Category Archives: Research

Childbirth rates in women with myeloproliferative neoplasms

Posted on by

Anna Ravn Landtblom, Therese M-L Andersson, Anna L. V. Johansson, Frida E. Lundberg, Jan Samuelsson, Magnus Björkholm & Malin Hultcrantz

Abstract

Myeloproliferative neoplasms (MPN) are associated with inferior pregnancy outcome, however, little is known about fertility and childbearing potential in women with MPN. In this study we aimed to describe reproductive patterns, as well as to quantify risk of miscarriage and stillbirth. Women aged 15–44 years with an MPN diagnosis 1973–2018, were identified in Swedish health care registers, and age-matched 1:4 to population controls. We identified 1141 women with MPN and 4564 controls. Women with MPN had a lower rate of childbirth (hazard ratio [HR] with 95% confidence interval was 0.78 (0.68–0.90)). Subgroup analysis showed that the rate was not significantly reduced in essential thrombocythemia, HR 1.02 (0.86–1.22) while the HR was 0.50 (0.33–0.76) in PV and 0.45 (0.28–0.74) in PMF. The risk of miscarriage was not significantly increased before MPN diagnosis, the HR during follow-up after diagnosis was 1.25 (0.89-1.76). Women with MPN were more likely to have had a previous stillbirth. Women with MPN had fewer children at diagnosis, and fewer children in total. In conclusion, the childbirth rate was lower among women with MPN than controls, but not among women with essential thrombocythemia.

Read more

 

Emerging Data Continue to Evolve Treatment Utilization in MPNs

Posted on by

Laura Joszt, MA

Emerging data are continually changing the knowledge base around how interferons should be used, despite being around for decades, in patients with myeloproliferative neoplasms (MPNs), says Raajit Rampal, MD, PhD, hematologic oncologist, associate attending physician, Memorial Sloan Kettering Cancer Center.

Transcript

How has the landscape for MPN treatment evolved since the introduction of interferons? How does it look different today?

I guess it’s more a question of utilization than the landscape, in the sense that both things like hydroxyurea and interferons and drugs, like an anagrelide for ET [essential thrombocythemia], have been around for quite some time. And I think that it hasn’t been clear for the majority of that time which drugs should be used when and by whom.

There is now randomized clinical trial data for pegylated interferon vs hydroxyurea, but more recently, particularly with regards to polycythemia vera, there’s randomized data with ropeginterferon and hydroxyurea. And at least in that data set, the [blood] count control was superior with ropeginterferon vs hydroxyurea over the course of a number of years. Initially, at 1 year, there wasn’t so much of a difference, but as time went on, there was clearly a difference that favored the use of ropeginterferon in terms of controlling the blood counts. Similarly, over time, there does seem to be a decrease in the JAK [Janus kinase] 2 mutation burden in the patients who got the ropeginterferon.

I think that there is an emerging data set that is arguing that there are benefits to interferon. Going back to the initial point here, the landscape has changed to some degree—with the introduction of something like ropeginterferon—but I think it’s more that the data is evolving, which is beginning to tell us maybe which drugs might be best for which patients. We’re not completely there by any stretch of the imagination, but the data is beginning to coalesce around the message.

Read more

Retrospective Study Shows HSCT Consolidation After Blast Reduction Improves OS in Chronic Phase–Reverted MPN

Posted on by

Ashling Wahner

Patients with myeloproliferative neoplasms in accelerated or blast phase (MPN-AP/BP) who revert to chronic phase (cMPN) after blast-reduction therapy, as well as those with complete response (CR) or CR with incomplete hematologic recovery (CRi) after blast reduction, experience improved overall survival (OS) outcomes after hematopoietic stem cell transplant (HSCT) consolidation therapy, according to findings from a single-center, retrospective analysis evaluating outcomes with intensive and nonintensive blast-reduction strategies in patients with MPN-AP/BP, which were published in Blood Advances.1

This study, which used clinically relatable response criteria developed at the Princess Margaret Cancer Centre, as well as the European LeukemiaNet (ELN) 2022 acute myeloid leukemia (AML) response criteria, found that patients who received intensive blast-reduction therapy achieved a best overall response rate (ORR) of 77% (n = 62/81) vs 39% (n = 21/54) in those who received nonintensive therapy. CR/CRi and cMPN reversions were observed in 24 and 38 patients in the intensive group and 4 and 17 patients in the nonintensive group, respectively.

