Chemotherapy-Phased Imatinib Pulses Improve Long-Term Outcome of Adult Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Northern Italy Leukemia Group Protocol 09/00
Chemotherapy-Phased Imatinib Pulses Improve Long-Term Outcome of Adult Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Northern Italy Leukemia Group Protocol 09/00
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DOI：
10.1200/jco.2010.28.1287
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发表时间：
2010-08-01
影响因子：
45.3
通讯作者：
Rambaldi, Alessandro
中科院分区：
文献类型：
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作者：
Bassan, Renato;Rossi, Giuseppe;Rambaldi, Alessandro
在94例患者(年龄19~66岁)中，35例为对照组(即伊马替尼阴性组)，59例为伊马替尼600 mg/d口服连续7天(即伊马替尼阳性组)。从化疗第1疗程第15天开始，第2~8疗程化疗前3天开始。完全缓解的患者可以接受异基因SCT，或接受大剂量的自体SCT治疗，然后用间歇性伊马替尼长期维持治疗。P=0.08；异基因SCT：63%vs39%；P=.041)。在中位观察时间为5年(范围为0.6至9.2年)时，IM阳性组有22名患者首次CR存活，而IM阴性组有5名患者存活(P=.037)。IM阳性组的患者总体和无病生存概率显著较高(总体：0.38比0.23；P=.009；无病：0.39比0.25；P=.044)，复发率较低(P=.005)。干细胞移植相关死亡率为28%(即54例患者中有15例)，移植后存活率为0.46。结论基于伊马替尼的方案改善了Ph阳性的成人ALL患者的长期预后。对于SCT，移植后的死亡率和复发仍然是进一步改善治疗的主要障碍。无论是选择接受SCT的患者还是无法接受SCT的患者，进一步加强伊马替尼治疗应能保证更好的分子反应和临床结果。
PurposeShort imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates.Patients and MethodsOf 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib.ResultsCR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall.ConclusionThis imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure.