Horn B, Soni S, Khan S, Petrovic A, Breslin N, Cowan M, Pelle-Day G, Cooperstein E, Baxter-Lowe L-A
Department of Pediatrics, UCSF Medical Center, University of California, San Francisco, CA 94143-1278, USA.
Bone Marrow Transplant. 2009 Mar;43(6):469-76. doi: 10.1038/bmt.2008.339. Epub 2008 Oct 27.
An increasing percentage of autologous cells (increasing chimerism) in the whole blood (WB) chimerism test following allogeneic transplant is related to a very high risk of relapse. Preemptive immunotherapy may decrease the risk of relapse in some patients. Our prospective multi-institutional study evaluated the feasibility of longitudinal chimerism testing in a central laboratory, compared WB, CD3+ and leukemia-specific lineage chimerism in patients with a variety of hematologic malignancies, and evaluated the feasibility of fast withdrawal of immunosuppression based on WB chimerism results. Centralized chimerism testing was feasible and showed low interassay variability. Increasing mixed chimerism (MC) in WB was not useful as a predictor of relapse in our study. The presence of full donor chimerism in WB, CD3+ and leukemia-specific lineages on all measurements was related to a significantly lower risk of relapse than the presence of MC in either subset (11 vs 71%, respectively; P=0.03). Increasing host chimerism in leukemia-specific lineage heralds relapse, but it was not detected early enough to allow immunotherapy. Further studies correlating lineage-specific chimerism and minimal residual disease are required. The goal of preemptive immunotherapy should be to achieve full donor chimerism in WB in CD3+ and leukemia-specific lineages.
异基因移植后全血（WB）嵌合试验中自体细胞百分比增加（嵌合率增加）与极高的复发风险相关。抢先免疫疗法可能会降低部分患者的复发风险。我们的前瞻性多机构研究评估了在中央实验室进行纵向嵌合检测的可行性，比较了多种血液系统恶性肿瘤患者的WB、CD3 +和白血病特异性谱系嵌合情况，并基于WB嵌合结果评估了快速停用免疫抑制的可行性。集中式嵌合检测是可行的，且检测间变异性较低。在我们的研究中，WB中混合嵌合率（MC）增加对复发并无预测价值。所有检测中，WB、CD3 +和白血病特异性谱系中存在完全供体嵌合与复发风险显著低于任一亚组中存在MC的情况相关（分别为11%和71%；P = 0.03）。白血病特异性谱系中宿主嵌合率增加预示着复发，但发现得不够早，无法进行免疫治疗。需要进一步开展将谱系特异性嵌合与微小残留病相关联的研究。抢先免疫疗法的目标应是在WB、CD3 +和白血病特异性谱系中实现完全供体嵌合。