Although allogeneic HSCT is the only therapy associated with long-term survival improvements for patients with MPN-AP/BP, this treatment strategy is typically reserved for patients who have achieved disease control. Other blast-reduction strategies include induction chemotherapy, as well as hypomethylating agents (HMAs)—such as azacitidine (Vidaza)—as monotherapy or in combination with agents such as venetoclax (Venclexta).2

“However, the optimal blast-reduction strategy and depth of disease clearance required before HSCT are unknown,” lead study author Marta B. Davidson, MD, PhD, FRCPC, of the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, and coauthors, wrote in the paper.1 “Moreover, a lack of standardized response criteria to evaluate the treatment of MPN-AP/BP poses challenges for understanding treatment efficacy between reported studies.”

Read more

Pegylated Interferons Have Promise but Also Unmet Potential in MPNs

Posted on by

Jared Kaltwasser

Pegylated interferons are a meaningful therapeutic option for the treatment of myeloproliferative neoplasms (MPNs), but a new review article says more research is needed to better understand the ideal usage of the therapy.

The report was published in Therapeutic Advances in Hematology.

Study investigators said several interferon products are currently available to treat patients with MPNs, but they said the short half-life of interferons and the risk of (AEs) effects have limited their usage. Pegylation can help overcome those issues, they said.

“Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule,” the authors wrote.

More research is needed to better understand when and in whom pegylate interferon therapy is most effective | Image Credit: Iamnee – stock.adobe.com

They said current National Comprehensive Cancer Network guidelines call for pegylated interferons to be used for polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Currently, there are 2 pegylated interferons available for patients with MPNs, they said: peginterferon alfa-2a (Pegasys; pharma&) and ropeginterferon alfa-2b-njft (BESREMi; PharmaEssentia). Both medications are recommended as cytoreductive therapies for PV, the investigators said.

Dr Raajit Rampal Highlights Emerging Therapies in MPNs

Posted on by

March 22, 2024

By Laura Joszt, MA

Interferons have been used for decades to treat myeloproliferative neoplasms (MPNs), and new emerging therapies, such as the Janus kinase (JAK) inhibitor ruxolitinib, are expanding the therapeutic armamentarium, said Raajit Rampal, MD, PhD, hematologic oncologist, associate attending physician, Memorial Sloan Kettering Cancer Center.

What is the importance of interferons as a treatment for MPNs, and what role do they play?

Interferons have been used now for decades in MPNs, and they demonstrate clinical efficacy, certainly in essential thrombocytopenia, in polycythemia vera, and there is data for prefibrotic myelofibrosis.1 Now there are a number of different interferons. There were interferons that were given 3 times a week, and pegylated interferon, which is what we use most often, and now there’s ropeginterferon, which is every 2 weeks as a treatment.

What the interferons can do, for sure, is that they can reduce blood counts. So, for people with the polycythemia or with essential thrombocytopenia, we can get a reduction in the blood counts in the majority of patients. What is also interesting is that—and as has been known now for a number of years—the allele burden, particularly of JAK2, can decrease over time with the treatment with interferons, which at least would suggest to us that you may be depleting part of the clone that causes the disease. So, there are certainly a number of important clinical benefits of interferons, but even potentially biological effects.

