Heart tissue heads to space for research on aging and impact of … – Cardiovascular Business

Other NASA experiments look at long spaceflight impact on the heart

Many recent medical studies on the space station use tissue chips like the Hopkins experiment. In other cases, tissues made from cells engineered to reproduce specific characteristics, and even organoid 3D structures made up of all the different types of cells in a particular organ including the heart, have been studied. These stand-ins for actual hearts enable new types of research and drug testing.

NASA said an investigation completed in 2018, Cardiac Myocytes, first showed that microgravity helps specially programmed stem cells move toward becoming new heart muscle cells. The experiment delivered frozen stem cells to the space station where crew members thawed and cultured them before returning the samples to Earth for analysis and comparison with control batches.

Subsequent research took advantage of microgravitys effect on cell behavior and growth to create tools for further research, model disease and test potential treatments for heart damage. TheMVP Cell-03study examined the production of heart cells from human-induced pluripotent stem cells (hiPSCs) in microgravity. Pluripotent cells are cells that have started to differentiate, making them more specialized than a stem cell, but that retain the ability to become multiple cell types. MVP Cell-03 showed that microgravity increased production of cardiomyocytes from hiPSCs. This increased production could make it possible to use cultured cells to help treat spaceflight-induced cardiac abnormalities and to replenish heart cells damaged or lost due to disease on Earth. Damaged human cardiac tissues cannot repair themselves, and loss of heart cells contributes to eventual heart failure.

If we want to use these cells for clinical applications, we need to be able to generate a lot of them in an efficient way, said MVP Cell-03 Principal Investigator Chunhui Xu, PhD, of the Emory University School of Medicine and Children's Healthcare of Atlanta in a statement. Heart replacement therapy, for example, requires at least a billion cardiomyocytes for just one patient.

The research also showed that space-grown cells have appropriate structure and function. That means they can be used to test drug safety. Now we can test in a dish whether a drug causes adverse effects, she said. This research can even use a persons own blood cells to produce hiPCS cells and, in turn, heart cells that can be used to determine how the individual might react to a specific drug.

The next step is to look at the quality of cells produced with the Project Eagle study, scheduled to launch later in 2023.

"What we have in our dish now is immature cells. They dont behave the way real heart cells behave, but are more similar to embryonic heart cells," Xu explained. "Transplanting those could be an increased risk for the patient. Project Eagle looks at whether microgravity might be an effective approach to push the cells to more mature stages.

Xus lab also tested using cryopreservation, a process of storing cells at -80C (-112F), as an alternative to delivering live cell cultures to the space station. The team determined that cryopreservation does not appear to negatively affect the cells and even protects them from the effects of excess gravity experienced during launch. This technique makes it easier to plan future research since experiments do not have to start as soon as the cells reach the station.

The Cardinal Heart study took place on the space station in 2021, which used engineered heart tissues to confirm that microgravity exposure causes significant changes in heart cell function and gene expression that could lead to damage. The study was a collaboration between Joseph Wu, MD, PhD, with Stanford University, andBeth Pruitt, PhD, with the University of California Santa Barbara.

The Cardinal Heart 2.0 study, which also was part of the payload in the March 14 resupply mission launch, takes this research to the next step. It uses a beating heart organoid that contains stem cell-derived cardiomyocytes, endothelial cells and cardiac fibroblasts, which form supportive connective tissue, to test whether certain drugs can reduce or prevent microgravity-induced changes. Using tissue chips to test new drugs could help reduce the need for the animal studies required before clinical trials in humans, potentially shortening the time between discovery of a drug candidate and its clinical use.

Funding for Cardinal Heart and the Engineered Heart Tissues research was provided by the National Institutes of Health (NIH).

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Heart tissue heads to space for research on aging and impact of ... - Cardiovascular Business

Improving Multiple Myeloma Diagnosis with Advanced Treatments – News18

Multiple myeloma is a type of blood cancer that affects the plasma cells, which are responsible for producing antibodies in the body. Being one of the most common blood cancer, it requires timely diagnosis and treatment. Over the years, there have been many advances in the diagnosis and treatment of multiple myeloma, leading to better outcomes for patients.

