新疆维吾尔族霍奇金淋巴瘤HLA—A高分辨基因多态性分析

目的：研究人类白细胞抗原（humanleukocyteantigen,HLA—A）高分辨等位基因型与新疆地区维吾尔族霍奇金淋巴瘤（hodgkin’Slymphoma,HL）易感性的关系,以揭示遗传因素在HL发病中的作用。方法：采用病例一对照的研究设计和DNA测序分型（SBT）法,对45例维吾尔族HL患者和110名健康者进行HLA—A基因座位的精确分型,计算HLA_A基因座位等位基因的相对频率（RF）及基因频率（AF）。结果：1）病例组共检出33个高分辨等位基因型,对照组中共检出44个高分辨等位基因型,HLA-A基因座位上等位基因频率分布均满足Hardy-Weninberg遗传平衡检验,P=0．61。2）与新疆地区维吾尔族人群比较,维吾尔族HL患者中等位基因HLA-A＊01：01：01：01（45．48％＂US16．04％）、A＊03：01（39．68％VS18．35％）、A＊01：01（33．91％vs18．35％）、A＊02：07（28．18％VS13．73％）高分辨等位基因分布频率较高,差异有统计学意义,P〈0．01。HLA—A＊02：01（69．05％vs85．47％）和A＊1l：01（16．81％VS32．34％）则相对较低,差异有统计意义,P〈0．01。3）新疆地区维吾尔族HL患者与维吾尔族健康人抗原型均以A2最为多见,各型在病例组与对照组之间分布差异无统计学意义,P〉0．05。结论：HLA-A＊01：01：01：01、A＊03：01、A＊01：01和A＊02：07基因型与维吾尔族HL存在阳性关联,可能为维吾尔族HL发病的易感基因,而HLA-A＊02：01、A＊ll：01可能为维吾尔族HL发病的拮抗基因。     

美罗华治疗32例弥漫型大B细胞性非何杰金氏淋巴瘤

目的 评价美罗华治疗弥漫型大B细胞性非何杰金氏淋巴瘤DLBCL的临床效果及不良反应。方法 用同期对照的前瞻性研究方法,将68例弥漫型大B细胞性NHL患者分为研究组(美罗华组)和对照组,前组32例用CHOP方案(环磷酰胺、阿霉素、长春新碱和强的松)联合美罗华治疗;后组36例单用CHOP方案。每4周循环1个疗程,3～6疗程后作评价。将两组患者按国际淋巴瘤预后因子指数(IPI)分为中低危组和高危组,分析其疗效与预后。全部患者6个疗程后停止治疗,随访观察生存情况。结果 美罗华组完全缓解率(CR)达56.3％,总有效率87.5%;对照组分别为13.9％、63.9%,两组疗效差异有统计学意义(P<0.001)。美罗华组6、12、24、36月总的生存率分别为96.9％、87.5％、71.9％和65.6％,对照组分别为91.7％、80.6％、58.3％和41.7％(P>0.05)。美罗华组中中低危组的CR及部分缓解率(PR)分别为68.4％、26.3％,高危组分别为38.5%、38.5％(P<0.01);对照组中低危组的CR及PR分别为15.8％、68,4％,高危组则分别为11.8％、29.4％(P<0.001)。结论 美罗华联合CHOP方案治疗DLBCL的疗效显著,3年生存率高,不良反应较单纯化疗少,可作为该病目前的首选方案。     

自体造血干细胞移植对预后不良非霍奇金淋巴瘤的效果

目的评价自体外周血造血干细胞移植(APBSCT)治疗预后不良非霍奇金淋巴瘤(NHL)病人效果。方法8例复发和具有不良预后因素晚期NHL病人,经BEAM方案预处理后采取APBSCT治疗。结果8例病人均获快速造血功能重建,中性粒细胞≥0.5×109/L时间为8~14 d,平均9 d,血小板≥20×109/L时间为8~17 d,平均11 d。其中4例移植时PR者3例达CR,1例为PR;另4例移植时CR的难治NHL病人已无病存活8~10个月。结论APBSCT支持下超大剂量化疗是治疗预后不良和复发非霍奇金淋巴瘤安全有效的方法。     

Hodgkin Lymphoma after Disseminated Mycobacterium genavense Infection,Germany

Mycobacterium genavense infection, a rare nontuberculous mycobacteria infection, occurs in heavily immunocompromised patients (i.e., those with advanced HIV disease, genetic disorders, or acquired immunologic disorders and those undergoing immunosuppressive therapy). We report a case of disseminated M. genavense infection preceding Hodgkin lymphoma in a patient without obvious risk factors for this infection.     

