Author: Beth

I was diagnosed with MM in January of 2003. I underwent various treatments, including thalidomide/dex, revlimid/dex, dex alone, a clinical trial of CNTO 328, and Velcade, Doxil and dex until late August, 2007, when I had an autologous stem cell transplant after high dose melphalan. I experienced what's known as a very good partial response (VGPR). Since then, my myeloma has been stable.

Boarding school

My nephew is going to be attending a school in Greensboro, NC next year. It’s not too far from here, so we may get to see him more often! AHA

This is where I went to school for most of high school. Why I left is a long story, having to do with misbehavior. It was a long time ago!

Bone Protein Can Reverse Kidney Failure

From Bob, on the ACOR MM list:

Date: 2003-06-30

New Study Demonstrates Bone Protein Can Reverse Kidney Failure

BOSTON – A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has shown that a protein used to heal fractured bones is effective in repairing and reversing chronic renal disease, a leading cause of morbidity and mortality throughout the U.S.

These findings, which are reported in the July 2003 issue of Nature Medicine, could help lead to the development of a therapeutic alternative for the nearly 300,000 kidney disease patients who are currently undergoing dialysis.

“Dialysis is not really a treatment, it’s just a means of survival until an opportunity for a transplant opens up,” notes the study’s senior author Raghu Kalluri, Ph.D., director of the Center for Matrix Biology at BIDMC and Associate Professor of Medicine at Harvard Medical School. “This is a very tedious way of living life,” he adds, explaining that the process of
mechanically filtering blood through a machine to remove waste products must be performed several times a week for a period of three to four hours per visit, posing risks of infection and other side effects. Furthermore, the procedure is extremely costly.

The kidneys function as a filtration system, keeping the body’s blood supply healthy by removing excess fluids and wastes, as well as by producing hormones. When kidneys “fail” – as can result from complications associated with diabetes, lupus or several other diseases – harmful wastes accumulate in the bloodstream, excess fluids build up in the body, and red blood cell production is impeded. Once chronic kidney disease develops, it cannot be reversed or repaired; when the organs cease to function, patients have no alternative but to undergo dialysis while awaiting a kidney transplant.

This new study looked at the role of a molecule called bone morphogenic protein (BMP)- 7 which, in its recombinant form, has been approved by the U.S. Food and Drug Administration for the treatment of bone fractures. Earlier studies had revealed that BMP-7 is highly expressed in the kidneys of healthy individuals. “We wanted to learn if this protein was somehow offering protection against kidney injury,” explains Kalluri.

The investigators used mouse models of chronic renal injury, characterized by the presence of scar tissue known as renal fibrosis; once kidney disease was well-established in the animals, they administered human recombinant BMP-7.

“We found that in the kidneys, BMP-7 reverses a process known as epithelial-to-mesenchymal transition, which generates scar-causing cells known as fibroblasts,” says Kalluri, explaining that BMP-7 first reduces the number of the fibroblast cells, and then replaces the damaged areas of the kidney tubules with healthy epithelial cells. “In effect,” he adds, “BMP-7 is decreasing the bad cells [in this context, fibroblasts] and converting them into good cells [in this context, epithelial cells].”

Although therapies exist to slow progression of kidney disease, once it has developed it becomes intractable, eventually leaving patients no alternative but to undergo dialysis. “The possibility of creating a cost-effective drug that would actually reverse renal injury could significantly reduce the need for dialysis and significantly improve the quality of life for these
patients,” says Kalluri.

### Study co-authors include BIDMC investigators Michael Zeisberg, M.D., Jun-ichi Hanai, M.D., Hikaru Sugimoto, M.D., Ph.D., Tadanori Mammoto, Ph.D., David Charytan, M.D., and Frank Strutz, M.D.

This study was funded by grants from the National Institutes of Health, Deutsche Forschungsgemeinschaft, and support from the Center for Matrix Biology, BIDMC. Ortho Biotech Products, L.P., is the exclusive licensee of BMP-7.

Beth Israel Deaconess Medical Center is a major patient care, teaching and research affiliate of Harvard Medical School, and ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a founding member of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox.

Editor’s Note: The original news release can be found here:
http://home.caregroup.org/newsnow/pr_out.asp?pr_id=431

Coumadin

I’m getting closer to my doctor’s desired INR for me. I’m now at 1.99, and he would like to see me between 2 and 3 (but closer to 2). I’ll stay on 10 mg of coumadin a day for now, to see if that gets me to 2.

We had a tornado in the area today. I didn’t know about it until I arrived at the clinic and saw that the lobby was virtually empty. They cleared people out as a precaution. It turns out the tornado was just passing by. It didn’t touch down.

Red face

I’ve noticed that when I take my weekly dex, the next day or so I have a really red face. It looks like I have sunburn! My skin even peels a bit. Usually by the end of the day on Wednesday I’ve recovered.

I have to have my INR checked today for coumadin. Let’s hope I don’t have to increase my dose anymore. I just hate having to take more pills.

If you’re reading this and you’re a smoker, please quit!

Moving on now

I signed up for two classes to continue with my graduate studies. I had taken off spring and summer semesters There was a lot to do and think about right after diagnosis, and I wanted to avoid the added stress of tests and paper deadlines. Also, my first dex pulses were 4 days on and 4 days off, and I was exhausted that entire time. I don’t think I could have done anything! If I miss more than 2 semesters, I have to reapply! What a pain that would be. So I went ahead and registered for classes for fall semester. After I finish fall semester, I’ll be half way through the program. I hope to have my master of science degree done in the following two semesters.

