Wednesday, December 30, 2009

More Great news........

I just love this........... Here is another person that is benefitting so well from the newer CML meds.... in her own words :) Thanks, Lottie for sharing this wonderful news! I can't wait for you to get your Zavie Zero Number - finally, after 14 and a half years! What a wonderful way to end one year and start another... So much hope, so much to be thankful for......

UPDATE!! Lottie has Zavie Zero Club # 1000!! Look at all those zero's! :)

A Short CML Success Story
by Lottie Duthu

If anyone in the medical field, like an oncologist had ventured to tell me over 14 years ago that I would still be here in spite of having CML, I would have had serious doubts about that doctor's ability to be truthful with his patients.

It's difficult to explain what leukemia is to someone who doesn't have it and has no background knowledge of anyone who does, or who has never met a CML patient. In all probability, they never met one. I have met several patients who never met another CML patient until they met me.

I have been in five trials, beginning with all trans retinoic acid (a high concentration of Vitamin A) and Hydrea (which controls high white counts). Included was allopurinol to keep from getting gout from the Hydrea. To make a long story short, I then went to Inteferon and HHT, then to Gleevec, then to Sprycel and lastly to SKI 606. I was not keen on getting this drug, as I hadn't heard of anyone who had achieved any remission. My doctor believed in it, however and even though I was on a sub-optimal dose because of severe side effects, he made me stay the course.

This week after over 14 years of waiting my turn to announce that I was in CCR, which meant that out of 20 cells examined, all were normal.

Even though we have billions of cells, we never know where the CML cells are hiding (quiescent cells), so we never know if we have gotten them all and this is only the first big step. (At the start, most CML patients may have all 20-25 cells with the Ph abnormality. With treatment one hopes that the number of Ph containing karyotypes decrease and eventually reach the magic zero number. When all cells are now zero and no Ph cells observed in the metaphases sampled, one is then deemed in complete cytogenetic remission CCR).

The fact that it took this long is reason to be hopeful. No matter what the situation, we look for a solution. Short term is sometimes all we can get, but it will get us to the next phase and give us us extra time; in the meantime, we move on, never giving up. Never allow yourself to spend too much time on a pity party, you are wasting your time on negative thinking. There is a time to cry and a time to dry the tears and get to work. The employees liked seeing me come in to the office supply stores, because they knew I was there to buy paper, printers, faxes, ink cartridges and a mass of other office supplies. In these 14 plus years, I have used up 4 computers, 2 faxes, ink cartridges and 6 or 7 printers, always keeping one black and white, and one for color. I made copies of everything; however, now I do less copying, as I have learned a little.

When Annie asked me to write something for her CML blog, I wondered what I had to offer and it is what I have learned from questions that have long been asked of me, and my answer is to always keep hope alive. If someone as old as me and having had CML as long as me has managed to hang in and live this long, then there must be hope for them, too. There is no free lunch, you have to work at it. Look for the best doctors and hospitals, join a support group and keep your mind active. Be thankful for what you have, there are billions of people who would trade places with you, just to have a clean bed to sleep in, a roof over their heads and 3 meals a day. I think I am pretty darn lucky to have been diagnosed just before the second generation CML drugs were approved and offered to everyone. What you don't know can hurt you, so I am of the opinion that we never finish learning - there is always one more person to teach me something I need to know and if I close my mind, I will never know what it was.


Just lovely, hey? :)
love and light

Monday, December 28, 2009

Hope is doing darn well!

Right before Christmas this wonderful news came through for Hans, who has had the unfortunate experiences of neither Gleevec or Sprycel doing what it needed to do for him...... Read his cml blog and his wonderful news here.

Basically Hans is a part of the Ariad trial of which I know very little apart from that it's giving him better results than he expected and so soon too! Hans, I just love your graph - it really makes it clear as to what is happening here. This wonderful news really made my day, kept an extra bit of smile on my face through the Christmas season - I can only imagine what it must have meant to you and your family.

