Category: Myeloma

Myeloma

Cancer Stem Cells

Read through this and let me know what you think. A lot of folks believe that there are cancer stem cells, and those need to be the target of research.

> Dear Friends,

> Dr. Matsui sent this wonderful reply to me late this evening.
> Describing the difficulties of getting people to believe the findings
> and then to test appropriate agents, he supports Dr. Richardson
> description of Matsui’s work as “preliminary.” I think he’d like
> the patient community to spread the word. (Or I would. Probably just
> reading between his lines!)
> His message clarifies (for me) why Hopkins is using Rituxan despite
> the fact that it will likely affect all B cells. They feel they can
> support those whose immune systems are suppressed as is already done
> for persons with genetic disorders that prevent normal development of
> antibodies. He is testing many other agents. He also mentions that
> proteasome inhibitors may attack cancer stem cells. This raises both
> velcade and NPI-504 in my mind. (Recall, taking Rituxan could
> disqualify one from the NPI-504 trial, as it does the PR-171 trial.)

> Finally, I note that he thinks that the active ingredient in fever
> few would be a good agent to test. Since I can buy some form —
> probably not strong or pure enough to matter — nonetheless, I’m
> giving it to my guy NOW.

> What an amazingly generous communication from such a busy, high-
> powered researcher! (Nick, thank you for helping refine the
> questions!)

> Best wishes,
> D.

> Begin forwarded message:

>> From: William Matsui
>> Date: February 22, 2006 10:53:50 PM EST
>> Subject: Re: Follow-up questions?

>> Dr. Wicha passed this message on to me and I had a few thoughts…

>>

>> Like our colleagues at Michigan, we (at Hopkins) believe that cance
>> stem cells lie at the heart of developing effective therapies that
>> can truly result in long-term remissions. The cancer stem cell
>> hypothesis currently is just that, a hypothesis. We believe that we
>> have solid evidence that specific cell populations (stem cells) are
>> able to give rise to myeloma in the laboratory, but the ultimate
>> proof will come from finding effective stem cell targeting agents,
>> then testing them in patients and showing that they can prolong their
>> lives. As you might imagine, this is a formidable task…. Using
>> acute leukemia (AML) as an example, the stem cells in this disease
>> were first identified in the early 90’s. Potential leukemic stem
>> cell targets (the interleukin-3
>> (IL-3) receptor and proteosomes) were described a few years later,
>> but neither of these targets have been seriously studied in the
>> disease (Velcade is a proteosome inhibitor and should have activity
>> against the cells, and has been tested only in a limited fashion in a
>> single published study). So AML (in which few would argue the
>> existence of stem
>> cells) illustrates the difficulties decscribing the laboratory
>> findings, getting people to believe the data, then carrying out a
>> clinical trial that would ultimately prove the point. Hopefully,
>> trials that suggest that the theory is correct, like our Rituxan
>> trial or the Michigan Bexxar trial (that would hopefully extend the
>> length of remissions, but are not likely to cure myeloma-since each
>> agent has curative benefit in only limited cases of lymphoma) will
>> give us the evidence we need to perform future clinical trials using
>> drugs that we think may truly eliminate myeloma stem cells.

>> For our trial at Hopkins, we chose to use Rituxan largely because of
>> its lack of serious side effects and our data from the laboratory.
>> I do
>> not know whether any other investigators have repeated our
>> experiments, but I do know many researcher have asked me to help them
>> with the laboratory assays to detect growth of the stem cells (so
>> maybe confirmatory results are coming). I agree that parthenolide is
>> a promising drug in leukemia and would certainally make sense to test
>> in MM. We are looking at several agents in the lab to test their
>> anti- stem cell activity. Some are focused on agents that can
>> inhibit B cells (regardless if they are myeloma derived or not),
>> others on pathways that we think are shared my stem cells from many
>> different tissues and organs. For the latter set of drugs, there is
>> certainally concern that they will affect normal stem cells so much
>> testing is likely needed prior to their standardly being used. As
>> for myeloma, my hope is that we can eliminate most all B cells since
>> the greatest risk of this approach would likely be a period of
>> immunodeficiency (due to the loss of normal antibody production).
>> But there are individuals with genetic defects that lead to
>> immunodeficient states that can really lead normal lives with
>> antibodies given every 1-2 weeks, and I would expect that the B cell
>> pool to be “replenished” by new B cells made from hematopoietic stem
>> cells.

>> Hope that this answers a few questions. Please don’t hesistate to
>> contact me if you have any others.

>> Bill

>> William Matsui, MD
>> Assistant Professor of Oncology
>> Division of Hematologic Malignancies
>> The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins The
>> Bunting Blaustein Cancer Research Building Room 245 1650 Orleans
>> Street Baltimore, MD 21231

Results!

Here’s what I just received by email:

Got your phone and e-mail, just been very busy with patients this am. Your values are much better. M-spike in beta 2 region is 0.29 G/dl, Gamma region is 0.18 G/dl. Your IGA is 1132, IGG 310, and IGM 37

My IgA was 2245 mg/dL when I started. My IgM is in the normal range for the first time ever! IgG still low.

