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Therapies for Chronic Myeloid Leukemia May Trigger PH Onset


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#1 gerry

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Posted 13 April 2017 - 08:12 PM

Pulmonary hypertension (PH) may be triggered by therapies used in chronic myeloid leukemia (CML) treatment, namely the drugs Gleevec (imatinib), Tasigna (nilotinib), or Sprycel (dasatinib), according to a recent study.

The study, titled "Comparative Analysis Of Pulmonary Hypertension In Patients Treated With Imatinib, Nilotinib And Dasatinib," was published in the journal Blood

Previous studies have reported that patients with CML treated with tyrosine kinase inhibitors (TKIs), namely Sprycel, may develop fatal PH. After discontinuing Sprycel,pulmonary hypertension symptoms improved in most patients, suggesting that perhaps only Sprycel triggered this condition.

Other studies, however, have suggested that other TKIs, such as Gleevec, can improve blood vessel resistance and PH symptoms in patients.

"To clarify the contradictory effects of TKIs, we used echocardiography to noninvasively screen CML patients who have been given imatinib, nilotinib or dasatinib," researchers wrote. "We assessed the incidence of TKI-associated PH and subclinical PH, and analyzed the factors associated with onset of PH."

The study enrolled 105 CML patients treated with Gleevec (37 patients), Tasigna (30), or Sprycel (38). Echocardiography allowed the assessment of triscupid regurgitation peak gradient (TRPG), an indicator of pulmonary arterial pressure (PAP). According to the criteria by the European Society of Cardiology, pulmonary hypertension is suspected when the TRPG is above 31 mmHg.

Results showed that the mean TRPG was 22.7 mmHg in the Gleevec group, 23.1 mmHg in the Tasigna group, and 23.4 mmHg for the Sprycel group. Although these values were not considered significantly different, they were higher than those in newly diagnosed CML patients not treated with TKIs (19 mmHg).

Importantly, nine out of the 105 patients had a TRPG above 31 mmHg, which signals PH development. Among the nine patients, one was treated with Gleevec, three were treated with Tasigna, and five received Sprycel.

Researchers also observed a tendency toward the association of TRPG with age or duration of TKI treatment.

Together, these results support that not only Sprycel, but also Gleevec and Tasigna, can be associated with the onset of subclinical pulmonary hypertension.

"Our study demonstrated high TRPG values in CML patients not only with dasatinib treatment but also with imatinib and nilotinib, suggesting that subclinical PH might be more common than expected in patients treated with any TKIs," researchers wrote. "Careful screening with echocardiography is necessary, especially for older patients who have received TKIs for a long time."



#2 jmoorhou

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Posted 13 April 2017 - 09:43 PM

Extremely interesting that Gleevec might help with PH, I hope it's true.  My lips were bluish about a year ago, but I don't see it anymore.  I'm retired and I use a small amount of cannibis every day sometimes, I guess that's not so good, because it also narrows arteries to heart.  


Diagnosed 3/2014 WBC 28 Non detectable within 3 monthsGleevec 400 mg 5/2014 one hour after dinner really improves nausea300 mg 12/15/2016200 mg and 300 mg Gleevec 2/25/2017 (after 3 years on Gleevec) For last four months taking 300 mg per day. Last CMC showed liver enzymes elevated, went to a good Naturopath and he recommended 4 Tumeric, 10,000 mg Vitamen D, and 3 milk thistle (silymarin) daily. Also use One<p>Day Detox Dandeloin tea, and Nettle Tea and a slice of ginger every day...in two months liver tests were below normal.Janis

#3 kat73

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Posted 14 April 2017 - 10:10 AM

Thanks, Gerry.  I'm so glad you find these things for us!  I find myself just so angry about this PH thing.  I just got an echo and I'm scared to call for the results.  Been on Sprycel 6 years and I'm 65.  I've had at least 2 pleural effusions.  I have put up with some really bad side effects, but this one is so darned serious for people, and it involves MORE pills to take.  It makes you wonder, did they study dasatinib (in particular) long enough before approval?  What else is out there to discover over time?  I guess I'm being childish, but I'm just so MAD.  To save one part of you only to destroy another, I mean, what is that all about?


Dx July 2009 on routine physical.  WBC 94.  Started Gleevec 400 mg Sept 2009.  MMR at 2yrs.  Side effects (malaise, depression/anxiety, fatigue, nausea, periorbital edema) never improved.  Kidney issues developed because of Gleevec.  Switched to Sprycel 70 mg in Aug 2011.  Above side effects disappeared or improved.  Have been MR3.5 - 4.5 ever since.  Two untreated pleural effusions followed by one treated by stopping Sprycel Jan 2017.  After 9 weeks, PCR showed loss of MMR; re-started Sprycel at 50 mg and in 3 months was back to <0.01% IS.  Pleural effusion returned within a couple of months, same as before (moderate, left side only).  Stopped Sprycel 50 mg for 12 weeks; pleural effusion resolved.  At about a monthoff the drug, PCR was 0.03; at 11 weeks it was 2.06 - lost CCyR? Have returned to 50 mg Sprycel for 3 weeks, intending to reduce to 20 mg going forward.


