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December 2011 Archives : Doctor Durie

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In presenting "What is myeloma" to newly diagnosed patients, Dr. Morie Gertz uses the comparison of myeloma to "weeds" in a garden, which in this case is the bone marrow microenvironment.  A recent book, Weeds: in defense of nature's most unloved plants, by Richard Mabey, provides wonderful insights into the analogy of myeloma cells as weeds.  

So what is a weed?  The first aspect is that it is not intentionally planted- so it is not a "plant" (or flower/tree/bush) which you wanted.  Certainly, this applies to myeloma cells nobody wants them.  There are truly intruders.  Other aspects which apply are: aggressive, resilient- hard to get rid of and spreading in an unwanted fashion.  What is the driving force behind all this?  Why do weeds keep popping up?

 The answers are interesting and important.  Weeds love "disturbed ground": areas recently dug up, bulldozed, abandoned, or contaminated with toxic waste.  Classic sites for weeds were bomb sites in London during the blitz of the Second World War.  Weeds unseen for generations, suddenly grew in profusion.  The weeds started a process of environmental healing: transitioning to new urban countryside.  So weeds function in a restorative fashion.

So what is myeloma?  Local sites of myeloma in damaged tissues do occur rarely but are quite remarkable.  For example, a gentleman struck by lightning on his leg bone went on to develop myeloma at that site.  Other examples include myeloma growing in the pocket for a cardiac pacemaker which became infected and myeloma growing alongside leaking silicone breast implants.  So the point is a disturbed, activated, and damaged microenvironment can enhance myeloma growth.

Weeds also outgrow new favorable environments.  If conditions are right, weeds can overtake any garden.  Myeloma cells do the same and continue to grow when conditions favor antibody production or production of the "monoclonal spike" in an effort to combat infection.  A "positive feedback loop" can be established whereby the disturbance, activation, or damage is not corrected (for example, breast implants are leaking and are not removed) and a favorable growth environment persists.  The myeloma monoclonal protein (or antibody) cannot do its job: the local situation is not corrected.  It is amazing to see the impact of what happens when the situation is corrected   with immune modulating agents such as thalidomide, Revlimid, and Pomalidomide.  The microenvironment is stabilized: growth slows or stops.  There is an opportunity for abnormal cells to be eliminated.  But, like weeds, myeloma cells are remarkably resilient.  We need ways to wipe out every last cell and/or keep the microenvironment hostile for new growth.

In nature, mature forests teach us many lessons.  Trees and shrubs dominate some weeds, those which are light dependent die off, others are not able to compete with large trees that change the soil chemistry.  So re-achieving balance is a natural strategy.  This provides hope and the expectation that correct maintenance strategies can work long term, if crafted with the aim of achieving the best immune and chemical balance. As we are learning from our fields and gardens, using stronger and stronger weed killers may not be the way to go.  So let's keep an eye on the weeds and see what more they have to teach us and help us in the search for the cure.

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Almost a decade ago now, I collaborated with Faith Reidenbach in publishing an article in CURE magazine describing the status of myeloma therapy (DEEP IN THE BONE: Managing Myeloma: CURE magazine Vol I: pp 31-38 2002: @ curetoday.com).  At that time, we were very excited about the recent availability of the novel agents, thalidomide (Thalomid�) and bortezomib (Velcade�).  Dramatic responses had occurred and patients previously without options were having new remissions lasting over 2 years (unheard of at that time).

I discussed the role of thalidomide plus dexamethasone pre-autologous transplant and the pros and cons of long term low dose thalidomide maintenance.  And so it began: the evaluation of combining novel and traditional high dose chemotherapy approaches.

So how far have we come in this last decade?  Patients are definitely living longer and better lives with many fewer complications of myeloma and side effects from treatment.  The average life expectancy has essentially doubled from 3 years to 6 years.  Patients under age 50 years with good risk features (i.e. low ISS stage; normal [or good risk] chromosomes on FISH testing) can reasonably expect to live in excess of 10 years.

 This is huge progress and pushes the search to find a cure in two directions.  Firstly, get the maximum mileage from novel combinations to further extend survival.  But, secondly look for something completely new to truly wipe out myeloma and establish a cure.

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As we look toward ASH for 2011, we see continued refinement of new combinations.  Since it takes time to assess long term follow-up, it is hard to know for sure the added value of ever more complex regimens.  Caution about potential toxicities is an increasing concern. Full discussion of ASH highlights will be posted next week.

The need for a continued search for a cure is emphasized by the current special issue of Science magazine: 25 November 2011, Vol. 334, pages 1046-1051, *Mysteries of the cell*.  Five articles discuss what we still need to understand about how the cells of the body function.  What is the exact structure of the cell membrane?  How does a cell control its size?  How does a cell organize the positioning of all the different pieces of the cell?  How do cells know when they need to eat to get more energy and nutrients?  And, finally, do genes function differently if in a new location within the cell?  All crucial questions!  So we need to be very humble as we pose new questions about myeloma.  We have so much to learn about how both normal and cancerous cells work!  It is truly amazing and encouraging that despite that, major progress is being made every single day as research moves ever forward.  

