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Scientists develop possible strategy for cancer drug resistance

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Post by MPN-MATE Admin » Fri Sep 06, 2019 2:07 am

Sept. 4, 2019

by National Institutes of Health

mpn-mate.com/forum/viewtopi...

Hey everyone... :-)

This is exactly the type of article that I believe holds much promise for preventing the Transition from Myelofibrosis to AML...

The Reference below to the Full – Peer Reviewed – article. However, it still requires payment for complete access at this point.

On the other hand, the text synopsis below clearly highlights the potentially exciting findings of what might come to pass into the 'Not-to-distant future'... Such is my fervent hope in any event.

I shall be very interested in any feedback too...

Best wishes 8-)

Steve

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Aneliv9 profile image
Aneliv9

Could I ask you if progression to acute myeloid leukemia is the risky thing if you have myelofibrosis? Is AML the reaaon for transplant? I try to understand what drug/ combination, will have the potential of total control of the disease,so no need for transplant..

socrates_8 profile image
socrates_8 in reply toAneliv9

Hey again Aneliv9...

Unfortunately, there are no guarantees, and none of us have a crystal ball... As to whether or not someone w/ MF will definitely progress to AML or not...

Many people w/ MF, also suffer from infections, and or strokes, (like having an incapacitating TIA or minor brain stroke).

Allogenic Stem Cell Transplants, (ASCTs), offer the only currently recognised curative option. However, it does come with serious risks too, and the success ratio, (depending upon who you ask...) is circa 50/50, which is not an overwhelming vote of confidence either. Even if the ASCT was successful, there is also still a uncertain amount of Graft Versus Host Disease (GVHD), that might eventuate after the procedure.

The article I have highlighted above, is a possible future remedy... However, and at this stage, it still has much testing to undergo and complete through lab tests and human trials...

Sometimes, one of the ways to benefit sooner is to sign up to a Trial...

There are many out there... However, location, and suitability of patients often also loom large as to accessing Trials...

The article pasted below explains a tad more about the phases of MF that one can transition through before reaching AML:

ARTICLE

BY BRIELLE URCIUOLI

PUBLISHED SEPTEMBER 28, 2018

Preventing Myelofibrosis from Progressing to Acute Myeloid Leukemia

Diagnosing and treating the disease before it turns into AML is a key area of study, said Srdan Verstovsek, M.D., Ph.D., medical oncologist and professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

Myelofibrosis, a type of myeloproliferative neoplasm (MPN), typically moves through two stages – chronic and accelerated – before reaching the blastic phase and turning into acute myeloid leukemia (AML). Diagnosing and treating the disease before it turns into AML is a key area of study, said Srdan Verstovsek, M.D., Ph.D., medical oncologist and professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

“A lot of effort is spent on understanding the transformation from chronic phase to blastic phase to AML because AML is very deadly,” Verstovsek said in an interview with OncLive, a sister publication of CURE. “Overall survival is about six to eight months. We put a lot of effort in treating and understanding how to benefit patients with AML that happens after myelofibrosis.”

The disease phase can be classified by the amount of atypical blood-forming cells called myeloblasts (commonly referred to as just “blasts”) in a patient’s blood. Patients with 0 to 10 percent blasts are in the chronic phase; 10 to 20 percent are in the accelerated phase; and 20 percent is the blastic phase, AML.

But Verstovsek mentioned that better measures are needed to determine the different phases and suggested that researchers start looking at certain molecular findings, or karyotype or chromosomal changes. Then, it would be a matter of getting the right intervention.

“If we can focus on this group of patients who are in transition, from more chronic and stable condition to blastic phase, then we can implement therapies earlier on and save their life or direct them to a transplant – the only possibility to cure them – sooner,” he said, noting that it is important to recognize this transitional phase and implement earlier therapy with hypomethylation agents, too, including chemotherapy agents such as azacitdine and decitabine.

Even so, these agents are not a cure-all, as their main function is just to control symptoms.

“Hypomethylating agents are provided to patients with accelerated- and blastic-phase disease because they have a potential to lower blasts. They cannot control disease,” Verstovsek said. “There are even reports of some complete responses and some partial responses, but the goal is really to put back patients in the chronic phase and then get them to transplant to save their life. “

If that is not possible, Verstovsek said, then patients can continue on the hypomethylation therapy, perhaps even introducing chemotherapy or the JAK inhibitor Jakafi (ruxolitinib) to control spleen and liver symptoms and improve quality of life.

