Abstract
Introduction Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by dysregulated proliferation and chronic inflammation. Emerging evidence suggests an increased incidence of autoimmune and inflammatory conditions in patients (pts) with MPNs, yet the clinical significance of this overlap remains poorly defined.
Methods We conducted a retrospective analysis of pts diagnosed with both an MPN and a concomitant autoimmune disorder. Baseline clinical/disease characteristics, treatments, and outcomes including disease transformation/survival were collected. All autoimmune diagnoses were confirmed by an academic rheumatologist.
Results
A total of 34 pts with dual MPN/autoimmune disorder (1989-2025) were included; 25 (75%) were female.
Median age at MPN diagnosis was 53 years [range, 12-80]. Diagnoses included MF (n=13), ET (n=11), PV (n=6), pre-fibrotic MF (n=2), and MDS/MF overlap (n=2). Driver mutations included JAK2 (n=25, 73%); CALR (n=4, 11%), MPL (n=1, 3%), and triple-negative (n=4, 12%). For pts with additional mutation testing (n=10), co-mutations included 4 TET2, 3 TP53, 2 KRAS, 2 DNMT3A, 1 ASXL1, 1 KIT. Most pts (74%) had at least one constitutional symptom due to MPN: fatigue (64%), night sweats/fever (24%), erythromelalgia (16%), headache (12%), weakness (12%). Four pts (12%) had thrombosis before MPN diagnosis with median time from thrombosis to MPN diagnosis of 99 months. Fibrosis grades were: MF 0-1+ (n=13), MF 1-2+ (n=10), MF 2-3+ (n=10), MF 4+ (n=1). Most pts required MPN treatment other than aspirin: hydroxyurea (n=20), ruxolitinib (n=14), momelotinib (n=2), interferon (n=2), phlebotomy (n=5), hypomethylating agent (n=5), investigational (n=12); 7 underwent allogeneic stem cell transplant (SCT). Three pts (9%) had thrombosis during follow-up.
Diagnoses included spondyloarthritis (n=10, 29%), rheumatoid arthritis (n=8, 24%), Raynaud's disease (n=4, 12%), lupus (n=3, 9%), Behcet's syndrome (n=2, 6%), Sjogren's syndrome (n=2, 6%), cutaneous sarcoidosis (n=2, 6%), dermatomyositis (n=1, 3%), giant cell arteritis (n=1, 3%), hypertrophic osteoarthropathy (n=1, 3%), mononeuritis multiplex (n=1, 3%), myositis (n=1, 3%), pyoderma gangrenosum (n=1, 3%), ulcerative colitis (n=1, 3%). The median age at the time of autoimmune disorder diagnosis was 51 years (23-81). Most pts (76%) were diagnosed with MPN prior to their autoimmune disorder by a median of 35 months; for the 7 pts who underwent allo-SCT, 4 pts (57%) were diagnosed with autoimmune disorder post-SCT. Most pts had symptoms related to the autoimmune disorder which were distinct from MPN symptoms; including joint pain (n=19) and skin rash (n=6). Pts received the following: steroids (n=13), NSAIDs (n=10), disease modifying antirheumatic drugs (DMARDs) (n=14), biologics (n=6). Of the 24 pts with HLA testing available, 17 (70%) had an HLA in either B35 (n=6, 38%), B15 (n=5, 29%), B27 (n=4, 25%), or B40 (n=2, 12%).
Median follow-up time from MPN diagnosis was 108 months (95% CI 47 months-not reached). Twelve pts (35%) experienced MPN progression; 6 (50%) progressed to post MPN-blast phase (BP), 4 (33%) progressed to post-MPN MF, 2 (17%) progressed to MF and then to post-MPN BP. The median time to progression to MF or AML for all pts was 92 mos; the median time to AML progression only was 87 months. For high-risk pts (MF or MDS/MF), the median time to progression was 78 months vs. for lower-risk (PV or ET), the median time to progression was 97 months (p=0.31). Of all pts who progressed, 7 (58%) were treated with steroids for their autoimmune disorder, 2 pts (17%) received DMARDs (p=0.11). Of the 22 pts who did not progress, 6 (27%) were treated with steroids for their autoimmune disorder, however 12 pts in this group (55%) were treated with DMARDs (p=0.06).
Conclusion In our cohort of pts harboring both an MPN and autoimmune disorder, we notably observed a higher rate of disease transformation (35%) than typically seen in pts with MPN. Furthermore, while the majority of pts who did not progress were treated with DMARDs for their autoimmune disorder, more pts treated with steroids had progression of their MPN. Our findings suggest a potential clinical overlap between underlying autoimmunity, background inflammation, and MPN, warranting further investigation into shared inflammatory pathogenic mechanisms and potential treatment implications.
