Management of hematological malignancies in patients affected by renal failure

The management of hematological malignancies (HM) in renally impaired patients may be a difficult task. Indeed, the kidney represents a major elimination pathway for many chemotherapeutic agents and their metabolites, whose serum levels are not usually measured in daily clinical practice. In addition, many antineoplastic drugs have a narrow therapeutic index for which they require dose adjustment when administered to patients with renal failure. Only limited data regarding the use of chemotherapy in patients with renal impairment and in those on dialysis are available. Indeed, renal patients with HM are often excluded from most clinical trials. Thus far, in order to provide recommendations, we have reviewed the pertinent literature, gathering information from published guidelines regarding chemotherapy in patients with kidney dysfunction and from articles describing the use of individual agents in renal patients with HM.     

Genistein and hematological malignancies

Genistein is an isoflavanoid from soybeans and promising cancer chemotherapeutic agent. Genistein exposure varies widely because of cultural differences in diet. Hypothetically, this could account for differential cancer risk across ethnic populations. Genistein inhibits the growth of many different cancer cell lines by increasing apoptosis, inducing cell cycle delays, and modulating intracellular signaling pathways. Data from recent studies suggest that the therapeutic potential of genistein extends to cancers that affect blood, bone marrow, and lymph nodes. The objective of this paper is to provide background information on genistein, and discuss its potential as a therapeutic agent for treating hematological malignancies.     

CD44与血液系统恶性肿瘤

CD44在许多恶性血液病中均有表达,其表达水平与疾病的临床状况及预后相关.对CD44及其单克隆抗体的研究在血液系统恶性肿瘤的诊断、预后和治疗中具有重要意义.     

Mcl-1与血液恶性肿瘤

Mcl-1（myeloid cell leukemia-1）是Bcl-2家族蛋白的一个抗凋亡的成员,在凋亡的调控中具有重要作用。Mcl-1基因在翻译过程中可产生全长Mcl-1和短型Mcl-1两种具有不同作用的蛋白质。Mcl-1在胚胎形成,T和B淋巴细胞的发育和维持以及中性粒细胞的生存调节中具有重要作用。Mcl-1过表达可以抑制细胞凋亡,延长细胞寿命,使细胞获得生存优势,从而导致恶性行为的发生。进一步研究表明Mcl-1表达和调节异常与血液恶性肿瘤的发生和发展有关,因此对Mcl-1的深入研究具有重要意义。     

Home care of hematological malignancies

Hematological malignancies such as leukemia or lymphoma are mainly treated by hospitalization or in outpatient clinics. Therefore, home care and home nursing are not so intensively done in the treatment of these malignancies. However, G-CSF administration against neutropenia after chemotherapy and administration of narcotics or opioids against severe pain have been performed sometimes during home care, and have been contributing to better QOL of the patients.     

Hematopoietic stem cell transplantation for hematological malignancies in Europe.

Hematopoietic stem cell transplants (HSCTs) are considered the best treatment option for many hematological malignancies, and transplant numbers have increased five-fold during the last decade. Only a few controlled prospective studies are available, and different opinions prevail. Data from 118 167 HSCT (36% allogeneic, 64% autologous) collected within the EBMT activity survey from 1990 to 2001 were used to assess trends over time, transplant rates and coefficient of variation (CV) of transplant rates among European countries for acute myeloid leukemia (AML; 18.5%), acute lymphocytic leukemia (ALL; 12%), chronic myeloid leukemia (CML; 11.5%), myelodysplastic syndromes (MDS; 3%), lymphoproliferative disorders (LPS; 36.3%) and multiple myeloma (MM; 18.7%). Transplant rates increased in all countries and for all indications from 1990 to 2001 from 1.7-fold (CML) to 24.8-fold (MM). Transplant rates have declined for CML since 1999. Autologous HSCT are the preferred choice for LPS and MM, allogeneic HSCT for ALL and myeloid malignancies. CVs of less than 50% suggest consensus for allogeneic HSCT in AML, ALL, CML, MDS and NHL, for autologous HSCT in LPS and MM. These data give an overview of the current status of HSCT for hematological malignancies in Europe and provide objective information for health-care providers and patient counselling.     

造血干细胞移植治疗恶性血液病临床研究

 目的 探讨造血干细胞移植（HSCT）治疗恶性血液病的临床疗效及并发症的防治。方法51例急慢性白血病、恶性淋巴瘤、多发性骨髓瘤患者中,36例选择自体造血干细胞移植（auto-HSCT）,15例接受异基因造血干细胞移植（allo-HSCT）,包括HLA不全相合3例及非血缘关系移植4例,混合移植2例;预处理自体移植主要选用CBV,BEAC方案,异基因移植采用BU／CY2及改良的BU／CY方案;移植物抗宿主病（GVHD）的预防采用CsA+MTX或CsA+MTX＋MMF方案。结果 51例患者中49例获得造血重建,在auto-HSCT和allo-HSCT后WBC≥1.0×109／L的中位时间分别为13 d和17 d,血小板≥20×109／L的中位时间分别为21和25 d;40 ％出现aGVHD,26.7 ％出现cGVHD;3.9 %出现HVOD;出血性膀胱炎发生率5.9 ％;CMV感染发生率33.3 ％;62.7 ％出现黏膜炎;54.9 ％出现不同部位的感染;移植相关死亡率3.5 %,随访3～95个月,移植后复发11例,其中auto-HSCT 9例,allo-HSCT 2例。结论 HSCT是目前治疗恶性血液病的最佳方法,但移植期间需要进一步探索如何减少其相关并发症,以提高血液肿瘤的治愈率及延长患者的无病生存时间。     

Microsatellite instability in hematological malignancies

The replication error (RER+) phenotype, characterized by microsatellite instability (MSI) has been recently related to mutations of genes involved in DNA mismatch repair pathway. These genetic alterations were first described in hereditary non polyposis colorectal cancer (HNPCC). We examined 44 patients with hematological malignancies (27 AML, 9 MDS, 2 CML-BP and 6 T-ALL) for evidence of MSI. Twenty seven percent of our patients showed differences for only one marker. In four cases (9.1%) MSI was observed in multiple markers and these cases were described as RER+ phenotype. Presented data suggest that this phenomenon may play a role in at least a subset of patients with hematological malignancies.     

