Mindfulness Minute: Sitting With Uncomfortable Feelings

Posted on by

By Natalie Giocondo

One of the benefits of regular yoga and meditation practice is the cultivation of tolerance. We become more tolerant of ourselves, more tolerant of others, and more tolerant of the way things are.

A dear friend and mentor, Ken Rosen, once told me that suffering is the place that exists between what is and what we want it to be. Ken was an MPN patient, a Zen Buddhist teacher, and a therapist who passed away not long after he presented on Mindfulness at an MPNA&EI conference in 2018. His yoga and meditation practice helped him to manage his yearslong experience with essential thrombocythemia, gave him peace during a major thrombotic episode that resulted in a month-long hospital stay, and I believe it gave him peace during the last months of his life.

Sitting with uncomfortable feelings is not just a useful skill when we are faced with illness or mortality, it also comes in handy when we are in a hurry and stuck behind a chatty Cathy in the supermarket checkout, or when someone cuts us off in traffic, or when we are waiting for important news. In many of these scenarios, our sympathetic nervous system is triggered and the body tells the mind to respond. This process, while useful in survival situations, is not so good for us when it happens multiple times a day or week and can produce.

In a recent Conversation with an MPN Specialist, Dr. Ellen Richie touched on some things we can do to reduce the body’s inflammatory response in addition to a low-inflammation diet, such as reducing stress by disconnecting from technology for periods of the day, finding quiet time, or listening to good music.

Another way to lower stress is to learn how to better tolerate it by practicing yoga and meditation. Now, this is not a no pain, no gain philosophy so when we talk about tolerating stress here, we do not mean how to grin and bear it. Instead, we learn to better observe the way our mind behaves when stress arises and then we train it to behave in a way that better supports us. The result? Stress reduction.

Join us online Thursday, April 18th from 12:00-12:40 pm EST for a Yin-Yoga practice. Yin-Yoga requires longer holds in each pose to encourage the fascia (webbing around the muscles) to release. Longer holds also allow us to sit and observe our body and mind. This is a great practice to create flexibility in the body and mind.

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

Disease Progression for Patients With Low-Risk Myelofibrosis Participating in the MOST Study

Posted on by

Grace Taylor

03/26/2024

A group of researchers presented data on disease progression for patients with low-risk myelofibrosis (MF) participating in the prospective observational Myelofibrosis and Essential Thrombocythemia Observational Study (MOST) at the 2023 ASH Annual Meeting & Exposition.

In order to qualify for the MOST study, participants were required to have a physician-reported diagnosis of MF (primary myelofibrosis [PMF], post progression of polycythemia vera [post-PV], or post essential thrombocythemia [post-ET). They also could not have any risk factors per the Dynamic International Prognostic Scoring System (DIPSS) criteria. However, participants could be aged 65 years or older. The number of patients with MF enrolled in the study was 232. Of this population, 205 met the study criteria and were included in cohort A. Although the remaining 27 patients had  ≥1 DIPSS risk factor, they were included in the study in a separate cohort B.

For the study, disease progression was defined by the worsening of clinical or laboratory parameters, which included one or more of the following criteria: hemoglobin (Hb) <10 g/dL, platelets <100×109/L, presence of constitutional symptoms (weight loss, fever, or sweats), new or worsening splenomegaly, blasts >1%, white blood cell count >25×109/L, death due to disease progression, leukemic transformation (LT), or >1 red blood cell transfusion. The median follow-up was 52.9 months (42-68).

Read more

Younger Patients With PV May Benefit From Earlier Treatment With Cytoreductive Therapies

Posted on by

Laura Joszt, MA

Although patients younger than age 60 with polycythemia vera (PV) are typically not treated with cytoreductive therapy due to treatment toxicity concerns, this may result in an undertreatment of patients as there is no clear evidence that the risk of toxicity exceeds the potential benefit of treatment, according to a study published in Blood Advances.1

PV causes an overproduction of blood cells in the bone marrow, which leads to high numbers of circulating red blood cells.2 This thickens the blood, which may not flow through smaller blood vessels properly. Although PV can be diagnosed at any age, it most often occurs in people over the age of 60 years.2

For most patients, phlebotomy is the standard treatment, and it may be the only treatment needed for years. However, additional treatment to suppress the formation of blood cells in the bone marrow may be needed. Cytoreductive therapies, such as interferons, hydroxyurea, ruxolitinib, and anagrelide, may be needed, particularly for high-risk patients.3

Currently, cytoreductive therapies are not routinely recommended by the European LeukemiaNet or National Comprehensive Cancer Network for patients with PV younger than 60 years who don’t have a history of thrombosis, a high symptom burden, or an intolerance to phlebotomy.

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.

Next-Generation JAK Inhibitors Signal the Future of Myelofibrosis Treatment Advances

Posted on by

Ashling Wahner

Newer-generation JAK inhibitors are increasingly adept at controlling symptoms in patients with myelofibrosis and may recapture treatment response in patients who have progressed on prior ruxolitinib (Jakafi), according to Joseph G. Jurcic, MD.

“Using drugs that target all these particular abnormalities can result in symptom and spleen improvement, and in some, a reduction in cytokines and allelic burden,” Jurcic said in an interview with OncLive®.

In the interview, Jurcic discussed the benefits and limitations of several JAK inhibitors for patients with myelofibrosis, highlighting the treatment advances that have been made since the introduction of ruxolitinib to the treatment paradigm, considerations for the use of fedratinib (Inrebic), and the potential advantages of pacritinib (Vonjo) for patients with anemia.

Read more

Rusfertide Treatment Strengthens Response and Decreases Erythrocytosis Among Patients With Polycythemia Vera

Posted on by

Jordan Kadish

03/22/2024

According to findings from the international phase 2 REVIVE trial published in The New England Journal of Medicine, treatment with rusfertide, a peptide mimetic of the master iron regulatory hormone hepcidin, strengthened responses and decreased erythrocytosis among patients with polycythemia vera (PV). Patients who received rusfertide demonstrated a mean hematocrit of less than 45% during the dose-finding period.

Marina Kremyanskaya, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, New York, and coauthors stated, “Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis,” or a high concentration of red blood cells in the blood. “The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown,” they added.

To expand on the available research, the study authors aimed to assess the efficacy of rusfertide among patients with polycythemia vera. The primary end point was a response, which was characterized by the hematocrit control, absence of phlebotomy, and finishing the trial regimen during part 2. The modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary was utilized to assess patient-reported outcomes of symptoms.

Read more

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.