Prognostic Utility of Routine Chimerism Testing at 2 to 6 Months after Allogeneic Hematopoietic Cell Transplantation

Prognostic Utility of Routine Chimerism Testing at 2 to 6 Months after Allogeneic Hematopoietic Cell Transplantation
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DOI:
10.1016/j.bbmt.2008.12.496
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发表时间:
2009-03-01
影响因子:
4.3
通讯作者:
Martin, Paul J.
Martin, Paul J.
中科院分区:
医学2区
文献类型:
--
作者:
Mossallam, Ghada I.;Kamel, Azza M.;Martin, Paul J.

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常规嵌合体分析作为清髓预适应方案异基因造血细胞移植(HCT)后预后的指标的有效性仍然存在争议。为了解决这一争议,对采用清髓调节方案的HCT后2-6个月的常规嵌合体试验结果进行了评估,以确定其与随后发生慢性移植物抗宿主病(GVHD)、无复发死亡率(NRM)、复发和总死亡率的相关性。1304名患者中只有70名(5%)的骨髓中有95%的供者来源的细胞。与高危疾病患者相比,低风险疾病患者骨髓中低供者嵌合体的发生率更高,并且与慢性移植物抗宿主病风险的降低显著相关。在接受评估的673名患者中,164名(24%)血液中有85%的供者来源的T细胞。与高危疾病相比,低风险疾病患者中低供者T细胞嵌合体的发生率更高,在接受白消安预适应的患者中,与接受全身照射的预适应患者相比,在低级别急性移植物抗宿主病患者中,低供者T细胞嵌合体的发生率更高。血液中供者T细胞嵌合率低与慢性移植物抗宿主病风险降低显著相关,但与复发、NRM或总死亡率的降低无关。骨髓移植后2~6个月骨髓和血液中嵌合体的常规检测可能有助于在临床试验中记录植入情况,但在临床实践中只能提供有限的预后信息。
The utility of routine chimerism analysis as a prognostic indicator of subsequent outcomes after allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning regimens remains controversial. To address this controversy, routine chimerism test results at 2 to 6 months after HCT with myeloablative conditioning regimens were evaluated for association with subsequent risk of chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, and overall mortality. Only 70 of 1304 patients (5%) had < 95% donor-derived cells in the marrow. Low donor chimerism in the marrow occurred more often in patients with low-risk diseases compared with those with higher-risk diseases and was significantly associated with a reduced risk of chronic GVHD. Among 673 patients evaluated, 164 (24%) had < 85% donor-derived T cells in the blood. Low donor T cell chimerism was more frequent in patients with low-risk diseases compared with those with higher-risk diseases, in those who received conditioning with busulfan compared with those who received conditioning with total body irradiation, and in those with lower-grade acute GVHD. Low donor T cell chimerism in the blood was significantly associated with a reduced risk of chronic GVHD but not with a reduced risk of relapse, NRM, or overall mortality. Routine testing of chimerism in the marrow and blood at 2 to 6 months after HCT with myeloablative conditioning regimens may be helpful in documenting engraftment in clinical trials, but provides only limited prognostic information in clinical practice.