Plasma cells, a subset of white blood cells that make antibodies, are the target of the malignancy known as multiple myeloma. Early diagnosis and treatment of multiple myeloma are crucial for improving outcomes and enhancing chances of survival," says Dr S Jayanthi, Senior Pediatric Oncologist, Kamineni Hospitals, Hyderabad.

The latest treatment approaches to enhance the chances of diagnosing multiple myeloma are offering promising new treatments. Many multiple myeloma patients receive chemotherapy in order to reduce or eliminate their cancer cells. In some cases, chemotherapy may also lead to cancer remission. However, long term cancer control can often be difficult to achieve with this approach alone. Allogeneic bone marrow transplantation is a new treatment option that has shown promise for many multiple myeloma patients and is considered a more aggressive approach than just chemotherapy alone," adds Dr Jayanthi.

Early diagnosis and treatment of multiple myeloma are essential for improving outcomes and enhancing chances of survival. The latest treatment approaches, such as advanced imaging tests, biopsy, genetic testing, targeted therapies, and immunotherapy, can help to diagnose multiple myeloma and provide personalized treatment plans for better outcomes.

Advancements in imaging technology, such as PET-CT and MRI scans have allowed for more precise assessment and can detect myeloma lesions earlier than traditional X-rays, which can be critical for early diagnosis and effective treatment. Another newer advance in the treatment of multiple myeloma is the use of precision medicine. Precision medicine involves using genetic testing to identify the specific genetic mutations that are driving the growth of myeloma cells. Once these mutations are identified, targeted therapies can be used to block their effects and stop cancer from growing. This approach can lead to more personalized and effective treatment for each individual patient," says Dr Ashish Dixit, Consultant, Haematology, Haemato Oncology & Bone Marrow Transplantation, Manipal Hospital Old Airport Road.

Targeted therapies are newer treatment options for multiple myeloma. These drugs are designed to target specific proteins or pathways that are essential for the growth and survival of myeloma cells. An example of targeted therapy for multiple myeloma can be proteasome inhibitors, such as bortezomib. These drugs block the breakdown of proteins in myeloma cells, leading to their death.

Another newer treatment option for multiple myeloma is monoclonal antibodies, which are designed to target specific proteins on the surface of myeloma cells. Daratumumab is an example of a monoclonal antibody used in treating multiple myeloma. This drug helps the immune system recognize and attack myeloma cells more effectively," adds Dr Dixit.

Stem cell transplantation is one of the standard treatments for multiple myeloma. Stem cell transplantation involves collecting healthy stem cells from the patient or a donor, and then administering high doses of chemotherapy to kill cancer cells. The healthy stem cells are then infused back into the patients body, helping to restore the immune system and blood cell production.

Targeted Immunotherapy is a treatment option that uses the bodys immune system to fight cancer cells. One type of immunotherapy used in multiple myeloma is called CAR T-cell therapy. This treatment involves modifying the patients own T-cells in a laboratory so that they can recognize and destroy myeloma cells more effectively," opines Dr Dixit.

These newer advances in the diagnosis and treatment of multiple myeloma offer hope for patients with this disease. With continued research and development, we may see even more effective treatments in the future. It is important for patients with multiple myeloma to work closely with their doctors to determine the best course of treatment for their individual needs.

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Improving Multiple Myeloma Diagnosis with Advanced Treatments - News18

Promise of targeted drug for rare leukemias comes with Karnataka connection – Deccan Herald

Targeted drugs have reinforced the treatment of cancer even as researchers fast-track studies on the resistance cancer cells develop against these precision therapies.

