Waldenstrom's macroglobulinemia: Treatment option analysis
I am writing this page to document the thought process I am using to decide
how I would like to be treated for WM. I hope it is useful to me, to the
physicians advising me, as well as to anyone else in a similar boat.
These are my personal opinions. Your conclusions may differ from mine. The
purpose of this page is just to explain my reasoning behind each therapy.
First, I'm extremely grateful to doctors Ranjana Advani (Stanford), and Irene
Ghobrial and Steve Treon (DFCI) for putting up with my endless amount of
questioning. Sadly, the information you need to make the best decision isn't
readily available on the web, so I've used up a lot of their precious time to
explain things to me and for that I am very grateful and I've tried my best to
accurately summarize it here so others can benefit from what I've learned.
My present situation is I'm a 50 years old male with an hct of 32, hgb of
10.7, and IgM serum of 4010, and SV of 2.9. Latest BMB was 40 to 50% involved.
The numbers for the hct and hgb are a bit "pumped up" from what they would be
because I was given 5 rounds (1 week per round) of IV iron (Ferrlecit). I was
asymptomatic (other than the anemia) until recently when I noticed blurry vision
in my right eye that would come and go. Treon told me to see an ophthalmologist
immediately. My pupils were dilated (note: Maureen who teaches ocular disease,
recommends with an IGM of 4,0000 one should have a dilated eye examination at
least twice a year) and two different docs looked into my eyes looking for
sausaging and/or enlarged veins. They said everything was normal except for a
small drop of blood in the periphery of my right retina which they said was
recent. Both eye doctors said both the drop of blood (a peripheral retina
hemorrhage) and the blurred vision was consistent with a high SV.
Note: that there isn't a formula for IgM level and SV. For example, one
person reported IGM at 4000 (same as me) and 4 viscosity (which is way higher
than my 2.9). However, the relationship is pretty linear for most datapoints
Arch Ophthalmol -- Hyperviscosity-Related Retinopathy in Waldenstrom
Macroglobulinemia, November 2006, Menke et al. 124 (11) 1601, Figure CS60051F1).
Upon hearing the news, Treon told me to drop out of the statin clinical
trial, get 3 rounds of PP (1x every other day for 3 sessions total; about 90
minutes per session), then start CPR which would be 1x every 3 weeks for a
minimum of 4 cycles and we'll go from there.
As I'm writing this on Saturday December 8, I just finished by first PP
round. Treatment day for CPR is scheduled for Thursday. So if I'm going to make
a different decision, I don't have a lot of time.
There is not enough known about WM to make a definitive treatment
recommendation and there is a cost/benefit tradeoff that different people weigh
differently. That is why 3 different docs gave me 3 different treatment
recommendations on the same symptoms. Everyone reacts differently and there
isn't a physician in the world who can accurately predict in advance what
treatment(s) are going to work on what patients and to what extent and for how
long. Nobody can predict CRs for any given in advance. However, there is lots of
data on what treatments are effective against your symptoms, e.g., if you have
swollen lymph nodes, some treatments are more effective than others in reaching
that. And there is lots of data on what treatments, in aggregate, produce the
There is also a difference in philosophy of whether to start by treating
pretty aggressively when you have your best shot (e.g., CPR as a first
treatment), or to treat starting with low side-effect drugs (e.g., Rituxan only)
and then escalating to harder drugs (e.g., CPR) if you don't respond or stop
I asked three different docs and got 3 different opinions for my case. Of
course, there are many more options available, but these are the 3 most favored
by my physicians. My 3 options being:
- Rituxan only
- Rituxan and Velcade (either off label or as part of a clinical trial)
For option 3, there are two variants. I could go on the Velcade + Rituxan
clinical trial that Irene is doing. Or, subject to the approval of my physician
(a low-probability event!), I could design my own off-label therapy since
Velcade is FDA approved.
The V+R clinical trial at DFCI run by Ghobiral is Velcade 1.6 mg/m2 once a
week for 3 weeks on an one week off for a total of 6 cycles ( 6 months). Rituxan
once a week for 4 weeks for cycle1 and cycle 4 (first and 4th month) based on
the extended rituxan trial.