I had quite an experience this year - and only realized it the next day... We spent Christmas Eve all together at Lisa and Brian's house..... Steven and Laura were there as was Joleen, all the kids, my sister, mom and nephew and his wife. It was altogether a lovely evening and I went to sleep feeling really great. And then, while chatting with Greg (read his blog here)half way through the next day, I realized that I had not thought of cml once - not once, the whole night! How absolutely amazing is that?

It's taken almost 4 years to get to this point and this when all is going so well with Steven... In a very small way for a very short time, I almost felt guilty for not thinking about it but then the smile came back and I am so glad, so incredibly glad.

2010 will mark 4 years since Steven's diagnosis, and Hans' great response on the Ariad Trial gives me so much hope for so many still struggling to get a drug to respond to their "version" of cml.

Hope lives, strong and beautiful.

love and light

Monday, December 21, 2009

The Star

This year I decided not to have a Christmas Tree. And then I decided to have one. Then I changed my mind again...... and again. Last night my daughter went to the store and saw a cute lonely little Christmas Tree, standing all by itself outside the door. It's just not possible to leave a tree out there all by itself like that in the cold! So off sweet Frank tootled to pick it up for me - as he says, he "trudged 5 miles in 4 foot of snow in subzero temperatures, uphill both ways", to get that tree for me..... all said with a wicked smile :) And so our tree came home.

It stood there in front of the fireplace, warming itself up and getting used to its new home while I sat eyeing it wondering just when I was going to work up the enthusiasm to put its Christmas clothes on.... And so the evening went by until I was ready to go to bed. Then I heard this little voice from the kitchen; it was faint, but definitely calling my name........ it was the sound of the beautifully chilled wine in the fridge singing in tune with my happy little wine glass. Again, can one resist such beautiful things? And then I saw that an episode of House had just started on tv, and I had not seen this one.

That program fascinates me - not for the normal reasons but because it seems to me that an incredible amount of false dx's are made and huge and dramatic treatments done or suggested at times and then so often, all is solved in a relatively simple way right at the end. I like the relatively simple fix, just not all the other options that seem to loom around every corner. Anyway - its interesting. Occasionally Dr House seems to flippantly demand a bone marrow transplant and I cringe........ that easily? Wow....... ya, ya, I know it's just the movies, but still.

Ok - back to the still naked Christmas Tree. What with House fixing people and a sparkling glass of wine I decided that I would dress the Tree and I was surprised at what happened.

My very first Christmas Tree in my very first apartment, which was a million years ago, was a special tree, an irreplaceable excitement and proof that I had grown up! I was 19 years old and had my very own Christmas tree......proof! The others that followed marked the years passing by, the first tree after Steven was born, then Lisa's first tree, then the first tree with Joleen too - all three kids together. As with most people, putting up the Christmas Tree became a tradition, something that simply gets done, something that is part of Christmas time and almost a chore......something that must be squeezed between everything else that needs to be done around this time of year.

I remember happy Christmas Trees, many obligation Christmas Trees, a particularly sad one and another that made me sob with every decoration I added. Then came a Christmas tree that was dressed with happiness again.... that was just a mere year ago.

And this year - this year was just lovely. I realized that I am no longer dressing a tree for anyone, from any obligation, for anyone or even the time of year. I looked at that naked tree, breathed deeply the fresh pine smell that oozed out of every limb and I smiled. I turned her around finding her best face and started..... Each bauble found it's home naturally, each light lay gently on a branch and lit the deep inside of the tree and added multiple color sparkles to the tinsel.... The little gifts that represent so many of my good and wonderful, strong and lovely friends nestled easily on the branches ....... my tree just came alive! She sparkled with life...... what a lovely surprise!

As I added the pretty things to her and the sounds of the tv faded way into the distance, I thought of all those that have come into my life in the last few years - the very real gifts - and how they have not only enriched me, but those around me too. I have learned so much, been humbled so many times, grown in leaps and bounds beyond what I thought possible and have learned to treasure every day. I have left my comfort zone so many times in these past almost 4 years since Steven was diagnosed with CML and have found this to be incredibly rewarding. I have learned to be happy, really happy.