#4 Frogiegirl

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Posted 14 April 2017 - 12:34 PM

I could not agree more Kat! I'm upset because I wanted to try 50 sprycel to start and my doc said 100 was the standard dose. ..he said also your young and can tolerate it better then most. Which makes me mad because in my mind I'm thinking so damage my body now because I'm young so when I'm older I have more to deal with? I feel you Kat, nothing but good thoughts coming your way;)

Diagnosed Oct 2013 Started 600mg of Tasigna  on Nov 4th. Lowered dose a few months later to 300mg due to side affects stayed here declining PCR until March 2015 small jump from 0.0072 to 0.0083 scarred my doc into full dose of Tasigna again 600mg(been miserable since) but reached PCRU 06/15/2015(next test) and have been there ever since. Hoping to have another little one. I have the support of my doc to go off anytime, just scared to jump. might go two years PCRU but he said it wont make much of a difference. I just figured I could possibly go into a trial while preggers if I got the two years behind me.

Nov 8th 2017 went off Tasigna

Dec 1st PCRU off TKI

Jan 5th PCR Detected .0625

Feb 1st PCR Detected .7815

Added 8-6 grams Curcumin daily in Feb

March 3rd PCR Detected 3.2646 YIKES!

 stopped trying for baby after February reading. will start new TKI march 16th 2017 (Sprycel)

FYI I'm not done trying for my last little one.


#5 kat73

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Posted 14 April 2017 - 04:34 PM

Thanks, Frogiegirl.  One good thing about your age is that you ARE going to get a cure - I believe it!  And then you won't have to worry about those long-term effects.


Dx July 2009 on routine physical.  WBC 94.  Started Gleevec 400 mg Sept 2009.  MMR at 2yrs.  Side effects (malaise, depression/anxiety, fatigue, nausea, periorbital edema) never improved.  Kidney issues developed because of Gleevec.  Switched to Sprycel 70 mg in Aug 2011.  Above side effects disappeared or improved.  Have been MR3.5 - 4.5 ever since.  Two untreated pleural effusions followed by one treated by stopping Sprycel Jan 2017.  After 9 weeks, PCR showed loss of MMR; re-started Sprycel at 50 mg and in 3 months was back to <0.01% IS.  Pleural effusion returned within a couple of months, same as before (moderate, left side only).  Stopped Sprycel 50 mg for 12 weeks; pleural effusion resolved.  At about a monthoff the drug, PCR was 0.03; at 11 weeks it was 2.06 - lost CCyR? Have returned to 50 mg Sprycel for 3 weeks, intending to reduce to 20 mg going forward.


#6 hannibellemo

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Posted 14 April 2017 - 05:14 PM

Hi, Kat,

 

I've said it before, we're all lab rats on this bus!  ;) But, that said, I'd rather be on the CML bus than any other cancer bus. What we may be experiencing is what every other cancer patient taking chemo is experiencing, but I truly believe their ride is rougher. Our treatment is fairly linear (not sure if that is the word I am looking for, perhaps "straightforward" is better) with the TKIs effecting relatively few additional cells in our bodies. That is not the case with traditional cancer chemotherapy which uses a shotgun effect for treatment, pretty much destroying everything in its path.

 

I'm your age exactly and I sympathize (and empathize) with your fears and frustrations. I hope all goes well with your echo. I am going to get a referral to a cardiologist next time I go in just to discuss my change to a "mild right heart dysfunction". That is my current freak out! I have a feeling I have no one to blame on this but myself; I've been fairly sedentary all my life.

 

Good luck!


Pat

 

"You can't change the direction of the wind but you can adjust your sails."

DX 12/08; Gleevec 400mg; liver toxicity; Sprycel 100mg.; CCyR 4/10; MMR 8/10; Pleural Effusion 2/12; Sprycel 50mg. Maintaining MMR; 2/15 PCRU; 8/16 drifting in and out of undetected like a wave meeting the shore. Retired 12/23/2016! 18 months of PCRU, most recent at Mayo on 7/25/17 was negative at their new sensitivity reporting of 0.003.<p>


#7 kat73

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Posted 14 April 2017 - 05:45 PM

Pat - I hearya on the sedentary.  The echo technician at one point just sort of randomly (or not???!?) asked, "Do you exercise?"  I thought a nanosecond about a whiny defense and/or asking why do you ask??!!? and then defaulted to a simple, glum and emphatic, "NO."  There were no further comments. 


Dx July 2009 on routine physical.  WBC 94.  Started Gleevec 400 mg Sept 2009.  MMR at 2yrs.  Side effects (malaise, depression/anxiety, fatigue, nausea, periorbital edema) never improved.  Kidney issues developed because of Gleevec.  Switched to Sprycel 70 mg in Aug 2011.  Above side effects disappeared or improved.  Have been MR3.5 - 4.5 ever since.  Two untreated pleural effusions followed by one treated by stopping Sprycel Jan 2017.  After 9 weeks, PCR showed loss of MMR; re-started Sprycel at 50 mg and in 3 months was back to <0.01% IS.  Pleural effusion returned within a couple of months, same as before (moderate, left side only).  Stopped Sprycel 50 mg for 12 weeks; pleural effusion resolved.  At about a monthoff the drug, PCR was 0.03; at 11 weeks it was 2.06 - lost CCyR? Have returned to 50 mg Sprycel for 3 weeks, intending to reduce to 20 mg going forward.





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