Starting second cycle

I started my second cycle of Rev/dex yesterday. So far, nothing bad! Just the dex sleeplessness and a bit of a headache. Normal dex stuff. Just 3 more months to go, and then I go to dex just 4 days a month and the Revlimid 21 days, like now. I had the quantitative Ig’s and SPEP done, as well as CBCs. The CBCs were all in the normal range. The RBC, HGB and HCT are all at the low end, but still in the normal range!

Wake Forest

This morning I got a call from the doc at Wake Forest University, telling me they’re now enrolling people in the Rev/dex EAP trial. That was good news for me. Winston-Salem is a lot better drive for me than Charlotte. I have an appointment next week. I’m dreading the dex, but am hoping it helps me.

Here is a quote published in Cure magazine this month from Dr. Paul Richardson, MD, clinical director of the Jerome Lipper Multiple Myeloma Center at Dana Farber Cancer Institute:
“I don’t want to overstate the case, but in myeloma patients who do respond to Revlimid, which is about one-third of patients, they can enjoy very durable disease control on the agent.”

Dr. Richardson is a wonderful, caring person. I wish I lived closer to Boston so he could be my doctor. :)

Bone Marrow Biopsy

I had a bone marrow biopsy yesterday. I got one of these, and decided to take a picture of it so you could see what the needle looks like. This time I had an IV of 2 mg ativan. I can’t say that it helps much, but it sure doesn’t hurt. I don’t know what all these parts are for, but here they are!

Goldenberg Snare Coil (Bone Marrow Biopsy Needle)

Manufacturer’s Home Page. This includes some video demonstrations of the Goldenberg Snarecoil in use.

Did you know this about melatonin?

If you’re on steroids, you should avoid melatonin.

Precautions: There are no known serious side effects to regulated melatonin supplementation. Some people may experience vivid dreams or nightmares. Overuse or incorrect use of melatonin could disrupt circadian rhythms. Long-term effects have not been well studied. In rats, melatonin decreases T4 and T3 uptake levels.

Melatonin can cause drowsiness if taken during the day. If morning drowsiness is experienced after taking melatonin at night, reduce dosage levels. In some cases of depression, daytime doses of melatonin can increase depression.

May be contraindicated for those with autoimmune disorders and immune system cancers (e.g., lymphoma, leukemia).

Because melatonin suppresses corticosteroid activity, those who are taking corticosteroids for anti-inflammatory or immune suppressive purposes (e.g., transplant patients) should exercise caution with melatonin supplementation.

Melatonin could interfere with fertility. It is also contraindicated during pregnancy and lactation.

Lack of sleep and insufficient exposure to darkness may suppress natural production of melatonin.
http://www.wellfx.com/InfoBase/vitamin_melatonin_.htm

24hr Urine 24 Mar 2003

Date of specimen: 3/24/2003

TEST RESULT LIMITS
Protein, Total, Urine 5.2 mg/dL 0.0 – 15.0
Protein, Urine 24 hr 150.8H mg/24 hr 30.0 – 150.0
Albumin, U 59.6 %
Alpha-1-Globulin, U 14.3 %
Alpha-2-Globulin, U 11.0 %
Beta Globulin, U 7.5 %
Gamma Globulin, U 7.6 %
M-Spike, % Not observed
Immunofixation result, urine
Bence Jones Protein positive lambda

Labs from 30 January 2003

Drawn: 01/30/2003

PROCEDURE
NORMAL
AB-
NORMAL
UNITS
REF RANGE
HEMATOLOGY
white cell count 6.8 10^3/uL 4.5 – 11.0
red cell count 3.96 10^6/ul 3.80 – 5.10
hemoglobin 13.0 g/dl 11.5 – 15.0
hematocrit 37.5 % 34.0 – 44.0
MCV 94.8 fl 82.0 – 101.0
MCH 32.9 pg 26.0 – 33.0
MCHC 34.7 g/dl 32.0 – 36.0
RDW 12.6 % 11.0 – 14.0
PLATELET CT 308 10^3/ul 140 – 400
MPV 6.8 fl 7.8 – 11.0
ALLEN’S SMEAR DONE
GENERAL CHEMISTRY
CREATININE 1.00 mg/dl 0.40 – 1.50
CALCIUM 9.1 mg/dl 8.4 – 10.6
ALKALINE PHOSPHATASE 166 iu/l 50 – 150
SGOT (AST) 27 iu/l 15 – 40
LDH 83 iu/l 100 – 190
URINALYSIS
COLOR yellow yellow
CLARITY slightly cloudy clear
SPECIFIC GRAVITY 1.010 1.005 – 1.030
pH 5.0 5.0 – 7.5
PROTEIN Negative Negative/trace
GLUCOSE Negative Negative
KETONES Negative Negative
URINE BILIRUBIN Negative Negative