Intrathoracic infections in Hodgkin lymphoma (HL) patients may cooperate with HL to trigger hemophagocytic lymphohistiocytosis: A retrospective study

Hodgkin lymphoma (HL)-related hemophagocytic lymphohistiocytosis (HLH) has been reported in the literature; however, there is almost no literature on the factors related to HL triggering HLH.One hundred forty patients with HL were retrospectively analyzed. The incidence of HL-related HLH (we call HL-related HLH as HL-HLH). And all HL-HLH patients in our cohort had HLH as the first manifestation and its clinical characteristics and the role of intrathoracic infection (ITI) in triggering HLH are discussed.The 140 patients with HL mainly included mixed-cellularity classic HL (MCCHL) in 81 (57.9%), nodular sclerosis classic HL (NSCHL) in 36 (25.7%), and lymphacyte-rich classic HL in 14 (10.0%) patients. Of the 137 patients who underwent chest computed tomography scans on admission, 44 had ITI, and most of these ITI were mildly ill and had no respiratory symptoms. Among 140 HL patients, 8 patients from MCCHL were diagnosed as HL-HLH. Among 81 MCCHL patients, 26 patients with ITI had a significantly higher incidence of HL-HLH than those without ITI (26.9% vs 1.8%, P = .002). The median survival time of 8 cases of HL-HLH was only 2 months.When HL patients were first admitted to the hospital, 5.7% had HLH as the first manifestation, and 32.1% had ITI. These ITI can cooperate with HL to trigger HLH, despite their mild illness. The prognosis of HL-HLH was poor.     

Protontherapy versus best photon for mediastinal Hodgkin lymphoma: Dosimetry comparison and treatment using ILROG guidelines

The purpose of this work was reducing treatment-related toxicity for Hodgkin lymphomas using practical procedure inspired by the ILROG guidelines. Reporting the first case of localized Hodgkin lymphoma treated with protontherapy in France. A 24-year-old female with mediastinal, bulky, localized, mixed-cellularity, classic Hodgkin lymphoma required an involved-site radiation therapy after complete response following polychemotherapy. Three-dimensional conformal radiation therapy was not acceptable due to high doses to breasts, heart and lungs. We realized a four-dimensional computed tomography (CT) to evaluate target movements and another CT with gating and breath-hold technique. Delineation was performed on both CT using the initial fluorodeoxyglucose positron-emission tomography/CT. One dosimetric plan with rotational intensity-modulated radiation therapy with a helical Tomotherapy© was realized and compared to another one with conformational protontherapy. Ninety-five percent of the planning target volume was covered by 98 and 99% of the prescribed dose with protontherapy and helical Tomotherapy©. Protontherapy provided the best organ at risk protection. Lung and heart protections were better with protontherapy: lung mean dose (3.7 Gy vs. 8.4 Gy) and median dose (0.002 Gy vs. 6.9 Gy), heart mean dose (2.6 Gy vs. 3.7 Gy). Breast sparing was better for both breasts using protontherapy: right breast mean dose (2.4 Gy vs. 4.4 Gy) and left (1.9 Gy vs. 4.6 Gy). The biggest difference was seen with low doses, which were better with protontherapy: volume of lung receiving 5 Gy was 17.5% vs. 54.2% with Helical Tomotherapy©. In view of these results, we decided to treat our patient with protontherapy using respiratory assessment. We delivered 30 Gy (15 fractions) using protontherapy with one direct anterior field using pencil beam scanning and deep inspiration breath-hold technique. We observed only grade 1 skin erythema during treatment and no toxicity during early follow-up.     

Nivolumab for the treatment of classical Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab

Cancer cells are able to escape surveillance from the immune system by co-opting physiologic mechanisms such as the programmed cell death-1 (PD-1) receptor pathway. Agents able to block the interaction between the PD-1 receptor and its ligands have the potential to release T cells from tumor-induced suppression and eradicate malignant cells. Nivolumab – a PD-1 inhibitor – is approved for the treatment of patients with metastatic melanoma and lung cancer. This agent has been tested in patients with advanced Hodgkin lymphoma (HL) and showed impressive results in a phase I trial. Here we review the profile of Nivolumab including its pharmacological properties, clinical efficacy and safety in patients with advanced classical HL.     

Proteasome inhibition in hematologic malignancies

Hematologic malignancies, including multiple myeloma (MM), will account for more than 100,000 new cases of cancer and over 57,000 deaths in the United States in 2003. Treatment of MM is a serious challenge, because despite a variety of available therapies, median survival is short. A new therapeutic area focuses on inhibiting the activity of the proteasome, a 26S protease complex involved in cell cycle regulation, cell adhesion, inflammation, and protein turnover. The novel proteasome inhibitor, bortezomib (Velcade®), was recently approved for use in patients with refractory and relapsed MM and to date is the only proteasome inhibitor to have entered clinical trials. Bortezomib has demonstrated activity with manageable toxicity in a variety of hematologic malignancies in addition to MM, including leukemia and non‐Hodgkin's lymphoma. This article reviews clinical information on bortezomib in hematologic malignancies both as monotherapy and in combination with dexamethasone. Preliminary reports of bortezomib in combination with Doxil (pegylated liposomal doxorubicin), melphalan, and thalidomide are discussed, and current trials are described. Available data suggest that bortezomib will be useful in the treatment of a variety of hematologic malignancies.     

Consenso Mexicano para el Tratamiento de la Hepatitis C

The aim of the Mexican Consensus on the Treatment of Hepatitis C was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitis C treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.