But what about the cure?  Not much to report yet.  Dr. Ed Stadmauer reports that two trials, using re-infused T-lymphocytes from patients "armed" (with carefully selected warheads) against myeloma, are ongoing with early but promising results.  A new vaccine trial at Hadassah University Medical Center in Jerusalem has been recently announced.  The "one shot cure" approach announced by Dr. Russell at the IMWG Summit in London in the summer is proceeding with a first trial reaching the phase I patient stage and a second approach (probably the more promising of the 2) for now, just at the level of animal testing of the "oncolytic" (cancer destroying) virus.

The IMF is committed to both, track and report, on these two research directions which can lead to both longer survival and ultimately a cure.  Stay tuned!

BrianGMDurieblog.pngOn the way to the Patient and Family Seminar in Rome, we had a side trip to Norcia, two hours northeast of Rome. Norcia is a beautiful small town (~5,000 inhabitants) where a young chef, Flavio Feadi, (Executive Chef at Palazzo Seneca) is creating food in a whole new way. Using fresh, local, organic produce is the key first step. In this amazing protected valley of Norcia, the healthy produce needed to create flavorful meals is less than 20 minutes away. One can start the day with free range eggs with a touch of olive oil and balsamic (from Modena), plus a touch of local cheese. For lunch, the wonderful small local lentils and beans are the building blocks for soups and side dishes.

 

But, a visit to the rolling hills close by reveals something truly unique: free range pigs! You have heard of free range chickens-- but pigs, that's unheard of! They roam, eating and reproducing in the woods above Norcia. They eat acorns plus other nuts, grasses, roots and herbs, resulting in products with both enhanced flavor and health value. This free range pig farm with approximately 300 pigs is unique in Italy: there are only 2 other similar farms in the whole of Europe! Norcia is so unique in fact that Michelle Obama's staffers recently visited to learn more.

 

These pigs live and sleep in the fields and woods completely unconstrained-- returning at a run to the whistle of the proud owner, Giusseppe. Meanwhile, across the valley, in higher more heavily wooded hills, organically fed sheep and goats wander the fields-- although they scuttle indoors if storms are coming. Caring attention from the farmer and his wife results in from wonderful milk and cheeses, including ricotta and harder aged varieties mixed with cow's milk as necessary.

 

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In the valleys, are fields of corn and grains, such as oats (avena in Italy). Tomatoes love the climate as do the grapevines of all types spread across the rolling hills. The vines of Monte Falco have been selected with science and intuition to produce special local wine: Sagrantino (Rosso)--red wine with a bold/ strong flavor and an earthy taste. It was interesting to learn that Montefalco red wines have the highest levels of health giving polyphenols of any wine. In the valley, leading into Norcia, flows the Nera River with plentiful trout and freshwater crayfish for the catching. This is truly the 21st century *land of milk and honey*. Close by are scattered hives of bees brought to areas of new blossoms to create unique flavorful honey.

 

If this was not enough, the specialty of this area of Norcia is Black Truffles (Tartuffinerie)! They grow 6-12 inches underground close to the small oak trees that cover the lower slopes the hills. There is a symbiosis: truffles get sugar from the trees; the truffles (a fungus) give much needed nitrogen (natural fertilizer) to the oak trees.

 

Early in the morning or late in the evening, when it is cooler, small dogs, often cocker spaniels, go out with their owners to sniff for truffles. The relationship between the dog and its master is something to see, a loving and respectful partnership resulting in a prized truffle.

 

On the surface, there is just rocky ground. But suddenly the small dog picks up speed and heads for one of many of the small oak trees. Frantically, it starts digging--then, turns its head to the owner-- can he help with a small pick to clear stones? Then, more digging and then with tail wagging in triumph, truffles are proudly revealed for all to see. The owner must snatch the truffle quickly-- dogs DO love truffles, but not as much as pigs.  Dogs have largely replaced pigs as truffle scouts for this reason. The dog goes from tree to tree, finding more black treasure-- worth 1000 Euro/truffle from Nov-Jan: high truffle season.

 

Back at Palazzo Seneca in Norcia, Flavio is quietly gathering herbs in his garden awaiting deliveries from the hills, valleys, and river. Avoiding heavy sauces, Flavio concocts fantastic dishes, blending the fine local produce into infinite combinations of delicious meals.


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The focus is local, organic, and healthy. Chef Flavio gives an unwitting *tip of the hat* to American nutrition guru, Michael Pollan, who cautions us not to eat what our grandmothers wouldn't recognize and to shop only at the "edges" of our supermarkets, where fresh items can be bought.  The unique difference is that Flavio can shop at the edge of his own valley, not a commercial supermarket!! This is the key to good nutrition: local, free range, and no added chemicals.

 

There is NO reason this approach cannot flourish elsewhere. It is not the wave of the future, but of NOW! Even within metropolitan London, as reported by Alice Rawsthorn (International Herald Tribune Mon Sept 19th), Paul Smyth is trying hydroponic farming and a range of other techniques to stock his East London Farm Shop. In the U.S. several cities now sanction chickens and goats as well as several types of agriculture within city limits. Affordable healthy food is becoming accessible. I am sure this is just the start of this burgeoning movement to achieve local, self-sufficiency with healthy food.

 

The side trip to Norcia was quite a trip!