Read more

The Role of DNA Repair (XPC, XPD, XPF, and XPG) Gene Polymorphisms in the Development of Myeloproliferative Neoplasms

Posted on by

by , , , , , and  

Abstract

Background and Objectives: Several polymorphisms have been described in various DNA repair genes. Nucleotide excision DNA repair (NER) detects defects of DNA molecules and corrects them to restore genome integrity. We hypothesized that the XPC, XPD, XPF, and XPG gene polymorphisms influence the appearance of myeloproliferative neoplasms (MPNs). Materials and Methods: We investigated the XPC 1496C>T (rs2228000, XPC Ala499Val), XPC 2920A>C (rs228001, XPC Lys939Gln), XPD 2251A>C (rs13181, XPD Lys751Gln), XPF-673C>T (rs3136038), XPF 11985A>G (rs254942), and XPG 3507G>C (rs17655, XPG Asp1104His) polymorphisms by polymerase chain reaction–restriction fragment length polymorphism analysis in 393 MPN patients [153 with polycythemia vera (PV), 201 with essential thrombocythemia (ET), and 39 with primary myelofibrosis (PMF)] and 323 healthy controls. Results: Overall, we found that variant genotypes of XPD 2251A>C were associated with an increased risk of MPN (OR = 1.54, 95% CI = 1.15–2.08, p = 0.004), while XPF-673C>T and XPF 11985A>G were associated with a decreased risk of developing MPN (OR = 0.56, 95% CI = 0.42–0.76, p < 0.001; and OR = 0.26, 95% CI = 0.19–0.37, p < 0.001, respectively). Conclusions: In light of our findings, XPD 2251A>C polymorphism was associated with the risk of developing MPN and XPF-673C>T and XPF 11985A>G single nucleotide polymorphisms (SNPs) may have a protective role for MPN, while XPC 1496C>T, XPC 2920A>C, and XPG 3507G>C polymorphisms do not represent risk factors in MPN development.

Disease-, Age-, Genomic-Specific Factors Increase Risk of ET, PV, PrePMF Developing Into Overt MF

Posted on by

Laura Joszt, MA

The risk of essential thrombocytopenia (ET), polycythemia vera (PV), and prefibrotic primary myelofibrosis (PrePMF) developing into overt myelofibrosis (MF) increases with age, the accumulation of mutations, and the activation of proliferative pathways, which identifies new targets for therapeutic intervention.

The findings, based on an analysis of the mutational landscape of more than 1700 genes and the gene expression of various cells from patients with myeloproliferative neoplasms (MPNs), was published in Clinical Cancer Research.1

ET, PV, PMF, and MF are all part of a group of diseases MPNs, in which a mutation in the bone marrow causes too many red blood cells, white blood cells, or platelets.2 In addition to being the most common MPNs, ET, PV, and PMF share the presence of mutations in either Janus kinase 2 (JAK2), calreticulin (CALR), and/or MPL.3 ET and PV are less aggressive forms of MPN, but they still can progress to MF. According to the Leukemia & Lymphoma Society, Pre-PMF will likely progress to PMF, “suggesting that more regular observations for pre-fibrotic PMF patients is warranted.”3

Read more

Childbirth rates in women with myeloproliferative neoplasms

Posted on by

Published March 9, 2024

Anna Ravn Landtblom, Therese M-L Andersson, Anna L. V. Johansson, Frida E. Lundberg, Jan Samuelsson, Magnus Björkholm & Malin Hultcrantz

Abstract

Myeloproliferative neoplasms (MPN) are associated with inferior pregnancy outcome, however, little is known about fertility and childbearing potential in women with MPN. In this study we aimed to describe reproductive patterns, as well as to quantify risk of miscarriage and stillbirth. Women aged 15–44 years with an MPN diagnosis 1973–2018, were identified in Swedish health care registers, and age-matched 1:4 to population controls. We identified 1141 women with MPN and 4564 controls. Women with MPN had a lower rate of childbirth (hazard ratio [HR] with 95% confidence interval was 0.78 (0.68–0.90)). Subgroup analysis showed that the rate was not significantly reduced in essential thrombocythemia, HR 1.02 (0.86–1.22) while the HR was 0.50 (0.33–0.76) in PV and 0.45 (0.28–0.74) in PMF. The risk of miscarriage was not significantly increased before MPN diagnosis, the HR during follow-up after diagnosis was 1.25 (0.89-1.76). Women with MPN were more likely to have had a previous stillbirth. Women with MPN had fewer children at diagnosis, and fewer children in total. In conclusion, the childbirth rate was lower among women with MPN than controls, but not among women with essential thrombocythemia.

