Bierings Marc, Bonfim Carmem, Peffault De Latour Regis, Aljurf Mahmoud, Mehta Parinda A, Knol Cora, Boulad Farid, Tbakhi Abdelghani, Esquirol Albert, McQuaker Grant, Sucak Gulsan A, Othman Tarek B, Halkes Constantijn J M, Carpenter Ben, Niederwieser Dietger, Zecca Marco, Kröger Nicolaus, Michallet Mauricette, Risitano Antonio M, Ehninger Gerhard, Porcher Raphael, Dufour Carlo
Department of Haematology and Stem Cell Transplantation, Utrecht University Children's Hospital, Utrecht, The Netherlands.
Federal University of Parana, Curitiba, Brazil.
Br J Haematol. 2018 Jan;180(1):100-109. doi: 10.1111/bjh.15006. Epub 2017 Nov 2.
The outcomes of adult patients transplanted for Fanconi anaemia (FA) have not been well described. We retrospectively analysed 199 adult patients with FA transplanted between 1991 and 2014. Patients were a median of 16 years of age when diagnosed with FA, and underwent transplantation at a median age of 23 years. Time between diagnosis and transplant was shortest (median 2 years) in those patients who had a human leucocyte antigen identical sibling donor. Fifty four percent of patients had bone marrow (BM) failure at transplantation and 46% had clonal disease (34% myelodysplasia, 12% acute leukaemia). BM was the main stem cell source, the conditioning regimen included cyclophosphamide in 96% of cases and fludarabine in 64%. Engraftment occurred in 82% (95% confidence interval [CI] 76-87%), acute graft-versus-host disease (GvHD) grade II-IV in 22% (95% CI 16-28%) and the incidence of chronic GvHD at 96 months was 26% (95% CI 20-33). Non-relapse mortality at 96 months was 56% with an overall survival of 34%, which improved with more recent transplants. Median follow-up was 58 months. Patients transplanted after 2000 had improved survival (84% at 36 months), using BM from an identical sibling and fludarabine in the conditioning regimen. Factors associated with improved outcome in multivariate analysis were use of fludarabine and an identical sibling or matched non-sibling donor. Main causes of death were infection (37%), GvHD (24%) and organ failure (12%). The presence of clonal disease at transplant did not significant impact on survival. Secondary malignancies were reported in 15 of 131 evaluable patients.
成人范可尼贫血（FA）患者移植后的结局尚未得到充分描述。我们回顾性分析了1991年至2014年间接受移植的199例成年FA患者。患者确诊FA时的中位年龄为16岁，移植时的中位年龄为23岁。在具有人类白细胞抗原相同同胞供者的患者中，从诊断到移植的时间最短（中位时间为2年）。54%的患者在移植时有骨髓（BM）衰竭，46%有克隆性疾病（34%为骨髓增生异常综合征，12%为急性白血病）。BM是主要的干细胞来源，预处理方案中96%的病例使用了环磷酰胺，64%使用了氟达拉滨。植入率为82%（95%置信区间[CI]76 - 87%），急性移植物抗宿主病（GvHD）II - IV级发生率为22%（95%CI 16 - 28%），96个月时慢性GvHD发生率为26%（95%CI 20 - 33）。96个月时非复发死亡率为56%，总生存率为34%，近期移植的生存率有所提高。中位随访时间为58个月。2000年后接受移植的患者生存率有所提高（36个月时为84%），使用来自相同同胞的BM并在预处理方案中使用氟达拉滨。多因素分析中与结局改善相关的因素是使用氟达拉滨以及相同同胞或匹配的非同胞供者。主要死亡原因是感染（37%）、GvHD（24%）和器官衰竭（12%）。移植时克隆性疾病的存在对生存率无显著影响。131例可评估患者中有15例报告发生了继发性恶性肿瘤。