A new study by researchers in Finland and Denmark has identified a targeted drug that could counter resistance in two rare subtypes of acute myeloid leukemia (AML) the cancer of the blood and bone marrow that have limited treatment options. The findings from the study conducted by the University of Helsinki, HUS Comprehensive Cancer Centre, and the University of Copenhagen are expected to improve the prognosis of erythroid and megakaryoblastic leukemias and make the selection of targeted drugs more precise. Studies estimate that the two subtypes account for less than 5 per centof all AML cases.

Also Read |Cancer, high BP, diabetes have treatment in Ayurveda but not in allopathy: Ramdev

The study showed that cells grouped under the two subtypes depended on BCL-XL for their survival. BCL-XL is a protein that prevents apoptosis or programmed cell death. The researchers tested 528 drugs for their efficacy on 21 human leukemic cell lines and AML patients and found BCL-XL protein inhibitors to be highly effective in killing the cancer cells.

Given the poor prognosis associated with erythroid and megakaryoblastic leukemias and the limited targeted therapy options, we propose BCL-XL as a viable target for further exploration in the treatment of these leukemia subtypes, the researchers said. The study has appeared in Blood, the peer-reviewed journal published by The American Society of Hematology.

An article on the study published on the University of Helsinkis website quoted Heikki Kuusanmaki, postdoctoral researcher, as saying that the findings validated patients with the two forms of leukemia as a promising group to test BCL-XL inhibitors efficacy in clinical use.

The Karnataka connection

Komal Kumar Javarappa, a translational scientist who worked as part of the research team at the University of Helsinki, told DH that the study analysed diverse leukemia subtypes with different genetic mutations to arrive at a potentially effective therapy. A native of Arakalgud in Karnatakas Hassan district, Komal is a specialist in flow cytometry a laser-based technique that is used to detect and analyse the properties of cells and other particles with research experience in immunology and hematological malignancies.

Komal, now doing research at the National University of Singapore, received his Masters degree and doctorate from the University of Mysore, in 2012. His postdoctoral research included work on stem cells and leukemia, at institutions in Sweden, Finland, and Denmark.

The study involved tracking of cell signaling pathways (which also indicates the characteristic changes in cancer cells). With a larger cohort, we can track the impact of the drug on a more diverse dataset, he said.

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Promise of targeted drug for rare leukemias comes with Karnataka connection - Deccan Herald

Complete Bone Response Observed in Trial of AB8939 for AML – Targeted Oncology

Treatment with AB8939, a microtubule destabilizer, resulted in a complete bone response in a patient with relapsed and refractory acute myeloid leukemia (AML) in a phase 1/2 study (AB18001; NCT05211570], according to a press release from AB Science.1

The patient had a reduction from 55% to 5% in bone marrow blast cells 1 month after receiving the second-lowest dose increment used in the trial. They also experienced no treatment-related toxicities.

It is remarkable that we rapidly observed a response in what is typically a difficult-to-treat patient population of refractory AML. We observe a clear blast count reduction for this patient and excellent tolerance so far, Pau Montesinos, MD, hematologist at the La Fe University Hospital and coordinator of the Spanish group of acute myeloblastic leukemia (PETHEMA), stated in the press release. It is all the more noteworthy because the initial disappearance of leukemic cells was obtained after only 3 days of AB8939 treatment at a very low dose, with a good response maintained after a second 3-day cycle at this dose.

The microtubule destabilizer AB8939 has broad antitumor activity with the capability to overcome P-glycoprotein and myeloperoxidase-mediated resistance that reduces the efficacy of microtubule-targeting chemotherapies. In preclinical studies, it showed activity across all AML subtypes and in AML that displays resistance to azacitidine (Onureg).2 It was granted orphan drug designation for AML by the FDA.1

AML is a serious life-threatening condition and the most common cause of leukemia-related mortality, in large part because patients develop chemoresistance to existing frontline AML drugs, Olivier Hermine, MD, president of the Scientific Committee of AB Science and member of the Acadmie des Sciences in France, said in the press release.1

The AB18001 trial is a phase 1/2, open-label, multi-center, non-randomized, 2-part study that is planned to enroll an estimated 78 patients with relapsed or refractory AML or refractory myelodysplastic syndrome. The first part is a dose escalation study with a primary end point of safety, tolerability, and pharmacokinetic profiles of AB8939. The second part is a dose expansion study using a recommended phase 2 dose to study the schedule for a phase 2 trial and assess efficacy.

