Amphotericin B lipid complex for the treatment of patients with acute leukemia and hepatosplenic candidiasis

Hepatosplenic candidiasis (HSC) is an emerging complication of the treatment of patients with acute leukemia. Treatment of this infection can be very difficult and data on the duration of antifungal therapy are not available. We evaluated the efficacy of amphotericin B lipid complex (ABLC) for the treatment of five patients with acute leukemia and HSC. The dose of the administered ABLC ranged between 5 and 11 mg/kg per day and the median duration of therapy was 4.3 months. Four patients had complete response to the above treatment with resolution of fever and improvement in the radiologic findings. One patient refused to continue treatment and subsequently died with relapsed leukemia and disseminated Candida infection. Preliminary data suggest that ABLC is a well-tolerated and effective treatment for HSC and should be considered for phase II trials as front line treatment for this type of deep seated fungal infections.     

Hepatosplenic candidiasis in children with acute leukemia

Three children with acute lymphoblastic leukemia developed disseminated fungal disease predominantly involving the liver and spleen. The three patients were undergoing induction chemotherapy and had neutropenia when they presented prolonged fever not responsive to antibiotics. Once neutropenia was recovered, hepatosplenomegaly leukocytosis, elevated serum alkaline phosphatase, and hypoechoic areas in the spleen and liver ultrasound were observed. All fungal blood cultures were negative, with the diagnosis being confirmed by histologic study. One of the patients died without achieving control of the candidiasis. The other two patients received prolonged antifungal treatment concurrently with chemotherapy and both are alive, one of them cured and in complete remission. The increasing frequency of this infection in recent years and the importance of a prompt and prolonged administration of antifungal therapy to obtain the cure are discussed.     

Orointestinal candidiasis with special emphasis on esophageal candidiasis

Orointestinal mycoses are localized mainly in the oral cavity and in the oesophagus. Candida oesophagitis is not only found in AIDS-patients, also in patients of risk admitted to intensive care units. Upper intestinoscopies were made in 124 patients. Oesophageal candidosis was found in 6 patients, two of them had also Candida plaques in the stomach. The patients of the intensive care unit had an Apache-II-score of 26.7, those with Candida oesophagitis were 29.5. A significant increase in Candida antibodies was observed with 59 of 124 patients (47.6%), including all patients with oesophageal candidosis. Obviously also Candida infections of other localisations must be suspected. There was a correlation between the severity of endoscopic aspects and the invasiveness observed microscopically.     

New drugs in the treatment of acute and chronic leukemia with some emphasis on m-AMSA

Several new cytostatic drugs have entered clinical phase I-II studies for the treatment of leukemia: the most promising are pyrimidine analogs such as 5-aza-cytidine, 5-aza-2'-deoxycytidine, 5-aza-cytosine arabinoside, and 2',2'-difluorodeoxycytidine. Fludarabine, a fluorinated purine analog, appears to be active in CLL and multiple myeloma. Deoxycoformycin, an adenosine analog, showed good activity in the treatment of hairy cell leukemia and T-cell neoplasias. 2-chloro-deoxyadenosine has recently been introduced into the treatment of CLL and hairy-cell leukemia refractory to deoxycoformicin. Tiazofurin, an antimetabolite which interferes with nicotine-adenine-dinucleotide (NAD) metabolism, has been applied in CML blast crisis. Other agents include 13-cis retinoic acid and 1, 25-dihydroxy vitamin D3 as differentiation inducers, and homoharringtonine, an alkylating agent which is widely used for ANLL treatment in China. Among new anthracyclines, aclarubicin, idarubicin, THP-adriamycin and fluoro-adriamycin should be mentioned. Mitoxantrone, a substituted anthraquinone, has successfully been applied in the treatment of relapsed and refractory ANLL. Amsacrine (m-AMSA), finally, is a synthetic aminoacridine which intercalates into DNA and inhibits DNA topoisomerase II. m-AMSA is not cross-resistant to anthracyclines and has been particularly active in ANLL treatment. Studies using m-AMSA alone or in combination revealed comparable results to anthracycline--containing regimens. Cardiotoxicity of the anthracycline congestive type has not been observed with m-AMSA. The EORTC Leukemia Cooperative Group has successfully used m-AMSA in several trials prepositioning this drug stepwise: from relapsed and refractory ANLL, into intensive maintenance treatment during first remission in ANLL, and, still on-going, into intensive consolidation.     

Fibrinolysis in patients with acute promyelocytic leukemia and disseminated intravascular coagulation during heparin therapy

Two patients diagnosed as having acute promyelocytic leukemia (APL) and disseminated intravascular coagulation (DIC) were closely followed by serial fibrinolysis and coagulation studies from the day of admission until completion of the first course of chemotherapy. One patient was treated with intravenous heparin and Trasylol (Bayer AG, West Germany) and the other received heparin therapy without Trasylol. In Patient 1, hyperfibrinolytic activity, not observed during the administration of Trasylol, developed with its discontinuance. In Patient 2, hyperfibrinolysis was observed coincidentally with a decrease in APL cells due to chemotherapy. These results indicate that hyperfibrinolysis in APL is not associated with DIC.     

