Splenic pooling and loss of VCAM-1 causes an engraftment defect in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation.
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.
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Germany christina.hart@ukr.de.
Christina
C
Hart
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Germany.
Sabine
S
Klatt
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Germany.
Johann
J
Barop
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Germany.
Gunnar
G
Müller
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Germany.
Roland
R
Schelker
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Germany.
Ernst
E
Holler
Institute of Pathology, University Hospital of Regensburg, Germany.
Elisabeth
E
Huber
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Germany.
Wolfgang
W
Herr
Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Germany.
Jochen
J
Grassinger
D000328:Adult; D000368:Aged; D064591:Allografts; D051799:Delayed Graft Function / Q000209:etiology*; D005260:Female; D006084:Graft Rejection / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D055728:Primary Myelofibrosis / Q000150:complications / Q000628:therapy*; D013154:Spleen / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019010:Vascular Cell Adhesion Molecule-1
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