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异基因造血细胞移植后骨髓纤维化中植入动力学的特征,包括新型预处理方案。

Characterization of engraftment dynamics in myelofibrosis after allogeneic hematopoietic cell transplantation including novel conditioning schemes.

作者信息

Jungius Sarah, Adam Franziska C, Grosheintz Kerstin, Medinger Michael, Buser Andreas, Passweg Jakob R, Halter Jörg P, Meyer Sara C

机构信息

Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.

Department of Biomedical Research, University of Bern, Bern, Switzerland.

出版信息

Front Oncol. 2023 Aug 10;13:1205387. doi: 10.3389/fonc.2023.1205387. eCollection 2023.

Abstract

INTRODUCTION

Myelofibrosis (MF) is a rare hematopoietic stem cell disorder progressing to bone marrow (BM) failure or blast phase. Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative therapy for a limited subset of patients with advanced MF, who are eligible, but engraftment in MF vs. AML is delayed which promotes complications. As determinants of engraftment in MF are incompletely characterized, we studied engraftment dynamics at our center.

METHODS

A longitudinal cohort of 71 allogeneic HCT performed 2000-2019 with >50% after 2015 was evaluated.

RESULTS

Median time to neutrophil engraftment ≥0.5x109/l was +20 days post-transplant and associated with BM fibrosis, splenomegaly and infused CD34+ cell number. Engraftment dynamics were similar in primary vs. secondary MF and were independent of MF driver mutations in JAK2, CALR and MPL. Neutrophil engraftment occurred later upon haploidentical HCT with thiotepa-busulfan-fludarabine conditioning, post-transplant cyclophosphamide and G-CSF (TBF-PTCy/G-CSF) administered to 9.9% and 15.6% of patients in 2000-2019 and after 2015, respectively. Engraftment of platelets was similarly delayed, while reconstitution of reticulocytes was not affected.

CONCLUSIONS

Since MF is a rare hematologic malignancy, this data from a large number of HCT for MF is essential to substantiate that later neutrophil and platelet engraftment in MF relates both to host and treatment-related factors. Observations from this longitudinal cohort support that novel conditioning schemes administered also to rare entities such as MF, require detailed evaluation in larger, multi-center cohorts to assess also indicators of long-term graft function and overall outcome in patients with this infrequent hematopoietic neoplasm undergoing allogeneic transplantation.

摘要

引言

骨髓纤维化(MF)是一种罕见的造血干细胞疾病,可进展为骨髓(BM)衰竭或急变期。异基因造血细胞移植(HCT)是晚期MF患者有限亚组的一种潜在治愈性疗法,这些患者符合条件,但与急性髓系白血病(AML)相比,MF患者的植入延迟,这会引发并发症。由于MF植入的决定因素尚未完全明确,我们在本中心研究了植入动态。

方法

对2000年至2019年进行的71例异基因HCT的纵向队列进行评估,2015年后进行的占比超过50%。

结果

中性粒细胞植入至≥0.5×10⁹/L的中位时间为移植后+20天,且与骨髓纤维化、脾肿大和输注的CD34⁺细胞数量相关。原发性与继发性MF的植入动态相似,且独立于JAK2、CALR和MPL中的MF驱动基因突变。在2000年至2019年以及2015年后,分别有9.9%和15.6%的患者接受了含噻替派-白消安-氟达拉滨预处理、移植后环磷酰胺和粒细胞集落刺激因子(TBF-PTCy/G-CSF)的单倍体相合HCT,中性粒细胞植入发生较晚。血小板的植入同样延迟,而网织红细胞的重建未受影响。

结论

由于MF是一种罕见的血液系统恶性肿瘤,来自大量MF患者HCT的数据对于证实MF患者中性粒细胞和血小板植入延迟与宿主及治疗相关因素均有关至关重要。该纵向队列的观察结果支持,对于MF等罕见疾病采用的新型预处理方案,需要在更大规模的多中心队列中进行详细评估,以评估接受异基因移植的这种罕见造血肿瘤患者的长期移植功能指标和总体结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e26/10449533/68513d80994b/fonc-13-1205387-g001.jpg

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