Reconstructing Skeletal Homeostasis through Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis
Abstract
Myeloproliferative neoplasm-associated myelofibrosis (MF) is a clonal stem cell disease characterized by pronounced bone marrow fibrosis associated with extramedullary hematopoiesis and splenomegaly. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment leading to MF regression. The involvement of skeletal homeostasis in the process of MF regression after allo-HSCT has remained unclear.
To delineate the dynamics leading to the resolution of MF after allo-HSCT we included 66 patients in this prospective cohort study of whom 40 (61%), 16 (24%), and 10 (15%) had primary myelofibrosis, essential thrombocythemia, and polycythemia vera, respectively. Most patients showed advanced MF grade with 73% of patients having MF-3 at time of allo-HSCT. To understand the changes to the bone and the bone marrow we collected bone marrow trephine biopsies before and after transplantation; and blood and urine samples before and on day 30, 100 and 365 after transplantation. In addition, we assessed the bone status by dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). Measurements were compared to a bone-healthy cohort by propensity score matching.
DXA measurements showed highly increased bone mineral density (BMD) at the lumbar spine compared to after allo-HSCT (T-score 1.4 ± 1.8 vs. 0.0 ± 1.2, P < 0.0001), often in the range of osteosclerosis. Similar results with even larger…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 66 participants or records.
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