Lack of Mutations Associated With Favorable Prognosis in MPN-U

Among patients with myeloproliferative neoplasm, unclassifiable (MPN-U), bone marrow blast and the Dynamic International Prognostic Scoring System (DIPSS) plus score can predict overall survival (OS), according to a study published in American Journal of Clinical Pathology.¹ In addition, the study found that the lack of certain mutations seemed to be associated with a better prognosis.

MPN-U is a type of MPN that doesn’t fit one of the other types of MPNs, such as chronic myelogenous leukemia (CML), myelofibrosis (MF), essential thrombocythemia (ET), or polycythemia vera (PV).² Janus kinase (JAK) mutations are often present in PV, ET, and primary MF; MPL or CALR mutations are often present in ET and primary MF; and chromosome errors are present in patients with CML.²

This study identified additional potential poor prognostic markers for patients with MPN-U, which is important as MPN-U is a heterogeneous category with features that typically preclude classification. MPN-U cases show “a range of clinicopathologic presentations and differences in prognosis depending on the stage of disease,” the authors explained. “Creating further challenges, MPN-U cases remain relatively understudied.”

This retrospective multicenter study aimed to define clinicopathologic features of outcomes of different subgroups of patients with MPN-U and evaluate the genetic features of the disease to determine whether a scoring system could provide improved prognostication of patients.

Overall, 94 patients with a pathological diagnosis of MPN-U from 7 institutions were included. The majority (68.1%) were classified as early stage, 27.7% as late stage, and 4.3% as having coexisting disorders. Eighty-five (90.4%) of patients had available data on karyotype and 37 (39.3%) were evaluable by next-generation sequencing (NGS).

Compared with patients who had advanced-stage disease, patients in the early-stage group were more likely to have an elevated platelet count (237.5 x 10³/μL vs 450.0 x 10³/μL) and a history of thrombosis (4.2% vs 27.8%). In general, patients with MPNs are at a higher risk of thrombosis, and complications related to thrombosis, as well as hemorrhage, are a major cause of morbidity and mortality for patients with MPNs.³

The lack of certain mutations seems to be associated with a better prognosis for patients with myeloproliferative neoplasm, unclassifiable.

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Regarding mutations, the researchers found:

• 60.9% had a JAK2 mutation
• 4.5% had an MPL mutation
• 8.6% had a CALR mutation
• 29.7% had an ASXL1 mutation
• 43.2% had the presence of high molecular risk mutation
• 35.1% had no known driver mutation

In the 45 evaluable cases, 20 had disease progression: 6 cases of acute myeloid leukemia, 6 cases of increased blasts, 5 cases of clonal evolution, 2 cases of progression to overt PV, and 1 case of progression to overt ET.

In addition, 1 patient developed a second malignancy, but this was not classified as progression.

Median OS for the full cohort was 54 months, with a shorter OS for patients who had advanced-stage disease or coexisting disorders, compared with patients who had early-stage disease.

Abnormal karyotype, which was present in 19.3% of patients, was associated with a shorter OS, as well as advanced-stage or coexisting disorders. During follow-up, 29.5% of patients with a JAK2 mutation, 54.8% without a JAK2 mutation, 46% with no mutation, and 80% with either a MPL or CALR mutation died. Patients who were JAK2 negative had a worse OS than those who were positive.

Applying DIPSS plus, which was initially developed to inform prognosis for primary MF, found patients with advanced-stage or coexisting disorders had higher scores and were considered higher risk than patients in the early-stage group. According to multivariate analysis for OS, DIPSS plus score, along with bone marrow blast count, were significant prognostic factors for the cohort.

“A subset of patients with MPN-U showing early-stage disease, thrombosis, and JAK2 mutation may warrant recognition based on very favorable prognosis, with treatment focused on management of thrombotic risk,” the study authors wrote.

References

1. Crane GM, Geyer JT, Thakral B, et al. Predictors of clinical outcome in myeloproliferative neoplasm, unclassifiable: a Bone Marrow Pathology Group study. Am J Clin Pathol. Published online April 10, 2024. doi:10.1093/ajcp/aqae033

2. Myeloproliferative neoplasms. Cleveland Clinic. September 1, 2022. Accessed April 24, 2024. https://my.clevelandclinic.org/health/diseases/24144-myeloproliferative-neoplasms

3. Joszt L. Patients with MPNs have increased risk of thrombosis, hemorrhage, leukemic transformation. The American Journal of Managed Care®. March 13, 2024. Accessed April 24, 2024. https://www.ajmc.com/view/patients-with-mpns-have-increased-risk-of-thrombosis-hemorrhage-leukemic-transformation