217例成人急性淋巴细胞白血病遗传学特征及其临床预后意义的研究

目的 研究成人急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)的细胞和分子遗传学特征及其临床预后意义.方法 通过常规细胞遗传学、荧光原位杂交、实时定量多聚酶链反应、巢式PCR扩增及测序等技术相结合,对217例成人ALL患者细胞及分子遗传学特征全面分析,并探讨其临床预后意义.结果 成人ALL遗传学异常以t(9;22)(q34;q11)/ BCR-ABL融合基因最常见(56.3％),其次为复杂核型(13.8％),其它异常占29.9％;经荧光原位杂交确诊BCR/ABL融合基因阳性患者中22.4％经常规细胞遗传学检测未发现Ph染色体;遗传学预后分组高危组患者随年龄增大递增;高危组B-ALL亚型高于标危组(98.4％ vs.65.7％,P=0.000),高危组3个月(67.3％ vs.85.1％,P=0.042)、6个月(55.1％vs.80.4％,P=0.008)、12个月(34.0％ vs.59.1％,P=0.017)和24个月(13.0％ vs.36.6％,P=0.010)总生存(overall survival,OS)率均显著低于标危组,中位OS时间高危组(11个月,95％CI:8.0～13.9)比标危组(19个月,95％CI:10.8～27.1)显著缩短(P=0.001).结论 成人ALL具有特征性遗传学异常,本组预后分组对判断患者预后、指导临床正确分层治疗具有一定临床意义.临床上单独应用常规细胞遗传学检测漏诊率高,建议常规细胞遗传学检测、荧光原位杂交技术和分子生物学技术相结合,提高细胞及分子遗传学亚型的正确诊断水平.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

母细胞性浆细胞样树突状细胞瘤

本文报告母细胞性浆细胞样树突状细胞瘤(BPDCN)1例。患者男,70岁。反复皮肤瘙痒伴红斑结节1年。皮损组织病理:瘤细胞在真皮内密集,呈结节、团块状浸润,核深染,形态不规则,可见病理性核分裂象。免疫组化:CD4、CD56、CD123、CD43、CD45RA均阳性。骨髓涂片:骨髓增生明显活跃,异常细胞占72.8%,骨髓流式免疫分型:人白细胞DR抗原(HLA-DR):98.6%,CD56:82.3%,CD38:83%,CD4:92%和CD123:94.6%。该文对BPDCN的诊断、鉴别诊断和治疗进行讨论,揭示该病呈高度侵袭性,预后差,生存期短。     

骨髓微环境对多发性骨髓瘤细胞microRNA-21和microRNA-30b表达的影响

目的 研究骨髓微环境对多发性骨髓瘤(MM)细胞mieroRNA(miR)-21和miR-30b的调变作用.方法培养破骨细胞,采用MACS法分选纯化CD138*骨髓瘤细胞.采用实时定量PCR的方法检测MM患者瘤细胞和细胞株以及与破骨细胞共培养的MM患者瘤细胞miR-21和miR-30b的表达量.结果 MM患者的外周血单个核细胞经破骨细胞培养基培养后10～14 d形成破骨细胞,瘤细胞与破骨细胞共培养组和未与破骨细胞共培养组相比较,细胞活力明显增高,miR-21的表达量增高了1.3～5.9倍,miR-30b表达量降低27.5%～76.9%.在正常浆细胞、MM患者瘤细胞和MM细胞株,miR-21表达水平分别为1.9±0.8、6.5±4.9和35.1±36.2,而miR-30表达分别为13.6±1.8、7.2±6.3和4.5±1.9.结论骨髓微环境可调控miR-21和miR-30b的表达,miR-21起癌基因作用,而miR-30b起抑痛基因作用.     

氟达拉滨和环磷酰胺联合利妥昔单抗治疗慢性淋巴细胞白血病疗效分析

目的 探讨氟达拉滨和环磷酰胺联合利妥昔单抗(FCR方案)治疗慢性淋巴细胞白血病(CLL)的效果.方法 采用FCR方案治疗21例CLL患者,其中10例为初治患者,11例为复治患者.FCR方案为氟达拉滨25 mg/m2,第2～4天,静脉滴注;环磷酰胺250 mg/m2,第2～4天,静脉滴注;利妥昔单抗375 mg/m2,第1天,静脉滴注.每28 d为1个疗程.采用多参数流式细胞术(FCM)检测微量残留病(MRD).同时对治疗前临床特点与完全缓解(CR)率行相关性分析.结果 11例(52.4%)患者获得CR,7例(33.3%)获得部分缓解,总有效率为85.7%;中位随访时间19(7～73)个月,总生存率为86.0%,无进展生存率为72.0%.单变量分析表明治疗前Binet分期为A+B、免疫球蛋白重链可变区基因有突变或ZAP-70阳性细胞率≤20%与高CR率相关;6例患者化疗后MRD低于1%.FCR方案的不良反应主要表现为骨髓抑制和胃肠道反应.结论 FCR方案对CLL的治疗有确切疗效.

