Bone marrow morphological features and therapy in patients with Philadelphia-negative neoplasms

ABSTRACT

Introduction Chronic myeloproliferative neoplasm (MPNs) are clonal malignant bone marrow (BM) diseases, arising from a hematopoietic stem cell. All therapies for these neoplasms have peculiar effects on the bone marrow, but little evidence has been described in the literature.

Areas covered This review examines BM morphological changes following the main treatments in Philadelphia-negative MPNs. Hydroxyurea can reduce the cellularity of the erythroid and megakaryocyte lineages but has minimal impact on fibrotic evolution. There is general agreement on its dysplastic effects, with a high incidence of acute myeloid leukemia and myelodysplastic syndrome. Interferon treatment can reduce or normalize BM cellularity, improve erythropoiesis, and reduce the number and atypicality of megakaryocytes. Most data describe reduction or complete resolution of marrow fibrosis; dysplastic effects are not reported. Anagrelide may induce an increase in the number of BM megakaryocytes, especially immature megakaryocytes or precursors, and a worsening of marrow fibrosis or increased transformation of essential thrombocythemia into myelofibrosis. Ruxolitinib can improve or stabilize BM fibrosis and reduces the frequency and dense clustering of megakaryocytes.

Expert opinion Since previous therapy can modify BM features, it is essential to obtain information on previous or current therapies and to collect complete clinical information.

KEYWORDS:

• Chronic myeloproliferative neoplasm
• bone marrow
• hydroxyurea
• ruxolitinib
• interferon
• anagrelide

Article Highlights

• Chronic myeloproliferative neoplasms are clonal malignant bone marrow (BM) diseases, arising from a hematopoietic stem cell in which driver mutations constitutively activate the JAK-STAT signalling

• Before the development of JAK2 inhibitors, patients were treated with phlebotomy, hydroxyurea, interferon preparations, anagrelide, and, in more aggressive cases, chemotherapy and transplant.

• Hydroxyurea can reduce BM cellularity, especially of the erythroid and megakaryocyte (MK) lineage but has little influence on fibrotic evolution.

• Interferon therapy can reduce or normalize BM cellularity, improve erythropoiesis, and reduce the MK number and atypia.

• Anagrelide may induce an increase in the MK number of BM, especially immature MKs or precursors, worsen marrow fibrosis and, in some cases, increase the transformation of Essential Thrombocythemia to secondary myelofibrosis.

• Ruxolitinib improves or stabilizes BM fibrosis, especially in Primary Myelofibrosis, and reduces the frequency and dense clustering of MKs.

Declaration of interest

G Benevolo is on the advisory boards of Takeda, Janssen, and Novartis. Editorial assistance, provided by Content Ed Net, and writing assistance, provided by Elisa Sala Ph.D., were utilized in the production of this manuscript and funded by Novartis Farma Italy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

A.P. and G.B. contributed equally to the planning and draft revisions. E.B., L.G., L.R., G.L. P.F., analyzed the literature and revised the manuscript; all authors approved the final version of the manuscript.

Additional information

Funding

This paper was funded in part by Novartis Farma Italy.