Read more

A Review About the Assessment of the Bleeding and Thrombosis Risk for Patients With Myeloproliferative Neoplasms Scheduled for Surgery

Posted on by

Mihaela Andreescu
Bogdan Andreescu

Published March 12, 2024

Abstract

Myeloproliferative neoplasms (MPNs) present a unique challenge in surgical management due to their inherent predisposition to both bleeding and thrombosis. MPNs are a heterogenous group of acquired clonal conditions. The three classic MPNs are essential thrombocythemia (ET), myelofibrosis (PMF), and polycythemia vera (PV). All subtypes of MPN are associated with both thrombotic and bleeding complications. There are four risk categories for thrombosis in MPN patients: age, thrombosis history, and JAK-2 mutation. They are further classified as very low, low, intermediate, and high risk. The genetic landscape of MPN is fascinating and complex like all myeloid disorders. Bleeding risk can be assessed through leukocytosis, thrombocytosis, acquired von Willebrand syndrome (AVWS), and a previous history of bleeding in a patient. Risk assessment and perioperative management are important aspects of improving the quality of life and preventing complications in surgeries. Preoperative management includes a risk assessment of venous thromboembolism, use of appropriate pharmacological treatment, platelet count control, and correction and cardiovascular risk factors. This review summarizes the assessment of bleeding and thrombosis risk for patients with MPNs scheduled for surgery. Furthermore, this review discusses various tools that can be used to identify MPN patients at risk of thrombosis prior to surgery.

Read more

 

Risk of thrombosis, hemorrhage and leukemic transformation in patients with myeloproliferative neoplasms: A nationwide longitudinal cohort study

Posted on by

Joon Young Hur, Nayeon Choi, Jung Hye Choi, Jiyeong Kim, Young-Woong Won

Abstract

Introduction

There are few large-scale, population-based studies detailing the risks of thrombosis, hemorrhage, leukemic transformation in patients with myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF).

Methods

We performed a nationwide longitudinal cohort study using the Korean National Health Insurance System (NHIS) database. MPN patients (n = 11,991) and their 1:4 age- and sex-matched controls (n = 47,964) were enrolled. The risk of thrombosis, hemorrhage, leukemic transformation was estimated using a Cox proportional hazards regression, and stratified analyses were performed for related factors.

Results

During a median of 7.8 years of follow-up, 30.1 % of MPN patients (3614/11,991) and 19.0 % of the matched controls (9141/47,964) developed arterial thrombosis, 11.6 % of MPN patients (1397/11,991) and 6.4 % of the matched controls (3099/47,964) developed venous thrombosis and 18.7 % of MPN patients (2251/11,991) and 12.1 % of the matched controls (5836/47,964) developed hemorrhage. 4.9 % of MPN patients (597/11,991) and 0.1 % of matched controls (50/47,964) developed leukemia. The overall risk of developing thrombosis, hemorrhage, leukemic transformation was higher in MPN patients (adjusted hazard ratio [aHR] 1.695, 95 % confidence interval [CI]: 1.629–1.765 for arterial thrombosis, aHR 1.963, 95 % CI: 1.838–2.096 for venous thrombosis, and aHR 1.714, 95 % CI: 1.630–1.802 for hemorrhage) than in the controls. Patients with MPNs had a 10-year cumulative incidence of leukemic transformation of 6.2 %.

Conclusion

The patients with MPNs have a higher risk of thrombosis, hemorrhage, and leukemic transformation than matched controls. Strategies are warranted to reduce the risk of thrombosis, hemorrhage, and leukemic transformation in MPN patients.

Read more