HEMATOLOGY

自1996年1月1日以来，NCCTG血液学组的癌症治疗方案累积了165例患者，平均每年41例患者。另外有162名患者进入了我们的随机研究，即促红细胞生成素用于化疗的贫血患者。在这段时间内启动了8项研究，4项已经完成，6项目前正在进行，2000年初将启动6项新的方案。如果目前所有的方案都按计划在2000年初启动，我们将在2000年开放12个NCCTG血液学方案。该小组发表了一篇关于CLL试验结果的手稿（93- 81-51），该试验测试了氯霉素和2-CDA对活动性、先前未治疗的疾病患者的治疗效果（Tefferi et al., American Journal of Clinical Oncology 22(5):509- 516,1999）。David Inwards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（Blood 94（10）增刊1 (660A), 1999）。有几项研究已经达到了目标，已经结束，正在等待最后的分析，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被用于辅助实验室研究，这些研究侧重于使用荧光原位研究检测肿瘤细胞中的细胞遗传学异常，这些研究侧重于使用荧光原位杂交（FISH）检测肿瘤细胞中的细胞遗传学异常，并通过流式细胞术检测表面标记物和粘附分子。我们对恶性b细胞中syndecan-1（成纤维细胞生长因子共受体）表达的研究结果已经发表（白血病和淋巴瘤31:1267-175,1998）。在过去的两年中，进入nctg血液学方案的患者数量明显过低。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。少量的积极研究是没有预料到的，这是由于以下几个原因：1)梅奥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) 4个已批准的试验因未能从制药申办者处获得药物而得以开放；3)来自ECOG的竞争限制了多发性骨髓瘤和急性白血病治疗方案的数量。社区血液学家对NCCTG血液学的支持仍然很高，因为该方案确实解决了他们在常规基础上看到的肿瘤部位（如CLL和NHL）。由于缺乏应计额，外部咨询小组建议在2000年2月的拨款申请中，血液学不作为一个完整的项目；然而，血液学将继续作为一个工作组，目标是在2000年春季之前激活所有正在开发的协议。然后我们计划在1-2年内作为一个完整的项目重新向国家癌症研究所提交一个非周期的财政支持请求。我们制定了一项加强nctg血液学项目的计划：1)增加有效方案的数量；2)专注于b细胞恶性肿瘤、骨髓增生异常综合征和骨髓增生性疾病；3)增加FTE对血液学项目的投入；4)缩短协议开发和激活时间。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血液学项目的申请是合理的。

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.