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采用清髓性预处理方案进行单份脐血移植后的植入动力学及移植物失败情况

Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen.

作者信息

Ruggeri Annalisa, Labopin Myriam, Sormani Maria Pia, Sanz Guillermo, Sanz Jaime, Volt Fernanda, Michel Gerard, Locatelli Franco, Diaz De Heredia Cristina, O'Brien Tracey, Arcese William, Iori Anna Paola, Querol Sergi, Kogler Gesine, Lecchi Lucilla, Pouthier Fabienne, Garnier Federico, Navarrete Cristina, Baudoux Etienne, Fernandes Juliana, Kenzey Chantal, Eapen Mary, Gluckman Eliane, Rocha Vanderson, Saccardi Riccardo

机构信息

Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, France Hospital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire, AP-HP, UPMC University of Paris 06, UMR-S 938, CEREST-TC EBMT, France Cord Blood Committee EBMT, University of Genova, Italy

Hospital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire, AP-HP, UPMC University of Paris 06, UMR-S 938, CEREST-TC EBMT, France.

出版信息

Haematologica. 2014 Sep;99(9):1509-15. doi: 10.3324/haematol.2014.109280. Epub 2014 Jun 27.

Abstract

Umbilical cord blood transplant recipients are exposed to an increased risk of graft failure, a complication leading to a higher rate of transplant-related mortality. The decision and timing to offer a second transplant after graft failure is challenging. With the aim of addressing this issue, we analyzed engraftment kinetics and outcomes of 1268 patients (73% children) with acute leukemia (64% acute lymphoblastic leukemia, 36% acute myeloid leukemia) in remission who underwent single-unit umbilical cord blood transplantation after a myeloablative conditioning regimen. The median follow-up was 31 months. The overall survival rate at 3 years was 47%; the 100-day cumulative incidence of transplant-related mortality was 16%. Longer time to engraftment was associated with increased transplant-related mortality and shorter overall survival. The cumulative incidence of neutrophil engraftment at day 60 was 86%, while the median time to achieve engraftment was 24 days. Probability density analysis showed that the likelihood of engraftment after umbilical cord blood transplantation increased after day 10, peaked on day 21 and slowly decreased to 21% by day 31. Beyond day 31, the probability of engraftment dropped rapidly, and the residual probability of engrafting after day 42 was 5%. Graft failure was reported in 166 patients, and 66 of them received a second graft (allogeneic, n=45). Rescue actions, such as the search for another graft, should be considered starting after day 21. A diagnosis of graft failure can be established in patients who have not achieved neutrophil recovery by day 42. Moreover, subsequent transplants should not be postponed after day 42.

摘要

脐带血移植受者面临移植物失败风险增加,这是一种导致移植相关死亡率升高的并发症。移植物失败后进行第二次移植的决策和时机颇具挑战性。为解决这一问题,我们分析了1268例急性白血病(64%为急性淋巴细胞白血病,36%为急性髓系白血病)缓解期患者(73%为儿童)在清髓性预处理方案后接受单单位脐带血移植的植入动力学和结局。中位随访时间为31个月。3年总生存率为47%;移植相关死亡率的100天累积发生率为16%。植入时间延长与移植相关死亡率增加和总生存期缩短相关。第60天中性粒细胞植入的累积发生率为86%,而达到植入的中位时间为24天。概率密度分析显示,脐带血移植后第10天之后植入的可能性增加,在第21天达到峰值,并在第31天缓慢降至21%。超过第31天,植入概率迅速下降,第42天之后植入的残余概率为5%。166例患者报告发生移植物失败,其中66例接受了第二次移植(同种异体移植,n = 45)。应考虑在第21天之后开始采取寻找另一移植物等挽救措施。对于在第42天仍未实现中性粒细胞恢复的患者可诊断为移植物失败。此外,后续移植不应在第42天之后推迟。

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