All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the MPN Advocates Network.

The MPN Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

Join our

Treatment sequencing for anemic myelofibrosis

with Jean-Jacques Kiladjian & Angela Fleischman

Monday, February 26, 2024 | 16:30 CET

This independent educational activity is supported by Bristol Myers Squibb. All content is developed independently by the faculty. The funder is allowed no influence on the content of this activity.


The MPN Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the MPN Hub cannot guarantee the accuracy of translated content. The MPN Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.

Steering CommitteeAbout UsNewsletterContact
You're logged in! Click here any time to manage your account or log out.
You're logged in! Click here any time to manage your account or log out.

Distinctive prognostic factors in patients with thrombocytopenic myelofibrosis

Oct 7, 2022
Learning objective: After reading this article, learners will be able to cite a new clinical development in myelofibrosis.

Bookmark this article

Thrombocytopenia is an adverse prognostic factor for myelofibrosis (MF) and presents several treatment-related challenges, including dose changes and treatment cessation, as well as exclusion from clinical trials.1 MF with thrombocytopenia has been considered a high-risk disease and associated with poor survival.1

Kuykendall, et al.1 conducted a study with the aim of investigating whether all patients with thrombocytopenia present with the same high-risk features or if any distinct characteristics within these patients would inform a different approach for risk stratification. The results were recently published in Cancer, and we summarize their findings below.

Study design

This retrospective cohort analysis identified patients from a database between 2001 and 2021. Clinical variables were recorded at diagnosis, while patients who had no available clinical data prior to receiving MF-associated therapy were excluded.

Patients with a pretreatment platelet count <100 × 109/L were compared with those with a preserved platelet count of >150 × 109/L. Patients with a platelet count between 100 × 109/L and 150 × 109/L were excluded.


A total of 137 patients with baseline thrombocytopenia (<100 × 109/L) were selected and compared with 628 nonthrombocytopenic patients (>150 × 109/L). The median follow-up time was 53.9 months. Full patient characteristics are shown in Table 1.

Table 1. Patient characteristics*

Variable, %
(unless otherwise stated)

Thrombocytopenic (platelet count <100 × 109/L) 

n = 137

Nonthrombocytopenic (platelet count >150 × 109/L)

n = 628

p value

Median age at diagnosis, years




Primary MF




Post-polycythemia vera MF




Post-essential thrombocythemia MF




Hgb <10 g/dL




Peripheral blasts ≥1%




Marked marrow fibrosis




Bone marrow cellularity ≤20%




Albumin <4.3 g/dL




High- or very high-risk cytogenetics




Deletion 20q




JAK2 mutation




JAK2 mutation allele burden ≥60%




CALR mutation




MPL mutation




U2AF1Q157 mutation




≥3 nondriver mutations




Hgb, hemoglobin; MF, myelofibrosis.
*Adapted from Kuykendall, et al.1
All variables with p < 0.10 were included in subsequent multivariate analysis and p values in bold highlight a significant statistical difference.

Patients with thrombocytopenia were more likely to have primary MF (p = 0.03) but were less likely to have MF after a diagnosis of essential thrombocythemia (p < 0.01). Patients with thrombocytopenia were also more likely to have a range of other symptoms and features, including anemia, peripheral blasts >1% and either high or very high-risk cytogenetics. There was no difference in the incidence of splenomegaly, leukocytosis, constitutional symptoms, and frequency of JAK2 mutations.

Interestingly, patients with thrombocytopenia were less likely to have a CALR mutation (p < 0.01). Among those with thrombocytopenia, 61% had one or more genetic abnormality. While anemia was more frequent in these patients, those with del(20q) were less likely to have concomitant anemia (33% vs 59%; p = 0.02). High/very high-risk cytogenetics had a greater chance of association with significant marrow fibrosis (p = 0.02). Overall survival (OS) and leukemia-free survival showed no difference based on genetic abnormalities. There were also similar rates of transformation to blast phase in patients with or without thrombocytopenia (12% vs 9%, respectively; p = 0.43). However, overall, patients with thrombocytopenia had a significantly shorter median OS and leukemia-free survival compared with patients without thrombocytopenia (p <0.01 for both variables; Figure 1).

Figure 1. Median overall survival and leukemia-free survival in patients with and without thrombocytopenia* 

*Adapted from Kuykendall, et al.1

Moreover, patients with thrombocytopenia were less likely to receive JAK inhibitor therapy compared with those without thrombocytopenia (35% vs 53%, respectively; p < 0.01).

Univariate analysis of patients with thrombocytopenia revealed several variables associated with inferior OS, including:

  • Age >65 years at diagnosis (p = 0.01)
  • Marked fibrosis (p = 0.05)
  • Albumin levels <4.3 g/dL (p = 0.02)
  • EZHZ mutation (p = 0.04)
  • TP53 mutation (p < 0.01)

Subsequent multivariate analysis initially included all clinical variables that were at least borderline significant (p < 0.1) in the univariate analysis, which revealed only serum albumin levels <4.3 g/dL to be a significant covariate (p = 0.2). A second multivariate analysis, performed in a genetically annotated subgroup, included all genetic variables. This demonstrated that the presence of SRSF2 or TP53 mutations significantly impacted OS (p = 0.2 and p < 0.01, respectively).

Univariate and multivariate analyses were also performed on patients without thrombocytopenia. Several significant covariates highlighted in previous prognostic models were identified, including the following:

  • Age >65 years
  • White blood cells >25 × 109/L
  • Hemoglobin <10 g/dL
  • Very high-risk karyotype
  • Albumin <4.3 g/dL
  • Mutations in ASXL, SRSF2, and RUNX1
  • Presence of ≥2 high molecular risk mutations

All data were then collated and used to create a three-tiered prognostic system in the thrombocytopenic cohort, with the following scoring:

  • Albumin <4.3 g/dL = 1 point
  • SRSF2 mutation = 1 point
  • TP53 mutation = 2 points

Individual patient scores were calculated and corresponded to their associated risk; 0, 1, and 23 points indicated low-, intermediate-, and high-risk, respectively. The median OS of the low-, intermediate-, and high-risk groups was 93.5 months, 29.5 months, and 7.2 months, respectively (p < 0.01). Low-risk patients accounted for 30% of the study population and had a similar OS to non-thrombocytopenic patients (93.5 months vs 80 months, respectively).


This study by Kuykendall, et al.1 demonstrated that conventional prognostic risk factors associated with MF are less effective for patients with thrombocytopenia. Patient outcomes were instead influenced by serum albumin levels and SRSF2 and TP53 mutations. Any patients lacking any of these factors recorded a survival rate comparable to that of patients with preserved platelet counts. While the results have clinical relevance, external validation would further enhance the findings.

  1. Kuykendall AT, Mo Q, Sallman DA, et al. Disease-related thrombocytopenia in myelofibrosis is defined by distinct genetic etiologies and is associated with unique prognostic correlates. Cancer. 2022;128(19):3495-3501. DOI: 1002/cncr.34414


Subscribe to get the best content related to MPN delivered to your inbox