And now, after a good many years and a good many changes in those years, I have found a place where putting up a Christmas Tree is something I already look forward to doing again next year. I see that this has become a tradition just for me..... I loved the thoughts that happened as I let my mind wander and watched how that naked, cold tree that waited just for me, turned into this beautiful Christmas Tree that just sparkles with joy and happiness.

I love the star the most of all the decorations. Many years ago when the kids were still kids and we could just not find that star that was perfect, Steven and his cousin James, got hold of a couple of coat hangers, some tinsel and an angel - and they made the very best Star possible. It makes me smile every time I look at it. It makes me thankful for the years that were easy, the years when cancer was not a player and for the years that led me to here, for the people and the circumstances that have helped me and walked with me during these times to the place I am now. It makes me thankful for all the years..

So with a very happy smile, a wonderful peace in my heart, a deep thankfulness for everyone in my life, I wish all of you a wonderful Star of your own. I wish you peace and gentle voices in your head, love and a simply wonder-filled Christmas.

Love and light

Friday, December 18, 2009

ASH Report by Jan Geissler......

Standing tall and strong against CML....

Here is a wonderful article written by Jan Geissler - a report on this year's ASH. I have highlighted some parts of this in red - these parts really sing to my soul, sooth me and keep that smile on my face. Here's a HUGE thanks not only to Jan Geissler for summarizing this for us all, but to all those scientists and doctors who are working so hard to literally keep my son alive for the next 80 years!

So you see, Steven....... you cannot feel old already - you have a loooooooong way to go! :)

Here it is..........

Tuesday, 15 December 2009

ASH 2009"Actually, why do I always spend St Nicholas in the US, instead of with my family", I asked myself when I boarded the plane to the USA on 4 Dec, in anticipation of a boring 16 hour trip to New Orleans, arriving jet-lagged, hiding for days in the dungeons of a large convention center, lacking any sense of the city I am in. Year by year, more than 20.000 hematologists and healthcare people attend the annual meeting of the American Society of Hematology, lovingly called 'the ASH' by repatriates. Its publications are all available on the Internet. "Is it really worth the effort being there again, instead of just using my browser?", I thought. It is. Definitely.

If there is a place to see latest research and treatments for blood disorders, it is 'the ASH' -- the place where just about every expert is that has a say in leukemia research. All top experts from the CML space are presenting their research here. I can't withstand the impression that the whole hematology community keeps quiet about a year of research results – just to be able compete for the hottest piece of news from trials at ASH. Some unnamed hematologist, when I asked, has admitted that they need to pick straws who has to stay at home to keep the clinic's services up and running
during their absence. It became already apparent on my flight from Munich to the USA: I had the impression I was almost the only one not knowing everyone else in the plane. A plane full of hematologists. So I went there again this year. It's all been a little compressed because I didn't want to spend too many days out of office and away from my family. Hence I missed the satellite symposia on Thursday as well as the last sessions on CML on Tuesday. But the days I've been there have been "full speed download" to my brain. Being back in Europe now, I am now trying to grasp the most important things I learned. I will share the most interesting abstracts in a separate document, so this is mainly to summarize what I found most impressive in the CML sessions.

