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Trend of circulating CD34⁺ cells in patients with myelofibrosis: Association with spleen response during ruxolitinib treatment.

ABSTRACT: We evaluated CD34⁺ cells in a single-centre series of 49 consecutive patients with myelofibrosis (MF) at baseline and during ruxolitinib therapy and examined any association with spleen response. The median (range) absolute number of circulating CD34⁺ cells was 0.0835 (0.001-1.528) × 10⁹ /L at diagnosis, and 0.123 (0.002-1.528) × 10⁹ /L at ruxolitinib start. With the exception of a transient increase after 3 months of ruxolitinib therapy, a progressive reduction in CD34⁺ cells count was documented, down to a minimum of 0.063 × 10⁹ /L after 36 months. We then assessed the association between spleen diameter expressed as the distance from the left costal margin (outcome) and log(CD34⁺ ) cells count using random-intercept and random slope multivariable regression models to take into account within subject correlation: after adjusting for time and ruxolitinib dosage, we estimated a 0.7 cm increase (95% confidence interval 0.2-1.2, p = 0.003) in spleen length for each unit increase in log(CD34⁺ ) cells count (× 10⁹ /L). Although our study has some limitations, mainly related to its retrospective design, our approach may introduce a reproducible and simple tool that could facilitate the assessment of spleen response more objectively in patients with MF treated with ruxolitinib.

SUBMITTER: Iurlo A

PROVIDER: S-EPMC10092026 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Trend of circulating CD34+ cells in patients with myelofibrosis: Association with spleen response during ruxolitinib treatment.

Iurlo Alessandra A Galli Nicole N Bucelli Cristina C Artuso Silvia S Consonni Dario D Cattaneo Daniele D

British journal of haematology 20221020 3

We evaluated CD34+ cells in a single-centre series of 49 consecutive patients with myelofibrosis (MF) at baseline and during ruxolitinib therapy and examined any association with spleen response. The median (range) absolute number of circulating CD34+ cells was 0.0835 (0.001-1.528) × 109 /L at diagnosis, and 0.123 (0.002-1.528) × 109 /L at ruxolitinib start. With the exception of a transient increase after 3 months of ruxolitinib therapy, a progressive ...[more]

PMID: 36266779

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Project description:Myelofibrosis is a BCR-ABL1-negative myeloproliferative neoplasm characterized by anemia, progressive splenomegaly, extramedullary hematopoiesis, bone marrow fibrosis, constitutional symptoms, leukemic progression, and shortened survival. Constitutive activation of the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway, and other cellular pathways downstream, leads to myeloproliferation, proinflammatory cytokine expression, and bone marrow remodeling. Transplant is the only curative option for myelofibrosis, but high rates of morbidity and mortality limit eligibility. Several prognostic models have been developed to facilitate treatment decisions. Until the recent approval of fedratinib, a JAK2 inhibitor, ruxolitinib was the only available JAK inhibitor for treatment of intermediate- or high-risk myelofibrosis. Ruxolitinib reduces splenomegaly to some degree in almost all treated patients; however, many patients cannot tolerate ruxolitinib due to dose-dependent drug-related cytopenias, and even patients with a good initial response often develop resistance to ruxolitinib after 2-3 years of therapy. Currently, there is no consensus definition of ruxolitinib failure. Until fedratinib approval, strategies to overcome ruxolitinib resistance or intolerance were mainly different approaches to continued ruxolitinib therapy, including dosing modifications and ruxolitinib rechallenge. Fedratinib and two other JAK2 inhibitors in later stages of clinical development, pacritinib and momelotinib, have been shown to induce clinical responses and improve symptoms in patients previously treated with ruxolitinib. Fedratinib induces robust spleen responses, and pacritinib and momelotinib may have preferential activity in patients with severe cytopenias. Reviewed here are strategies to ameliorate ruxolitinib resistance or intolerance, and outcomes of clinical trials in patients with myelofibrosis receiving second-line JAK inhibitors after ruxolitinib treatment.

Dataset Information

Trend of circulating CD34⁺ cells in patients with myelofibrosis: Association with spleen response during ruxolitinib treatment.

Publications

Trend of circulating CD34<sup>+</sup> cells in patients with myelofibrosis: Association with spleen response during ruxolitinib treatment.

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