Moreton Paul, Kennedy Ben, Lucas Guy, Leach Michael, Rassam Saad M B, Haynes Andrew, Tighe Jane, Oscier David, Fegan Christopher, Rawstron Andy, Hillmen Peter
Leeds Teaching Hospitals, NHS Trust, Great George St, Leeds, LS1 3EX United Kingdom.
J Clin Oncol. 2005 May 1;23(13):2971-9. doi: 10.1200/JCO.2005.04.021. Epub 2005 Feb 28.
To test whether eradication of minimal residual disease (MRD) in B-cell chronic lymphocytic leukemia (CLL) by alemtuzumab is associated with a prolongation of treatment-free and overall survival.
Ninety-one previously treated patients with CLL (74 men and 17 women; median age, 58 years [range, 32 to 75 years]; 44 were refractory to purine analogs) received a median of 9 weeks of alemtuzumab treatment between 1996 and 2003. Regular bone marrow assessments by MRD flow cytometry were performed with the aim of eradicating detectable MRD (< 1 CLL cell in 10(5) normal cells).
Responses according to National Cancer Institute-sponsored working group response criteria were complete remission (CR) in 32 patients (36%), partial remission (PR) in 17 patients (19%), and no response (NR) in 42 patients (46%). Twenty-two (50%) of 44 purine analog-refractory patients responded to alemtuzumab. Detectable CLL was eradicated from the blood and marrow in 18 patients (20%). Median survival was significantly longer in MRD-negative patients compared with those achieving an MRD-positive CR, PR, or NR. Patients achieving an MRD-negative CR had a longer treatment-free survival than patients with MRD-positive CRs, PR, or NR: MRD-negative CRs, not reached; MRD-positive CRs, 20 months; PRs, 13 months; NR, 6 months (P < .0001). Overall survival for the 18 patients with MRD-negative remissions was 84% at 60 months. Eight (47%) of the MRD-negative patients converted to MRD positivity at a median of 28 months.
MRD-negative remission in CLL is achievable with alemtuzumab, leading to an improved overall and treatment-free survival.
检测阿仑单抗清除B细胞慢性淋巴细胞白血病（CLL）微小残留病（MRD）是否与无治疗生存期和总生存期的延长相关。
91例既往接受过治疗的CLL患者（74例男性，17例女性；中位年龄58岁[范围32至75岁]；44例对嘌呤类似物耐药）在1996年至2003年间接受了中位9周的阿仑单抗治疗。采用MRD流式细胞术定期进行骨髓评估，目的是清除可检测到的MRD（每10⁵个正常细胞中<1个CLL细胞）。
根据美国国立癌症研究所资助的工作组反应标准，32例患者（36%）达到完全缓解（CR），17例患者（19%）达到部分缓解（PR），42例患者（46%）无反应（NR）。44例对嘌呤类似物耐药的患者中有22例（50%）对阿仑单抗有反应。18例患者（20%）的血液和骨髓中可检测到的CLL被清除。MRD阴性患者的中位生存期显著长于达到MRD阳性CR、PR或NR的患者。达到MRD阴性CR的患者比MRD阳性CR、PR或NR的患者有更长的无治疗生存期：MRD阴性CR患者未达到；MRD阳性CR患者为20个月；PR患者为13个月；NR患者为6个月（P<.0001）。18例MRD阴性缓解患者的60个月总生存率为84%。8例（47%）MRD阴性患者在中位28个月时转为MRD阳性。
阿仑单抗可使CLL患者达到MRD阴性缓解，从而改善总生存期和无治疗生存期。
