异基因造血干细胞移植后白血病复发的危险因素

目的探讨异基因造血干细胞移植后白血病复发的危险因素。方法回顾性选择71例行异基因造血干细胞移植术的白血病患者,采用单因素、COX多因素回归法分析71例患者性别、年龄、疾病类型、诱导疗程数、初诊白细胞计数、巨细胞病毒感染、移植物来源、供受者HLA配型、急性移植后移植物抗宿主病、慢性移植后移植物抗宿主病与复发的相关性。结果71例患者中14例复发。单因素分析结果表明,初诊白细胞计数、诱导疗程数、移植物来源及慢性移植物抗宿主病史是异基因造血干细胞移植后复发的危险因素,P<0.05;Cox多因素回归分析结果表明,诱导疗程数多、无慢性移植物抗宿主病是异基因造血干细胞移植后复发的独立危险因素,P<0.05。结论无慢性移植物抗宿主病、诱导疗程数多是异基因造血干细胞移植后复发的危险因素。     

影响老年急性髓系白血病患者预后的危险因素分析

目的 探讨影响老年急性髓系白血病患者预后的危险因素.方法 回顾性分析121例老年急性髓系白血病患者的临床资料.对比不同临床资料患者的完全缓解率和中位生存期.通过多因素Cox模型分析统计影响老年急性髓系白血病患者预后的危险因素.结果 本研究患者的中位生存期为131 d(95%可信区间109~154 d),诱导化疗后的完全缓解率为29.75%.年龄≤70岁、PS评分﹤2分、原发急性髓系白血病、骨髓原始细胞比例≤50%、接受标准化疗以及白细胞CD34表达阴性患者的完全缓解率升高(P﹤0.05);年龄≤70岁、PS评分﹤2分、原发急性髓系白血病、初治时的白细胞计数≤50×109/L、骨髓原始细胞比例≤50%、接受标准化疗以及白细胞CD34表达阴性患者的中位生存期延长(P﹤0.05);多因素Cox模型分析结果显示,年龄、PS评分、初治时白细胞计数以及治疗方案是影响老年急性髓系白血病患者预后的危险因素(P﹤0.05).结论 年龄、PS评分、初治时白细胞计数以及治疗方案是影响老年急性髓系白血病患者预后的危险因素.临床应通过整体评估,制定个体化的化疗方案,以改善患者的预后.     

急性髓系白血病儿童DKK3基因启动子高甲基化的临床价值

目的：检测急性髓系白血病（AML）患儿骨髓DKK3基因启动子甲基化情况并研究其临床意义。方法选择急性髓系白血病患儿（AML组）80例和血液系统良性疾病患儿（CON组）40例为研究对象,采用甲基化特异性PCR检测两组患儿骨髓DKK3基因启动子甲基化并比较其差异,分析AML组患儿不同临床病理因素中DKK3基因启动子甲基化的差异,对比DKK3基因启动子甲基化与未甲基化患儿3年生存率及总生存时间的差异。检测髓系白血病细胞株DKK3基因启动子甲基化状态。结果 AML组患儿骨髓DKK3基因启动子甲基化率高于CON组（P﹤0.05）;AML组患儿骨髓DKK3基因启动子甲基化在性别、年龄、初诊发热、外周血白细胞（WBC）、外周血红细胞（RBC）、外周血血小板（PLT）和FAB分型方面比较,差异均无统计学意义（P﹥0.05）,在骨髓原始细胞比例、核型类型和诱导化疗疗效方面比较,差异均有统计学意义（P﹤0.05）;随访3年,AML组DKK3基因启动子甲基化患儿的生存率和生存时间均较DKK3基因启动子未甲基化患儿低（P﹤0.05）;HL-60、KG-1和K562白血病细胞株DKK3基因启动子均处于甲基化状态。结论急性髓系白血病患儿骨髓DKK3基因启动子处于高甲基化状态,在病情及预后评估中具有一定价值。     