But again, Jakafi is not the magic bullet needed in treating this disease.

“In fact, the use of ruxolitinib, the only approved JAK inhibitor, is endorsed very much by NCCN (National Comprehensive Cancer Network) guidelines for patients with accelerated- or blastic-phase, regardless of their blood cell counts, to use in an appropriate dose in the individual setting that will be there to control the symptoms, not to do anything about the blasts or progressive nature of the disease,” he said.

Ultimately, more work is needed in preventing myelofibrosis from turning in to AML, thus greatly extending patients’ lives.

“We call myelofibrosis a chronic disease, but it doesn’t stay chronic forever,” Verstovsek said.

Hope this might help your further understanding of the possible progression of MF & AML etc...

However, please do try to remain optimistic because far more people DO NOT transition to AML, than those who do... :-)

Best wishes

Steve

Aneliv9 profile image
Aneliv9

I appreciate your answer and of course i understand that no one can predict if someone with MF will progress to AML. Somy short-type question is: IF a potential drug like this one ,(OR like Prm-151 that will decrease fibrosis) eventually work, it means that doctors will have the disease under control and slow down progression? Or in another way: What will the long term benefit be?

socrates_8 profile image
socrates_8 in reply toAneliv9

Hey again... :-)

I am not sure that one could then say: "... that they would then have the disease under control..."

That is a big statement at this early juncture... We still have so much to learn, in my view...

However, and that said, any measure that might slow progression would be most welcome, and extremely helpful to our longevity, that much is true I am sure...

The important thing is to remain always optimistic, pro-active, and always being our own best advocates to manage our MPNs...

We all must be assertive in our own best interest, in my view...

Everyday, we are hopefully learning more about MPNs, and with greater funding and research continuing to be undertaken by a growing host of individuals and organisations, who knows how long it might be before someone discovers the next best treatments, or even a complete cure?

Best wishes

Steve

Aneliv9 profile image
Aneliv9 in reply tosocrates_8

So until now, the only road for all with MF is transplantation? Will all patients with MF eventually will have transplantation?

socrates_8 profile image
socrates_8 in reply toAneliv9

No... I do believe that you might be putting words into my mouth...

As I did not say that...

Ane, I am an MF patient too... And I believe, (as I stated earlier), that only a very small percentage of MF sufferers actually transition to AML...

There are many hopeful research efforts out there right now that should provide all of us with some level of hope for an increased Quality of Life (QoL), if not a better all-round treatment regime...

The important thing is to remember that in most cases, we can live pretty normal length of life! If we so choose... :-)

That also means that we MUST take better care of ourselves by living a better lifestyle, which includes diet and exercising on a consistent basis...

I am 60 now, and these days I am training to cycle around Australia to raise funds for MPN research, and I have no intention of yielding to this condition without first trying everything I can to live a happy & contented life... I love my family, and grandchildren are simple amazing to watch them grow and blossom into little people...

...there is still so much to see and do... ;-)

Best wishes...

Steve

Aneliv9 profile image
Aneliv9 in reply tosocrates_8

I don't want to put words in your mouth, my English are not so good ,so I can't express better what i want to ask, thats why we have so big conversation! I just try to understand how the future from drugs a patient with MF might change

socrates_8 profile image
socrates_8 in reply toAneliv9

Hey... :-)

No problem... And I am just making sure that I too am trying to be very clear with my answers to you, that's all...

Best

Steve

Aneliv9 profile image
Aneliv9 in reply tosocrates_8

Thank you very much for alla thw answers and the time you spent writing this. It is so relieving to me toi understand that a patient with MF can live now days almost normal life expectancy. I thought it was death sentence and i was terrified because of this misunderstanding . I have read a lot about MF and my understanding was a lot different than what you described me above

socrates_8 profile image
socrates_8 in reply toAneliv9

Ane... :-)

I am most glad that I have been able to allay some of your fears... :-)

MF, is still a very serious condition that requires continued monitoring, and regular consultations with your medical team, (GP & Specialist).

However, while MF is a serious condition, if we do our best to stay healthy, with a good diet and plenty of exercise... We might all live to be much older than we first thought... :-)

Best wishes and always try to stay positive... :-)

Steve

Gabrielle79 profile image
Gabrielle79

sci-hub.tw/10.1126/scitrans...

hi socrates, here you can find full article

kind regards, Gabriella

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