I just took Ambien. I don’t want to be up until the sun comes up. :)

Angiopoietin expression in multiple myeloma

This is an abstract brought to our attention by K.B. on the MM listserv.

Published online July 15, 2003

Blood, 15 July 2003, Vol. 102, No. 2, pp. 417-418

Angiopoietin expression in multiple myeloma

Multiple myeloma demonstrates a progressive, and usually fatal,course, with current treatments generally producing only temporary remissions. Antiangiogenic therapies represent a potential new approach to treating this cancer. While it is well established that growth in solid tumors is dependent on angiogenesis, the role of this process in hematopoietic tumors is not fully appreciated. There is a strong correlation between increased angiogenesis and poor survival in myeloma patients. Furthermore, both cellular and circulating levels of vascular endothelial growth factor (VEGF) are often elevated in hematologic malignancies, including myeloma, and have been shown to predict for a poor outcome, lending additional support to the concept that angiogenic cytokines are involved in the growth and progression of these malignancies.
In this issue, Giuliani and colleagues (page 638) extend our knowledge of marrow angiogenesis with their report on the expression of angiopoietin-1 in myeloma cell lines and patient samples.
Angiopoietin-1 (Ang-1) was found to be expressed in 47% of the patient samples examined. Bone marrow angiogenesis was examined and found to be elevated in 12 of 15 patients examined (80%), and there was a significant correlation between Ang-1 expression and microvascular density (MVD), although no such correlation was present between Ang-1 and Tie2 expression. Giuliani and colleagues were also able to demonstrate that myeloma cells could up-regulate the angiopoietin receptor Tie2 in human bone marrow endothelial cells. Conditioned medium from myeloma cell lines was capable of stimulating angiogenesis, although such stimulation did not occur in the presence of an anti-Tie2 antibody. Angiopoietins, while not believed to be involved in the initial stages of angiogenesis, are known to play an essential role. Ang-1, acting through Tie2, contributes to the stabilization of newly formed vessels via recruitment of peri-endothelial supporting cells as well as endothelial cells, whereas Ang-2, also acting through Tie2, reduces these interactions, leading to vascular regression. It has also been reported that coexpression of Ang-2 and VEGF promotes new vessel sprouting and has been shown to predict a poor prognosis in myeloma and other malignancies.

The role, if any, of angiopoietins in myeloma is far from clear, however. Uneda et al have also recently reported their findings regarding angiopoietin expression in myeloma (Haematologica.
2003;88:113-115). In their study, 27 of 36 multiple myeloma patients studied showed expression of Ang-2 by reverse transcriptase˝polymerase chain reaction (RT-PCR) and immunohistochemistry. Coexpression of VEGF and Ang-2 was detected in 18 of the myeloma samples. The survival rate was significantly lower in those patients expressing Ang-2. Interestingly, and in contrast to the findings by Giuliani et al, they found no evidence of Ang-1 expression.

The seemingly contradictory findings of Ang-1 and Ang-2 expression in these 2 studies should be carefully interpreted in the context of how the cells were isolated and examined. Both studies examined relatively few patients, and in neither study was the effect of the bone marrow microenvironment on expression of these molecules fully taken into account.

Several important outstanding questions remain to be addressed. First, the apparent contradiction in the results from these 2 studies must be resolved. Does expression of Ang-1 or Ang-2 have prognostic value in myeloma? The results from Uneda et al would suggest so. Does angiopoietin expression vary with the stage of the disease? Do the angiopoietins represent valid therapeutic targets? Even if the angiopoietins are not the major driving factors in marrow angiogenesis, the results of Giuliani et al suggest that they may represent a valid target. Although it is too early to answer these questions, the preliminary evidence is tantalizing.

William T. Bellamy
University of Arizona

Related Articles in Blood Online :

Proangiogenic properties of human myeloma cells: production of
angiopoietin-1 and its potential relationship to myeloma-induced
angiogenesis.
Nicola Giuliani, Simona Colla, Mirca Lazzaretti, Roberto Sala,
Giovanni Roti, Cristina Mancini, Sabrina Bonomini, Paolo Lunghi, Magda
Hojden, Giovenzio Genestreti, Mirija Svaldi, Paolo Coser, Pier Paolo
Fattori, Gabriella Sammarelli, Gian Carlo Gazzola, Regis Bataille,
Camillo Almici, Cecilia Caramatti, Lina Mangoni, and Vittorio Rizzoli
Blood 2003 102: 638-645.

Dentist

I’ll be seeing the dentist in July. They have me scheduled for cleanings three times a year instead of the typical two. My dentist wants to keep the bacteria in my mouth under control, since I have an immune system that’s not up to speed. She’s also going to have me take some kind of antibiotic before the cleaning, so the bacteria won’t infect me if it gets into my blood stream as a result of the cleaning.

I think the coumadin must be doing its job. I noticed tonight that my gums bleed pretty freely when I floss now.

Ambien

Ugh! I had a long nap yesterday afternoon, so that disrupted my sleeping schedule. Here I am, wide awake at 4:00 am. I decided to try Ambien. Dr. O. told me to start with 1/2 tablet to see how it works for me. I just took the 1/2 tablet and will see how effective it is. I’m hoping it works. Tonight I’ll be taking dex, so I don’t need an extra sleepless night.