TNF-α和IL-6在急性淋巴细胞白血病儿童血清中的水平及其临床意义

目的 探讨急性淋巴细胞白血病患儿血清中肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6水平及其临床意义.方法 选择80例急性淋巴细胞白血病患儿,其中初诊44例、完全缓解24例、难治复发12例,同期收集在我院行体检的健康儿童50例为对照组.检测所有研究对象血清中TNF-α和IL-6水平.分析急性淋巴细胞白血病初诊患儿血清TNF-α和IL-6水平与临床特征的关系.结果 与对照组相比,急性淋巴细胞白血病初诊组患儿血清TNF-α和IL-6水平明显降低(P<0.01).与初诊组相比,急性淋巴细胞白血病完全缓解组患儿血清中TNF-α和IL-6明显升高(P<0.01).与初诊组相比,急性淋巴细胞白血病复发难治组患儿血清中TNF-α和IL-6水平明显降低(P<0.01).急性淋巴细胞白血病初诊患儿血清中TNF-α和IL-6水平与其年龄、性别、FAB分型、肝肿大及淋巴结肿大无明显相关性(P>0.05),与危险度分型呈显著相关(P<0.01).结论 急性淋巴细胞白血病患儿血清中TNF-α和IL-6水平明显降低,与急性淋巴细胞白血病患儿的危险度分型呈显著性相关.     

急性白血病患者异基因造血干细胞移植术后复发危险因素分析

目的 探讨急性白血病(AL)患者异基因造血干细胞移植(allo-HSCT)术后复发危险因素.方法 回顾性分析郑州大学第一附属医院造血干细胞移植中心自2003年12月至2013年12月行allo-HSCT的157例AL患者的临床资料,应用Cox回归法分析受者年龄、性别、疾病类型、初诊白细胞计数、诱导疗程数、人类白细胞抗原(HLA)配型、急性移植物抗宿主病(aGVHD)、慢性移植物抗宿主病(cGVHD)、移植物来源、巨细胞病毒(CMV)感染与移植后复发的关系.结果 157例患者中32例在移植后24个月内复发.单因素分析结果示:初诊白细胞计数(P=0.023)、诱导疗程数(P=0.074)、移植物来源(P=0.044)、cGVHD(P=0.033)是allo-HSCT后复发的影响因素.多因素Cox回归分析结果示:诱导疗程数(P=0.027)、cGVHD(P=0.011)是allo-HSCT后复发的独立影响因素.结论 诱导疗程数多、未发生cGVHD是allo-HSCT后复发的危险因素.     

GGLG-08方案联合伊马替尼治疗儿童Ph阳性急性淋巴细胞白血病的疗效与安全性分析

目的 研究GGLG-08方案联合伊马替尼治疗儿童Ph阳性急性淋巴细胞白血病的效果与安全性.方法 回顾性分析51例儿童Ph+急性淋巴细胞白血病患儿的临床资料,给予对照组患儿CCLG-ALL2008化疗方案,治疗组患儿采用伊马替尼联合CCLG-ALL2008化疗方案,比较2组患儿的治疗疗效及不良反应,同时分析影响患儿诱导缓解后5年生存率的主要因素.结果 对照组患儿诱导治疗后完全缓解(CR)率为92.86％,治疗组患儿CR率为95.65％;治疗组患儿1年无事件生存率(EFS)为91.30％,3年无事件生存率(EFS)为69.57％,5年无事件生存率(EFS)为65.22％.与对照组比较,治疗组未增加化疗相关毒性.导致患儿诱导缓解后5年生存率降低的独立风险因素为:患儿对糖皮质激素诱导不敏感、治疗依从性差、治疗中复发以及首次诱导缓解失败.结论 GGLG-08方案与伊马替尼联合使用治疗儿童Ph阳性急性淋巴细胞白血病的临床疗效明显,安全性良好.     

生存五年以上死亡急性白血病17例报告

目的:探讨急性白血病(AL)生存五年以上死亡原因.方法:采用回顾性系列研究,统计本院生存五年以上死亡急性白血病患儿的发病年龄、性别、化疗前病程、分型、病史、临床表现、血常规、骨髓象、并发症、微小残留病灶检测(MRD)、染色体检测、诱导方案、完全缓解(CR)时间、复发时间、直接死因等进行分析.结果:急性淋巴细胞白血病、男性、白细胞数过高、化疗强度不够、出现髓外白血病、MRD( )易复发,复发后放弃治疗或不规则治疗易全身浸润造成多器官脏器功能衰竭(MOF)死亡,化疗后骨髓抑制易出血、感染死亡.结论:白血病应坚持规范化、个体化长期治疗,停药后仍应定期监测以防复发,复发再诱导缓解后应进行干细胞移植根治白血病.     