Education Session

Brian Druker On the first day, I attended the Education Sessions. It is thought to give hematologists an overview on the current status quo of managing CML. Dr Druker, Talpaz, Goldman and Hughes spoke. In the room I felt like a single BCR-ABL gene in a good molecular response – the biggest meeting room in the convention center can probably hold 10.000 people at a time -- a couple of hundred participants almost got lost in there. It was impressive because Dr Druker held a keynote, honouring the 10th anniversary of Imatinib given to CML patients. A chart what the CML survival was in the pre-Imatinib era again struck me. Before bone marrow transplants were introduced in the 1980s, the only way to treat CML was palliative, meaning, reduction of symptoms until the unavoidable death within months. Today the key challenges in CML are managing resistances and relapses in those patients that to not achieve good remission, or to investigate whether stopping or less aggressively maintaining therapy in good remission is feasible. Overall survival rates in early diagnosed CML are pretty close to the general (healthy) population. We've come quite far, fortunately. But not far enough. People still become resistant or cannot tolerate the drugs, and need to cope with a life-long therapy. Dr Talpaz and Dr Goldman summarized quite well where we stand in CML therapy today:

* What we have: effective first line and second line treatment;
* What could be improved: managing toxicity, improving response rate and duration, avoiding development of resistance, when to change drugs, coverage of "Archilles heel" mutations;
* What is missing: T315I inhibition, elimination of the leukemic stem cells, and treatment discontinuation.

I was glad to see how active the CML research community is to close these gaps.

First line CML therapy

In terms of first line therapy after diagnosis, it's been quite simple for newly diagnosed, chronic phase CML patients over the last four, five years: Imatinib was the the gold standard, the only first treatment of choice. Clear treatment guidelines were provided, based on the "ELN recommendations" which were updated just last summer. At this year's ASH, all experts seemed to refer to these criteria and recommendations on managing standard treatment, suboptimal response, treatment failure and monitoring. Now, with the new "second generation" drugs striving for "first line" treatment, we can see a number of new options (and questions) coming up. At ASH 2009, the first line data of comparing Nilotinib and Imatinib in newly diagnosed patients was presented. In the past I have always been a little
suspicious about the enthusiasm for Nilotinib and Dasatinib becoming first-line: for Novartis to be ready with something equally expensive when the Glivec-patent ends in 2016, or for BMS to get a larger piece of the tasty (and huge) Glivec cake. Now there is first evidence that a more powerful treatment at the start might actually make sense.

We know from the IRIS trial, whose 8 year data was presented just with a poster showing that no new surprises came up in long-term follow-up, that relapses on Imatinib happen mostly in the first years of treatment: about 6% of all patients relapse in the first three years, then the relapse rate drops near zero. Now with the ENESTnd trial directly comparing Imatinib 400mg/day with Nilotinib 2x400mg/day and 2x300mg/day, not only quicker responses were observed on Nilotinib, but also the progression rate in year 1 was significantly lower than on Imatinib. Of 282 patients in on Nilotinib, only 1 progressed to advanced disease, while of 283 patients on Imatinib, 11 progressed. In addition, the frequency of treatment interruptions due to side effects was comparable between the options. This was only a 12 months follow-up, some more years are required to get more clarity – but it is an interesting perspective. The challenge of adherence to Nilotinib due to a twice daily schedule, as well as the requirement not to eat before and after taking the drug, will remain a challenge though. Off the record, I heard that similar comparative first-line data on Dasatinib and Imatinib might get ready for publication by EHA in June 2010. This is where it will get really interesting, as it will allow us to compare response rates, progression rates, and side effect profiles of all three drugs in first-line.

Along these lines I found interesting that Imatinib-800mg frontline therapy in chronic phase has come a little out of focus. Last year at ASH, some experts were still enthusiastic about "more-is-better" and proposed 800mg/day as first-line, given it had shown quicker responses than Imatinib-400mg. The latest results from the the TOPS and GIMEMA studies have now marginalized that after 18 months: There seems to be no advantage in outcome of Imatinib-800mg in comparison to 400mg. In addition, other comparisons presented by Dr Cortes have shown that response rates of both
Nilotinib and Dasatinib are higher than Imatinib-800mg, with less side effects. So high dose imatinib as initial therapy in chronic phase seems to be no longer regarded
(in chronic phase – in advanced phases of course this
seems to be a different story). Other approaches that were discussed by Prof Goldman as initial therapy were combining Imatinib with familiar agents (Cytarabine, Interferon/IFN, Omacetaxine, Arsenicals), or the three TKIs in varying sequence.The French SPIRIT study, as presented by Dr Guilhot, has demonstrated a significant higher rate of optimal molecular responses in the Imatinib-IFN combination (BCR-ABL/ABL below 0.1% at 18 months: 36% on Imatinib400+IFN vs. 19% in Imatinib400 alone). Similar findings were presented on a poster by Dr. Simonsson from Sweden (major molecular responses after 12 months: 86% of those on Imatinib400+IFN, 54% on Imatinib400 alone). More about that below.

