Dose escalation prophylactic donor lymphocyte infusion after T-cell depleted matched related donor allogeneic hematopoietic cell transplantation is feasible and results in higher donor chimerism, faster immune re-constitution, and prolonged progression-free survival
Dose escalation prophylactic donor lymphocyte infusion after T-cell depleted matched related donor allogeneic hematopoietic cell transplantation is feasible and results in higher donor chimerism, faster immune re-constitution, and prolonged progression-free survival
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DOI：
10.1038/s41409-020-0798-4
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发表时间：
2020-01
影响因子：
4.8
通讯作者：
S. Kothari;A. Artz;S. M. Lee;N. Fulton;Jae-Hyun Park;W. Stock;R. Larson;O. Odenike;J. Kline;J. LaBelle;S. Kosuri;P. Riedell;Yusuke Nakamura;M. Bishop;Hongtao Liu
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作者：
S. Kothari;A. Artz;S. M. Lee;N. Fulton;Jae-Hyun Park;W. Stock;R. Larson;O. Odenike;J. Kline;J. LaBelle;S. Kosuri;P. Riedell;Yusuke Nakamura;M. Bishop;Hongtao Liu
预防性供体淋巴细胞输注（pDLI）是延长接受同种异体造血干细胞移植（alloc - sct）患者缓解期的一种潜在干预措施，然而，最佳时间和剂量尚不清楚。我们进行了一项前瞻性试验，探讨了高风险血液恶性肿瘤患者在阿仑单抗为基础的t细胞耗尽治疗后，在第60天早期停用免疫抑制（WOI）并增加pDLI剂量的可行性。在第75天至第90天给予pDLI，并在4-8周的间隔内再次接受最多5次pDLI输注。46例匹配相关供者（MRD）和29例匹配无关供者（MUD）被考虑。28例MRD患者能够接受WOI， 26例（93%）患者接受了至少1次pDLI， 16例（57%）接受了3+，7例（25%）接受了5次pDLI。只有7例MUD患者能够接受WOI， 4例（57%）接受了至少1次pDLI， 1例（14%）接受了3次DLI，没有患者接受了全部5例。研究中患者的中位PFS为366天。所有患者的估计2年PFS和OS率分别为41% （95% CI, 32-54%）和51% (95% CI, 41-63%)，而接受至少一次pDLI的患者的2年PFS和OS率分别为57% （95% CI, 41-77%）和67% （95% CI, 52-86%）。此外，接受pDLI的MRD患者免疫重建更快，供体嵌合性改善。我们的试验提出了一种新的pDLI剂量和治疗方案，该方案对于接受MRD allo-SCT的患者是可耐受的，并导致改善的结果。
Prophylactic donor lymphocyte infusion (pDLI) is a potential intervention to prolong remission for patients receiving allogeneic hematopoietic stem cell transplantation (allo-SCT), however, the optimal timing and dose are unknown. We conducted a prospective trial exploring the feasibility of early withdrawal of immunosuppression (WOI) at day 60 followed by dose escalation of pDLI after alemtuzumab-based, T-cell depleted conditioning for patients with high-risk hematologic malignancies. pDLI were administered at day 75 to day 90 and again in 4–8 week intervals with receipt of up to 5 pDLI infusions. Fourty-six patients with matched-related donors (MRD) and 29 patients with matched-unrelated donors (MUD) were considered. Twenty-eight MRD patients were able to undergo WOI, 26 patients (93%) received at least 1 DLI, 16 patients (57%) received 3+, and 7 patients (25%) received 5 pDLI. Only 7 MUD patients were able to undergo WOI, 4 (57%) received at least 1 pDLI, 1 patient (14%) received 3 DLI, and no patients received all 5. Median PFS for patients on the study was 366 days. The estimated 2-year PFS and OS rates for all patients were 41% (95% CI, 32–54%) and 51% (95% CI, 41–63%) compared with 57% (95% CI, 41–77%) and 67% (95% CI, 52–86%) for patients who received at least one pDLI. In addition, MRD patients receiving pDLI had faster immune re-constitution and improved donor chimerism. Our trial proposes a novel dosage and treatment schedule for pDLI that is tolerable for patients who have received MRD allo-SCT and leads to improved outcomes.