儿童急性淋巴细胞白血病并发肿瘤溶解综合征18例临床分析

目的:探讨儿童急性淋巴细胞白血病（acute lymphoblastic leukemia,ALL）并发肿瘤溶解综合征（tumor lysis syndrome,TLS）的临床特点,分析TLS的危险因素以及预后。方法:回顾性收集2015年01月01日至2020年06月30日期间于我院就诊的253例ALL患儿的临床资料。分析TLS的危险因素以及TLS对ALL患儿预后的影响。结果:253例患儿中,18例（7.1%）患儿发生TLS,男女比例2.6∶1,中位年龄8.1岁。TLS患儿较非TLS患儿更容易出现窦性心动过速、前臂心肌复极异常以及QT间期延长（P<0.05）。初诊高白细胞计数（WBC≥50×109/L）与初诊非高白细胞TLS患儿的血尿酸、LDH、血肌酐、血钾、血校正钙及肌酐清除率（creatinine clearance,Ccr）之间没有统计学差异（P>0.05）。多因素分析显示初诊LDH≥900 U/L是TLS发生的独立危险因素。TLS组与非TLS组的EFS及OS没有统计学差异（P>0.05）。结论:初诊LDH≥900 U/L是TLS发生的独立危险因素。TLS并不影响ALL患儿的远期预后。     

急性早幼粒细胞白血病长期生存相关因素分析

  目的　研究影响急性早幼粒细胞白血病（APL）长期生存的相关因素。方法　回顾性分析62例APL的临床资料,应用Log-Rank检验和COX回归模型对62例患者的性别、年龄、初诊时白细胞计数、初诊时血小板计数、初诊时血清乳酸脱氢酶水平、诱导缓解方案、获得缓解所需时间、缓解后治疗方案进行单因素和多因素分析。结果　62例患者中位随访31（6～102）个月,5年预计总体生存率（OS）为（77.1±6.2）%,5年预计无复发率（RFS）为（71.4±3.68）%。单因素分析显示,初诊时白细胞计数、诱导缓解方案、获得缓解所需时间、缓解后治疗方案是影响APL患者长期生存的主要因素;多因素分析显示,初诊时白细胞计数、缓解后治疗方案是影响APL患者长期生存的独立因素。结论　APL患者获得完全缓解后,应用全反式维甲酸（ATRA）+三氧化二砷（As2O3）+化疗的序贯治疗方案将显著延长患者的生存时间。     

儿童复发/难治性急性T淋巴细胞性白血病的诊治研究进展

近年来儿童急性T淋巴细胞性白血病的长期生存率已明显提高,尤其是欧美发达国家,5年总生存率接近90%,但我国目前报道的长期生存率较国际领先水平尚有一定差距。急性T淋巴细胞性白血病易出现诱导失败且复发率较高,而复发/难治性急性T淋巴细胞性白血病的治疗又极其棘手,有效的治疗药物非常有限,预后极差,长期生存率不到25%,极大影响急性T淋巴细胞性白血病的治疗效果。为了提高对复发/难治性急性T淋巴细胞性白血病的诊治水平,本文对其复发的危险因素、复发和耐药机制以及治疗进展进行综述。     

