美国血液学会(ASH)年会热点预览

本周末，美国血液学会2013年会将在新奥尔良举行，我们将在第一时间为您现场报道有关血液学疾病病因学、诊断和治疗的最新研究进展，敬请关注。

以下是12月8日全体大会将要报告的部分论文摘要，让我们先睹为快。

治疗相关性AML早期TP53突变

一项新的研究表明，与自然衰老相关的获得性杂合TP53突变在细胞毒性治疗情况下被选择突变，导致治疗相关性急性髓性白血病(AML)和骨髓增生异常综合征。研究者既往已发现，治疗相关性和原发性AML患者体细胞单核苷酸变异总数和颠换百分比相似，没有证据表明化疗可导致治疗相关性AML患者全基因组DNA损伤。

圣路易斯华盛顿大学的Terrence Neal Wong博士及其同事将详细介绍细胞毒性治疗如何导致血液干细胞发生选择性TP53突变。该研究结果提供了一种用以解释治疗相关性AML和骨髓增生异常综合征患者TP53突变率较高的可能机制。研究者推测，初始克隆中早期获得性TP53突变很可能促使细胞遗传学异常，并使这些患者对化疗应答不佳。

CCL11试验第2阶段结果

德国CLL研究组、科隆大学医院的ValentinGoede医生将报告CLL11试验第2阶段研究结果：与利妥昔单抗+苯丁酸氮芥相比，慢性淋巴细胞白血病(CLL)初治患者接受CD20抗体obinutuzumab+苯丁酸氮芥治疗完全应答率更高且无进展生存期更长。

中位19个月随访后的第2阶段结果显示，obinutuzumab+苯丁酸氮芥治疗组与输注有关的反应和中性粒细胞减少症更为多见，但未见感染增加。研究者认为，obinutuzumab+苯丁酸氮芥联合治疗优于利妥昔单抗+苯丁酸氮芥。

FIRST(来那度胺+地塞米松与标准沙利度胺对比研究)试验

FIRST试验是一项多中心、开放性III期试验，旨在比较来那度胺+地塞米松与马法兰、泼尼松和沙利度胺用于不适合干细胞移植的新确诊多发性骨髓瘤患者治疗的有效性和安全性。

结果显示，与标准马法兰、泼尼松和沙利度胺三联治疗相比，来那度胺+地塞米松联合持续治疗可改善患者无进展生存率这一主要终点指标。法国里尔Claude Huriez医院的Thierry Facon医生及其同事将报告有关试验结果。

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Our onsite coverage of the American Society of Hematology’s annual meeting in New Orleans begins this weekend, bringing you timely insights on the latest research into the etiology, diagnosis, and treatment of hematologic disorders.

To preview our coverage, enjoy this summary of just a few of the reports scheduled for presentation at the plenary session on Sunday, Dec. 8.

Early TP53 Mutations in Therapy-Related AML

New research suggests that heterozygous TP53 mutations, acquired as a function of normal aging, are selected for in the presence of cytotoxic therapy and result in therapy-related acute myeloid leukemia (AML) and myelodysplastic syndrome. The insights come from the research group that previously reported that there is no evidence that chemotherapy induces genome-wide DNA damage in therapy-related AML, based on their finding of similar total numbers of somatic single nucleotide variants and percentages of transversions in therapy-related and de novo AML.

Dr. Terrence Neal Wong of Washington University, St. Louis, and his colleagues will detail how hematologic stem cells that acquire heterozygous TP53 mutations as a function of normal aging may be selected for in the presence of cytotoxic therapy. Their findings provide a potential mechanism for the high incidence of TP53 mutations in therapy-related AML and myelodysplastic disorder. They speculate that early acquisition of TP53 mutations in the founding clone likely contribute to the cytogenetic abnormalities and poor response to chemotherapy in these disorders.

Final Stage 2 Results of the CLL11 Trial

Obinutuzumab, a CD20 antibody, in combination with chlorambucil, was associated with a higher complete response rate and longer progression-free survival as compared with rituximab and chlorambucil in previously untreated patients with chronic lymphocytic leukemia and comorbidities, based on results to be presented by Dr. ValentinGoede of the German CLL Study Group and the University Hospital Cologne, Germany.

After a median 19 month follow-up, the final stage 2 results of the CLL11 Trial found infusion-related reactions and neutropenia were more common with obinutuzumab and chlorambucil without an increase in infections. The researchers will present data to support their conclusion that the obinutuzumab and chlorambucil combination is superior to rituximab and chlorambucil.

The FIRST (Frontline investigation of lenalidomide + dexamethasone vs. standard thalidomide) Trial

The FIRST trial is a multicenter, open-label, phase III trial comparing the efficacy and safety of lenalidomide + dexamethasone vs. melphalan, prednisone, and thalidomide in newly diagnosed multiple myeloma patients ineligible for stem cell transplants.

Dr. Thierry Facon of Hôpital Claude Huriez, Lille, France, and his colleagues will present data indicating that continuous treatment with the all oral doublet lenalidomide + dexamethasone significantly improved the primary endpoint of progression-free survival, compared with the standard triplet melphalan, prednisone, and thalidomide.