Have We Achieved a Goldilocks Grade of Graft-Versus-Host Disease?
Have We Achieved a Goldilocks Grade of Graft-Versus-Host Disease?
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我们是否已经达到了移植物抗宿主病的金发姑娘级别？
DOI：
10.1016/j.bbmt.2019.04.009
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Jaglowski,Samantha
中科院分区：
文献类型：
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作者：
Vasu,Sumithira;Jaglowski,Samantha
移植后环磷酰胺（PTCy）使接近普遍的供体准入，并扩大了符合单倍体相合同种异体移植的患者库。虽然经常与钙调磷酸酶抑制剂（CNI）联合使用，但它可用作清髓性预处理后HLA相合移植中唯一的移植物抗宿主病（GVHD）预防。先前使用无CNI方法的方法包括使用CD 34+细胞的免疫磁性选择的离体T细胞去除和使用抗胸腺细胞球蛋白1、2的体内T细胞去除。[3]评价了在清髓性骨髓移植（BMT）的情况下，当PTCy用作唯一的GVHD预防时GVHD的发生率。作者报告了298例成人受者的回顾性研究，其中187例接受了来自同一机构的匹配同胞供体（MSD）移植，111例接受了来自同一机构的匹配无关供体（MUD）移植。所有患者在白消安联合氟达拉滨或环磷酰胺预处理后接受目标剂量为4× 10 8/kg的骨髓移植，然后在第3天和第4天接受PTCy。作者详细描述了无GVHD、II级急性GVHD（aGVHD）、III至IV级aGVHD和慢性GVHD（cGVHD）对总生存期（OS）、无进展生存期（PFS）、非复发死亡率和复发率等结局的影响。值得注意的是，58%的患者在移植时有活动性疾病或可测量的残留疾病。第100天II级aGVHD的发生率在MSD中为35%，在MUD受体中为57%。正如预期的那样，58%的II级aGVHD患者仅累及皮肤，其中14%进展为III至IV级GVHD，而42%的患者累及肠道或肝脏而不累及皮肤，其中31%进展为III至IV级GVHD。MUD中GVHD的中位发病时间为33天，而MSD BMT中为38天。在对整个队列进行的100天里程碑式分析中，II级aGVHD患者的4年复发率为33%，而无GVHD患者的4年复发率为49%。无GVHD患者的4年OS为57%，PFS为40%，而II级GVHD患者的OS为68%，PFS为54%。在患有II级GVHD和cGVHD的患者中观察到复发率明显降低，从而导致OS增加。
Posttransplantation cyclophosphamide (PTCy) has enabled near-universal donor access and expanded the pool of patients eligible for a haploidentical allogeneic transplant. Although often used in combination with a calcineurin inhibitor (CNI), it can be used as sole graft-versus-host disease (GVHD) prophylaxis in HLA-identical transplantation following myeloablative conditioning. Previous approaches using CNI-free approaches have included ex vivo T cell depletion using immunomagnetic selection of CD34+ cells and in vivo T cell depletion using antithymocyte globulin 1, 2.The article by McCurdy et al.[3] evaluates the incidence of GVHD when PTCy is used as a sole GVHD prophylaxis in the setting of a myeloablative bone marrow transplant (BMT). The authors report a retrospective review of 298 adult recipients, 187 of whom received a matched sibling donor (MSD) graft and 111 from a matched unrelated donor (MUD) from a single institution. All patients received a marrow graft with a goal dose of 4× 10 8/kg following conditioning with busulfan combined with either fludarabine or cyclophosphamide and followed by PTCy on days+ 3 and 4. The authors describe in granular detail the impact of no GVHD versus grade II acute GVHD (aGVHD) versus grade III to IV aGVHD and chronic GVHD (cGVHD) on outcomes such as overall survival (OS), progression-free survival (PFS), nonrelapse mortality, and relapse. It is important to note that 58% of patients had active disease or measurable residual disease at the time of transplant. Day 100 incidence of grade II aGVHD was 35% in MSD and 57% in MUD recipients. As expected, 58% of patients with grade II aGVHD had skin-only involvement, 14% of whom progressed to grade III to IV GVHD, whereas 42% of patients had gut or liver involvement without skin involvement, 31% of whom progressed to grade III to IV GVHD. The median onset to GVHD was 33 days in MUD versus 38 days in MSD BMT. In a landmark analysis at 100 days for the entire cohort, 4-year relapse incidence was 33% in those with grade II aGVHD versus 49% in those without GVHD. Four-year OS was 57% and PFS was 40% in those without GVHD versus 68% OS and 54% PFS in those with grade II GVHD. A definite decrease in relapse incidence was observed in those who had grade II GVHD and cGVHD with a resultant increase in OS.