomide regime for Chinese patients with IPSS low/intermediate- 1 myelodysplastic syndromes (MDS) without del（5q）and the predictive variables which could impact the response to the therapy.nnnMETHODSnSeventy-six MDS patients who were treated with these drugs at a single institute in China were retrospectively analyzed. The polymorphism of cereblon gene, rs1672753, was detected in patients of this cohort by PCR and direct sequencing.nnnRESULTSnA total of 53% of patients showed hematological improvement（HI）to the therapy. Thirty-one patients（31/73, 43%）achieved erythrocyte response（HI-E）; 15 patients（15/50, 30%）achieved neutrophil response（HI-N); 18 patients（18/58, 31%）achieved platelet response（HI-P). Twenty-seven of the 50 patients（46%）who were dependent on red blood cell transfusion achieved HI- E and became independent of transfusion. The median duration of response among the responders was 22 months (range, 1- 131 + months). Bone marrow blasts ≤2% was the only factor associated with longer response duration in univariate analysis （P=0.010）. There was no significant difference between the two groups of celeblon gene rs1672753 polymorphism either on the response rate or the response duration. The median survival of 67 patients without stem cell transplantation was 82 months. In multivariate analyses, factors significantly correlated with survival were IPSS-R（HR=3.461, 95%CI 1.126-10.639, P=0.030), age ≥ 60 y（HR=4.120, 95%CI 1.070-15.867, P=0.040）and HI-N（HR=7.733, 95%CI 1.007-59.396, P=0.049).nnnCONCLUSIONnCsA combined with thalidomide regime could improve the anemia symptom in low/int-1 risk MDS patients without del（5q）. The predictive value of cereblon gene polymorphism, rs1672753, could not be verified in this study.目的 评价环孢素（CsA）联合沙利度胺治疗国际预后积分系统（IPSS）低危／中危-1骨髓增生异常综合征（MDS）患者的远期疗效及预后影响因素。 方法 回顾性分析CsA联合沙利度胺治疗的76例IPSS低危／中危-1 MDS患者临床资料。采用PCR联合直接测序法检测患者cereblon基因rs1672753位点基因型。 结果 76例患者中，男48例，女28例，中位年龄41(18~70）岁。CsA联合沙利度胺治疗后，40例（53%）获得血液学改善（HI），其中红系反应（HI-E）率为43%（73例中31例），中性粒细胞反应（HI-N）率为30%（50例中15例），血小板反应（HI-P）率为31%（58例中18例）。59例红细胞输注依赖患者中27例（46%）获得HI-E并脱离输血。HI中位维持时间为22(1~131+）个月。单因素分析显示骨髓原始细胞≤2％的患者疗效持续时间更长（P=0.010）。cereblon基因rs1672753位点基因型与HI率及治疗反应的维持时间均无明显相关性（P值均>0.05）。67例未行造血干细胞移植患者中位生存时间为82（95% CI 38~126）个月。多因素分析显示IPSS-R分组（HR=3.461，95% CI 1.126~10.639，P= 0.030）、年龄≥60岁（HR=4.120，95% CI 1.070~15.867，P=0.040）以及HI-N（HR=7.733，95% CI 1.007~59.396，P=0.049）为影响患者生存时间的独立预后因素。 结论 CsA联合沙利度胺治疗能长期改善IPSS低危／中危-1 MDS患者贫血症状，不良反应轻。在此组患者中未能验证cereblon基因rs1672753位点基因型对疗效的预测价值。

[Comparison of low-dose thalidomide and prednisone combined with or without danazol for the treatment of primary myelofibrosis-associated anemia].

OBJECTIVEnTo observe the clinical effects of low-dose thalidomide (THAL) and prednisone (PRED) with or without danazol (DANA) in patients with primary myelofibrosis (PMF) associated anemia.nnnMETHODSnA cohort of 58 PMF patients with anemia (Hb<100 g/L) were retrospectively studied. Of them, 28 patients were treated with THAL and PRED (THAL-PRED group), and the rest with THAL, PRED and DANA (THAL-PRED-DANA group). The hematological response was assessed according to the modified criteria of the International Working Group in 2006, and the myelofibrosis degree was evaluated at 3 and 12 month after treatment.nnnRESULTSnThe total response rate was 56.9%(33/58) including 1.7% (1/58) partial remission (PR) and 55.2% (32/58) clinical improvement (CI). There was no statistical difference in the response rate between THAL-PRED and THAL-PREDDANA groups (50.0% vs 63.3%, P=0.306). However, the median response duration of clinical improvement, erythroid response (CI-E) and total response prolonged in THAL-PRED-DANA than THALPRED group (61.5w vs 22w, P=0.015; 75w vs 30w, P=0.007, respectively). Myelofibrosis degree at 3 and 12 months after treatment decreased significantly than before treatment (P=0.000 and 0.005, respectively). Side-effects in both groups were only grade 1-2.nnnCONCLUSIONnLow-dose THAL together with PRED appeared to be effective in the treatment of PMF-associated anemia, and the response duration would prolong significantly if combined with DANA.

A study of prognostic value of cytogenetics in patients with primary myelofibrosis

OBJECTIVEnTo evaluate the prognostic value of cytogenetics in Chinese with primary myelofibrosis (PMF).nnnMETHODSnFour hundred and thirty-nine Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, the Log-rank test, the likelihood ratio test and the COX proportional hazards regression model were used to evaluate the prognostic scoring systems.nnnRESULTSnFour hundred and thirty-nine Chinese patients with PMF were analyzed with a median age of 56 years (range: 8-83), including 298 males and 141 females. The DIPSS-plus system could effectively evaluate prognosis in Chinese patients with PMF. There was significantly higher predictive power for survival for the DIPSS-plus group compared with the DIPSS group (P=0.006, -2 log-likelihood ratios of 989.5 and 1001.9 for the DIPSS-plus and DIPSS systems, respectively). Univariate analysis indicated that the patients with a normal karyotype, a complex karyotype that was not a monosomal karyotype, +8 only or a balanced translocation only had better survival. Following two cytogenetic risk categories were constructed: favorable karyotype including subjects with a normal karyotype, a complex karyotype that was not a monosomal karyotype, +8 only or a balanced translocation only and unfavorable karyotype included all others. The modified DIPSS-Chinese prognostic model was proposed by adopting cytogenetic categories and DIPSS- Chinese risk group. The median survival of patients classified in low risk (163 subjects), intermediate-1 risk (187 subjects), intermediate-2 risk (82 subjects) and high risk (7 subjects) were not reached, 74 (95% CI 42-106), 39 (95% CI 26-52) and 12(95% CI 1-25)months, respectively, and there was a statistically significant difference in overall survival among the four risk groups (P<0.01).nnnCONCLUSIONnThe DIPSS-plus had significantly higher predictive power than the DIPSS group in Chinese patients with PMF and the modified DIPSS-Chinese system based on the cytogenetic features of Chinese patients was proposed and worked well for prognostic indication.