Managing Resistance

Much has been published in recent months about managing resistance to Imatinib. While only a small proportion (15%) of patients treated in chronic phase develop a resistance or show suboptimal response, choosing the most
promising follow-up treatment has been a key topic of interest. More than 100 different mutations are known today. Only a very small number, mainly the fearsome T315I mutation which makes up around 15% of all mutations, is resistant to all of Dasatinib, Nilotinib and Bosutinib. Most mutations can be overcome by dose increase or one of the three drugs – but which one to pick in which case is still a key question. To have a tool for decision making, researchers compiled a table of sensitivities of mutations based on "IC50 values", which measure the level of inhibition of cells in vitro. However, first question marks came up, when Dr Laneuville observed discrepancies between IC50-insensitivities in the lab, and observed response in real patients. He said that obviously some mutations respond differently in the body than in-vitro data would predict. More data on real-life results would need to be collected and documented.

In terms of T315I, Dr Cortes reported about Omacetaxine (Homoharringtonine) which is an intravenous chemotherapy with specificity against CML cells in general, but also frequent side effects. About 27% of patients achieved a major cytogenetic response, even though it was not very durable (median 5 months). More than half of chronic phase patients with T315I have seen a reduction of T315I clone, but only 9% a complete reduction. More pulsating, there are two new promising targeted therapies to BCR-ABL, using a different mechanism than Dasatinib, Nilotinib and Bosutinib. They seem to be effective on the T315I mutation with good tolerability: Deciphera's DCC-2036 and Ariad's AP24534. Dr Talpaz presented first facts on oral DCC-2036, even though he mentioned first trial data won't be available before ASH next year. Dr Cortes presented a phase I study with oral AP24534 where 43% of patients with T315I achieved a major cytogenetic response – quite encouraging. Furthermore, there were reports of MK0457 and XL228, both aurora kinase inhibitors which block an important signaling pathway in leukemogenesis independent of T315I/BCR-ABL. However these are both given intravenous.

However, experience with these drugs are still very early, and trials are rare – so as Dr Nicolini presented, bone marrow transplant currently remains the treatment of choice in case of T315I, if a donor is available.

Stopping treatment

Dr Hughes presented the Australian "Imatinib cessation" study. In that study, 32 patients were included that had shown complete molecular remission for at least 2 years prior to the study. 17 of them were previously treated
with IFN and then Imatinib, 15 had Imatinib as initial therapy. About half of them relapsed within 18 months, most of them within 6 months after cessation of Imatinib, independent of IFN pre-treatment. Dr. Mahon presented the "STIM" (Stop Imatinib) study. In the pilot study, patients needed to be in complete molecular response (PCR negative) for at
least 2 years before entering the study. 69 patients were included, 34 with previous IFN treatment and 35 only with Imatinib. Of these 69 patients, 41 patients relapsed within the first 7 months. There was no difference between the groups that were pre-treated with IFN, or those that did not have IFN before. He concluded that it is possible to stop treatment in patients with sustained complete molecular response, but recommends discontinuing only in a clinical trial with strict molecular monitoring. During the discussion of STIM, Dr. Talpaz raised the question about the
anxiety of patients stopping therapy. Dr. Mahon answered that patients seemed to be happy because Imatinib side effects disappeared with cessation of the therapy. However this was debated because by experience, side effects
would have been minor in most patients after the 2nd year of Imatinib already.