Percutaneous MR-guided cryoablation for malignancies,with a focus on renal cell carcinoma

Cryosurgery is the oldest thermal ablation method, and was first performed in the mid-nineteenth century. Since the development of cryosurgical systems capable of delivering liquid nitrogen, organs in various regions have been treated with cryosurgery. However, the lack of an adequate monitoring modality during the freezing process did not allow the precise and complete destruction of lesions deep inside the parenchyma. This led to local recurrences caused by unsatisfactory results of treatment. Recently, a magnetic resonance (MR)-compatible argon-based cryoablation sytem has been developed, and a combination of this cryoablation system and MR imaging has been shown to be an effective method for treating malignant tumors. In this article, we describe our clinical experience of percutaneous MR-guided cryoablation for malignancies, focusing on renal cell carcinoma.     

Ifosfamide in hematological malignancies of adults

Ifosfamide is an alkylating agent with a broad spectrum of activity in solid tumors and hematological malignancies. In this review we will illustrate its use in the treatment of lymphomas and Hodgkin's disease and the results of the principal studies which have investigated ifosfamide-containing regimens. Ifosfamide has been mainly used, in combination with other drugs, as a component of salvage regimens for relapsed or primarily refractory lymphoma. These regimens induced a variable clinical response rate (complete remissions ranging from 6 up to 73% and overall response rate from 24 to 72%). High-dose ifosfamide, in combination with etoposide or mitoxantrone, showed a good potential for mobilization of peripheral stem cells while reducing the tumor burden. Ifosfamide-based regimens are also being evaluated in the treatment of newly diagnosed patients in sequential, response-based protocols, using many non-cross-resistant drugs.     

异基因造血干细胞移植在血液肿瘤治疗中的研究进展

异基因造血干细胞移植(allo-HSCT)是治愈恶性血液病的有效乃至唯一手段,多种单倍型相合移植方案的建立解决了供者来源问题.文章从供者选择、移植物抗宿主病防治以及植入失败防治等3个方面选取了第58届美国血液学会(ASH)年会的代表性报道,总结了allo-HSCT在血液病治疗中的应用进展.     

Angiogenic and lymphangiogenic molecules in hematological malignancies

In this review, the role of angiogenic and lymphangiogenic growth factors in hematological malignancies is summarized, alongside with possible therapeutic applications. Recent data demonstrate the importance of angiogenesis in hematologic malignancies including leukemia, lymphoma, and multiple myeloma. Expression of angiogenic polypeptides vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) associate with clinical characteristics in human leukemia and lymphoma, and their serum concentrations serve as predictors of poor prognosis. VEGF and VEGF-C also act as survival factors on leukemia. Furthermore, certain hematological malignancies both produce angiogenic or lymphangiogenic growth factors including VEGF and VEGF-C, and also express their receptors, resulting in the generation of autocrine loops that may support cancer cell survival and proliferation. Inhibition of the action of key regulators of endothelial cell growth, alone or in combination with other antiangiogenic drugs and/or established chemo- or immunotherapy regimens, is a potential target for therapeutic intervention in hematological malignancies.     

A renal cell carcinoma mimicking a multilocular renal cyst

A 38-year old man was admitted to the hospital for an investigation of abnormal ultrasonographic findings of the left kidney. Ultrasonography demonstrated multiple, fluid-filled masses separated by a highly echogenic septa and CT revealed a large cystic mass and a thick, irregular wall in the upper and middle poles. Selective, left renal arteriography showed a hypovascular mass. Thus, a presumptive diagnosis was made of multilocular renal cysts. Taking into accounted the possibility of a renal cell carcinoma. Surgical exploration and a left nephrectomy was performed. Microscopically, a multiloculated renal cell carcinoma thus was diagnosed, A definite, preoperative diagnosis is very difficulty to make in most cases, and surgical exploration is considered to be the only way to achieve an accurate diagnosis. Treatment for a multiloculated cystic renal mass containing multilocular renal cysts is a total or partial nephrectomy.     

New combination therapies in hematological malignancies

New combination therapies against hematological malignancies have recently been reported. Anti-CD20 chimeric antibody adds a therapeutic benefit to standard-dose CHOP therapy without causing significant additional toxicity in the treatment of indolent B cell lymphoma. Multidrug resistant modifiers such as PSC833 and MS209 in combination with chemotherapy are useful for treating poor risk AML patients, whose leukemia/lymphoma cells express P-glycoprotein. Fludarabine containing FL and FLAG therapy were effective in patients with AML in relapse. The early addition of chemotherapy to ATRA, and maintenance therapy with chemotherapy and intermittent ATRA, can reduce the incidence of relapse in cases of acute promyelocytic leukemia.