蛋白C检测在急性白血病合并DIC中的意义

 目的　探讨蛋白C（PC）在急性白血病（AL）合并弥散性血管内凝血（DIC）的诊断和预后中的意义。方法　采用全自动血凝仪对AL合并DIC患者44例和健康体检者30名进行部分活化凝血酶时间（APTT）、凝血酶原时间（PT）、D-二聚体（D-Dimer）和纤维蛋白原（Fbg）含量检测，发色法底物检测抗凝血酶（AT）和PC活性。t检验比较组间凝血、抗凝血和纤溶指标之间的差异性；Pearson相关分析分析各指标与DIC评分之间的相关性。结果　AL合并DIC患者PC活性为67.03±36.98，较对照组的99.53±46.20明显下降，其阳性率达86.36 %；PC与DIC评分呈负相关，与疾病的严重性相关。AL合并DIC患者中APTT、PT延长，D-dimer、Fbg升高， AT活性下降，与对照组相比，差异均有统计学意义。结论　AL合并DIC患者存在凝血系统过度活化和纤溶系统异常状态，PC 可作为AL合并DIC的敏感指标和预后指标。     

Analysis of factors related to the occurrence of chronic disseminated candidiasis in patients with acute leukemia in a non-bone marrow transplant setting: a follow-up study.

BACKGROUND: Chronic disseminated candidiasis (CDC) is a serious complication of treatment in patients with acute leukemia. Although some general risk factors are known to predispose to systemic fungal infections, few studies have addressed the relevance of certain clinical and laboratory features in patients with CDC. PATIENTS AND METHODS: To define a subset of patients at high risk for CDC, the authors evaluated the demographics and clinical and laboratory characteristics of 423 patients with acute leukemia. Patients who had bone marrow transplant before the diagnosis of CDC were excluded from the analysis. The diagnosis of CDC was based on blood cultures, liver biopsy, and imaging studies. The authors conducted 2 separate regression analyses on 3 subsets of patients: patients without documented candidiasis (n = 374), patients with CDC (n = 23), and patients with candidemia (n = 26). RESULTS: According to multivariate analysis, younger age (P = 0.009; odds ratio [OR], 1.96; 95% confidence interval [CI], 1.72-2.99), duration of neutropenia of 15 days or longer (P = 0.0003; OR, 11.7; 95% CI, 3.04-45.1), and use of prophylactic quinolone antibiotics (P = 0.039; OR, 3.85; 95% CI, 1.11-13.4) emerged as independent factors related to the development of CDC in patients with acute leukemia. The presence of severe mucositis, colonization with Candida, and administration of high-dose ara-C were statistically significant parameters in univariate analysis only (P = 0.0001, P = 0.003, and P = 0.058, respectively). CONCLUSIONS: On the basis of the results of this investigation, it is possible to define a subset of patients with acute leukemia at very high risk for CDC. Because of the morbidity and mortality of this infection, a targeted prophylactic approach may be more effective and less costly than the random administration of antifungal agents.     

急性早幼粒细胞白血病合并弥散性血管内凝血183例

目的探讨急性早幼粒细胞白血病（APL）合并弥散性血管内凝血（DIC）的治疗效果。方法对全反式维甲酸（ATRA）＋三氧化二砷（As2O3）或两者交替、单用ATRA、造血干细胞移植（HSCT）3种治疗方案的疗效进行比较。结果采用ATRA＋As2O3或者两者交替组获得CR中位时间分别为34d、35．5d,单用ATRA获得CR中位时间为62d,差异有统计学意义（P〈0．05）。ATRA＋As2O3组或两者交替组,3年无病生存率分别为78％和80％,与单用ATRA组比较,差异有统计学意义（P〈0．05）,DIC纠正时间为16～18d,三种治疗方案差异无统计学意义。15例行HSCT者,仅2例复发,其余13例中位无病生存时间（DFS）为13．5年,该13例PCR检测PML-RAα仅融合基因阴性。结论应用ATRA＋As2O3或两者交替加成分血、抗纤溶纠正DIC及其化疗治疗APL获得CR时间明显缩短,而且3年无病生存率相对较高。缓解后6个月讲行HSCT者．DFS可讲一步延长。     

老年急性髓系白血病治疗进展

 由于老年患者本身的特点及疾病的生物学特征,老年急性髓系白血病（AML）患者的疗效及预后均较差。近年老年AML患者的治疗取得许多进展诸如标准化疗方案的改良、新化疗药物的应用、免疫治疗、表观遗传学治疗药物及靶向治疗药物的研发等,临床试验结果提示部分患者疗效改善。     

Amsacrine treatment of patients with supraventricular arrhythmias and acute leukemia