Imatinib-Interferon combination

Dr. Guilhot presented the French SPIRIT Trial on 12 month follow-up with 695 newly diagnosed patients. Treatment arms were Imatinib-400mg, Imatinib-600, Imatinib-400+AraC, and Imatinib+PegIFN. 636 patients were now analyzed. Now at 24 months, there was a clear advantage of the Imatinib+IFN group, with 46% of patients in optimal molecular response (PCR smaller 0.1%), while only 26% of the Imatinib-400mg patients achieved the same response. 22% of Imatinib-PegIFN-patients became PCR-negative, compared to 10% on Imatinib only. Overall, 5-10% of patients discontinued Imatinib during the first year, and 45% of patients discontinued PegIFN. Average doses of Peg-IFN were
54µg/week. He concluded that the superiority of Imatinib+PegIFN combination in term of molecular responses was confirmed at 24 months. Weekly dose of PegIFN has now been decreased to 45µg for the first 3 months of treatment.

There is a relationship between duration of PegIFN exposure and the depth of molecular reponses (which seemed to say, my personal interpretation: better a constant low dose, rather than a high dose of IFN with the risk of
interruptions). In a Nordic CML Study Group (Denmark, Finland, Norway and Sweden) and Israel multicenter study a total of 130 newly diagnosed patients were randomized. CML patients had to be in complete hematological remission following 3 months of Imatinib-400mg induction therapy. The study arms were Imatinib-400mg, and the combination of Imatinib-400mg and Peg-IFNa2b (PegIntron, Schering-Plough). Imatinib dose was fixed at 400mg. Peg-IFN was
started at 30 µg/week but could be escalated to 50 µg/week or reduced down to 15 µg/week depending on tolerability. Major molecaluar response rate at 52 weeks was significantly higher in the Imatinib+PegIFN arm (82%) compared
to the Imatinib-only arm (54%). No unpredictable complications or adverse events were reported.

Interestingly, the presented observation in the German CML-IV Study (comparing Imatinib-400, Imatinib-400+AraC, Imatinib-400+IFN, Imatinib-800, and Imatinib-after-IFN-failure) did not come to the same conclusions. In the trial, so far 954 patients were evaluated. In this study, incidence of major molecular response was higher in Imatinib-800 (61%) as compared to 42% (Imatinib-400) and 45% (Imatinib-400+IFN). Overall survival by therapy did not show any significant difference between the arms. When I asked off the record, some were assuming that the difference might be due to "normal" Interferon being used in the CML-IV study, while the above studies used pegylated Interferon, leading to better tolerability and hence better exposure of the CML cells to Peg-IFN.

Lastly, the Italian GIMEMA trial comparing Imatinib-400mg with Imatinib-400+IFN: While there had been initial advantages of the combination arm, at 24 months these differences were lost. No surprise: the proportion of patients in this trial continuing IFN dropped from 41% at 12 months to 18% at 18 months, 13% at 24 months, 3% at 36 months, and by the end of the fourth year, all patients were off IFN. No information about IFN dosage was given (but some might suspect dosage was the problem).

Interferon maintenance

Dr Burchert (Marburg) presented an update to the German Peg-IFN maintenance study. He reported that while Imatinib has shown high efficacy, it fails to eradicate leukemic stem cells and suppresses leukemia-specific immue responses. At the same time, Interferon stimulates T-lymphocytes against CML cells. In the study, 20 patients were treated with Imatinib+IFN. 19 were in complete cytogenetic response, 15 in major molecular response, and 2 were PCR negative. Patients stopped Imatinib and continued with Interferon only. After 2.8 years, 4 had further improved their response, 9 remained stable, and 5 had a gradual relapse. As a conclusion,Dr Burchert said that achieving PCR negativity would not be a prerequisite for successful Imatinib termination and IFN maintenance therapy.

