HEMATOLOGY

自1996年1月1日以来，NCCTG血液学组癌症治疗方案迄今已累计165例患者，平均每年41例患者。另外162例患者进入我们的随机研究促红细胞生成素对贫血患者化疗。在此期间，已启动了八项研究，四项已经完成，六项正在进行中，六项新的议定书将于2000年初启动。如果到2000年初，目前所有的协议都按计划启动，我们将在2000年开放12个NCCTG血液学协议。该小组已经发表了一份关于CLL试验结果的手稿（93- 81-51），该试验测试了苯丁酸氮芥和2-CDA用于患有活动性的、先前未治疗的疾病的患者（Tefferi等人，American Journal of Clinical Oncology 22（5）：509-516，1999）。大卫·英沃兹博士最近在美国血液学年会上介绍了NCCTG 95-80-53的结果，该结果研究了2-CDA作为先前未经治疗的套细胞淋巴瘤的初始治疗，这些结果现在以摘要形式发表（血液94（10）增刊1（660 A），1999）。几项研究已经达到了预期的累积目标，已经关闭，正在等待最后分析，然后以摘要和完整的手稿形式提交。进入NCCTG CLL试验的患者的肿瘤细胞已用于辅助实验室研究，重点关注使用荧光原位研究在肿瘤细胞中检测到的细胞遗传学异常，重点关注使用荧光原位杂交（FISH）在肿瘤细胞中检测到的细胞遗传学异常以及通过流式细胞术检测表面标志物和粘附分子。我们对恶性B细胞的多配体蛋白聚糖-1（成纤维细胞生长因子的共受体）表达的研究结果已经发表（Leukemia and Lymphoma 31：1267-175，1998）。在过去的两年中，很明显，进入NCCTG血液学方案的患者数量太少。累积不足的主要原因是缺乏开放方案，而不是开放研究的累积不足。未预期到少量的积极研究，这是由于以下几个原因：1）马约诊所研究基地的一些重要的试点研究没有显示出足够的活动来保证完整的NCCTG试验; 2）由于未能从制药申办者获得药物，四项已批准的试验已经能够开放; 3）来自ECOG的竞争限制了多发性骨髓瘤和急性白血病的方案数量。社区血液学家对支持NCCTG血液学的兴趣仍然很高，因为这些方案确实解决了他们常规看到的肿瘤部位（如CLL和NHL）。由于缺乏应计费用，外部咨询小组建议在2000年2月的拨款申请中不将血液学作为一个完整的项目;但是，血液学将继续作为一个工作组，目的是在2000年春季之前激活所有正在开发的方案。然后，我们计划在1-2年内向国家癌症研究所重新提交一份不定期的财政支持申请，作为一个完整的项目。我们制定了一项计划，通过以下方式加强NCCTG血液学项目：1）增加有效方案的数量; 2）将我们的工作重点放在B细胞恶性肿瘤、骨髓增生异常综合征和骨髓增生性疾病上; 3）增加FTE对血液学项目的承诺; 4）缩短方案制定和激活时间。我们完全打算在未来几年内建立一个坚实的跟踪记录，这将证明NCI支持NCCTG血液学项目的合理性。

The accrual of NCCTG Hematology Group cancer treatment protocols to date has been 165 patients since January 1, 1996 with an average of 41 patients per year. An additional 162 patients have entered our randomized study of erythropoietin for anemic patients on chemotherapy. Eight studies have been activated during this time period, four have been completed, six are currently active, and six new protocols will be activated in early 2000. If all protocols that are currently are activated as planned by early 2000, we will have 12 NCCTG Hematology protocols open in 2000. The group has published one manuscript on the results of a CLL trial (93- 81-51) that tested chlorambucil and 2-CDA for patients with active, previously untreated disease (Tefferi et al., American Journal of Clinical Oncology 22(5):509-516, 1999). Dr. David Inwards recently presented at the annual meeting of the American of Hematology the results of NCCTG 95-80-53 which studied 2-CDA as initial treatment for previously untreated mantle cell lymphoma and these results are now published in abstract form (Blood 94 (10) Suppl 1 (660A), 1999). Several studies have met their targeted accrual, are closed, and are awaiting final analysis before submission in abstract and full manuscript form. Tumor cells from patients entering the NCCTG CLL trials have been used for ancillary laboratory investigations that have focused on cytogenetic abnormalities detected in tumor cells using fluorescence in situ investigations that have focused on cytogenetic abnormalities detected in tumor cells using fluorescence in situ hybridization (FISH) and detection of surface markers and adhesion molecules by flow cytometry. The results of our study of syndecan-1 (co-receptor for fibroblast growth factor) expression of malignant B-cells have been published (Leukemia and Lymphoma 31:1267-175, 1998). During the past two years, it has become apparent that the number of patients entering NCCTG Hematology protocols was too low. The primary reason for the inadequate accrual was a lack of open protocols rather than poor accrual to open studies. The small number of active studies was not anticipated and is due to several reasons: 1) some important pilot studies at the Mayo Clinic research base did not show adequate activity to warrant full NCCTG trials; 2) four approved trials have been able to open because of failure to obtain drug from pharmaceutical sponsors; 3) competition from ECOG has limited the number of protocols in multiple myeloma and acute leukemia. Interest on the part of the community hematologists remains high in support of NCCTG Hematology, because the protocols do indeed address tumor sites (such as CLL and NHL) that they see on a routine basis. Because of lack of accrual, it was recommended by External Advisory Group that Hematology not be included as a full program in the February, 2000, grant submission; however, Hematology will continue as a working group with the aim of activating all of the protocols in development by Spring, 2000. We then plan to resubmit an out-of-cycle request for financial support to the National Cancer Institute as a full program in 1-2 years. We have developed a plan to strengthen the NCCTG Hematology Program by 1) increasing the number of active protocols; 2) focusing our efforts on the B-cell malignancies, myelodysplastic syndromes, and myeloproliferative disorders; 3) increasing the FTE commitment to the Hematology Program; and 4) shortening the protocol development and activation time. We fully intend to establish a solid track record over the next few years which will justify submission for NCI support of an NCCTG Hematology Program.