Characterizing the Bone Marrow Environment in Advanced-Stage Myelofibrosis during Ruxolitinib Treatment Using PET/CT and MRI: A Pilot Study

Tomography. 2023 Feb 21;9(2):459-474. doi: 10.3390/tomography9020038.

Abstract

Current diagnostic criteria for myelofibrosis are largely based on bone marrow (BM) biopsy results. However, these have several limitations, including sampling errors. Explorative studies have indicated that imaging might form an alternative for the evaluation of disease activity, but the heterogeneity in BM abnormalities complicates the choice for the optimal technique. In our prospective diagnostic pilot study, we aimed to visualize all BM abnormalities in myelofibrosis before and during ruxolitinib treatment using both PET/CT and MRI. A random sample of patients was scheduled for examinations at baseline and after 6 and 18 months of treatment, including clinical and laboratory examinations, BM biopsies, MRI (T1-weighted, Dixon, dynamic contrast-enhanced (DCE)) and PET/CT ([15O]water, [18F]NaF)). At baseline, all patients showed low BM fat content (indicated by T1-weighted MRI and Dixon), increased BM blood flow (as measured by [15O]water PET/CT), and increased osteoblastic activity (reflected by increased skeletal [18F]NaF uptake). One patient died after the baseline evaluation. In the others, BM fat content increased to various degrees during treatment. Normalization of BM blood flow (as reflected by [15O]water PET/CT and DCE-MRI) occurred in one patient, who also showed the fastest clinical response. Vertebral [18F]NaF uptake remained stable in all patients. In evaluable cases, histopathological parameters were not accurately reflected by imaging results. A case of sampling error was suspected. We conclude that imaging results can provide information on functional processes and disease distribution throughout the BM. Differences in early treatment responses were especially reflected by T1-weighted MRI. Limitations in the gold standard hampered the evaluation of diagnostic accuracy.

Keywords: MRI; PET/CT; diagnostic accuracy; myelofibrosis; ruxolitinib.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow / diagnostic imaging
  • Bone Marrow / pathology
  • Fluorodeoxyglucose F18
  • Humans
  • Magnetic Resonance Imaging / methods
  • Pilot Projects
  • Positron Emission Tomography Computed Tomography* / methods
  • Primary Myelofibrosis* / diagnostic imaging
  • Primary Myelofibrosis* / drug therapy
  • Primary Myelofibrosis* / pathology
  • Prospective Studies

Substances

  • ruxolitinib
  • Fluorodeoxyglucose F18

Grants and funding

Funding was received from Novartis Pharma. Novartis was not involved in the design of the study or in collection, analysis, and interpretation of data. Novartis was also not involved in the writing of, or the decision to publish, the current manuscript.