初次骨髓完全缓解时血象恢复不良急性髓系白血病患者临床特征及预后分析

目的 探讨初次骨髓完全缓解(CR)时血象恢复不良[血小板计数(Plt)<100×109/L或中性粒细胞绝对值(ANC)<1.0×109/L]急性髓系白血病(AML)患者的临床特征和预后因素.方法 回顾性分析2010年1月至2015年9月郑州大学第一附属医院血液科收治的302例初次骨髓CR的AML患者(M3除外)病例资料,根据初次获骨髓CR时血象恢复情况分为血象CR组(Plt≥100×109/L且ANC≥1.0×109/L)和血象未达CR组(Plt<100×109/L或ANC<1.0×109/L),比较两组患者临床特征和预后差异,并通过单因素和多因素分析对血象未达CR的AML患者复发和生存情况进行分析.结果血象CR组216例(71.5%),血象未达CR组86例(28.5%),两组年龄、就诊时高白细胞患者比例、外周血原始细胞比例、法美英协作组(FAB)分型、细胞遗传学危险度分层和FLT3-ITD/NPM1基因突变比较差异均无统计学意义(均P>0.05).血象CR组就诊时骨髓原始细胞数和首疗程化疗获骨髓CR比例高于血象未达CR组(均P<0.05),初次骨髓CR时微小残留病(MRD)阳性比例低于血象未达CR组(P=0.004),且初次骨髓CR时血象CR组骨髓增生程度更活跃(P=0.001).血象CR组3年复发率低于血象未达CR组(P=0.003),总生存(OS)率和无病生存(DFS)率高于血象未达CR组(P=0.002,P=0.040).多因素分析显示,对于血象未达CR的AML患者,高危染色体核型、诱导疗程数≥2个、初次骨髓CR时外周血中性粒细胞未恢复是复发率、OS率和DFS率的共同独立危险因素(均P<0.05).FLT3-ITD基因突变阳性是OS率的独立危险因素(P<0.001),就诊时外周血原始细胞比例≥0.60是DFS率的独立危险因素(P=0.047).结论 初次骨髓CR时血象未达CR的AML患者预后较差,且高危染色体核型、诱导疗程数≥2个、中性粒细胞恢复不良者可能预后更差,应视为高危人群,考虑更积极的治疗.     

Chronic myelomonocytic leukemia coexisting with B-cell chronic lymphocytic leukemia

Coexistence of B-cell chronic lymphocytic leukemia (B-CLL) and chronic myelomonocytic leukemia (CMML) is an unusal event, and to our knowledge, only four such cases have been reported in the literature. We report a 68-year-old white woman in whom these two diseases were diagnosed concomitantly. The diagnosis was made on the basis of peripheral blood count, morphology and immunophenotyping, and bone marrow cytology and histology. Interphase FISH analysis detected a 13q14.3 deletion in lymphocytes nuclei and no such abnormality in monocytes nuclei. The PCR analysis of IgH gene rearrangement in the bone marrow, as well as the peripheral blood lymphocytes, showed two different monoclonal IgH configurations as the result of biallelic clonal rearrangement of IgH genes suggesting an origin of lymphocytes from B-cell progenitors. The patient was originally treated with prednisone 1 mg/kg/day because of progressive significant thrombocytopenia, without improvement. Subsequently, she received one course of cladribine (2-CdA). Significant reduction of lymphocytes in the peripheral blood was observed. However, rapid increase of monocytes was seen shortly after the 2-CdA treatment. Subsequently, she received hydroxyurea (1.5 g/day) without hematological improvement. The patient died in January 2003, three months after diagnosis because of progression of both leukemias and associated pneumonia. Possible etiopathogenic relationship between both disorders is discussed.     

Factors associated with prolonged survival in chronic myeloid leukemia.

Four patients who demonstrated unusually prolonged survival with Philadelphia chromosome positive Ph' (+) chronic myeloid leukemia (CML) were analyzed for factors associated with survival. Survival duration from initial diagnosis ranged from 120 to 222 months, with a mean of 170 months. At diagnosis, age, symptoms, liver or spleen size, hematocrit, white blood cell count, absolute peripheral myeloblast plus promyelocyte count, and uric acid did not have unique prognostic significance. At diagnosis all four patients had normal or low-normal platelet counts, (range: 170,000 to 248,000/mm3). Thrombocytopenia occurred during treatment in three patients. None of the four patients, however, developed severe marrow hypoplasia or leukopenia during treatment for the chronic phase. Cytogenic studies performed from 103 to 156 months after diagnosis did not reveal a large subpopulation of marrow cells with a normal karyotype or cells with the XO genotype in the male patients. These observations suggest that prolonged survival in CML 1) is not contingent upon intensive treatment resulting in marrow hypoplasia, and 2) does not require the persistence of a clone of karyotypically-normal bone marrow cells or a clone of marrow cells in males which has lost the Y chromosome. A normal or low-normal platelet count at diagnosis may be a favorable prognostic indicator.     

