柔红霉素治疗小儿急性白血病心脏毒性观察

目的分析柔红霉素治疗小儿急性白血病的心脏毒性。方法纳入收治的小儿急性白血病患儿120例,以随机数字表法分为甲、乙、丙三组各40例,甲组接受小剂量柔红霉素治疗、乙组接受中剂量柔红霉素治疗、丙组接受大剂量柔红霉素治疗,对比三组临床疗效、心肌损害发生率、治疗前后血清硫化氢(H2S)水平。结果 (1)三组临床总有效率相比无明显差异(P0.05)。(2)甲组心肌损害发生率(5.00%)显著低于乙组(17.50%),乙组心肌损害发生率显著低于丙组(30.00%),差异均具有统计学意义(P0.05)。(3)甲组治疗后血清H2S水平显著低于乙组,乙组治疗后血清H2S水平显著低于丙组,差异均具有统计学意义(P0.05)。结论柔红霉素应用于小儿急性白血病治疗中,剂量越小,产生的心脏毒性越小,柔红霉素剂量高低与心脏毒性轻重成正比。     

高三尖杉酯碱、阿糖胞苷、去甲氧柔红霉素联合诱导治疗初治急性髓系白血病临床研究

本研究探讨高三尖杉酯碱(homoharringtonine)、阿糖胞苷(Ara-C)、去甲氧柔红霉素(idambin)组成的联合化疗方案(HAI)治疗初治急性髓系白血病(AML)(除外急性早幼粒细胞白血病)的疗效和安全性.31例初治AML患者接受HAI诱导化疗,统计1个疗程的缓解率、长期生存率及无复发生存率,比较WHO亚型、遗传学及初始白细胞计数等不同预后分组患者疗效,按照WHO抗癌药物不良反应评估标准进行安全性评价.结果表明,26例患者1个疗程后获完全缓解(CR),CR率为84％.染色体核型预后良好组(n=10)、预后中等组(n=16)、预后不良组(n=5)患者1个疗程的CR率分别为90％、88％、60％,组间差异无统计学意义(p=0.28).7例高白细胞数(白细胞计数≥100×109/L)患者均获CR,24例非高白细胞数组患者19例获CR.中位随访期15(2 -56)个月,全部患者3年累积生存率44％.26例CR患者3年累积生存率52％,3年无复发生存率为51％.所有31例患者均完成HAI诱导化疗,无化疗相关死亡病例.在诱导治疗期间所有患者均发生严重骨髓抑制,中性粒细胞绝对值＜0.2×109/L持续的中位时间为16(6 -24)天.31例患者均发生Ⅲ-Ⅳ级严重感染,抑制期中位发热持续时间为6(1 -36)天.败血症发生率为19.4％ (6/31);侵袭性真菌病发生率45.2％( 14/31),Ⅲ-Ⅳ级非血液学毒性反应以发热(非感染性)、谷丙转氨酶升高、腹泻、胆红素升高、口腔炎等最为常见,发生率分别为6.5％、6.5％、3.2％、3.2％、3.2％.结论:HAI方案治疗初治AML疗效肯定,特别是1个疗程的缓解率明显高于DA标准诱导方案.HAI方案安全性较好,除非发生严重感染.     

全反式维甲酸联合高三尖杉酯碱治疗急性早幼粒细胞白血病的临床研究

目的观察全反式维甲酸(ATRA)联合高三尖杉酯碱(HHT)治疗初发急性早幼粒细胞白血病(APL)的疗效和生存情况。方法 ATRA联合HHT治疗初治APL患者75例,观察患者临床特征、疗效及生存情况。结果 58例患者获得完全缓解(CR),CR率77.3%;17例患者诱导失败,其中16例死于诱导治疗早期。在平均36个月的中位随访时间中,分别有2例和3例患者死于巩固和维持治疗阶段。患者预期3年总生存率为71.5%,3年无事件生存率为61.0%,获得CR患者3年无事件生存率为78.9%。结论 ATRA联合HHT治疗初发APL患者疗效好,长期生存率高,且价格经济,是APL治疗的合理选择之一。     

