Differential prognostic impact of cytopenic phenotype in prefibrotic vs overt primary myelofibrosis

Coltro, Giacomo; Mannelli, Francesco; Loscocco, Giuseppe Gaetano; Mannarelli, Carmela; Rotunno, Giada; Maccari, Chiara; Pancani, Fabiana; Atanasio, Alessandro; Vannucchi, Alessandro M.; Guglielmelli, Paola

doi:10.1038/s41408-022-00713-6

Cited by 13 publications

(13 citation statements)

References 17 publications

(19 reference statements)

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“…A cytopenic phenotype was associated with prognostically detrimental genetic markers (HMR mutations and unfavorable karyotype) and with higher DIPSS/MYSEC‐PM risk category. These results are in line with those observed in a cohort of patients with prefibrotic and overtly fibrotic PMF at diagnosis 12 . Notably, the percentage of patients who started ruxolitinib at intermediate 1 risk was high overall (55.2%) and increased over the years up to 70%.…”

Section: Discussionsupporting

confidence: 90%

“…Also, survival was worse in patients with cytopenic PMF and SMF and in those with more than one cytopenia. The substantial overlap between this outcome result and that observed in a retrospective cohort of patients with PMF undergoing heterogeneous therapeutic strategies 12 suggests that the cytopenic phenotype has a key prognostic value, likely because of its association with high‐risk biological features, which ruxolitinib does not significantly alter. Additionally, both absence of spleen response and ruxolitinib discontinuation are associated with worse 23,31 outcome.…”

Section: Discussionmentioning

confidence: 75%

“…These results are in line with those observed in a cohort of patients with prefibrotic and overtly fibrotic PMF at diagnosis. 12 Notably, the percentage of patients who started ruxolitinib at in- the demonstration that early treatment could improve the likelihood of responses, without worsening the toxicity profile at least in the short to medium term, and possibly improving survival. [22][23][24][25][26] The presence of cytopenias resulted in using lower doses of ruxolitinib, both at the beginning of therapy and on average during the first 3 months and throughout the observation period.…”

Section: Discussionmentioning

confidence: 99%

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Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome

Palandri

Breccia²,

Mazzoni

et al. 2023

Cancer

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Background: Patients with cytopenic myelofibrosis (MF) have more limited therapeutic options and poorer prognoses compared with patients with the myeloproliferative phenotype.Aims and Methods: Prognostic correlates of cytopenic phenotype were explored in 886 ruxolitinib-treated patients with primary/secondary MF (PMF/SMF) included in the RUX-MF retrospective study. Cytopenia was defined as: leukocyte count <4 � 10 9 /L and/or hemoglobin <11/<10 g/dL (males/females) and/or platelets <100 � 10 9 /L.Results: Overall, 407 (45.9%) patients had a cytopenic MF, including 249 (52.4%) with PMF. In multivariable analysis, high molecular risk mutations (p = .04), intermediate 2/high Dynamic International Prognostic Score System (p < .001) and intermediate 2/high Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia Prognostic Model (p < .001) remained associated with cytopenicThe first two and last two authors contributed equally to the manuscript.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

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Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome

Palandri

Breccia²,

Mazzoni

et al. 2023

Cancer

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“…The most important indices were thrombocytopenia and anemia. The published results further extend the characterization of cytopenic features in PMF with a new understanding of the differences be-tween the prefibrotic and overt fibrotic stages [20]. Primary myelofibrosis is characterized by anemia, which is detected in 50% of cases.…”

Section: Discussionsupporting

confidence: 62%

Clinical patterns and complete blood count parameters in the young patients with primary myelofibrosis in the prefibrotic stage

Sghibneva-Bobeico¹,

Musteata²,

Robu³

et al. 2022

MJHS

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Introduction. Primary myelofibrosis is a rare myeloproliferative neoplasm that affects 0.2-1.5 people per 100,000. As a rule, the diagnosis is confirmed after 60 years, but recently, hematologists around the world have encountered the problem of primary myelofibrosis in young people. The classic manifestations of myelofibrosis are characterized by splenomegaly, cytopenia, and bone marrow fibrosis, but in patients younger than 40 years, the diagnosis is most often made in the prefibrotic stage of the neoplasm. The aim of the paper is to identify and evaluate the clinical and hematological features of primary myelofibrosis in young patients in the prefibrotic stage. Material and methods. A retrospective study was performed on clinical cases of primary myelofibrosis, registered at the Oncological Institute of the Republic of Moldova. The diagnosis was confirmed according to 2016 WHO criteria based on histological and molecular studies. We enrolled young patients under the age of 40 who had been diagnosed with prefibrosis in our study and analyzed them for clinical manifestations and complete blood count parameters. To optimize the analysis, all patients were divided into two groups according to their age: 18–29 and 30–40 years old. Results. Changes in the complete blood count, manifested by thrombocytosis and leukocytosis, are the main laboratory patterns of primary myelofibrosis in young patients in the prefibrotic stage. The most relevant clinical features are splenomegaly and hepatomegaly, but no correlation between these manifestations has been found. Conclusions. The classical clinical and hematological characteristics of primary myelofibrosis do not specify lowand intermediate-risk patients’ management in the prefibrotic stage, as compared with the other chronic myeloproliferative BCR-ABL-negative neoplasms. The proliferation type of primary myelofibrosis is characteristic for young patients with pre-fibrotic stage. According to our results, the main manifestations in the prefibrotic stage are detected in a complete blood count and comprise anemia, leucopenia, leukocytosis, and thrombocytosis.

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“…Again, cytopenic sMF patients had shorter OS (median, 44 vs 105 months; p < 0.0001). Median OS was significantly inferior in those with ≥2 cytopenias compared with one cytopenia (median, 27 vs 58 months, respectively; p < 0.0001) [ 55 ].…”

Section: Introductionmentioning

confidence: 99%

Biological drivers of clinical phenotype in myelofibrosis

et al. 2022

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Myelofibrosis (MF) is a myeloproliferative disorder that exhibits considerable biological and clinical heterogeneity. At the two ends of the disease spectrum are the myelodepletive or cytopenic phenotype and the myeloproliferative phenotype. The cytopenic phenotype has a high prevalence in primary MF (PMF) and is characterized by low blood counts. The myeloproliferative phenotype is typically associated with secondary MF (SMF), mild anemia, minimal need for transfusion support, and normal to mild thrombocytopenia. Differences in somatic driver mutations and allelic burden, as well as the acquisition of non-driver mutations further influences these phenotypic differences, prognosis, and response to therapies such as JAK2 inhibitors. The outcome of patients with the cytopenic phenotype are comparatively worse and frequently pose a challenge to treat given the inherent exacerbation of cytopenias. Recent data indicate that an innate immune deregulated state that hinges on the myddosome-IRAK-NFκB axis favors the cytopenic myelofibrosis phenotype and offers opportunity for novel treatment approaches. We will review the biological and clinical features of the MF disease spectrum and associated treatment considerations.

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Differential prognostic impact of cytopenic phenotype in prefibrotic vs overt primary myelofibrosis

Cited by 13 publications

References 17 publications

Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome

Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome

Clinical patterns and complete blood count parameters in the young patients with primary myelofibrosis in the prefibrotic stage

Biological drivers of clinical phenotype in myelofibrosis

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