Patients are ineligible for the study if they are eligible for standard of care or hematopoietic stem cell transplantation, have active central nervous system leukemia, or acute promyelocytic leukemia.

The patient who had the bone marrow response was 65 years old and previously failed treatment with azacitidine and had a MECOM gene rearrangement which is a biomarker associated with resistance to standard chemotherapies and is linked to disease progression.1,3 Overexpression of MECOM occurs in approximately 10% of patients with AML, and they have poor prognosis. AB Science has submitted a provisional patent application for this subpopulation of patients with AML.

The patient received a 1.8 mg/m2 intravenous dose for 3 consecutive days on a 28-day cycle.3 They were noted for benefiting at the second lowest of 13 potential dose levels in the dose escalation part of the trial. They received further treatment with AB8939 at the request of the investigator. One month after the second treatment cycle of 3 consecutive days at the same dose, they maintained a good response of 10% bone marrow blasts, and a third treatment cycle was initiated.

The patient also had an increase in neutrophils from 200/Lto 260/L after the first cycle and 480/L after the end of the second cycle. They had an increase in platelet count from 3000/L to 11000/L after 1 cycle and 12000/L after 2 cycles of treatment.

Investigators reported that overall, there have been no signs of moderate, severe, or serious toxicities in the trial.1,3 Approximately 50% of patients enrolled have requested further treatment cycles after receiving the first cycle and a measurement at day 28. In addition, 70% of patients had an increase in platelets and 90% had an increase in neutrophils.3 The first 4 dose levels have been completed, with the fifth dose level cohort of 9.0 mg/m2 being ongoing.

AB Science is planning to complete phase 1 in 2023 and initiate phase 2 in 2023 or 2024. The planned design for phase 2 may involve patient selection based on MECOM and other genetic factors and will enroll fewer than 100 patients. [The] AML indication fits the criteria for accelerated approval pathway based on compelling phase 2 (FDA), hematological response being a validated surrogate endpoint of efficacy, they stated in the webcast.3

This preliminary clinical data provides the most encouraging signs to date that AB8939 may be well-suited for treatment of high-risk relapsed/refractory AML, said Hermine.1

REFERENCES

1. AB Science reports a first complete bone marrow response in a relapsed refractory acute myeloid leukemia patient from the very low dose arm of its AB8939 Phase I/II clinical trial (AB18001). News release. March 13, 2023. Accessed March 22, 2023. https://bit.ly/3JxnmJa

2. Hermine O, Humbert M, Goubard A, et al. B8939, a novel microtubule-destabilizing agent for the treatment of acute myeloid leukemia. Presented at: 2020 Annual Congress of the European Hematology Association; June 11-20, 2020; virtual. Accessed March 23, 2023. https://bit.ly/3LMnpUm

3. AB Science Webconference microtubule destabilizer agents (MDA). March 16, 2023. Accessed March 23, 2023. AB Science. https://bit.ly/3z20Kvq

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Complete Bone Response Observed in Trial of AB8939 for AML - Targeted Oncology

Living with leukaemia: ‘My ethnicity means I’ve only a 37% chance of … – inews

I didnt really notice when it all began. I just assumed, round about December, that I had flu. It was very odd, though, as it just wouldnt go away. I had it for five weeks. I tested myself for Covid. I just couldnt work out why it wouldnt go away.

I got antibiotics and steroids from my GP. I struggled to get an appointment because the nurses were on strike, so I didnt really know I had anything other than flu and a really bad sore throat I even went hoarse as well.

I was about to start a new job on 16 January this year, so on the day before I said to my husband Im going to A&E, because I wanted to start the new job and feel healthy, and I felt so unwell.