维甲酸联合亚砷酸、小剂量柔红霉素治疗急性早幼粒细胞白血病18例临床护理

目的：探讨维甲酸联合亚砷酸、小剂量柔红霉素治疗急性早幼粒细胞白血病（APL）的效果与护理方法。方法：将34例初治APL患者随机分为两组,维甲酸组16例,给予维甲酸治疗;联合治疗组18例,给予维甲酸、亚砷酸、小剂量柔红霉素治疗。判断两组疗效及毒副作用。结果：联合治疗组完全缓解率94．4％,较单用维甲酸组的62．5％差异有统计学意义（P〈0．05）;获得完全缓解中位时间30d,与单用维甲酸组的58d比较,差异有统计学意义（P〈0．05）。联合治疗组无一例发生高白细胞综合征及维甲酸综合征。结论：维甲酸联合亚砷酸、小剂量柔红霉素治疗APL完全缓解率明显升高,达完全缓解时间明显缩短,维甲酸所致的毒副作用明显减少。     

维甲酸联合亚砷酸、小剂量柔红霉素治疗急性早幼粒细胞白血病18例临床护理

目的:探讨维甲酸联合亚砷酸、小剂量柔红霉素治疗急性早幼粒细胞白血病(APL)的效果与护理方法.方法:将34例初治APL患者随机分为两组,维甲酸组16例,给予维甲酸治疗;联合治疗组18例,给予维甲酸、亚砷酸、小剂量柔红霉素治疗.判断两组疗效及毒副作用.结果:联合治疗组完全缓解率94.4%,较单用维甲酸组的62.5%差异有统计学意义(P<0.05);获得完全缓解中位时间30 d,与单用维甲酸组的58 d比较,差异有统计学意义(P<0.05).联合治疗组无一例发生高白细胞综合征及维甲酸综合征.结论:维甲酸联合亚砷酸、小剂量柔红霉素治疗APL完全缓解率明显升高,达完全缓解时间明显缩短,维甲酸所致的毒副作用明显减少.     

去甲氧柔红霉素治疗成人急性白血病的临床疗效观察

蒽环类药物联合阿糖胞苷是成人急性白血病(AML)诱导治疗的经典方案,在年龄<60岁的青壮年患者中该方案达完全缓解率为70%.笔者采用了改变经典方案中化疗药物结构的方法--脂质体阿霉素代替柔红霉素,治疗AML取得了较好的疗效,现报告如下.     

去甲氧柔红霉素治疗成人急性白血病的临床疗效观察

蒽环类药物联合阿糖胞苷是成人急性白血病（AML）诱导治疗的经典方案,在年龄〈60岁的青壮年患者中该方案达完全缓解率为70％。笔者采用了改变经典方案中化疗药物结构的方法——脂质体阿霉素代替柔红霉素,治疗AML取得了较好的疗效,现报告如下。     

全反式维甲酸和小剂量三尖杉酯碱治疗急性早幼粒细胞白血病的临床观察

目的:观察全反式维甲酸(ATRA)和ATRA加小剂量三尖杉酯碱(LDH)治疗急性早幼粒细胞白血病(APL)的疗效。方法:66例急性早幼粒细胞白血病患者分成A、B两组:A组29例单用ATRA,B组37例ATRA和LDH合用。结果:完全缓解率A组为82.7％,B组为94.4％。两组完全缓解时间分别为39.50d±7.43d和24.12d±3.60d(P<0.001)。高白细胞综合征发生率分别为34.4％和5.5％(P<0.05)。结论:ATRA和LDH联合治疗APL可提高完全缓解率,缩短完全缓解时间,减少高白细胞综合征发生率,降低早期死亡率,因此本方法治疗APL有推广应用价值。     

柔红霉素联合阿糖胞苷对急性白血病患儿免疫功能的影响

目的：探讨注射用盐酸柔红霉素联合注射用盐酸阿糖胞苷对急性白血病患儿免疫功能的影响。方法：选择2022年1～12月医院收治的100例急性白血病患儿,按随机对照原则分组。对照组(50例)接受常规治疗+注射用盐酸柔红霉素(静脉滴注),研究组(50例)在上述基础上另给予患儿注射用盐酸阿糖胞苷(静脉滴注),连续治疗1个月。对比两组临床疗效、免疫功能、血清学指标、生活质量评分(GQOLI-74)、药物不良反应。结果：研究组临床总有效率比对照组高(P<0.05);研究组治疗1个月后CD3⁺、CD4⁺水平与GQOLI-74评分比对照组高,且血清可溶性细胞间黏附分子-1(s ICAM-1)、可溶性血管细胞黏附分子-1(s VCAM-1)水平比对照组低(P<0.05);治疗期间,研究组药物不良反应发生率相比对照组(4.00%vs 10.00%),差异无统计学意义(P>0.05)。结论：注射用盐酸柔红霉素联合注射用盐酸阿糖胞苷对急性白血病患儿的治疗效果确切,其能够调节患儿免疫功能、提高生活质量,还可降低血清s ICAM-1、s VCAM-1水平,...     

