Hart, Christina and Klatt, Sabine and Barop, Johann and Mueller, Gunnar and Schelker, Roland and Holler, Ernst and Huber, Elisabeth and Herr, Wolfgang and Grassinger, Jochen (2016) Splenic pooling and loss of VCAM-1 causes an engraftment defect in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation. HAEMATOLOGICA, 101 (11). pp. 1407-1416. ISSN 0390-6078,
Full text not available from this repository. (Request a copy)Abstract
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 CD34(+) CD38-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTERNATIONAL WORKING GROUP; BONE-MARROW; PROGENITOR CELLS; MYELOPROLIFERATIVE NEOPLASMS; EXTRAMEDULLARY HEMATOPOIESIS; MYELOID METAPLASIA; CD34(+) CELLS; IWG-MRT; NICHE; SPLEEN; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Apr 2019 12:14 |
| Last Modified: | 12 Apr 2019 12:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3981 |
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