Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
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DOI：
10.3324/haematol.2014.118588
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发表时间：
2015-05-01
期刊：
影响因子：
10.1
通讯作者：
O'Brien, Susan
中科院分区：
文献类型：
--
作者：
Daver, Naval;Thomas, Deborah;O'Brien, Susan
我们以前曾报道过20例新诊断的费城阳性急性淋巴细胞白血病患者接受hyper-CVAD方案（环磷酰胺、长春新碱、阿霉素和地塞米松）和伊马替尼联合以伊马替尼为基础的巩固/维持治疗的疗效和耐受性。在这里，我们介绍了我们研究的13年随访。入组了54例新诊断的费城阳性急性淋巴细胞白血病患者：39例（72%）为新发疾病，6例（11%）在诱导治疗后为原发难治性疾病（无酪氨酸激酶抑制剂），9例（17%）在一个疗程的诱导治疗后完全缓解（无酪氨酸激酶抑制剂）。45例接受活动性疾病治疗的患者中有42例（93%）达到完全缓解，1例达到完全缓解伴血小板不完全恢复，1例达到部分缓解，1例在诱导期间死亡。19例（35%）患者存活，18例完全缓解。所有患者的5年总生存率为43%。总生存率的显著负性预测因素为年龄超过60岁、p190分子转录本和入组时的活动性疾病。16例（30%）患者接受了异基因干细胞移植。接受移植的患者的中位总生存期并没有显著增加。3个月时有残留分子疾病的患者，移植后完全缓解时间延长。联合用药组的血液学恢复和严重毒性的中位时间与常规化疗组相比无显著差异。只有1名患者因毒性而停止治疗。HyperCVAD化疗联合伊马替尼是治疗费城阳性急性淋巴细胞白血病的有效方案。移植可能并不适用于所有费城阳性急性淋巴细胞白血病患者。
We have previously reported on the efficacy and tolerability of hyper-CVAD regimen (cyclophosphamide, vincristine, Adriamycin, and dexamethasone) and imatinib followed by imatinib-based consolidation/ maintenance therapy in 20 patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Here, we present the 13-year follow up of our study. Fifty-four patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia were enrolled: 39 (72%) with de novo disease, 6 (11%) whose disease was primary refractory after induction (without a tyrosine kinase inhibitor), and 9 (17%) in complete remission after one course of induction therapy (without tyrosine kinase inhibitor). Forty-two (93%) of the 45 patients treated for active disease achieved complete remission, one achieved complete remission with incomplete recovery of platelets, one achieved partial remission and one died during induction. Nineteen (35%) patients are alive and 18 are in complete remission. The 5-year overall survival rate for all patients was 43%. Significant negative predictors of overall survival were age over 60 years, p190 molecular transcript, and active disease at enrollment. Sixteen (30%) patients underwent allogeneic stem cell transplantation. Median overall survival was not significantly greater for patients who underwent transplant. Patients with residual molecular disease at three months had improved complete remission duration with transplant. The median time to hematologic recovery and severe toxicities with combination were not significantly different from those observed with conventional chemotherapy. Only one patient discontinued therapy due to toxicity. HyperCVAD chemotherapy and imatinib is an effective regimen for Philadelphia-positive acute lymphoblastic leukemia. Transplant may not be indicated in all patients with Philadelphia-positive acute lymphoblastic leukemia.