CML in Children

One of the unforeseen surprises was the presentation of data on Imatinib treatment of children with CML. Childhood CML is extremely rare, with only 2% of all childhood leukemia cases, so data is very limited. Prof Suttorp from Dresden presented the results of the PAED-II study. 51 patients were recruited. Median age was 11 years (1-20), 48 in chronic phase, 1 in accelerated phase, and, 3 in blast crisis. 6 of 42 patients stopped Imatinib because of insufficient response. 4 received 2nd generation TKIs, 2 opted for stem cell transplant. 49 of 51 patients are alive today. The researchers observed an impact on bone metabolism: the effect is that Imatinib decreases osteoblast development and activity, decreasing bone growth. As a conclusion, Suttorp said Imatinib treatment results in high response rates, while side effects are tolerable. Therefore, stem cell transplant has been shifted to a 2nd line strategy also in pediatrics. Changes in bone marrow metabolism and growth impairment are of special concern in not yet outgrown pediatric patients.


The issue of adherence, or compliance to therapy, remains to be a challenge with TKIs. Dr Goldman presented data collected at the Hammersmith hospital. In a trial, they had provided patients with a medication bottle whose cap had some electronics built in. The bottle automatically recorded each time the bottle was opened. That way they observed that more than every fourth CML patient did take less than 90% of the prescribed dose, and every seventh less than 80%. They found a strong association of response to therapy with adherence rate: the 6-year probability of achieving major molecular response was 28% with those patients taking less than 90% of prescribed doses, and 95% for those that were adherent. The same applied for complete molecular response (0% vs 44%). Interestingly, when comparing the electronic measurement against what patients said to their doctor, patients claimed to be much more compliant than they actually were. This shows the lack of adherence remains largely underestimated (Abstract 3290).


It was again a great time at ASH, not only from the perspective to meet friends and top doctors, but also from coming home with the confidence that even though CML therapy has already radically improved over the last years, there is exciting progress and a lot of enthusiasm to close the existing gaps. There is still a lot of room for improvement – about every seventh CML patient does not respond to Imatinib up front, and a number of patients can't tolerate it. However, the second line data of (lower dose) Nilotinib, Dasatinib and Bosutinib presented this year seems to be a great step forward, and for the "last bastion", the T315I, there are a number of new drugs in trials which seem to be targeted, promising and tolerable. This is great news to me, in comparison to ASH 2008.

In terms of finding a cure, there could still be more progress. However, I could see progress in research targeting residual stem cells, understanding mechanisms behind suboptimal response, avoiding early progression with improved first-line treatment, and considering new (and/or more affordable and/or more tolerable) long-term maintenance therapies. In contrast, the results of the "STOP" trials from France and Australia have not convinced me – if the relapse risk is fifty-fifty, I would be hesitant trying it if I can tolerate treatment well, even if re-starters seem to respond again to

Recent reports about low-dose Interferon as maintenance therapy in minimal residual disease – in combination with Imatinib or not – are promising, as shown in Germany and Sweden. Maybe further research will show who has an immune response to Interferon, and those might have a minimal relapse even after stopping all therapies. However, it seems low dose Interferon requires adaptive dosing: In the Italian GIMEMA trial all patients stopped Interferon treatment within 3 years because of side effects, while the Swedish and the two German trials had shown long-term benefits with good tolerability. But one of the best ASH messages for me was from Childhood CML: In CML kids, whose decisions should be based on the expectation that they should expect another 80 years of life, transplantation has now become second line after Imatinib. I think – and hope – this is a message for all CML patients: that experts are expecting current therapies to keep us alive in the long term. Chances seem to be good that we have the chance to grow very old, as long as we adhere to therapy – until someone has found the bullet to kill also the
small gang of stubborn CML stem cells off.

All this is encouraging. And this is why I spend St. Nicholas in the US.

Jan Geissler, 13 Dec 2009

Wednesday, December 16, 2009

Look who's here!

Presenting Steven William Cothran

Brian (Dad) and Steven

Lisa and Baby Steven
Just too beautiful for words!
Steven's namesake arrived on December 14th at 11.22pm after a very short labor - from my point of view anyway. He weighed in at 9.9lbs and took up a goodly amount of the tape measure.......... I dont have those numbers - but he is a big boy...

