修订的国际分期系统（R-ISS）对初诊多发性骨髓瘤患者预后评估价值及局限性

  目的  探讨修订的国际分期系统（revised international staging system，R-ISS）在真实世界中对初诊多发性骨髓瘤（multiplemyeloma，MM）患者预后评估价值及局限性。  方法  回顾性分析2002年6月至2017年11月中国医学科学院血液病医院新诊断的568例MM患者临床资料。所有患者均接受基于硼替佐米或沙利度胺/来那度胺为主的方案诱导治疗≥4个疗程。以ISS分期为对照，分析R-ISS分期的预后意义。考虑到R-ISSⅡ期的MM患者之间存在较大的异质性，本研究将R-ISSⅡ期患者分成四组:第1组患者ISSⅠ期伴有乳酸脱氢酶（lactate dehydrogenase，LDH）水平升高或高危遗传学异常；第2组患者ISSⅡ期无LDH水平升高及高危遗传学异常；第3组患者ISSⅡ期伴有LDH水平升高或高危遗传学异常；第4组患者ISSⅢ期无LDH水平升高和高危遗传学异常。在此分组条件下对这部分患者进行生存分析。  结果  568例MM患者中，男性347例，女性221例，中位发病年龄56（25~83）岁，中位随访33（4~203）个月。采用R-ISS分期，Ⅰ、Ⅱ、Ⅲ期患者分别为59例（12%）、310例（62%）、130例（26%），中位总体生存（median overall survival，mOS）时间分别为142、86和40个月（χ2=29.588，P < 0.001）；采用ISS分期，Ⅰ、Ⅱ和Ⅲ期患者分别为106例（19%）、210例（37%）和252例（44%），mOS时间分别为142、71和40个月（χ2=22.099，P < 0.001）。采用Cox回归分析，ISS分期Ⅲ期对Ⅰ期HR=2.903，P < 0.001，ISS分期Ⅱ期对Ⅰ期HR=1.985，P=0.005；而R-ISS分期Ⅲ期对Ⅰ期HR=5.441，P < 0.001，R-ISS分期Ⅱ期对Ⅰ期HR=2.844，P=0.003。R-ISS分期Ⅱ期的4组患者的mOS时间分别为126、83、49（95%CI:33~65）、65（95%CI:44~86）个月（P=0.131）。总体上，四组OS无显著性差异，但是第2组和第3组OS相比呈显著性差异（χ2=4.916，P=0.027）。  结论  R-ISS分期相对于ISS分期能够更好地区分MM患者预后。对于有髓外浸润、有1q21扩增、不同年龄分组（年龄≥65岁和年龄 < 65岁）、不同治疗方案（硼替佐米治疗组及沙利度胺治疗组）、不同染色体倍数（低二倍体、非低二倍体）的患者OS均具有较高的预后判断价值。但R-ISS分期同为Ⅱ期患者的生存情况仍存在差异，需要临床上予以重视。      

203例慢性淋巴细胞白血病患者预后相关因素分析

Objective To explore prognostic factors in patients with chronic lymphocytic leukemia (CLL). Methods Two hundred and three CLL patients in our hospital between 2000 to 2007 were retro-spectively reviewed for prognostic factor analysis. Survival was analysed by Kaplan-Meier analysis, univariate analysis by Log-rank test and multivariate analysis by COX regression model. Results With a median follow-up time of 48.0 (3.0 - 156.0) months, the 5-year overall survival (OS) rate was (87.3 ± 2.4) % and 10-year OS rate was (77.4 ± 3.3) %. Forty-eight (23.6%) patients died. Univariate analysis indicated that ad-vanced clinical stage, B symptoms, extranodal involvement, number of lymph node regions involved ≥3, en-larged liver, Hb < 100 g/L, BPC < 100 × 109/L, absolute lymphocyte count (ALC) > 50 × 109/L, atypical cell morphology, progression to stage, non-respons to treatment, complicating infections and secondary cancer or disease transformation were associated with poor prognosis. And on multivariate analysis, lymph node re-gion involvod≥3 and atypical cell morphology were independent poor prognostic factors. Based on the two in-dependent poor prognostic factors, three risk groups were defined: low- (0 factor), intermediate-(one factor) and high-(two factors) groups. The 5 year OS rates were (89.8 ± 3.5) % , (66.4 ～ 7.2) % and (15.0 ±13.8)%, respectively, and the difference between them was statistically. Conclusion The number of lymph node region involved and cell morphology are useful for assessing CLL patients prognosis.     

