Improved GRFS after posttransplant cyclophosphamide-based vs ATG-based HLA-mismatched unrelated donor transplant.
Improved GRFS after posttransplant cyclophosphamide-based vs ATG-based HLA-mismatched unrelated donor transplant.
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DOI：
10.1182/bloodadvances.2022007596
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发表时间：
2022-08-09
期刊：
影响因子：
7.5
通讯作者：
Shaffer, Brian C.
中科院分区：
文献类型：
--
作者：
Jimenez, Antonio Jimenez;Komanduri, Krishna;Brown, Samantha;Wang, Trent;Pereira, Denise;Goodman, Mark;Beitinjaneh, Amer;Lekakis, Lazaros;Chinapen, Stephanie;Devlin, Sean;Ponce, Doris;Sauter, Craig;Perales, Miguel-Angel;Shaffer, Brian C.
预防来自HLA错配的无关供体（MMUD）的异基因造血细胞移植（HCT）后移植物抗宿主病的常用方法是他克莫司、甲氨蝶呤和抗胸腺细胞球蛋白（ATG）。在MMUD HCT的前瞻性试验中，移植后环磷酰胺（PTCy）的使用显示出希望。我们比较了128例接受MMUD HCT后基于他克莫司/甲氨蝶呤/ATG（ATG组，n = 46）与PTCy、吗替麦考酚酯和他克莫司或西罗莫司（PTCy组，n = 82）预防的受者的1年无移植物抗宿主病、无复发生存率（GRFS）。纳入了接受来自MMUD的HCT的患者，该MMUD在HLA-A、HLA-B、HLA-C和HLA-DRB 1中存在≥1个位点错配。两组在HCT适应症、高危疾病和HCT合并症指数方面匹配良好，而PTCy组接受骨髓（50% vs 26%; P = 0.01）和>1个位点HLA不匹配（30.5% vs 2.2%; P = 0.001）移植的患者更多。ATG和PTCy组的1年GRFS分别为16%（95%置信区间（CI）：8%-31%）和54%（95% CI：44%-66%; P < .001）。使用PTCy时，GRFS的多变量校正风险比为0.34（95% CI：0.21-0.55; P <0.001）。ATG组的1年总生存率为45%（95% CI：32%-62%），而PTCy组为75%（95% CI：66%-85%）（P <0.001）。复发率相似。ATG预防治疗后1年无复发死亡率更高：38%（95%CI：23%-52%）vs 16%（95%CI：9%-25%），P <0.001。总之，PTCy-based预防导致MMUD接受者的上级GRFS和总生存率。与MMUD同种异体HCT后基于ATG的预防的接受者相比，PTCy改善了GRFS。基于ATG预防的同种异体移植受者有更高的非复发死亡率和受损的体液免疫重建。
A common method to prevent graft-versus-host disease after allogeneic hematopoietic cell transplantation (HCT) from an HLA-mismatched unrelated donor (MMUD) is tacrolimus, methotrexate, and antithymocyte globulin (ATG). The use of posttransplant cyclophosphamide (PTCy) showed promise in a prospective trial for MMUD HCT. We compared 1-year graft-versus-host disease–free, relapse-free survival (GRFS) in 128 recipients of prophylaxis based on tacrolimus/methotrexate/ATG (ATG group, n = 46) vs PTCy, mycophenolate mofetil, and tacrolimus or sirolimus (PTCy group, n = 82) after MMUD HCT. Patients receiving HCT from a MMUD mismatched at ≥1 locus among HLA-A, HLA-B, HLA-C, and HLA-DRB1 were included. The 2 groups were well matched for HCT indication, high-risk disease, and HCT comorbidity index, whereas more patients on PTCy received bone marrow (50% vs 26%; P = .01) and >1 locus HLA-mismatched (30.5% vs 2.2%; P = .001) grafts. The 1-year GRFS was 16% (95% confidence interval (CI): 8%-31%) vs 54% (95% CI: 44%-66%; P < .001) in the ATG and PTCy groups, respectively. The multivariable adjusted hazard ratio for GRFS was 0.34 (95% CI: 0.21-0.55; P < .001) with the use of PTCy. The 1-year overall survival in the ATG group was 45% (95% CI: 32%-62%) vs 75% (95% CI: 66%-85%) in the PTCy group (P < .001). Relapse incidence was similar. One-year nonrelapse mortality was greater after ATG-based prophylaxis: 38% (95% CI: 23%-52%) vs 16% (95 CI: 9%-25%), P < .001. In summary, PTCy-based prophylaxis resulted in superior GRFS and overall survival in recipients of MMUD. PTCy improved GRFS compared with recipients of ATG-based prophylaxis after MMUD allogeneic HCT. Allograft recipients of ATG-based prophylaxis had higher nonrelapse mortality and impaired humoral immune reconstitution.
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影响因子：
6.5
作者：
Mehta RS;Saliba RM;Chen J;Rondon G;Hammerstrom AE;Alousi A;Qazilbash M;Bashir Q;Ahmed S;Popat U;Hosing C;Khouri I;Shpall EJ;Champlin RE;Ciurea SO
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