It was just fantastic being at the birth - thanks Lisa and Brian! Joleen was there too and was roped in to help during the labor. She also got to cut the umbilical cord. It was just a wonderful experience.

I had the camera in there with me and got a good many really beautiful photos of some lovely moments - so many good memories recorded.

So now I am Granny Annie to 5 beautiful children - what a richness this is!

love and light

Saturday, December 05, 2009

Preliminary Good News from ASH.....

ASH: New CML Drug Overcomes Resistance Mutation

By Ed Susman, Contributing Writer, MedPage Today
Published: December 05, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Earn CME/CE credit
for reading medical news

Action Points
  • Explain to interested patients that this report describes preliminary findings about an investigational drug that is not FDA approved and is not available for clinical use.

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
NEW ORLEANS -- Promising preliminary findings from a small study suggest a possible treatment for imatinib (Gleevec)-resistant chronic myeloid leukemia (CML), researchers reported here.

Researchers had already identified the the cause of resistance -- the T3151 mutation -- and now they may have a fix for the problem that has become the Achilles' heel of CML therapy, Jorge Cortes, MD, professor of medicine at the University of Texas, M.D. Anderson Cancer Center.

The investigational drug, omacetaxine, being developed by ChemGenex Pharmaceuticals Limited, based in Menlo Park, Calif., and Melbourne, Australia, "represents a new potential therapy for patients with T315I-positive chronic myeloid leukemia," Cortes said at the American Society of Hematology meeting.

That hopeful note emerged from a study designed to evaluate the safety and efficacy of subcutaneously administered omacetaxine in patients with imatinib resistant T315I Philadelphia chromosome-positive chromin myeloid leukemia. Patients were given 1.25 mg/m2subcutaneous omacetaxine twice daily for 14 days every 28 days until hematologic response for induction therapy.

For maintenance therapy, patients were dosed twice daily for seven days every 28 days.

Although the mean follow-up time was short, Cortes said the early results revealed a number of promising findings including:

  • After a mean of nine months follow-up, 86% of the 49 chronic phase patients in the study who no longer were controlling their disease with imatinib had achieved a complete hematological response.
  • About 27% of patients had achieved a major cytogenetic response, defined as absence of Bcr-Abl mutation in at least 35% of cells.
  • Roughly 18% of the patients had achieved a complete cytogenetic response -- all the cells appear to have lost the Bcr-Abl mutation.

The median age of the patients in the study was 58 years, and ranged from 19 to 83. Their median time diagnosed with chronic myeloid leukemia was 54 months. Imatinib failed to control the disease in all the patients; 79% had failed two or more prior tyrosine kinase inhibitors. The presence of baseline T315I mutation was confirmed in all patients.

Cortes said the study did not have a control arm because there is no established treatment for patients whose disease has progressed despite use of imatinib and other tyrosine kinase inhibitors in the face of the T315I mutation.

He explained that omacetaxine, which is not approved in the U.S. or Europe, has been used to treat leukemia in China for many years and it appeared to work against the mutation in the laboratory.

"What is encouraging is that we are seeing that patients are able to respond to this therapy," he said at a press briefing here. "It is self-administered subcutaneously and we have seen that it is very well tolerated."

"One can draw a parallel between the acquisition of antibiotic resistance in bacterial infections and the development of drug resistance due to a mutation in this case which blocks the binding of drugs like imatinib to the active site in chronic myeloid leukemia cells," said Richard Larson, MD, professor of medicine at the University of Chicago, who acted as a moderator at the press briefing.

He said omacetaxine and other drugs in the development pipeline will be important in treating even small groups of patients.

"It is fair to say that therapeutic breakthroughs never occur quickly enough to help everyone. The good news is there are a lot of new agents in the pipeline. The challenge is that each subset of disease becomes smaller," Larson said.