If I "designed my own", I'd do V+R once a week for 4 weeks, while
simultaneously doing 20 mg oral simvastatin once a day. If my numbers started
heading up, I'd do a 1x/week for 3 weeks of Velcade. So it's similar to the V+R
clinical trial, but only repeats the Velcade only if required to keep the
numbers heading in the right direction.
is basically rCHOP but without the Vincristine/PN risk and without the
doxorubicin (aka hydroxyldaunorubicin so it is the H in CHOP). There is a wonderful writeup of rCHOP in "Patient from Hell" (herein after
referred to PFH), pp. 67-91 which I've used in the Pro/Con table below because
Schneider's writeup talks about things that the doctors may not tell you about
beforehand (they didn't tell him beforehand either). rCHOP has more drugs than
CPR; CPR basically omits the Vincristine which didn't add much to the
effectiveness, but caused lots of peripheral neuropathy (PN).
Here are the pro/con arguments for each of the options. ORR=overall response
rate (>25% reduction), MRD=median response duration, Minor Response is >=25%
reduction; Major Response aka Partial Response is >=50% reduction in IgM.
Treon strongly favors this. It's a time proven therapy with the most
data behind it (because it's basically an abbreviated form of rCHOP). It
gives me the best chance of a permanent CR which is important because
the fewer drugs you have to use, the better. The side effects are pretty
minimal (relatively benign compared to other chemo therapy). Most
importantly, the long term side effects are thought to be insignificant.
Plus, there is no risk of PN since there is no Velcade or Vincristine.
If you want to minimize the total amount of drugs you have to take to
get to stable disease or CR, this is your best shot because the three
drugs enhance each other. CPR is also excellent at reaching WM in the
lymph nodes (mine are somewhat enlarged). In general, second remissions
are harder to achieve than firsts, so if you are going to take a shot,
this is the best shot. You could be totally done with just 4 doses (if
you are lucky).
Rituxan flare is reduced (compared to Rituxan alone). That's quite
important since you don't want to do PP after the treatment since it
will get rid of the Rituxan. Also, you don't want to risk eye damage,
etc. caused by IgM flare.
You probably won't miss any work. The Prednisone will give you a 5
day "high", so you'll see an energy drop on day 10 to 14 of each cycle.
Since their is no doxorubicin, it's unlikely you'll lose your hair.
Most people don't lose their hair from the cytoxan.
Note: Be sure not to wait too long between Compazine doses (PFH, p.
81) and drink plenty of water to help move out the chemo from your body
and keep it from toxifying your liver.
When Cytoxan is given via IV,
there is minimal toxicity to cells (i.e., permanent cellular damage to
stem cells) which is why cytoxan is often given before stem cell
Note: Cytoxan is 1gm/m2, Prednisone is 100mg/day for 5 days,
Rituxan is 375mg/m2. Cycle is 3 weeks. 2 weeks after the 3rd cycle, he
wants 3 red tops overnighted to DFCI. Treon and others recommend that C
is given before R, but others say it doesn't matter. P is given
after the infusion.
There is a some collateral damage from the cytoxan. You have a small
chance of losing your hair during treatment and it may not
grow back the same way (could be curly or less thick). You will be given
extra meds to control side effects (like nausea). Your white cell counts
may drop requiring neulasta with the second cycle. According to PFH (pg.
11), 20% of patients end up needing Neupogen or neulasta due to low
white cell counts (neutrophils) during
chemo, but at my age, it's less than 20% and PFH was on CHOP, not CPR
which is more mild. Worst case is you may have to stay at home
for a week (PFH, p.11), but most don't lose any time at work. Food will taste pretty bad while you are on
chemo (PFH, pg. 83), although one person said a few puffs of marijuana
gets rid of the bad chemo feeling and restores your taste. You'll
probably suffer from a bad temper when you do a cold-turkey stop on the
prednisone in each cycle (PFH, p. 82-83 and the story on p. 87).
white and red blood cells and platelets may temporarily decrease. This
can put you at increased risk for infection, anemia and/or bleeding.
Your ability to conceive or father a child may be affected by Cytoxan
Prednisone will make you hungry and cause you to gain weight. It will
also make it very hard to sleep.
Of course, the above are relatively minor, short-lived consequences.