Summary Three patients with a history of supraventricular arrhythmia presented with relapse of acute leukemia. Two of the three patients were in sinus rhythm, receiving digoxin and/or verapamil daily. The third patient was in atrial fibrillation, but her heart rate was controlled with daily digoxin. All three patients received amsacrine without the occurrence of cardiac events. Although amsacrine may cause ventricular arrhythmias in the setting of hypokalemia, correction of the electrolyte abnormality permits its use in patients with a history of supraventricular arrhythmias.This work is supported by the Chemotherapy Foundation     

老年人急性髓系白血病治疗研究进展

老年人急性髓系白血病(AML)的发病率逐年上升,平均发病年龄为67岁,由于老年患者易合并脏器功能不全,因此治疗尚无统一标准.文章结合第58届美国血液学会年会报道,对老年AML患者治疗方面的一些研究进展进行总结.     

Chronic neutrophilic leukemia with acute myeloblastic transformation

We report a rare case of chronic neutrophilic leukemia (CNL) which terminated in acute myeloblastic transformation 3 years after the onset of the disease. The increased leukocytes were mainly neutrophils at various maturational stages until 1 month before transformation without dysplastic hematopoietic cells or other myeloproliferative disorders. Repeated analyses for the Philadelphia chromosome (Ph1), rearrangement of the BCR gene or chimeric BCR/ABL mRNA, major, minor and mu, were negative. Genomic analysis of granulocyte colony-stimulating factor (G-CSF) receptor did not reveal any abnormality. The clinical manifestations were characterized by hyperleukocyte syndrome with respiratory distress and ischemic legs with gangrene.     

Chronic myelogenous leukemia: update on biology and treatment

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that follows a characteristic clinical course in which a chronic phase of variable duration precedes an accelerated, and ultimately blastic, phase, which is generally fatal. This disorder results from a clonal expansion of transformed hematopoietic progenitor cells and includes myeloid, monocytic, erythroid, megakaryocytic, and lymphoid lineages. At the molecular level, CML is characterized by the bcr-abl fusion gene, which results from the reciprocal translocation t(9;22)(q34;q11), creating the Philadelphia (Ph) chromosome. Chronic myelogenous leukemia was the first human disease for which a specific karyotype abnormality was demonstrated and could be linked to pathogenetic events of leukemogenesis. The outlook for patients with CML has changed dramatically over the last decade. The median survival time of patients has doubled to 5 to 7 years, with up to 50% of patients alive at 5 years. This development is due to refinements in allogeneic stem-cell transplantation and growing expertise in the use of interferon-alfa (Intron A, Roferon-A), a biological agent that has been shown to suppress the leukemic clone and to prolong survival in patients with CML. This review provides a concise update of the biology of CML, as well as current therapeutic options and management strategies.     

Diagnosis and management of acute promyelocytic leukemia with disseminated intravascular coagulopathy: a case study

One of the less common leukemias, acute promyelocytic leukemia, is associated with disseminated intravascular coagulopathy (DIC). If patients are able to survive the DIC, there is hope for long-term survival in complete remission and a chance for cure. This case study reviews the disease, risk factors, treatment, and nursing care required by this patient population and compares it to the existing literature.     

急性淋巴细胞白血病合并肝脾念珠菌病三例并文献复习

目的 提高对急性淋巴细胞白血病(ALL)合并肝脾念珠菌病的认识.方法 回顾性分析2010年6月至2016年1月河南省肿瘤医院血液科收治的3例ALL合并肝脾念珠菌病患者的临床资料.结果 3例ALL患者均被确诊合并肝脾念珠菌病,并接受针对性抗真菌治疗.结论 ALL合并肝脾念珠菌病并非少见,具有高危因素且出现广谱抗生素治疗无效的高热时应高度疑诊该病,影像学检查对其诊疗及随访至关重要,针对性抗真菌治疗需要足量、足疗程.     

Aleukemic leukemia cutis manifesting with disseminated nodular eruptions and a plaque preceding acute monocytic leukemia: a case report

Aleukemic leukemia cutis (ALC), a discrete tumor of leukemic cells involving the skin, may be the first manifestation of acute myeloid leukemia, preceding the onset in marrow and blood by months and years. ALC is often difficult to diagnose and is associated with a dismal prognosis. A 63-year-old male presented with nodular swellings on the face, a plaque extending over the right shoulder and multiple enlarged cervical lymph nodes. The skin biopsy of the plaque lesion showed a diffuse neoplastic infiltration extending from the dermis to subcutaneous tissue with diffuse positivity for myeloperoxidase and focal positivity for CD34 on immunohistochemical staining. The diagnosis was leukemia cutis. One month later, acute monocytic leukemia (FAB AML-M5b) was diagnosed. The patient died on the seventh month of diagnosis.     

Chronic lymphocytic leukemia: Biology and current treatment

There has been considerable recent progress in understanding of the biology of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). These accomplishments have been accompanied by progressive improvement in the management of CLL and its complications. This review summarizes these changes and provides guidelines for a comprehensive approach to patient care.