Bone Marrow Fibrosis Holds Potential as Independent Prognostic Factor in MDS

Myelodysplastic syndrome has a variety of clinical presentations, including bone marrow fibrosis. Previously, the presence of fibrosis has not been considered in disease risk scoring in MDS, but recent research suggests it may be a valuable risk factor.

Bone marrow fibrosis (BMF) is one of a variety of manifestations of myelodysplastic syndrome (MDS), a hematological malignancy caused by irregularities in blood cell lineages in bone marrow (BM) or ineffective blood cell production. Outside the current scoring systems used to calculate risk and determine treatment courses, BMF has been found an independent risk factor in patients with MDS. A recent review suggests the prognostic impact of BMF should be considered in regular clinical practice.

Currently, standard prognostication systems such as the revised International Prognostic Scoring System (IPSS-R) are used to grade MDS severity. Thus, clinicians often do not consider BMF, which has been identified as a distinct risk factor for poor survival regardless of a patient’s IPSS-R risk level. BMF is also not typically included in standardized scoring systems.

The study, published in Annals of Laboratory Medicine, reviewed available literature about patients with concurrent MDS and BMF (MDS-F) to provide insight into the prognosis and clinical presentation in this subset of MDS patients.

The IPSS-R for MDS currently classifies 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 MDS diagnosis. BMF is not 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 for determining the prognostic risk,” the authors wrote. “However, it was discounted as an additive factor for predicting survival in MDS because of its low prevalence and discrepancies in the evaluation of the degree of BMF across institutions.”

Despite its exclusion from grading systems, moderate to severe BMF in conjunction with MDS has been associated with worsened disease characteristics such as multilineage dysplasia, transfusion dependence, 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 linked with BMF. Collagen fibers are more significantly linked with abnormal blood counts and worse outcomes. Reticulin fibrosis is also often reversible with therapeutic intervention, while collagen fibrosis is more difficult to eradicate.

Patients with MDS-F whose BMF is moderate to severe and who undergo hematopoietic allogeneic stem cell transplant (alloSCT) are likely to have worse event-free survival, with delayed engraftment post-procedure reported more often in MDS patients with any level of fibrosis. The pathophysiology of BMF is also not well-understood, although increased cytokine production from megakaryocytes and platelets—which have been found to be higher in patients with BMF—are one possible mechanism.

Still, patients with MDS-F are generally treated with similar strategies to those without fibrosis. Notably, if BMF were taken into consideration in grading severity, more patients might be considered for alloSCT, which is the only potentially curative therapy for MDS.

The impact of BMF in prognosis for MDS patients is crucial when it comes to survival and disease progression. One study found that the rate of acute myeloid leukemia transformation was greater in patients with BMF who did not undergo alloSCT, OS was lower (21 months vs. 42 months), and leukemia-free survival was lower (52 months vs. 120 months). Other studies have shown significantly shorter OS in MDS-F patients, as well as shorter OS in patients with severe BMF versus mild BMF.

Overall, the study authors suggest that BMF is a poor prognostic variable at any point in disease for MDS patients based on the most current 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 current systems.

More research is still needed to clarify the pathobiology of BMF and the effectiveness of possible treatments for MDS-F.

Reference

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