抗HCCR单克隆抗体的制备及其鉴定

目的制备抗人宫颈癌癌基因（HCCR）单克隆抗体（mAb）,并进行鉴定。方法以HCCR重组蛋白免疫BALB/c小鼠,取免疫小鼠的脾细胞和同系小鼠的骨髓瘤细胞SP2/0进行细胞融合,常规筛选杂交瘤细胞。腹水诱导法制备抗人HCCR单克隆抗体,并经蛋白A亲合层析进行纯化。用Western blot和免疫荧光等方法检测HCCR mAb的特异性。用纯化HCCR蛋白进行包被,建立间接ELISA方法,检测系列稀释的HCCR mAb,确定其灵敏度。结果筛选出2株分泌抗人HCCR mAb的杂交瘤细胞株。Western blot结果表明抗人HCCR抗体能与HCCR蛋白特异性结合,免疫荧光结果显示肝癌HepG2细胞中胞浆和胞膜均呈阳性染色。间接ELISA方法检测HCCR mAb的灵敏度可达到1μg/L。结论成功制备并鉴定了特异性抗人HCCR mAb的杂交瘤细胞株,为进一步深入研究HCCR的生物学特征和临床应用打下基础。     

Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia.

We studied the pathogenesis of the bleeding disorder in acute promyelocytic leukemia by measuring procoagulant, profibrinolytic, and proinflammatory mediators in peripheral blood and bone marrow cells from 25 previously untreated patients. Patients were induced with either all-trans retinoic acid (ATRA) or chemotherapy. Plasma levels of fibrinopeptide A (FPA), fibrin d-dimer, thrombin antithrombin (TAT) complex, prothrombin fragment 1.2 (F1.2), urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor 1 (PAI-1) were measured before and after therapy, as was the cellular expression of the genes for tissue factor (TF) and interleukin-1 beta (IL-1 beta). The mean plasma levels of fibrin d-dimer, F1.2, TAT and FPA were markedly elevated prior to therapy and declined during the first 30 days of treatment with either ATRA or chemotherapy, but more rapidly and to a greater extent in patients treated with ATRA. ATRA treatment was associated with a significant decrease in TF gene expression in bone marrow cells during the first 30 days of treatment, whereas IL-1 beta gene expression, which decreased in the cells of six patients treated with either chemotherapy or ATRA, actually increased in the remaining six patients treated with either chemotherapy or ATRA. In patients with APL, treatment with either chemotherapy or ATRA rapidly ameliorates the coagulopathy, as indicated by an abrupt decline in markers of clotting activation. An increase in cytokine gene expression (e.g. IL-1 beta) may provide an explanation for the persistent hypercoagulability observed in some patients with APL, regardless of therapeutic approach. Our data confirms and extends earlier observations by others that ATRA is more effective than chemotherapy alone in rapidly reducing the procoagulant burden of APL tumor cells. However, our data also suggests that cytokine expression in some patients may be accelerated by either chemotherapy or ATRA. The implications of this observation for understanding the retinoic acid syndrome will require further studies.     