203例慢性淋巴细胞白血病患者预后相关因素分析

Objective To explore prognostic factors in patients with chronic lymphocytic leukemia (CLL). Methods Two hundred and three CLL patients in our hospital between 2000 to 2007 were retro-spectively reviewed for prognostic factor analysis. Survival was analysed by Kaplan-Meier analysis, univariate analysis by Log-rank test and multivariate analysis by COX regression model. Results With a median follow-up time of 48.0 (3.0 - 156.0) months, the 5-year overall survival (OS) rate was (87.3 ± 2.4) % and 10-year OS rate was (77.4 ± 3.3) %. Forty-eight (23.6%) patients died. Univariate analysis indicated that ad-vanced clinical stage, B symptoms, extranodal involvement, number of lymph node regions involved ≥3, en-larged liver, Hb < 100 g/L, BPC < 100 × 109/L, absolute lymphocyte count (ALC) > 50 × 109/L, atypical cell morphology, progression to stage, non-respons to treatment, complicating infections and secondary cancer or disease transformation were associated with poor prognosis. And on multivariate analysis, lymph node re-gion involvod≥3 and atypical cell morphology were independent poor prognostic factors. Based on the two in-dependent poor prognostic factors, three risk groups were defined: low- (0 factor), intermediate-(one factor) and high-(two factors) groups. The 5 year OS rates were (89.8 ± 3.5) % , (66.4 ～ 7.2) % and (15.0 ±13.8)%, respectively, and the difference between them was statistically. Conclusion The number of lymph node region involved and cell morphology are useful for assessing CLL patients prognosis.     

硼替佐米为主的联合化疗方案加或不加造血干细胞移植治疗多发性骨髓瘤疗效分析

目的 观察以硼替佐米为主的联合化疗方案加或不加造血干细胞移植(SCT)治疗多发性骨髓瘤(multiple myeloma,MM)患者的疗效及不良反应.方法 31例初治或复发(难治)MM患者接受硼替佐米为主治疗.之后有6例患者接受SCT治疗.按照EBMT标准评价疗效,WHO标准判断不良反应.结果 ①有5例患者由于急性肾功能衰竭、肿瘤溶解综合征等原因终止治疗,其中3例死亡.可以统计疗效的26例患者共完成了99个疗程的治疗,总有效率(ORR)为80.8%.15例初治患者的ORR为100.0%.11例复发(难治)患者的ORR为54.6%.②15例初治患者中有7例完成了8个疗程的治疗,动态观察发现随着疗程的延长疗效不断提高.③6例初治患者化疗达完全缓解(CR)或接近CR(mCR)后行SCT治疗,其中1例复发,5例随访至移植后6～11个月仍持续CR.未采取SCT巩固的9例初治患者中除1例持续CR外有6例在停药后1～3个月复发或进展,2例失访.④多数治疗相关不良反应为l～2级,有3例患者因为末梢神经炎、窦性心动过缓等原因降低硼替佐米的用量,5例因严重不良反应终止治疗.结论 硼替佐米治疗初治及复发(难治)MM疗效肯定,但可能需要进行巩固治疗(如SCT)以维持疗效.硼替佐米不良反应多数轻微且可以耐受,但也应注意少见的严重不良反应.     

急性白血病诱导化疗合并院内感染100例临床分析

急性白血病诱导化疗合并院内感染１００例临床分析中国医学科学院血液学研究所血液病医院（３０００２０）薛艳萍卞寿庚赵耀中周世勇魏晓溪陈玉梅急性白血病（ＡＬ）诱导治疗中的两大死亡原因是出血和感染，特别是院内感染是影响ＡＬ疗效及生存期的一大问题。现将我院住院...     

增生性瘢痕组织中肿瘤坏死因子α R1 mRNA的表达及意义

目的：从基因水平探讨肿瘤坏死因子受体(TNF-α R1)在增生性瘢痕组织发生、发展过程中的作用，为增生性瘢痕的基因治疗探索一条有效途径。方法：以正常瘢痕为对照，利用RT-PCR技术检测1年以上增生性瘢痕组织成纤维细胞中TNF-α R1 mRNA的表达情况。结果：1年以上增生性瘢痕组织中TNF-α R1 mRNA的表达稳定，与正常瘢痕比较含量明显下降。结论：增生性瘢痕的形成与TNF-α R1的表达低下有一定关系。用基因治疗的方法提高早期增生性瘢痕中TNF-α的含量或者提高靶细胞膜上TNF-α R1的数目与活性可能为增生性瘢痕的康复治疗的有效途径。     

