Hart Christina, Klatt Sabine, Barop Johann, Müller Gunnar, Schelker Roland, Holler Ernst, Huber Elisabeth, Herr Wolfgang, Grassinger Jochen
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Germany
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Germany.
Haematologica. 2016 Nov;101(11):1407-1416. doi: 10.3324/haematol.2016.146811. Epub 2016 Aug 4.
Myelofibrosis is a myeloproliferative neoplasm that results in cytopenia, bone marrow fibrosis and extramedullary hematopoiesis. Allogeneic hematopoietic stem cell transplantation is the only curative treatment but is associated with a risk of delayed engraftment and graft failure. In this study, patients with myelofibrosis (n=31) and acute myeloid leukemia (n=31) were analyzed for time to engraftment, graft failure and engraftment-related factors. Early and late neutrophil engraftment and late thrombocyte engraftment were significantly delayed in patients with myelofibrosis as compared to acute myeloid leukemia, and graft failure only occurred in myelofibrosis (6%). Only spleen size had a significant influence on engraftment efficiency in myelofibrosis patients. To analyze the cause for the engraftment defect, clearance of hematopoietic stem cells from peripheral blood was measured and immunohistological staining of bone marrow sections was performed. Numbers of circulating CD34 were significantly reduced at early time points in myelofibrosis patients, whereas CD34CD38 and colony-forming cells showed no significant difference in clearance. Staining of bone marrow sections for homing proteins revealed a loss of VCAM-1 in myelofibrosis with a corresponding significant increase in the level of soluble VCAM-1 within the peripheral blood. In conclusion, our data suggest that reduced engraftment and graft failure in myelofibrosis patients is caused by an early pooling of CD34 hematopoietic stem cells in the spleen and a bone marrow homing defect caused by the loss of VCAM-1. Improved engraftment in myelofibrosis might be achieved by approaches that reduce spleen size and cleavage of VCAM-1 in these patients prior to hematopoietic stem cell transplantation.
骨髓纤维化是一种骨髓增殖性肿瘤，可导致血细胞减少、骨髓纤维化和髓外造血。异基因造血干细胞移植是唯一的治愈性治疗方法，但存在移植延迟和移植失败的风险。在本研究中，对31例骨髓纤维化患者和31例急性髓系白血病患者的移植时间、移植失败及移植相关因素进行了分析。与急性髓系白血病患者相比，骨髓纤维化患者的早期和晚期中性粒细胞植入以及晚期血小板植入明显延迟，且移植失败仅发生在骨髓纤维化患者中（6%）。在骨髓纤维化患者中，仅脾脏大小对植入效率有显著影响。为分析植入缺陷的原因，检测了外周血造血干细胞的清除情况，并对骨髓切片进行了免疫组织化学染色。骨髓纤维化患者在早期时间点循环CD34数量显著减少，而CD34CD38和集落形成细胞的清除无显著差异。骨髓切片中归巢蛋白染色显示骨髓纤维化患者VCAM-1缺失，外周血中可溶性VCAM-1水平相应显著升高。总之，我们的数据表明，骨髓纤维化患者植入减少和移植失败是由CD34造血干细胞早期在脾脏中蓄积以及VCAM-1缺失导致的骨髓归巢缺陷引起的。在造血干细胞移植前，通过减小脾脏大小和裂解VCAM-1的方法可能会改善骨髓纤维化患者的植入情况。
