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Incorporating posttransplant cyclophosphamide-based prophylaxis as standard-of-care outside the haploidentical setting: challenges and review of the literature.
Bone Marrow Transplantation ( IF 4.5 ) Pub Date : 2019-12-10 , DOI: 10.1038/s41409-019-0771-2
I García-Cadenas 1 , R Awol 1 , A Esquirol 1 , S Saavedra 1 , A Bosch-Vilaseca 1 , S Novelli 1 , A Garrido 1 , J López 1 , M Granell 1 , C Moreno 1 , J Briones 1 , S Brunet 1 , J Sierra 1 , R Martino 1
Affiliation  

Posttransplant high-dose cyclophosphamide (PTCy) effectively prevents GvHD after haploidentical SCT. However, its use in HLA-matched SCT has been less explored. Fifty-six consecutive patients who underwent allo-SCT for hematological malignancies have been included in this prospective single-center protocol. Donors have been HLA-identical siblings, fully-matched unrelated or 1-allele-mismatched unrelated donors in 30%, 32%, and 37% of cases, respectively. Nine patients have received a TBI-containing MAC regimen, while the remaining (84%) received RIC platforms based on Fludarabine plus Busulfan/Melphalan. Due to the high graft failure (GF) rate (21%) in a preliminary analysis in the allo-RIC cohort (n = 29), protocol amendments have been implemented, with no further cases of GF after the introduction of mini-thiotepa (0/18). The overall incidence of grade II–IV acute GvHD is 24% (95% CI: 17–31%) with four steroid-refractory cases. Severe chronic GvHD has occurred in only 1 of 43 evaluable cases. The 1-year NRM and relapse are 18% (95% CI: 12–26%) and 30% (18–42%) and the OS and DFS are 78% and 64%, respectively. These outcomes support the feasibility of using PTCy as a SOC outside the haplo-setting, albeit mini-thiotepa (3 mg/kg) was incorporated in the standard allo-RIC platforms to prevent GF. Despite the limitations of a single-center experience and the short follow-up, these protocols show promising results with particular benefit in reducing the occurrence of moderate-to-severe GvHD.



中文翻译:

将移植后基于环磷酰胺的预防措施纳入单倍体环境之外的护理标准:挑战和文献综述。

移植后大剂量环磷酰胺(PTCy)可有效预防单倍SCT后的GvHD。但是,它在HLA匹配SCT中的用途已很少探索。该前瞻性单中心研究方案包括了接受血液异种肿瘤异基因-SCT治疗的56例连续患者。供体是HLA相同的同胞,分别是30%,32%和37%的完全匹配的无关或1等位基因不匹配的无关供体。9名患者接受了含TBI的MAC方案,其余(84%)患者接受了以氟达拉滨加白消安/美法仑为基础的RIC平台。由于同种异体RIC队列(n = 29),已经实施了方案修正案,在引入小硫替比(0/18)之后不再有GF的病例。II级至IV级急性GvHD的总发病率为24%(95%CI:17-31%),其中有4例激素治疗难治性病例。在43例可评估病例中,只有1例发生了严重的慢性GvHD。一年的NRM和复发率分别为18%(95%CI:12–26%)和30%(18–42%),OS和DFS分别为78%和64%。这些结果支持将PTCy用作单倍型设定以外的SOC的可行性,尽管在标准的allo-RIC平台中加入了微型硫替泰(3 mg / kg)来预防GF。尽管单中心经验有限且随访时间短,但这些协议仍显示出令人鼓舞的结果,特别有利于减少中度至重度GvHD的发生。

更新日期:2019-12-11
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