三氧化二砷联合全反式维甲酸治疗急性早幼粒细胞白血病的初步观察

目的　观察三氧化二砷 (As2 O3 )联合全反式维甲酸 (ATRA)治疗急性早幼粒细胞白血病(APL)的疗效和不良反应。方法　As2 O3 联合ATRA治疗初治和复发APL患者 2 0例 (可评价的患者 18例 )。治疗方法如下 :As2 O3 (0 .1%溶液 ) 10ml加入 5 0g L葡萄糖溶液 5 0 0ml静脉点滴 ,持续 4～ 6h ,1次 d ;ATRA 2 5mg·m- 2 ·d- 1 ,分 2～ 3次服用。结果　 17例患者获得完全缓解 (CR) ,CR率 94.4%。 14例初治患者均获得CR ,4例复发患者中 3例取得CR。均在 30d内达CR。没有发现明显的不良反应。结论　ATRA联合As2 O3 治疗APL患者不仅能获得好的疗效 ,而且能缩短达CR的时间。     

急性早幼粒细胞白血病170例长期生存分析

本研究探讨影响急性早幼粒细胞白血病(APL)患者长期生存的预后因素。在回顾性分析了1990年1月至2004年12月本院170例APL患者的临床资料后,应用Log-Rank检验和Cox回归模型对170例患者的性别、年龄、初诊时白细胞(WBC)计数、血清乳酸脱氢酶水平、诱导缓解方案、获得缓解时间、缓解后治疗方案、PML/RARα阳性率进行单因素和多因素综合分析。结果表明:170例患者中位随访36个月(6-185个月),5年预计总体生存率(OS)为(80.9±4.0)%,5年预计无复发生存率(RFS)为(71.0±4.0)%。23例患者于中位缓解后15个月(6-70个月)复发。单因素分析显示,初诊时WBC计数、诱导缓解方案、获得缓解时间、缓解后治疗方案、PML/RARα阳性率均为影响APL患者长期生存的主要因素;多因素分析显示,缓解后治疗方案是影响APL患者长期生存的重要的独立因素。结论:在APL患者获得完全缓解后,应用化疗+维甲酸+砷剂的缓解后治疗方案将显著延长患者的生存时间。     

43例淋巴母细胞淋巴瘤患者临床特点及疗效分析

Objective To investigate the clinical features and treatment outcomes of different regimens in Chinese patients with lymphoblastic lymphoma(LBL). Methods Forty-three patients with LBL were retrospectively analysed, of which 30 were T-LBL, and 13 B-LBL. Results ①Most patients were young men with a median age of 21, and 63.0％ of the T-LBL patients had mediastinal masses. ② Treatment outcome could be assessed in 37 cases, of which the response rate (RR) was 81.1％ and complete remission (CR) rate was 67.6％. The RR and CR rates in patients treated with regimens for ALL (ALL-like group) and those treated with regimens for NHL(NHL-like group) were 94.4％ , 68.4％ and 83.3％ , 52.6％ , respectively. ③The estimated median overal survival(OS) and progression free survival (PFS) of hematopoietic stem cell transplantation (HSCT) group were significant longer than those of ALL-like group(P =0.018, P=0.025) and NHL-like group(P = 0. 016, P = 0. 011). The OS at 5 years in NHL-like group, ALL-like group and HSCT group were (14.4 ± 9.4) ％ , (20.2 ± 12.7) ％ and (79.5 ± 13.1) ％, respectively. Conclusion ①LBL is more common in young men, with less involvement of peripheral blood. Compared with B-LBL, T-LBL often has a mediastinal mass and serious cavity effusion. ② Intensive treatment regimens for ALL should be used in LBL. HSCT at CR1 can improve outcome obviously.     

206例多发性骨髓瘤患者不同方案疗效分析

目的　探讨不同化疗方案对多发性骨髓瘤(MM)患者的治疗效果。方法　回顾性分析了206例MM患者的治疗情况,对不同治疗方案的疗效进行比较。结果　200例药物治疗患者的中位生存期为30. 5个月, 3年和5年实际生存率分别为32. 01%和15. 8%。195例行常规化疗患者的总有效率为45. 6%,其中完全缓解率14. 9% (29例),部分缓解率30. 8% ( 60例)。联合化疗组的总有效率为50. 3%,明显高于MP(马法兰和泼尼松)方案组的总有效率(30. 4% ) (P<0. 05);这两组的中位生存期分别为30. 5个月和30. 0个月、3年和5年生存率分别为35. 0%和22. 0%, 16. 7%和13. 2%,差异无统计学意义(P值均>0. 05)。合并干扰素治疗组的有效率为53. 6% ,中位生存期52. 0个月,与未用干扰素治疗组(分别为34. 4%, 27. 0个月)相比,有效率提高(P<0. 05)、生存期延长(P<0. 01)。合并沙利度胺治疗的总有效率为65. 5%。6例外周血造血干细胞移植患者有5例存活,平均生存期为(73. 0±12. 5)个月。结论　联合化疗的有效率高于MP方案,但两组的总生存率差异无统计学意义。干扰素能使化疗有效率增加,中位生存期延长。沙利度胺也能够提高MM患者的治疗有效率。对于年龄较轻、一般状态较好的患者,自体干细胞移植可明显提高生存期。