Alternative treatments for Busulfan

[Folly41]

My wife was diagnosed with E.T. five and half years ago, she is 78 and lives in the UK.

At the time, the main treatments were Hydroxycarbamide, followed by Anagrelide and Busulfan as a last resort.

She was first treated with Hydrox but the side effects were severe and she was then treated with Anagrelide but after a period this was changed to Busulfan as her platelets increased. She was treated with Busulfan for short periods until her platelets reduced to an acceptable level and coped well when treated. She had quite long periods without treatment but is now back on Busulfan and feeling less well, she has also had two venesections. The only other medication she has is statins as she has had two T.I.A.s.

We are concerned that Busulfan may be getting no longer suitable. We have attended several MPN forums and Busulfan is rarely mentioned and it appears that Pegasus Interferon is more popular. This has been mentioned, when she has gone for blood tests, but it has been suggested that it is more suitable for younger patients and has to be authorised due to the cost.

We would be interested in the experiences of people who have been in a similar situation and where they progressed in their treatment, any difficulty getting this including Pegasus Interferon.

[hunter5582]

Busulfan has fallen out of favor due to the adverse effects, though it is still used when there are no other viable options. It seems a bit odd that they would have done venesections for ET as this tends to increase platelet levels. Did her erythrocyte (red blood cell) levels go up? Has the doc mentioned progression to Polycythemia? Is your wife positive for the JAK2 mutation? Lots of factors to consider in figuring it all out.

I would certainly think that consideration of Pegasys (peg-interferon) would make sense. May well be easier to tolerate and more effective than Busulfan. However, all of these chemotherapies have their own risk-benefit profile and we each respond differently to them. Sadly, in some health care systems cost is a driving factor in prescribing medications rather than what is in the patient's best interests. You have to be a strong advocate for yourself in these situations. Assertive patients receive higher quality care. Passive patients do not. Please be sure to advocate for what is best - not what is cheapest.

All the best.

[Folly41 in reply to hunter5582]

I did send you a reply but I have just changed My EMail and cannot be sure that it was sent.

Thank you for your very useful reply. In response to your questions - she had the venesections, even though it is known that it may increase her platelets, because her red blood cells were high, there has been no mention of P.V. but we will ask next time we go for blood tests, and finally she is positive for Jack2 mutation.

At present she is going for blood tests every two weeks. The haematologist is cautious and wants to get her platelets well below 450, at the last visit they were 380 and we are hopeful that she will have a break soon from Busulfan.

[hunter5582 in reply to Folly41]

Please do be sure to follow up regarding possible progression to PV. Erythrocytosis + thrombocytosis + JAK2 positive is an indicator for PV rather than ET. Venesection is the recommended treatment protocol for PV not ET. I know from personal experience. I had ET for about 30 years, then it progressed to PV about 6 years ago. The hematologist I saw at the time missed the progression and left me misdiagnosed as ET. The old doc actually fired himself when the missed diagnosis became evident and referred me to a colleague with greater expertise in blood cancers.

One relevant factor to find out about is the JAK mutant allele burden, the percentage of the JAK2 gene profile that is mutated. Broadly speaking, less than 50% is predictive of a milder course of the MPN. (Mine is 25%). If not already done, the test is called a JAK2 Mutation Quantitative Analysis (or similar).

Unfortunately, many hematologists do not have the KSAs to effectively treat MPNs as they are rare disorders. Even the local, more knowledgeable, hematologist I now see has only seen about 5-6 MPN cases in his entire career. He is a great doc, but I am only his second PV case. I also have a consulting hematologist who is a MPN expert, but he is a two hour drive away. The expert consultant works with me and my local doc regarding my PV treatment. I found the expert doc on this list of patient-recommended MPN experts mpnforum.com/list-hem/ .

Please do not be afraid to ask the current doc about his/her level of experience in treating MPNs. If this doc is not a MPN expert, then you may have to travel to find one. My own experience is that it is totally worth it to do this. The local doc can work collaboratively with the MPN expert regarding the MPN treatment. Note: any doc that would put their ego ahead of your wife's receiving the best possible / most expert-informed treatment does not deserve to be your wife's doc.

Hope that helps. All the best

[Folly41 in reply to hunter5582]

Thank you for your detailed reply.

We will ask about the possibility of a change to PV.

I do not know how MPN patients there are locally, but do know that there some and I have been surprised of their knowledge of MPN, it being a rare condition. There is a known MPN specialist within travelling distance, which is good to know.

Thank you again for your help.

[Andrew8]

I was diagnosed with ET in April 2016, and prescribed hydroxycarbamide , which reduced my platelet level from 1100k TO 350k, but by December 2016 was getting severe fatigue episodes, then changed to anagrelide, fatigue continued, then my doctor detected abnormal heart rhythm, diagnosed with Atrial Fibrilation ( known side effect of hydroxyl ), started treatment for heart, April 2017, re-diagnosed after bone marrow test, with Myelofibrosis, and put on Jakavi ruxolitinib . August 2017 developed shingles symptoms (?) which slowly reduced - known side effect of ruxolitinib, but not admitted by haematologist. Still taking ruxolitinib and have some continuing shingles rash, and still being treated for AT, 3rd Cardioversion next week. There are side effects with all drugs, but from MY experience, I would not take hydroxycarbamide or statins . There have also been side effects from the heart drugs, which have included potential lung damage, pneumonia May this year, and thyroid problems. But having said that, I am still here, which I am grateful for. It is almost certain that my ET was due to long term exposure to petroleum products. I would be interested to hear if anyone else had a similar link between ET and benzene or tolene.