Caballero Dolores, García-Marco Jose A, Martino Rodrigo, Mateos Victoria, Ribera José M, Sarrá José, León Angel, Sanz Guillermo, de la Serna Javier, Cabrera Rafael, González Marcos, Sierra Jorge, San Miguel Jesús
Hospital Clínico Universitario de Salamanca, Spain.
Clin Cancer Res. 2005 Nov 1;11(21):7757-63. doi: 10.1158/1078-0432.CCR-05-0941.
To evaluate the efficacy of reduced intensity conditioning (RIC) allogeneic transplant in 30 patients with poor-prognosis chronic lymphocytic leukemia (CLL) and/or high-risk molecular/cytogenetic characteristics.
Eighty-three percent of patients had active disease at the moment of transplant. That is, 14 of the 23 patients analyzed (60%) had unmutated immunoglobulin variable heavy-chain gene (IgV(H)) status; 8 of 25 patients (32%) had 11q-, with four of them also displaying unmutated IgV(H); and six (24%) had 17p- (five were also unmutated).
After a median follow-up of 47.3 months, all 22 patients alive are disease free; overall survival and event-free survival (EFS) at 6 years were 70% and 72%, respectively. According to molecular/cytogenetic characteristics, overall survival and EFS for unmutated CLL and/or with 11q- aberration (n = 13) were 90% and 92%, respectively, not significantly different to those with normal in situ hybridization, 13q- and +12, or mutated CLL (n = 7). All six patients with 17p deletion were transplanted with active disease, including three with refractory disease; all except one reached complete remission after the transplant and two are alive and disease free. Nonrelapse mortality (NRM) was 20%; more than two lines before transplant is an independent prognostic factor for NRM (P = 0,02), EFS (P = 0.02), and overall survival (P = 0.01). Patients older than 55 years have a higher risk of NRM (hazard ratio, 12.8; 95% confidence interval, 1.5-111). Minimal residual disease was monitored by multiparametric flow cytometry in 21 patients. Clearance of CD79/CD5/CD19/CD23 cells in bone marrow was achieved in 68% and 94% of the patients at days 100 and 360, respectively.
According to these results, RIC allogeneic transplant could overcome the adverse prognosis of patients with unmutated CLL as well as those with 11q- or 17p-.
评估减低强度预处理（RIC）异基因移植对30例预后不良的慢性淋巴细胞白血病（CLL）患者和/或具有高危分子/细胞遗传学特征患者的疗效。
83%的患者在移植时患有活动性疾病。也就是说，在分析的23例患者中，有14例（60%）免疫球蛋白可变重链基因（IgV(H)）未发生突变；25例患者中有8例（32%）存在11q-，其中4例同时显示IgV(H)未发生突变；6例（24%）存在17p-（5例也未发生突变）。
中位随访47.3个月后，所有22例存活患者均无疾病；6年时的总生存率和无事件生存率（EFS）分别为70%和72%。根据分子/细胞遗传学特征，未发生突变的CLL和/或伴有11q-异常（n = 13）患者的总生存率和EFS分别为90%和92%，与原位杂交正常、13q-和+12或发生突变的CLL患者（n = 7）相比，差异无统计学意义。所有6例存在17p缺失的患者均在患有活动性疾病时接受移植，其中3例为难治性疾病；除1例患者外，所有患者移植后均达到完全缓解，2例患者存活且无疾病。非复发死亡率（NRM）为20%；移植前接受过两种以上治疗方案是NRM（P = 0.02）、EFS（P = 0.02）和总生存率（P = 0.01）的独立预后因素。年龄大于55岁的患者NRM风险更高（风险比，12.8；95%置信区间，1.5 - 111）。对21例患者采用多参数流式细胞术监测微小残留病。分别在第100天和第360天，68%和94%的患者骨髓中CD79/CD5/CD19/CD23细胞清除。
根据这些结果，RIC异基因移植可克服未发生突变的CLL患者以及伴有11q-或17p-患者的不良预后。