Whenever my husband and I go to A&E we always drop each other off, we never stay with each other because we know its going to take at least four hours to be seen. So I went in and they did all the various tests. They did a blood test and this particular doctor came up to me and told me that they were going to have to keep me in longer. I said no. no, no. I start a new job on Monday. But she said: Janice, you cannot go anywhere. You have leukaemia. You have blood cancer.

I asked if they had made a mistake and then phoned my husband telling him he better come to the hospital. Thats all how it started. Me just wanting to find out what was going on. Then another doctor came in and confirmed it with my husband there, as I was in disbelief at this stage.

My white blood cells count was 136. If it was a mistake my white blood cells would have been between 5 and 26. You cannot make a mistake with 136. Then they left the room, closed the curtain and thats when it really hit me. I wouldnt even say crying, I was bawling my eyes out. It was horrible. My husband was just hugging me.

I just thought this cant be real. I donate blood. I run. I do the odd Tesco cancer research run, I do the Macmillan one. I do all these runs raising money for charity and Im one of those people now. I couldnt believe it. I was shocked.

I was in Hillingdon Hospital, near Hayes, west London, for two days then they transferred me to Hammersmith Hospital and I was there for 42 days receiving chemotherapy treatment via IV and tablets, and other medications as well. I had blood transfusions 10 units of blood, 14 units of platelets. It was so much.

I knew within my community Im 56 and of Black British Caribbean descent, with Grenadian heritage that what I do need is a stem cell donor. And we dont donate enough blood, certainly not stem cells. So, from the get go, I wasnt going to lie down and cry. Im going to start raising awareness and thats exactly what Ive done.

I contacted Antony Nolan [the blood cancer charity] who saw my own posters, which said If I cannot save myself, maybe I can save someone else, and how much I was doing to raise awareness, we teamed up. Being positive has been my drive.

The place where I was going to work were willing to hold it for a couple of weeks, but it turned out I was in hospital for six weeks and sick with it as well so it would have been unfair, really. I wouldnt have had the strength to work. This is the first time in my life, since I was 17, that I havent been working. Ive always worked.

Im still in Hammersmith Hospital and going to be coming here for another four months so it wasnt worth thinking about work. The hospital lets you go home for your sanity for a week or 10 days or so. Now Im back for another month for all the treatment again. If youre okay the cycle repeats itself. Theyll keep doing that for five months. Hopefully, in the interim, theyll be looking for a donor.

They tried my two brothers and my sister but they were not a match because our antibodies conflicted. It takes about four weeks for them to do the initial blood test to wait to see if youre a match with your siblings. I had no doubt they would be a match 100 per cent Im going to be saved. Everything will be fine. On 8 March I got a call at home to say they were not a match. The older you get your antibodies change through having children, an infection, any sort of illness they are your defence mechanism. Theyre special for you and build up an immune system specifically for you. So I guess my siblings, whatever theyve had in their life, their antibodies have built up an immune system which conflicts with mine now.

I was just as devastated as when they told me I had leukaemia and I cried just the same, let me tell you. They also said there were no matches on any stem cell register around the world, so I kind of lost hope. What am I going to do? My brothers and sisters were supposed to be a 100 per cent match.

My two daughters are a 50 per cent match, meaning their antibodies might not be a problem so the doctors are going to look at them as a potential new option if something can be worked out. Im now waiting another month while they are tested. Its a waiting game. We dont know whats going to happen. I remain positive and hopeful that it has to be. Its very daunting.

The big issue for me is how difficult it is for non-White people to find a match [Currently people from a minority ethnic background have just a 37 per cent chance of finding an unrelated stem cell donor on the register, compared to 72 per cent for white Northern European patients]. I knew within the ethnic minority community we just dont donate enough, so I reached out to family and friends, my work colleagues. We know a lot of people between us all. I was targeting everyone of any colour my White friends, my Asian friends, they must know Black people just reach out and get the word out there.

