Department of Women's and Children's Health, Pediatric Hemato-Oncology, University Hospital of Padova, Padova, Italy.
Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Biol Blood Marrow Transplant. 2018 Jun;24(6):1223-1231. doi: 10.1016/j.bbmt.2018.01.022. Epub 2018 Feb 2.
We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34 cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft.
我们报告了 109 例接受同种异体造血干细胞移植(HSCT)的噬血细胞性淋巴组织细胞增多症(HLH)患者的情况,这些患者于 2000 年至 2014 年在与意大利儿科血液学和肿瘤学协会相关的中心接受了 126 次手术。遗传诊断为 FHL2(32%)、FHL3(33%)或其他已知引起 HLH 的明确疾病(15%);在其余患者中未发现遗传异常。首次移植的供体为 25 例患者(23%)的 HLA 匹配同胞、73 例患者(67%)的无关供体和 11 例患儿(10%)的 HLA 部分匹配家族供体。61 例患者(56%)采用以白消安为基础的预处理方案、21 例患者(20%)采用以噻替哌为基础的预处理方案和 26 例患者(24%)采用以氟达拉滨为基础的预处理方案。总生存(OS)和无事件生存(EFS)的 5 年概率分别为 71%和 60%。26 例患者(24%)死于与移植相关的原因,14 例(13%)和 10 例(9%)患者分别经历了移植物排斥和/或复发。14 例移植失败/复发患儿中有 12 例接受了第二次 HSCT,目前仍存活且无疾病。在多变量分析中,使用 HLA 部分匹配家族供体与移植物失败和 EFS 降低相关(但与 OS 无关)。移植时的活动性疾病并未显著影响预后。这些数据证实 HSCT 可治愈大多数 HLH 患者,活动性疾病不排除成功移植。由于在 HLH 患者中,通过 CD34 细胞阳性选择进行 HLA 单倍体相合 HSCT 被发现与供体细胞的持续植入不良相关,因此需要为接受这种同种异体移植的患者提供能够保证更强大植入的创新方法。