HEMATOLOGY

自1996年1月1日以来，NCCTG血液病集团癌症治疗方案至今已累计治疗165名患者，平均每年41名患者。另有162名患者参加了我们的促红细胞生成素治疗化疗贫血患者的随机研究。在此期间启动了8项研究，4项已完成，6项目前正在进行中，6项新议定书将于2000年初启动。如果目前所有的方案都按计划在2000年初激活，我们将在2000年有12个NCCTG血液学方案开放。该小组发表了一篇关于CLL试验结果的手稿(93-81-51)，该试验测试了百菌清和2-CDA对活动的、以前未治疗的疾病的患者(Tefferi等人，美国临床肿瘤学杂志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的研究结果，该研究将2-CDA作为以前未治疗的套细胞淋巴瘤的初始治疗方法，这些结果现已以摘要形式发表(血液94(10)Suppl 1(660a)，1999)。有几项研究已达到预期目标，现已结束，正在等待最终分析，然后再以摘要和完整的手稿形式提交。参加NCCTG CLL试验的患者的肿瘤细胞已被用于辅助实验室研究，重点是使用荧光原位杂交(FISH)检测肿瘤细胞中的细胞遗传学异常以及通过流式细胞仪检测表面标记和黏附分子来检测肿瘤细胞中的细胞遗传学异常。我们对恶性B细胞表达Syndecan-1(成纤维细胞生长因子的共同受体)的研究结果已发表(白血病和淋巴瘤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。应计费用不足的主要原因是缺乏开放的方案，而不是开放研究的应计费用很少。为数不多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先导性研究没有显示出足够的活性，不足以保证进行全面的NCCTG试验；2)由于未能从药品赞助商那里获得药物，已有4个已批准的试验得以开启；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，因为这些方案确实涉及他们在常规基础上看到的肿瘤部位(如CLL和NHL)。由于缺乏应计利润，外部咨询小组建议，血液学不应作为一个完整的计划列入2000年2月的拨款申请；然而，血液学将继续作为一个工作组，目标是在2000年春季之前启动所有正在开发的方案。然后我们计划在1-2年内重新向国家癌症研究所提交一个周期外的财政支持请求，作为一个完整的计划。我们已经制定了一项加强NCCTG血液学计划的计划，通过1)增加有效方案的数量；2)将我们的努力集中在B细胞恶性肿瘤、骨髓增生异常综合征和骨髓增殖性疾病上；3)增加对血液学计划的FTE承诺；以及4)缩短方案开发和激活时间。我们完全打算在未来几年建立一个可靠的记录，这将证明提交NCI支持NCCTG血液学计划是合理的。

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.