Remission from central nervous system involvement in adults with acute leukemia. Effect of intensive therapy and prognostic factors

Eighty-seven adult patients who had achieved bone marrow remission of leukemia developed one or more episodes of meningeal leukemia. Multiple patient characteristics were examined for their effect on probability of achieving complete remission from meningeal disease and for their effect on duration of meningeal remission. Presence of obtundation (P less than 0.01) or other symptoms of meningeal disease (P = 0.02) were associated with a low remission induction rate. Other factors which tended (P = 0.06-0.20) to be associated with low remission induction rates included high cerebrospinal fluid (CSF) opening pressure, absence of splenomegaly at initial diagnosis, high peripheral blood leukocyte count (WBC) at the episode of marrow disease most recently preceding the meningeal disease, and use of only one as opposed to two or more intrathecal drugs as treatment. Factors associated with long duration of meningeal remissions included diagnosis (AML greater than acute undifferentiated leukemia greater than ALL, P = 0.05), absence of symptoms (P = 0.04), low CSF WBC (P = 0.01), rapid attainment of meningeal remission (P = 0.01), rapid attainment of initial bone marrow remission (P = 0.02), and long duration of initial bone marrow remission (P less than 0.01). Absence of cranial or peripheral neuropathies, low CSF protein and opening pressure, and short time interval between diagnosis of marrow and meningeal disease also tended (P = 0.06-0.20) to be associated with long meningeal remissions. Patients treated according to an intensive protocol utilizing cranial irradiation and triple drug treatment via an Ommaya reservoir had substantially longer meningeal remissions than did patients treated with less intensive therapy (P = 0.01). Relapse-free survival curves suggest that some patients are cured of their meningeal disease.     

Peripheral Blasts on Day 21 of Induction Chemotherapy in a Patient With Core Binding Factor Acute Myeloid Leukemia: More Than Meets the Eye

The combination of fludarabine, high-dose cytarabine, gemtuzumab ozogamicin, and granulocyte colony-stimulating factor (G-CSF), the FLAG-GO protocol, has resulted in excellent response rates and superior relapse-free survival as first-line therapy for patients with core binding factor acute myeloid leukemia (AML). A side effect of administration of G-CSF is an increase in peripheral white blood cell count and blast cell percentage during the recovery phase of the bone marrow after induction chemotherapy. A 60-year-old man with inversion 16 AML was admitted for induction chemotherapy with the FLAG-GO protocol at our institution. On day 21 of his induction regimen, he was noted to have blasts in both the peripheral smear and in the bone marrow that resolved on their own without any intervention by day 28. Our case report underscores the importance of recognizing this phenomenon associated with the administration of G-CSF, and waiting for 5-7 days before administering re-induction therapy or classifying the disease as primary refractory AML.     

Periodic oscillation of blood leukocytes,platelets, and hemoglobin in a patient with chronic eosinophilic leukemia

Chronic eosinophilic leukemia (CEL) is a rare myeloproliferative disease in which autonomous, clonal proliferation of eosinophilic precursors results in persistent increase of eosinophils in the blood and bone marrow. A case of CEL spontaneous oscillation of white blood cell (WBC) count is presented. The cycle of WBC variation comprised about 60 days. Similar cyclic variations were noted in his platelet count, hemoglobin level and bone marrow cellularity, as well as in the spleen size, which was directly correlated with the WBC count. The numbers of bone marrow erythroid colony-forming units (CFU-E), granulocyte-macrophage colony-forming units (CFU-GM) and the serum level of colony-stimulating factors (CSFs) were also regularly changed during the oscillation of WBC. Bone marrow hyperplasia was accompanied with the increase in peripheral WBC count, suggesting that the variation of cell production caused the cyclic oscillation.     

WT1 expression as a marker of minimal residual disease predicts outcome in acute myeloid leukemia when measured post-consolidation

WT1 levels may be a useful predictor of leukemia free survival (LFS) following treatment of acute myeloid leukemia (AML). We report a retrospective study in which levels of WT1 expression from patients with de novo AML were measured from bone marrow and peripheral blood at diagnosis, post-induction, post-consolidation and relapse. We demonstrate that higher levels of WT1 in peripheral blood at diagnosis are associated with poorer LFS independent of age and cytogenetic risk-group (n=85, p=0.028). When measured at post-consolidation, the presence of detectable WT1 is associated with poorer LFS in univariate analysis of both peripheral blood (p=0.024) and bone marrow (p=0.019). In a multivariate analysis including age and cytogenetic risk, the association remained significant for bone marrow (p=0.016) with a trend observed for peripheral blood (p=0.06). These findings have formed the basis for ongoing research.     

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.