Introduction

Haploidentical (HAPLO) stem cell transplantation (SCT) has been shown to be associated with lower incidence of severe acute graft-versus-host (aGVHD) compared with 8/8 HLA-matched unrelated donor (MUD) SCT. However, no information is available regarding aGVHD characteristics comparing these 2 donor sources.

Methods

We aimed to compare aGVHD characteristics and non-relapse mortality (NRM) in adult patients with grade 2-4 aGVHD after HAPLO (N=758) or MUD (N=2586) SCT that were reported to the Center for International Blood and Marrow Transplant Research (Table 1). GVHD prophylaxis included a calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and post-transplant cyclophosphamide (PTCy) in HAPLOs, and CNI with MMF or methotrexate in MUDs.

Results

The 6-m cumulative incidence (CumInc) of grade 2-4 aGVHD (35 vs 45%, <0.001) was significantly lower in HAPLOs, with a lower prevalence (28% vs 39%, p=0.001) of grade 3-4. Median (range) time from SCT to aGVHD was 35 (5-218) and 33 days (7-374) in the 2 groups, with comparable proportions (4 and 6%, p=0.2) diagnosed after day 100. Skin (66 vs 67%, p=0.8) and lower (L) gastrointestinal (GI) (76 vs 78%, p=0.4) involvement did not differ between the 2 groups; however, upper GI (46 vs 53%, p=0.04) and liver (11 vs 15%, p=0.06) involvement were less frequent in HAPLOs (Table 2). The total number and organ severity were reduced in HAPLOs with lower prevalence (26 vs 35%, p=0.008) of >2 organs involved, stage 4 skin (1 vs 5%, p=0.01), and stage 3-4 liver (4 vs 7%, p=0.04) or LGI (14% vs 21%, p=0.01). The 2-yrs and overall CumInc of NRM since aGVHD was 18% (95% CI 14-23) and 19% (95% CI 14-24) in HAPLOs; and 30% (95% CI 27-33) and 51% (95% CI 30-68) in MUDs. In multivariate analysis, grade 2-4 aGVHD in HAPLOs was associated with significantly lower NRM, but this effect was limited to donor-recipient pairs [CumInc: 15 vs 30%, HR=0.5, p=0.002] that were not sex-mismatched (female to male). In sex-mismatched pairs [CumInc: 30% vs 26%, HR=1.2, p=0.6], NRM was comparable between HAPLOs and MUDs. Subset analyses in recipients (N=718) ≥60 years also showed HAPLOs (N=92) to have a lower 6-m CumInc of grade 2-4 (29 vs 44%, p<0.001) and lower prevalence (25 vs 41%, p=0.003) of grade 3-4. Median (range) time to aGVHD diagnosis was relatively delayed [38 (11-200) vs 34 (7-374) days, p=0.04] in HAPLOs. Organ involvement did not differ between the 2 groups; however, stage 4 was less frequent in HAPLOs. This difference was most pronounced for LGI (3 vs 13%, p=0.004). In multivariate analysis, grade 2-4 aGVHD in HAPLOs was associated with significantly lower [CumInc: 11 vs 33%, HR=0.2, p=0.001] NRM only in the absence of sex-mismatch.

Conclusions

Compared with 8/8 HLA-matched unrelated SCT with standard GVHD prophylaxis, aGVHD tends to be less severe and associated with lower NRM after HAPLO SCT with PTCy GVHD prophylaxis. This effect is more pronounced in recipients ≥60 years of age.

中文翻译：

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急性移植物抗宿主病的严重程度较轻，单环移植后采用环磷酰胺预防可降低非复发死亡率

介绍

与8/8 HLA匹配的无关供体（MUD）SCT相比，单倍型（HAPLO）干细胞移植（SCT）与严重急性移植物抗宿主（aGVHD）的发生率较低相关。但是，尚无有关比较这两个供体来源的aGVHD特性的信息。

方法

我们旨在比较向国际血液和骨髓移植中心报告的HAPLO（N = 758）或MUD（N = 2586）SCT后成年2-4 aGVHD的成年患者的aGVHD特征和非复发死亡率（NRM）研究（表1）。预防GVHD包括在HAPLO中使用钙调神经磷酸酶抑制剂（CNI），霉酚酸酯（MMF）和移植后环磷酰胺（PTCy），以及在MUD中使用含有MMF或甲氨蝶呤的CNI。

结果

在HAPLO中，2-4年级aGVHD的6个月累积发生率（CumInc）（35 vs 45％，<0.001）显着降低，而3-4年级的患病率较低（28％vs 39％，p = 0.001） 。两组中从SCT到aGVHD的中位（范围）时间分别为35（5-218）和33天（7-374），在第100天后被诊断出的比例相当（分别为4和6％，p = 0.2）。皮肤（66两组之间的受累率分别为：67％，p = 0.8）和较低的（L）胃肠道（GI）（76 vs 78％，p = 0.4）。然而，HAPLOs的上消化道受累（46％vs 53％，p = 0.04）和肝脏（11％vs 15％，p = 0.06）的发生率较低（表2）。HAPLOs的总数和器官严重性降低，患病率> 26的患病率较低（26 vs 35％，p = 0.008），第4期皮肤（1 vs 5％，p = 0.01）和3-4期肝（ 4比7％，p = 0.04）或LGI（14％比21％，p = 0.01）。自从aGVHD以来，HAPLO中NRM的2年和总体CumInc为18％（95％CI 14-23）和19％（95％CI 14-24）；和30％（95％CI 27-33）和51％（95％CI 30-68）。在多变量分析中，HAPLO中的2-4级aGVHD与NRM显着降低有关，但这种影响仅限于性别不匹配的供者-受体对[CumInc：15％对30％，HR = 0.5，p = 0.002]。 （女性对男性）。在性别不匹配的配对中[CumInc：30％vs 26％，HR = 1.2，p = 0.6]，在HAPLO和MUD之间NRM相当。接受者（N = 718）≥60岁的亚组分析还显示，HAPLO（N = 92）的6个月CumInc较低，为2-4级（29 vs 44％，p <0.001），患病率较低（25 vs 41） ％，p ＝ 0.003）为3-4级。在HAPLO中，aGVHD诊断的中位（范围）时间相对延迟[38（11-200）天vs 34（7-374）天，p = 0.04]。两组之间的器官受累没有差异。但是，在HAPLO中，第4阶段的频率较低。对于LGI，这种差异最为明显（3％vs 13％，p = 0.004）。在多变量分析中，只有在没有性别不匹配的情况下，HAPLO中的2-4级aGVHD才与NRM显着降低[CumInc：11％对33％，HR = 0.2，p = 0.001]。

结论

与具有标准GVHD预防措施的8/8 HLA匹配无关SCT相比，预防性PTCy GVHD预防性HAPLO SCT后aGVHD的严重性较轻，且NRM较低。在≥60岁的接受者中，这种影响更为明显。