Myelodysplastic syndrome has a variety of clinical presentations, including bone marrow fibrosis. Previously, the presence of fibrosis was not factored into disease risk scoring in MDS, but recent research suggests it may be a valuable risk factor.
Bone marrow fibrosis (BMF) is one of many manifestations of myelodysplastic syndrome (MDS), a malignant blood disease caused by irregularities in blood cell lines in the bone marrow (BM) or inefficient production of blood cells . Outside of current scoring systems used to calculate risk and determine treatments, BMF has been shown to be an independent risk factor in patients with MDS. A recent review suggests that the prognostic impact of BMF should be considered in regular clinical practice.
Currently, standard prognostic systems such as the Revised International Prognostic Scoring System (IPSS-R) are used to assess the severity of MDS. Thus, clinicians often overlook BMF, which has been identified as a distinct risk factor for poor survival, regardless of the patient’s IPSS-R risk level. The BMF is also not commonly included in standardized rating systems.
The study, published in Annals of Laboratory Medicine, reviewed the available literature on patients with MDS and BMF (MDS-F) to provide insight into prognosis and clinical presentation in this subset of patients with MDS.
The IPSS-R for MDS currently classifies the disease from very low risk to very high risk using cytogenetics, BM blasts and laboratory parameters including hemoglobin, platelets and absolute neutrophil count (ANC). ) at the time of MDS diagnosis. BMF is not listed in the IPSS-R and the WHO considers MDS-F an unclassified MDS subtype as of 2016.
“When the IPSS-R prognostic criteria were first established, BMF was considered a potential factor in determining prognostic risk,” the authors wrote. “However, it has been ruled out as an additive factor in predicting survival in MDS due to its low prevalence and differences in assessment of the degree of BMF across institutions.”
Despite its exclusion from grading systems, moderate to severe BMF associated with MDS has been associated with worsening of disease features such as multilineage dysplasia, transfusion dependency, and severe cytopenia. Overall survival (OS) is also worse in these patients, possibly due to increased BM failure or leukemic transformation.
Reticulin fibers and collagen fibers are both related to BMF. Collagen fibers are more significantly linked to abnormal blood counts and poorer outcomes. Reticulin fibrosis is also often reversible with therapeutic intervention, while collagenous fibrosis is more difficult to eradicate.
Patients with MDS-F with moderate to severe BMF who undergo allogeneic hematopoietic stem cell transplantation (alloSCT) are likely to have worse event-free survival, with delayed engraftment after the procedure reported more often in MDS patients with any level of fibrosis. The pathophysiology of BMF is also not well understood, although increased production of cytokines by megakaryocytes and platelets – which have been shown to be higher in patients with BMF – is a possible mechanism.
Yet patients with MDS-F are generally treated with similar strategies as those without fibrosis. Notably, if BMF were considered in severity grading, more patients could be considered for alloSCT, which is the only potentially curative treatment for MDS.
The impact of BMF on the prognosis of patients with MDS is crucial in terms of survival and disease progression. One study found that acute myeloid leukemia transformation rate was higher in BMF patients who had not undergone alloSCT, OS was lower (21 months vs. 42 months), and leukemia-free survival was lower (52 months versus 120 months). Other studies have shown significantly shorter OS in patients with MDS-F, as well as shorter OS in patients with severe BMF compared to mild BMF.
Overall, the study authors suggest that BMF is a poor prognostic variable at any stage of the disease for patients with MDS based on the most recent research. They recommend its inclusion in currently used grading systems and note that patients with moderate to severe BMF should be considered for transplantation as a potential treatment, even if their overall disease is not classified as high risk in the current systems.
Further research is still needed to clarify the pathobiology of BMF and the effectiveness of possible treatments for MDS-F.
Jain AG, Zhang L, Bennett JM, Komrokji R. Myelodysplastic syndromes with bone marrow fibrosis: an update. Ann Lab Med. 2022;42(3):299-305. doi:10.3343/alm.2022.42.3.299