Abstract：

Objective To evaluate the efficacy of combination chemoimmunotherapy of fludarabine,cyclophosphamide and rituximab (FCR) in chronic lymphocytic leukemia (CLL). Methods Twenty-one patients with CLL were treated with FCR regimen which consisted of fludarabine (25 mg/m2, days 2 to 4),cyclophosphamide (250 mg/m2, days 2 to 4) and rituximab ( 375 mg/m2, day 1 ) in a course of 28 days.The minimal residual disease (MRD) was determined by multiparameter flow cytometry. The correlation between the pretreatment characteristics and complete remission (CR) rate was analyzed. Results Eleven patients (52.4%) achieved CR, 7 (33.3%) achieved partial remission (PR) with a overall response (OR)rate of 85.7%. With a median follow-up time of 19 (7 -73 ) months, the overall survival (OS) was 86.0%,and the progression-free survival (PFS) was 72.0%. Pretreatment parameters independently associated with higher CR rates were Binet stage A + B, IgVH mutated and ZAP-70 less than 20%. MRD was less than 1% in 6 patients. The most common toxicities were myelosuppression and gastrointestinal reaction. Conclusion FCR is an effective regimen for CLL patients.     

典型与不典型免疫表型慢性淋巴细胞白血病的预后相关因素分析

Objective To analyze the proguostic factors for chronic lymphocytic leukemia (CLL) with typical and atypical immunophenotype. The parameters analyzed included sex, age, Binet stages, abso-lute lymphocyte count (ALC), immunoglobulin heavy-chain variable region (IgVH) gene mutation status, ZAP-70 protein, CD38 expression and cytogenetic aberrations. Methods According to the clinical guideline and scoring system for CLL in Britain, among 77 patients, 61 patients with score 5 called typical immunophe-notype CLL, 16 with score 4 or 3 were atypical immunophenotype CI,L. Multiparameter flow cytometry was employed for immunophenotypic analysis in 77 CLL patients for CD5, CD19, CD23, FMC7, slg, CD20, CD79h expression and ZAP-70 protein and CD38. IgVH mutation status was detected by multiplex RT-PCR and sequencing of the purified PCR amplification products. Fluorescence in situ hybridization (FISH) and a panel of probes were used to detect cytogenetic aberrations. Results There was no significant difference be-tween the two groups in sex, age, ZAP-70 and IgVH mutation status (P =0.398, P =0. 189, P =0.268 and P =0. 131, respectively). The incidence of ALC≥50 × 109/L, Binet B + C, CD38 ≥30% in atypical CLL patients(43.8%, 87.5% and 43.8%, respectively) were higher than that in typical group (16.4%, 36.1% and 16.4%, respectively) (P = 0. 026, P < 0. 01 and P = 0. 026, respectively). The proportion of typical patients (26. 8%) with a 13q14 deletion as sole abnormality was higher than that of atypical patients (7.6%), and that with deletion of 11q22 or 17p13 was lower than that of atypical patients (12.2% vs 46.2%) (P = 0. 022). Conclusion There were obvious differences between the typical immunophenotype CLL and atypical CLL in ALC, Binet stages, CD38 expression level and cytogenetic aberrations.     

慢性NK细胞增多症伴嗜血细胞综合征一例报告附文献复习

慢性NK细胞增多症(Chronic NK-cell lymphocytosis.CNKL)是起源于成熟NK细胞系的罕见恶性淋巴细胞增殖性疾病,作为WHO关于淋巴造血组织肿瘤分类中极少见的类型.关于CNKL的诊断目前争议颇多.我们报道1例CNKL伴嗜血细胞综合征患者,并结合文献进行讨论.     

伴显著淋巴结腺体肿大的inv(16)AML一例

为了探讨伴inv（16）急性髓细胞白血病（AML）预后的异质性，本研究报道1例伴有显著淋巴结腺体肿大inv（16）AML的诊治经过，并对相关的问题进行了讨论。结果显示：患者男，13岁，确诊M4Eo伴inv（16），并全身显著淋巴结肿大，予以大剂量阿糖胞苷（HDAC）的方案化疗。荧光原位杂交（FISH）技术监测疗效显示患者对HDAC反应不敏感。结论：伴有淋巴结腺体肿大的inv（16）AML对HDAC反应不敏感，预后较不伴淋巴结腺体肿大者差。inv（16）AML预后存在异质性。FISH技术是准确可靠的inv（16）检测手段，可用于监测inv（16）的微小残留病灶。     

29例慢性淋巴细胞白血病Ki-67和Bcl-2的表达及临床意义

为了观察Ki-67抗原和抗凋亡蛋白Bcl-2在慢性淋巴细胞白血病（CLL）中的表达,探讨其与CLL疾病分期和预后的关系,用链霉菌抗生物素蛋白-碱性磷酸酶（SAP）免疫组织化学染色的方法,对29例CLL患者的骨髓或外周血的增殖相关抗原Ki-67和抗凋亡蛋白Bcl-2进行检测.结果显示：Ki-67抗原在晚期CLL中的表达较早期CLL中的表达高,且差异有显著性;Bcl-2蛋白在晚期CLL中的表达也高于早期CLL中的表达,但差异无显著性;高Ki-67表达组的活存期比低表达组的活存期短,且有显著性差异,而Bcl-2的表达在两组之间无差异.结论：对CLL患者进行增殖相关抗原Ki-67和抗凋亡蛋白Bcl-2的检测,其结果能反映患者肿瘤细胞的增殖活性和凋亡受抑的情况;Ki-67与CLL疾病分期和预后密切相关.