In hospital, I have nine days of IV chemo and you get that twice a day. I feel fine with that one but now Im on a twice-a-day, 14-day chemo which makes me feel very nauseous, but they give you anti-sickness medication to help. If youre really bad they give you a shot in the arm, so theyre on board with any kind of side effects. The tablets really take it out of me though, so most of the time Im in bed. But I get up and try and do something.

Before I was sick I used to do my 10,000 steps a day. In here I cant really go that far walking in the room or in the corridor but Id do about 2,000 steps when I can, if Im well enough. Then its whether I need a blood or platelet transfusion. I think I respond well to treatment, because Ive always been a positive, strong person. If youre positive and strong that helps with our illnesses, Ive always thought. If youre wallowing in sorrow and feeling sorry for yourself, I dont think that helps at all.

So through this journey, every time the doctors come in theyve been very impressed with me. I say to people this is a temporary inconvenience and that is how Im going to see it. Although I dont want to be in hospital, if I was at home Id be cooking, cleaning, doing the washing Im seeing this as a holiday as well. I dont have to think about what to cook. I get three meals a day, I get my bed changed, I mean come on! I have to look at it positively.

I was told it normally takes between three and five months to find a donor. Usually, there is something they can do even if it is not a full match. Theres no real date. Its a waiting game. I cannot be on this treatment forever as youre prone to infection and its not good for your body anyway.

Ive set up a family WhatsApp group for daily updates as when everyone heard they were all devastated of course. My father died of prostate cancer 11 years ago. We saw how he went from being medium-sized to skin and bones. It was awful, so my family were so worried and thought the same thing would happen to me. Even I thought the same thing when I first heard my diagnosis. Am I going to lose my hair and am I going to die? Well, I did lose my hair, but Im still here, thank God.

Me being so positive is keeping my family upbeat and strong as well. They are all rooting for me. If Im feeling down I put it on the group chat, but most of the time its all positive. Believe you me, I really want to go home.

For more information about stem cell donation visit the following websites:

https://www.dkms.org.uk/

https://www.anthonynolan.org

htttps://wmda.info/

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Living with leukaemia: 'My ethnicity means I've only a 37% chance of ... - inews

Abbas Assesses the Use of Allogenic Transplant In MPNs – Targeted Oncology

CASE SUMMARY

A 68-year-old woman presented to her physician with symptoms of mild fatigue, moderate night sweats and abdominal pain/fullness lasting 4 months; she also reported increased bruising and unexplained weight loss. Her spleen was palpable 8 cm below the left costal margin. Genetic testing showed she was negative for a JAK2V617F or CALR mutation. Her karyotype was 46XX and a bone marrow biopsy showed megakaryocyteproliferation and atypia with evidenceof reticulin fibrosis.

A blood smear revealedleukoerythroblastosis and she was diagnosed with primary myelofibrosis with a DIPSS (Dynamic International Prognostic Scoring System) risk score of intermediate-2 and also had an intermediate MIPSS70 risk score.

DISCUSSION QUESTIONS

In your practice:

JONATHAN ABBAS, MD: Is this a patient where from day 1 youre talking about an allogeneic [hematopoietic stem cell] transplant [HSCT] referral? Is this a patient that a transplanter would want to see early in the disease course or is this something that you might want to hold off on a HSCT consult until something isn't behaving as well as it could?

Jonathan Abbas, MD

Director, Acute Leukemia Program

Ascension St. Thomas Midtown Hospital

Tennessee Oncology

Nashville, TN

JEREMY PANTIN, MD: The [patient is] approaching the age limit where things are going to start getting [difficult] and not somebody that we'll take straight to allogeneic HSCT transplant, but you probably want to consider therapy to reduce that spleen size. If the patient appears to not have comorbidities and may be a good candidate for HSCT, the intermediate-2 or greater risk will certainly allow them to move forward, in terms of the favorable risk-to-benefit ration, if everything is aligned.

