Ravandi Farhad, Othus Megan, O'Brien Susan M, Forman Stephen J, Ha Chul S, Wong Jeffrey Y C, Tallman Martin S, Paietta Elisabeth, Racevskis Janis, Uy Geoffrey L, Horowitz Mary, Takebe Naoko, Little Richard, Borate Uma, Kebriaei Partow, Kingsbury Laura, Kantarjian Hagop M, Radich Jerald P, Erba Harry P, Appelbaum Frederick R
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
SWOG Statistical Center, Seattle, WA.
Blood Adv. 2016 Dec 27;1(3):250-259. doi: 10.1182/bloodadvances.2016001495.
This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100. Others received maintenance therapy with vincristine and prednisone for 2 years and dasatinib indefinitely. 97 patients (94 evaluable) with median age of 44 years (range, 20 - 60) and median WBC at presentation of 10 × 10/L (range, 1 - 410 × 10/L) were accrued. 83 (88%) patients achieved CR or CR with incomplete count recovery (CRi) and 41 underwent ASCT in CR1. Median follow-up is 36 months (range, 9 - 63). For the overall population, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) at 3 years were 69%, 55%, and 62%, respectively. The 12-month RFS and OS after transplant were 71% and 87%, respectively. Landmark analysis at 175 days from the time of CR/CRi (longest time to HCT), showed statistically superior advantages for RFS and OS (p=0.038 and 0.037, respectively) for the transplanted patients. Addition of dasatinib to chemotherapy and HCT for younger patients with Ph+ ALL is feasible and warrants further testing.
这项多中心试验旨在确定在费城染色体阳性（Ph+）急性淋巴细胞白血病（ALL）患者中，在化疗后加用达沙替尼并随后进行异基因造血细胞移植（HCT）是否可行。年龄≥18岁且≤60岁的新诊断Ph+ ALL患者接受多达8个周期的交替高剂量环磷酰胺、长春新碱、阿霉素和地塞米松（hyperCVAD）以及大剂量阿糖胞苷和甲氨蝶呤联合达沙替尼治疗。有可用的匹配同胞或无关供者的患者在首次完全缓解（CR1）时接受异基因HCT，从第100天开始每日服用达沙替尼。其他患者接受长春新碱和泼尼松维持治疗2年，并无限期服用达沙替尼。共纳入97例患者（94例可评估），中位年龄44岁（范围20 - 60岁），初诊时中位白细胞计数为10×10⁹/L（范围1 - 410×10⁹/L）。83例（88%）患者达到完全缓解（CR）或血细胞计数未完全恢复的完全缓解（CRi），41例在CR1时接受了自体干细胞移植（ASCT）。中位随访时间为36个月（范围9 - 63个月）。对于总体人群，3年时的总生存期（OS）、无事件生存期（EFS）和无复发生存期（RFS）分别为69%、55%和62%。移植后12个月的RFS和OS分别为71%和87%。从CR/CRi时间（至HCT最长时间）起175天的标志性分析显示，移植患者的RFS和OS在统计学上具有显著优势（分别为p = 0.038和0.037）。对于年轻的Ph+ ALL患者，在化疗和HCT中加用达沙替尼是可行的，值得进一步研究。
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