71例急性早幼粒细胞白血病患者白血病细胞免疫表型分析

本研究通过回顾性分析急性早幼粒细胞白血病(APL)患者骨髓异常早幼粒细胞的免疫表型及患者初诊资料,探讨其免疫表型特点及其意义。利用常规6色免疫分型方法对71例APL患者的白血病细胞进行免疫表型分析。结果发现:MPO、CD33和CD13在所有患者的APL细胞中都有较强表达,其平均阳性细胞比例达到88%以上。CD117的阳性表达率为50.7%,其平均阳性细胞比例为52.5%。约10%患者的白血病细胞表达CD15,但大部分病例的阳性细胞率都集中在20%-40%的弱表达范围内,其平均阳性细胞比例为42.5%。少数患者的异常细胞表达CD34和HLA-DR,且表达强度较弱。约25%患者的APL细胞跨系表达了CD2、CD56,大部分也都集中于20%-60%的低表达范围内,其平均阳性细胞比例分别为39.3%和42.3%。由此认为,APL的典型免疫表型为MPO+CD13+CD33+CD117±CD15±CD34-HLA-DR-。CD2和CD56在CD34+或HLA-DR+组(包括CD34+HLA-DR+、CD34+HLA-DR-和CD34-HLA-DR+)的阳性比例明显高于CD34-和HLA-DR-组。初诊患者外周血白细胞计数、血小板计数、外周血中异常早幼粒细胞比例及CD13的阳性比例在CD15<10%、10%20%3组均出现显著的统计学差异。结论:APL患者的异常早幼粒细胞的免疫表型具有独特的特征,多色流式细胞术检测可辅助APL的快速诊断,对分析白血病细胞的来源和判断患者预后亦可能有着重要意义。     

55例急性早幼粒细胞白血病形态学、细胞免疫学、细胞遗传学及分子生物学(MICM)分型的回顾性分析

为了解在已经确诊的急性早幼粒细胞白血病(APL)患者中骨髓细胞形态学(M)、细胞免疫学(Ⅰ)、细胞遗传学(C)和分子生物学(M)4者即MICM的关系及对临床诊断的指导意义，对55例APL患者的MICM分型检测结果进行了回顾性总结分析。结果显示，以FAB分型为基础的形态学确诊率可达96．4％；免疫表型检测以CD33和CD13阳性共表达率为最高，达96．4％；APL特征性染色体异常检出率为87．3％，其中核型为t(15；17)(q22；q21)100％易位者(单纯型)占75％，其它可累及的染色体有1，8，9，11，12，21号；PML/RARα基因检测阳性率达96．4％。但MICM联合检测用于APL诊断的准确率可达100％。结论：骨髓细胞形态学观察仍然是APL确诊的基础，MICM联合应用可显著提高APL的确诊率，减少误诊率；MICM联合检测，可能为发现APL新的亚型提供线索。     

酷似急性早幼粒细胞白血病表现的髓系/NK细胞急性白血病

为了提高对髓系/NK细胞急性白血病的认识,减少临床误诊,本文报告1例酷似急性早幼粒细胞白血病(APL)表现的髓系/NK细胞急性白血病并结合文献进行分析。对患者进行了一系列临床检查,血细胞形态学和免疫表型分析,以及细胞遗传学和分子生物学等检测。结果表明:患者无肝脾、淋巴结肿大,贫血伴血小板减少,白细胞增高,白血病细胞酷似异常早幼粒细胞尤其是变异型M3(M3v)细胞;免疫表型主要为CD34-、HLA-DR-、CD117+、CD33+、CD13-、CD15+、CD56+、cMPO+和CD16-,伴有del(7)(q22q32)染色体异常,但无t(15;17)改变和PML/RARα融合基因阴性,全反式维甲酸(ATRA)治疗反应不佳。结论:髓系/NK细胞急性白血病临床少见,易与APL尤其是M3v混淆,应采用急性髓系白血病化疗方案进行治疗。     

Role of promyelocytic leukemia (PML) protein in tumor suppression

The promyelocytic leukemia (PML) gene encodes a putative tumor suppressor gene involved in the control of apoptosis, which is fused to the retinoic acid receptor alpha (RARalpha) gene in the vast majority of acute promyelocytic leukemia (APL) patients as a consequence of chromosomal translocations. The PMLRARalpha oncoprotein is thought to antagonize the function of PML through its ability to heterodimerize with and delocalize PML from the nuclear body. In APL, this may be facilitated by the reduction to heterozygosity of the normal PML allele. To determine whether PML acts as a tumor suppressor in vivo and what the consequences of deregulated programmed cell death in leukemia and epithelial cancer pathogenesis are, we crossed PML(-/-) mice with human cathepsin G (hCG)-PMLRARalpha or mammary tumor virus (MMTV)/neu transgenic mice (TM), models of leukemia and breast cancer, respectively. The progressive reduction of the dose of PML resulted in a dramatic increase in the incidence of leukemia, and in an acceleration of leukemia onset in PMLRARalpha TM. By contrast, PML inactivation did not affect neu-induced tumorigenesis. In hemopoietic cells from PMLRARalpha TM, PML inactivation resulted in impaired response to differentiating agents such as RA and vitamin D3 as well as in a marked survival advantage upon proapoptotic stimuli. These results demonstrate that: (a) PML acts in vivo as a tumor suppressor by rendering the cells resistant to proapoptotic and differentiating stimuli; (b) PML haploinsufficiency and the functional impairment of PML by PMLRARalpha are critical events in APL pathogenesis; and (c) aberrant control of programmed cell death plays a differential role in solid tumor and leukemia pathogenesis.     