MICHAEL T. BYRNE, MD: I think we used to argue about this, not argue [necessarily], but these were the hard patients because nobody knows what to do with them. She's the right age for transplant, but also, transplant is not without risk. Quality of life is probably worse after an allogeneic HSCT than it could be without, so I don't know. I think you plug her in then you see what her donor search looks like, and regardless of whether she goes to treatment, I think this is somebody that you probably treat if for no other reason than to try and improve her quality of life.

OLALEKAN O. OLUWOLE, MBBS, MD: I completely agree with what my colleague just said. We have several targeted therapies in this area, and we can just find 1 to give them to control their symptoms.1 If that fails, there will be another. There are many in development, so for those who are not keen on getting transplanted, there is a viable pathway to just keep treating them. Now for the patient who says, I want to see what the odds are, like what [Dr. Bryne] said, find out if they have a donor, talk about the risk-benefit, and go for it.

ABBAS: From my HSCT days, I would totally agree with you. I think this is a patient I would want to see early, to explain that you might not need me now, but you might need me one day. You've potentially got years left of transplant eligibility, and we dont have a crystal ball about how your response to treatment is going to be and where this disease is going.

Then just to be the devil's advocate for the case, this is a lucky one where we had intermediate risk with 1% blasts. If this [patient] had 6% or 7% of 8% blasts and we were now nudging closer to high risk, that might sway all of us to maybe think initially therapy might be more of a bridge to HSCT, because there might be a little bit less stable disease.

[This] is a symptomatic patient. Is there anybody out there who would watch and wait with this patient regardless of whether they are seeing the allogeneic HSCT team or not? Or does everyone feel this patient warrants some therapy?

RYAN CARR, MD: Yes, based on her symptoms, if you tried to watch and wait, so [the patient] might end up seeing somebody else.

ABBAS: I agree with you. She will certainly be finding another group in town if you said, You have [myelofibrosis], but it's not that big a deal. Let's just see you back in 3 months. I think it's unanimous this is a [patient] who's not a watch-and-wait case. They are out there, but this is not her.

CASE UPDATE

Additional lab values showed the following counts:

DISCUSSION QUESTIONS

ABBAS: [If there is] thrombocytopenia at baseline, I guess we have 2 options for this. One would be; are we comfortable still sticking with ruxolitinib [Jakafi], which we all agree on [in a patient case like this], but dose modifying potentially for thrombocytopenia or would just any thrombocytopenia necessarily make us think about another agent, if anybody wants to weigh in on it?

BRYNE: I think a thrombocytopenia of 140 109/L is different than thrombocytopenia of 30 109/L. That's quite a difference [between the level where a patient should receive] ruxolitinib vs pacritinib [Vonjo].

ABBAS: Yes, I would agree with you. Without the specific measurements, it's hard to say. Just also remember you certainly can, and we've been doing for years is dose decreasing the ruxolitinib with a lot of benefit.2 Unless you're in that extreme situation like down below 50 109/L platelet count, I still think there's a window to go with the tried and true [method here].

How about frailty? How about if this woman, let's say she was extremely frail and it wasn't necessarily a disease-related frailty, just other comorbidities? Would that sway us? Do we feel that JAK inhibitors are particularly tough on patients? Would this factor in at all if she were 78 years old or if she was 88 years old?

JACK ERTER, MD: No. I think this drug is, all things considered, quite on target and easy to take for most patients. I would certainly have no hesitation to give an 88-year-old a trial at a dose-modified start of ruxolitinib.

References

1. Li B, Rampal RK, Xiao Z. Targeted therapies for myeloproliferative neoplasms. Biomark Res. 2019 Jul 16;7:15. doi: 10.1186/s40364-019-0166-y

2. Mesa RA, Cortes J. Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing. J Hematol Oncol. 2013 Oct 22;6:79. doi: 10.1186/1756-8722-6-79

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Abbas Assesses the Use of Allogenic Transplant In MPNs - Targeted Oncology