Cell-depleted marrow in MF-3 myelofibrosis marks higher-risk disease

Design

Multicentre retrospective clinicopathological cohort

Population

241 patients with MF-3 or osteosclerotic myelofibrosis (141 depleted, 100 cellular)

Primary outcome

Morphological, molecular and survival differences

Effect

Shorter overall survival in depleted marrows (p = 0.001); enriched ASXL1, U2AF1, EZH2, MPL mutations

This Bone Marrow Pathology Group study collected trephines meeting criteria for advanced fibrotic myelofibrosis, with MF-3 fibrosis or osteosclerosis, from eleven institutions. It compared 141 cell-depleted marrows, defined as haematopoietic cellularity under 30% below age 70 or under 20% above it, with 100 normocellular or hypercellular controls.

Depleted cases had lower haemoglobin and platelets and more circulating blasts and basophils, more osteosclerosis (p < 0.001), and more ASXL1, U2AF1, EZH2 and MPL mutations. Overall survival was significantly shorter (p = 0.001). The authors note that cellularity was not independently prognostic once other features were accounted for, so it travels with high-risk biology rather than adding to it.

For the reporting pathologist, the message is that cellularity in a fibrotic marrow is worth stating explicitly rather than folding into 'fibrotic, difficult to assess'. It is a morphological signal of advanced disease that the treating haematologist can weigh alongside the molecular panel and prognostic scores.

• State haematopoietic cellularity explicitly in every MF-3 trephine report, using age-adjusted terms.
• Report osteosclerosis separately from reticulin and collagen grade.
• Flag a cell-depleted fibrotic marrow to the haematologist as a feature of advanced disease.
• Correlate with the myeloid mutation panel, particularly ASXL1, U2AF1 and EZH2.
• Do not present cellularity as an independent prognostic factor; in this study it was not.

Why it matters

A finding often dismissed as an unassessable fibrotic marrow carries information about how advanced the disease is.

Don't overread it

Cellularity was not independently prognostic, so it should not change risk scores on its own.

The statistics, in plain English

The survival difference was significant (p = 0.001), but in multivariable analysis cellularity did not add prognostic value of its own. That means depletion is a marker that goes with high-risk disease, not a separate predictor to add to existing scores.

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