Pb2231: an overlooked mimic? autoimmune myelofibrosis - a scoping review of the literature

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Autoimmune myelofibrosis (AIMF) is an uncommon but important differential for neoplastic (or ‘primary’) myelofibrosis (PMF)1. Characteristic differences observed in AIMF include an absence of driver mutations (including JAK2, CALR and MPL); a milder degree of fibrosis; relative absence of teardrop cells; and the presence of lymphoid marrow infiltrates. AIMF can be secondary to a defined autoimmune condition, or primary, in the setting of presumed autoimmune activation. While PMF often confers a poor prognosis, AIMF appears to be relatively benign, responding well to immune suppression. However, the two can be difficult to distinguish, and have frequently been muddled in the literature to date. Aims: In order to better characterize incidence and natural history of AIMF, we performed a scoping review of the surrounding literature, gathering information on patient presentation, treatment and outcomes from relevant prior studies. Methods: We performed a defined literature search of Embase, Medline and Web of Science databases for AIMF cases, using a strict case definition based on prior work by Vergara-Lluri et al2. Two reviewers separately screened results, with conflict settled on discussion. Included cases involved patients >18 years old with clinical and pathological evidence of myelofibrosis, with no other evident cause. Resulting cases were analyzed in terms of patient and disease characteristics, including biological sex; presentation; autoimmune disease; bone marrow morphology; treatments received, and outcome. Results: 3415 studies were screened, resulting in 62 studies (Figure 1) and 58 individual AIMF cases for analysis. Included cases ranged from 1978-2022, and were aged 18-73 years old (median 40 years). 45/58 were females, 13/58 were male. 13/58 had no identifiable autoimmune disorder, while 45/58 (78%) did. The most common ‘secondary’ cause was systemic lupus erythematous (SLE - 35/58). Less common were Sjogren’s disease (5/58); multiple sclerosis (1/58); autoimmune hemolytic anemia (1/58); thyroiditis (1/58) autoimmune hepatitis (1/58) and rheumatoid arthritis (1/58). Most patients (31/58) had a hypercellular bone marrow. 51/58 patients received glucocorticoids; other treatment included cyclosporine, hydroxychloroquine, cyclophosphamide, mycophenolate, rituximab, IVIg, and plasma exchange. 35/58 patients had resolution of symptoms with their first treatment; 47/58 patients had resolution of symptoms at some point. 20/22 patients with repeat marrows had evidence of improvement post-treatment. 5/58 patients died during follow-up. Summary/Conclusion: Here we support the existence of AIMF as a distinct clinical entity, using strict case criteria to seek reported cases, and clarifying its modes of presentation, clinical behavior, and response to treatment. We show that AIMF typically occurs in younger females, often – but not always - with pre-existing autoimmune conditions (most typically SLE), and that it frequently responds well to immune suppression. We hope that our work will increase the index of suspicion for AIMF among clinicians going forwards. Figure 1 – Study Inclusion FlowchartReferences 1.Marcellino B, El Jamal SM, Mascarenhas JO. Distinguishing autoimmune myelofibrosis from primary myelofibrosis. Clin Adv Hematol Oncol. 2018 Sep;16(9):619-626. PMID: 30256778. 2.Vergara-Lluri ME, Piatek CI, Pullarkat V, Siddiqi IN, O’Connell C, Feinstein DI, Brynes RK. Autoimmune myelofibrosis: an update on morphologic features in 29 cases and review of the literature. Hum Pathol. 2014 Nov;45(11):2183-91. doi: 10.1016/j.humpath.2014.07.017. Epub 2014 Aug 13. PMID: 25282037. Keywords: Myelofibrosis, Systematic review, Autoimmune disease