MLL‐ELL fusion gene in an acute myelomonocytic leukemia patient transformed from acute promyelocytic leukemia

We report an extremely rare case of acute myelomonocytic leukemia (M4) with an MLL‐ELL fusion gene lacking the PML‐RARα rearrangement that transformed from hypergranular acute promyelocytic leukemia (APL) without showing any karyotypic evolution. The treatment was effective with chemotherapy for M4 and idarubicin plus a cytarabine‐based chemotherapy protocol without ATRA.     

221例急性早幼粒细胞白血病免疫表型特点与微小残留病检测及基因标志的关系

本研究探讨急性早幼粒细胞白血病（APL）患者的免疫表型特点与微小残留病（MRD）检测及基因标志之间的关系。采用四色流式细胞术（FCM）分析了221例初诊APL患者的免疫表型,其中87例加做CD123抗体,196例同时运用PCR检测特异融合基因pml-rarer。结果发现：初诊APL患者中CD123、CD33和CD9的阳性表达率分别为100％、99．1％和96．0％,阳性患者中平均阳性细胞比例均在90％左右;虽然CD117、CD13、CD38及CD64的阳性表达率均高于96％,但阳性患者中阳性细胞比例分布不一致,平均阳性细胞比例在70％左右;部分患者表达CD15、CD56和CD11b,多数患者不表达CD34和HLA-DR,阳性患者中阳性细胞的平均比例均较低。196例初诊APL患者中,pml—rara基因的不同转录本bcr1、bcr2和bcr3所占比例分别为63．3％、4．6％和32．1％。bcr3型基因与CD34的阳性表达相关,以20％为界时bcr3和bcr1型中CD34^＋患者的比例分别为15．4％（10／65）和3．3％（4／121）（P〈0．05）;以10％为阳性界限,bcr3和bcr1型中CD34^＋患者的比例分别为47．7％（31／65）和5．8％（7／121）（P〈0．001）;其余抗原的表达无明显区别。APL细胞中CD34为阳性且表现为非高侧向角（NL-SSC）时高度提示基因为bcr3型。结论：APL患者的免疫表型具有独特特征,CD123、CD33和CD9更适用于APL的MRD检测,CD34的阳性表达、NL-SSC与bcr3基因亚型相关,CD34的阳性界限设为10％更能提示基因类型与抗原表达的关系。     

Ofatumumab,a human anti-CD20 monoclonal antibody

Importance of the field: Since relapse of chronic lymphocytic leukemia (CLL), and refractoriness to treatment following relapse, is inevitable after initial treatment, development of novel treatment strategies is necessary.

Areas covered in this review: CD20 as a therapeutic target for CLL, successes and limitations of current anti-CD20 monoclonal antibody (mAb) therapy, and implications of preclinical and clinical developments of novel alternatives, including ofatumumab, that may enhance anti-CD20 mAb therapy are reviewed. The literature reviewed encompasses papers and congress abstracts from the past 13 years.

What the reader will gain: While rituximab combined with chemotherapy has considerably improved outcomes for some but not all CLL patients, single-agent use is limited in relapsed/refractory CLL. Novel anti-CD20 mAbs in development, such as ofatumumab, may bypass some limitations by virtue of alternative epitope binding and modified effector functions. Ofatumumab induces significant complement-dependent cell lysis in vitro, particularly in cells with low CD20 expression. The FDA recently approved ofatumumab for treatment of CLL refractory to fludarabine and alemtuzumab.

Take home message: CD20-targetting chemoimmunotherapeutic options have advanced treatment of CLL. Results for single-agent ofatumumab and other new CD20 mAbs, in different lines of therapy and in combination with chemotherapy, will guide optimal use of these alternative therapies for B-cell malignancies.