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外周血干细胞单倍体移植中联合抗胸腺细胞球蛋白降低移植后环磷酰胺剂量

Reduced post-transplant cyclophosphamide dose with antithymocyte globulin in peripheral blood stem cell haploidentical transplantation.

作者信息

Duléry Rémy, Malard Florent, Brissot Eolia, Banet Anne, Sestili Simona, Belhocine Ramdane, Calabro Martina, Van de Wyngaert Zoé, Bonnin Agnès, Ledraa Tounes, Legrand Ollivier, Labopin Myriam, Capderou Elodie, Cohen Ariel, Ederhy Stéphane, Mohty Mohamad

机构信息

Department of Clinical Hematology and Cellular Therapy, Sorbonne University, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

INSERM, UMRs 938, Centre de recherche Saint Antoine (CRSA), Paris, France.

出版信息

Bone Marrow Transplant. 2023 Nov;58(11):1215-1222. doi: 10.1038/s41409-023-02085-2. Epub 2023 Aug 18.

DOI:10.1038/s41409-023-02085-2
PMID:37596473
Abstract

Post-transplant cyclophosphamide (PT-Cy) is effective for graft-versus-host disease (GVHD) prophylaxis, but it may cause dose-dependent toxicities, particularly in frail patients. Therefore, we compared the outcomes with a reduced PT-Cy total dose (70 mg/kg) to those with the standard PT-Cy dose (100 mg/kg) in haploidentical hematopoietic cell transplantation (HCT) patients aged ≥ 65 years and those with cardiac comorbidities. All consecutive patients with a hematological malignancy receiving peripheral blood stem cells (PBSCs) after a thiotepa-based conditioning with low-dose antithymocyte globulin were included. Thirty-three patients received PT-Cy at 70 mg/kg and 25 at 100 mg/kg. PT-Cy dose reduction did not increase the risk of GVHD and was associated with faster neutrophil and platelet recovery, and lower cumulative incidences of bacteremia (38% versus 72%, p = 0.004) and cardiac complications (12% versus 44%, p = 0.028). At 2 years, GVHD-free, relapse-free survival (GRFS) was higher with the reduced dose compared to the standard dose (60% versus 33%, p = 0.04). In conclusion, reducing PT-Cy total dose to 70 mg/kg is a safe and valid approach for elderly patients and those with cardiac comorbidities underdoing haploidentical HCT with PBSCs and low-dose antithymocyte globulin. The reduced PT-Cy dose was associated with improved hematological count recovery, lower incidence of toxicities, and higher GRFS.

摘要

移植后环磷酰胺(PT-Cy)对预防移植物抗宿主病(GVHD)有效,但可能会引起剂量依赖性毒性,尤其是在体弱患者中。因此,我们比较了年龄≥65岁且患有心脏合并症的单倍体造血细胞移植(HCT)患者中,PT-Cy总剂量降低(70mg/kg)与标准PT-Cy剂量(100mg/kg)的疗效。纳入所有在接受基于噻替派的预处理并使用低剂量抗胸腺细胞球蛋白后接受外周血干细胞(PBSC)移植的血液系统恶性肿瘤连续患者。33例患者接受70mg/kg的PT-Cy,25例接受100mg/kg的PT-Cy。PT-Cy剂量降低并未增加GVHD风险,且与中性粒细胞和血小板恢复更快、菌血症(38%对72%,p=0.004)和心脏并发症(12%对44%,p=0.028)的累积发生率较低相关。在2年时,与标准剂量相比,降低剂量组的无GVHD、无复发生存率(GRFS)更高(60%对33%,p=0.04)。总之,对于接受单倍体HCT联合PBSC和低剂量抗胸腺细胞球蛋白治疗的老年患者和患有心脏合并症的患者,将PT-Cy总剂量降至70mg/kg是一种安全有效的方法。PT-Cy剂量降低与血液学计数恢复改善、毒性发生率降低和GRFS升高相关。

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