Gaballa Sameh, Saliba Rima, Oran Betul, Brammer Jonathan E, Chen Julianne, Rondon Gabriela, Alousi Amin M, Kebriaei Partow, Marin David, Popat Uday R, Andersson Borje S, Shpall Elizabeth J, Jabbour Elias, Daver Naval, Andreeff Michael, Ravandi Farhad, Cortes Jorge, Patel Keyur, Champlin Richard E, Ciurea Stefan O
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Transplant Myeloid Study Group, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Am J Hematol. 2017 Apr;92(4):331-337. doi: 10.1002/ajh.24632. Epub 2017 Feb 13.
In patients with AML with FMS-like tyrosine kinase 3 (FLT3) mutations, the significance of minimal residual disease (MRD) detected by PCR before allogeneic stem cell transplantation (SCT) on outcomes after transplant remains unclear. We identified 200 patients with FLT3-AML who underwent SCT at our institution. Disease status at transplant was: first or second complete remission (CR1/CR2, n = 119), high-risk CR (third or subsequent CR, marrow hypoplasia, or incomplete count recovery) (CR-HR, n = 31), and morphological evidence of active disease (AD, n = 50). The median follow-up was 27 months, and the 2-year overall and progression-free survival were 43% and 41%, respectively. Relapse was highest in the AD group (85%) and the CR-HR FLT3 MRD positive group (72%), followed by CR-HR FLT3 MRD negative (58%), CR1/CR2 FLT3 MRD positive (39%), and lowest in the CR1/CR2 FLT3 MRD negative group (23%). On multivariate analysis, independent factors influencing the risk of relapse were detectable morphological disease and FLT3 MRD by PCR pre-transplant. Factors that did not influence the relapse risk included: age, graft type, graft source, type of FLT3 mutation, or conditioning intensity. Morphologic and molecular remission status at the time of transplant were key predictors of disease relapse and survival in patients with FLT3-AML.
在伴有FMS样酪氨酸激酶3（FLT3）突变的急性髓系白血病（AML）患者中，异基因造血干细胞移植（SCT）前通过聚合酶链反应（PCR）检测到的微小残留病（MRD）对移植后结局的意义仍不明确。我们纳入了200例在本机构接受SCT的FLT3-AML患者。移植时的疾病状态为：首次或第二次完全缓解（CR1/CR2，n = 119）、高危完全缓解（第三次或后续完全缓解、骨髓发育不全或计数未完全恢复）（CR-HR，n = 31）以及有活动性疾病的形态学证据（AD，n = 50）。中位随访时间为27个月，2年总生存率和无进展生存率分别为43%和41%。复发率在AD组最高（85%），其次是CR-HR FLT3 MRD阳性组（72%），然后是CR-HR FLT3 MRD阴性组（58%）、CR1/CR2 FLT3 MRD阳性组（39%），最低的是CR1/CR2 FLT3 MRD阴性组（23%）。多因素分析显示，影响复发风险的独立因素是移植前可检测到的形态学疾病和通过PCR检测到的FLT3 MRD。不影响复发风险的因素包括：年龄、移植物类型、移植物来源、FLT3突变类型或预处理强度。移植时的形态学和分子缓解状态是FLT3-AML患者疾病复发和生存的关键预测因素。
