Background: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm, characterized by progressive bone marrow fibrosis driven by activated fibroblasts, pro-inflammatory cytokines, and various genetic and epigenetic alterations. Allogeneic stem cell transplantation (allo-SCT) remains the only curative therapy. However, early, accurate, and non-invasive assessment of therapeutic response and fibrotic remodeling remains a major clinical challenge due to sampling errors and lack of standardized analysis in bone marrow histology. Fibroblast activation protein inhibitor (FAPI) PET/CT is an emerging molecular imaging modality targeting fibroblast activation protein (FAP), which is highly expressed on activated stromal fibroblasts but minimally on quiescent tissue. This technique enables whole-body visualization of fibrotic activity and may serve as a novel tool for monitoring treatment response in MF.

Methods: This preliminary analysis aims to evaluate the diagnostic and prognostic utility of FAPI PET/CT for longitudinal assessment of fibrotic remodeling and treatment response in patients with primary or secondary MF undergoing allo-SCT. Adult patients scheduled for transplantation between 2024 and 2025 undergo FAPI PET/CT scans at three standardized timepoints: pre-transplant (baseline), day +100, and day +365 post-transplant. Imaging assessments include qualitative visual analysis and quantitative parameters, including standardized uptake values (SUVmax, SUVmean, SUVpeak) and volumetric measurements. Imaging results are correlated with clinical outcomes, hematologic reconstitution, donor chimerism, bone marrow histopathology, and molecular/cytogenetic findings obtained at the same timepoints.

Results: To date, 13 patients (median age 62 years; range 48–71) completed baseline FAPI PET/CT; 6 have undergone day +100 imaging. Of these, 8 (62%) were diagnosed with primary myelofibrosis, while 5 (39%) with a secondary MF. Histologically, 7 patients (54%) had MF.3, 3 (23%) MF.2, and 3 (23%) MF.1 prior to allo-SCT. Most patients were high-risk based on prognostic scores: 85% (11/13) by MIPSS70+, and 69% (9/13) by DIPSS-plus. Median number of prior therapies before allo-SCT was 3 (range, 1–5). Eleven out of 13 patients, (85%) underwent allo-SCT from a matched unrelated donor (MUD), while 2 patients (15%) received a mismatched unrelated donor (MMUD) transplant. Myeloablative conditioning was used in 7 patients (54%), and reduced-intensity conditioning (RIC) in 6 (46%). Four patients (31%) received splenic irradiation (2 Gy, fractionated) prior conditioning to reduce spleen size. Day +365 follow-up imaging is ongoing. Preliminary results show a consistent reduction in FAPI uptake from baseline to day +100 across multiple skeletal sites. In the lumbar spine, the SUVmax decreased from 3.62 ± 1.62 (95 % CI: 2.63–4.59) to 1.85± 0.65 (95 % CI: 1.16–2.53). In the iliac bone, SUVmax declined from 3.04±1.47 (95 % CI: 2.14–3.93) to 1.78±0.81 (95 % CI:0.93 –2.63). In the contralateral bone marrow biopsy site SUVmax decreased from 2.96±1.36 (95 % CI: 2.13–3.78) to 1.63±0.77 (95 % CI: 0.82–2.44), while SUVmax at the biopsy tract itself declined from 3.07± 1.64 (95 % CI: 2.07–4.05) to 1.90 ±0.91 (95 % CI: 0.93–2.86). All patients initially presented with splenomegaly (median size 170±59.5 mm, palpable by 54% of the patients), which decreased to 145 ±68.5 mm by day +100. Imaging findings correlated with histologic regression of marrow fibrosis, reduced spleen size, improved hematologic reconstitution, and achievement of molecular remission in 5 out of 6 cases. No unexpected tracer uptake or safety concerns were reported.

Conclusion: FAPI PET/CT seems to be a promising non-invasive tool for dynamic assessment of bone marrow fibrosis and treatment response in MF patients undergoing allo-SCT. Early data demonstrate that reductions in FAPI uptake align with clinical, histopathologic, and molecular improvement. Ongoing follow-up data collection and expansion of the cohort will clarify the prognostic relevance of FAPI PET/CT for post-transplant disease monitoring, graft success, long-term survival and personalized treatment strategies.

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2025
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