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Multiple Myeloma high dose or total therapy: did we collect enough stem cells?

currently I am analyzing the possibility of the state-of-the art treatment of multiple myeloma for an about 40 year old patient, i.e. the high dose or total therapy whith tandem transplants according to the definition of Dr. Barlogie [Blood, Vol 93, No 1 (January 1), 1999: pp 55-65].

In all the procedures and protocols described there, I noticed a detail that apparently is very important in the whole procedure and that is the following. Before applying Melphalan (MEL) it is essential to gather the peripheral blood stem cells (PBSC). After the Melphalan Therapy, the stem cell might be of lower quality because of a stem-cell toxic effect.

Now my understanding is that the high dosis or total therapy protocol schedules Melphalan as one of its core drug. So after the completion of the high dose therapy, no PBSC with good quality is longer possible. In other word, if I plan 2 high dose therapies as in the the Total Therapy of Dr. Barlogie, I have to collect at least the amout of stem cells needed for these 2 high dose therapies, in the hope that nothing goes wrong with the cells. If it would, it was a pity.

My question to anybody who has some experience on the issue:

1) how can we make sure (by practical means) that the stem cells are savely stored.
2) For how many high dose therapies should the stem cells be collected
3) In his above mentioned article, Dr. Barlogie suggests for future investigation "...standard dose consolidation chemotherapy versus additional cycles of PBSC-supported high-dose therapy after man MEL-based tandem transplant deserves exploration." To be able to do this, we need stem cells for >=3 high dose therapy, don't we?


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there's been a lot published on tandem transplants since then. there's a
*very* open q (and conflicting data) as to the extent, if any, of survival benefits. there's an open q as to impact on quality of life. yes, this is true of any alkylating agent. also note there's a lot of recent stuff on a wide variety of mobilization protocols (eg, d-tec), which whoever is doing this should be familiar with. i believe the problem is collecting target quantities of cd34+ cells. generally speaking, cryoperservation with dmso, storage with liquid nitrogen, and a great deal of caution to ensure no transient temp rises
(even -80 can damage cells). while i could point you to some docs/articles proceeding on that basis is really foolish, you would be better off contacting one of the many top flight facilities providing this treatment today for adequate protocols. and your best bet may to contact one of the many private companies providing this specific service. this shouldn't be screwed up.

you're an isolated comment and turning it into a pretty bold speculative leap. do you know *anybody* who has tried a third HDT/transplant? are you and the pt the really the ones to forge new ground? you are aware there is a material TRM just with two transplants (though obviously not comparable to allogeneic), right? Other maintenance ideas in addition to chemo include ifn-a (royal marsden), thalidomide (very hot right now, +dexamethasone 70% response as 1st line -- see IGFM as consolidation), biophosphonates (eg, zometa), a wide variety of experimental immune therapies, some experimental brms. you might want to talk to Inter Groupe Francais du Myéloma re the significance of B2-microglobulin measurements re their tandem results. if a compatible sibling is available allogeneic might even be an option for high risk pts. the only limit to collecting/storing cells is wallet toxicity.

 


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