Hahn M, Böttcher S, Dietrich S, Hegenbart U, Rieger M, Stadtherr P, Bondong A, Schulz R, Ritgen M, Schmitt T, Tran T H, Görner M, Herth I, Luft T, Schönland S, Witzens-Harig M, Zenz T, Kneba M, Ho A D, Dreger P
Department Medicine V, University of Heidelberg, Heidelberg, Germany.
Department Medicine II, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Bone Marrow Transplant. 2015 Oct;50(10):1279-85. doi: 10.1038/bmt.2015.150. Epub 2015 Jul 6.
To elucidate factors contributing to the effectiveness of allogeneic hematopoietic stem cell transplantation (alloHCT) in high-risk CLL, immune interventions, GvHD and clinical outcome of 77 consecutive patients allografted for CLL were analyzed. Immune modulation (immunosuppression tapering, rituximab-augmented donor lymphocyte infusions) was guided by minimal residual disease (MRD) monitoring and commenced at a median of 91 (22-273) days after alloHCT, resulting in a probability of being event free and MRD-negative 1 year after transplant of 57% (84% in those encountering chronic GvHD). Patients who were event free and MRD-negative at the 12-month landmark had a 4-year PFS of 77% and largely remained durably MRD-negative if MRD clearance had occurred subsequent to immune modulation. Three-year overall survival, PFS, relapse incidence and non-relapse mortality of all 77 patients were 69, 57, 26 and 24%, respectively. Survival was not affected by EBMT risk category but by active disease at alloHCT, which could not be overcome by intensification of conditioning. Twenty-three patients who experienced relapse post alloHCT had a survival of 56% at 2 years after CLL recurrence. In conclusion, MRD-guided immune modulation after alloHCT for high-risk CLL can provide durable MRD clearance in more than half of the patients.
为阐明异基因造血干细胞移植（alloHCT）治疗高危慢性淋巴细胞白血病（CLL）有效性的相关因素，对77例连续接受CLL异基因移植患者的免疫干预、移植物抗宿主病（GvHD）及临床结局进行了分析。免疫调节（免疫抑制逐渐减量、利妥昔单抗增强的供体淋巴细胞输注）以微小残留病（MRD）监测为指导，于alloHCT后中位数91（22 - 273）天开始，移植后1年无事件且MRD阴性的概率为57%（发生慢性GvHD的患者中为84%）。在12个月节点时无事件且MRD阴性的患者4年无进展生存期（PFS）为77%，如果在免疫调节后出现MRD清除，大多仍持久保持MRD阴性。77例患者的3年总生存期、PFS、复发率和非复发死亡率分别为69%、57%、26%和24%。生存不受欧洲血液与骨髓移植协会（EBMT）风险类别影响，但受alloHCT时的活动性疾病影响，强化预处理无法克服这一影响。23例alloHCT后复发的患者在CLL复发后2年生存率为56%。总之，高危CLL患者alloHCT后MRD指导的免疫调节可使半数以上患者实现持久的MRD清除。
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