Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.
Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.
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DOI：
10.1002/cncr.29646
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发表时间：
2015-12-01
期刊：
影响因子：
6.2
通讯作者：
Kantarjian HM
中科院分区：
文献类型：
--
作者：
Ravandi F;O'Brien SM;Cortes JE;Thomas DM;Garris R;Faderl S;Burger JA;Rytting ME;Ferrajoli A;Wierda WG;Verstovsek S;Champlin R;Kebriaei P;McCue DA;Huang X;Jabbour E;Garcia-Manero G;Estrov Z;Kantarjian HM
联合化疗与达沙替尼治疗费城染色体阳性（Ph+）急性淋巴细胞白血病（ALL）患者的长期疗效尚未明确。患者接受达沙替尼治疗，8个周期交替hyperCVAD和高剂量阿糖胞苷和甲氨蝶呤。完全缓解（CR）患者继续维持达沙替尼、长春新碱和泼尼松2年，随后无限期接受达沙替尼治疗。符合异基因干细胞移植（SCT）条件的患者在首次CR时接受了SCT。72例中位年龄为55岁（范围21 - 80岁）的患者接受了治疗; 69例（96%）达到CR。其中，57例（83%）患者在1个周期后达到细胞遗传学（CG）CR，64例（93%）患者在中位4周（范围，2 - 38周）时达到主要分子学缓解（MMR）。在中位数为3周（范围，2-37）时，65例（94%）患者通过流式细胞术检测的微小残留病变为阴性。达沙替尼相关的3级和4级不良事件包括出血、胸腔/心包积液和转氨酶升高。中位随访时间为67个月（范围，33-97），33例患者（46%）存活，30例（43%）达到CR; 12例接受了同种异体SCT。39例患者死亡（3例在诱导期，19例在复发后，7例在CR 1中进行SCT后，10例在CR中）。中位无病生存期和总生存期分别为31个月（范围0.3 - 97）和47个月（范围0.2 - 97）。7例复发患者有ABL突变，包括4例T315 I。化疗联合达沙替尼可有效实现新诊断Ph+ ALL患者的长期缓解。
The long-term efficacy of combination of chemotherapy with dasatinib in patients with Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is not well-established. Patients received dasatinib with 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate. Patients in complete remission (CR) continued maintenance dasatinib, vincristine and prednisone for 2 years followed by dasatinib indefinitely. Patients eligible for allogeneic stem cell transplant (SCT) received it in first CR. 72 patients with a median age of 55 years (range 21 – 80) were treated; 69 (96%) achieved CR. Among them, 57 (83%) achieved cytogenetic (CG) CR after 1 cycle and 64 (93%) achieved a major molecular response (MMR) at a median of 4 weeks (range, 2 – 38 weeks). Minimal residual disease by flow cytometry was negative in 65 (94 %) patients at a median of 3 weeks (range, 2–37). Dasatinib-related grade 3 and 4 adverse events included bleeding, pleural/pericardial effusions, and elevated transaminases. With a median follow-up of 67 months (range, 33–97), 33 patients (46%) are alive and 30 (43%) are in CR; 12 underwent an allogeneic SCT. Thirty nine patients have died (3 at induction, 19 after relapse, 7 post SCT performed in CR1, and 10 in CR). The median disease free and overall survival are 31 months (range, 0.3 to 97) and 47 months (range, 0.2 to 97). Seven relapsed patients had ABL mutations including 4 T315I. Combination of chemotherapy with dasatinib is effective in achieving long-term remissions in patients with newly diagnosed Ph+ ALL.