However, some people have reported some loss of mental and physical
vitality after lots chemo treatments (but not 4 doses of this one
specifically). If you only took less than 8 cycles of CPR and have long
term mental or physical vitality differences, please let me know!
There is a slight risk of developing a blood cancer such as leukemia
or myelodysplasia after taking Cytoxan.
Chemo drugs may
permanently affect brain function
(e.g., chemo brain).
Cytoxan, Cyclophosphamide, Neosar - Chemotherapy and Side Effects
80% get at least a 50% IgM reduction after 6 to 8 cycles
20% are estimated to get CRs on CPR per Treon verbal
Advani favors this as an initial therapy. Rituxan is a very targeted
therapy very little "collateral damage" with good results. Your numbers
can get better for years after your last treatment (because you are
killing both the B lymphocyte and the lymphoplasmacytic cells, both of
which express CD20).
Her reasoning is to start with this, see how it
goes, and escalate later to CPR, R + V, or something else if needed. You
risk only having wasted a little time. R has very little side effects
and mostly limited to the first hour of infusion. You likely aren't
going to miss work or be incapacitated in any way.
The fewer the drugs, the less the side effects.
The good thing about R alone is you can chart your personal reaction
to R so you can better plan the timing of future treatments and
maintenance. In engineering, we'd call it plotting out the impulse
A start with R alone seems intuitively more consistent with the
disease. Before my vision problems, it was debatable as to whether I
"needed" treatment. The vision symptom pushes me over that line. But CPR
is like chemical warfare compared to R only which is like a surgical
strike. Intuitively it feels a bit odd to go from "treatment optional"
to chemical warfare. However, on the other hand, there is a good case to
be made for CPR above since the weapons are synergistic with each other.
Nobody ever gets a CR from Rituxan alone, so you are going to have to do
more treatments after this. If you want to go for a quick possibly
permanent fix in just a few visits, this isn't it.
It is unknown if
starting with R only reduces your chances for best effect compared to
CPR as an initial treatment, but Advani thinks probably not. However, if
you want to be super safe, you should assume that your best shot is your
first shot; for example, see the story of Sharon below where R-CVP
worked for 18 months then everything stopped working.
You risk the biggest R flare using R alone. CPR has less flare and
V+R has even lower IgM flare risk (and lower flares if they do occur).
For 4 cycles, there is 27% partial response (>50% igm decrease). For
4+4, it is 40% to 45% PR.
There are never any CRs.
longest mean was 16 months (Dimopoulos) per Table 7 in Merlini, Treon
R + V (clinical trial)
Ghobrial favors this approach. Her reasoning is that it has minimal side
effects, but about the same success numbers as CPR. So the benefits are
the same as CPR, but the strain on your body is minimal and confined
pretty much to a low risk of PN that appears to be both temporary and
reversible. On her clinical trial, the amount of PN was minimal and it
was all reversible. Chance of R flare is minimal and if there is one,
it's relatively small.
You can join the clinical trial at DFCI and
help add to the knowledge of this disease.
People have reported great efficacy with Velcade alone and there is a
synergistic effect with Rituxan.
Others claim that in test results in other lymphomas, Velcade even once
a week can cause significant PN. Some people never experience PN with
Velcade, even at 2X/week dosage over 4 years. If you start experiencing
PN with Velcade, my opinion is you should stop immediately. Guy Sherwood
tried to be a hero since he was getting great numbers with Velcade on
Treon's trial, but later regretted his toughing out the PN during
treatment; after treatment stopped, he suffered through 18 months of
excruciatingly painful PN.
There is less data on R + V than on CPR.
Unlike with Rituxan, there are reports that the gains you make while
on V disappear pretty rapidly after you stop taking it.
R + V (custom)
Should produce a better benefit than R alone, but since there are only 4
V doses, the PN should be minimal if at all. So this should be better
than R alone, with no additional side effects.
Very hard to find a physician who will allow you to design your own
treatment protocol, not matter how logical it is.
Note: That is too bad in my opinion because each patient is different
in their response and each of us have a different risk-reward metric. It
would be nice if medicine can be tailored to our individual responses
rather than applied cookie cutter style to all patients, but I can also
understand why this isn't done (because docs shouldn't experiment on
patients outside of clinical trials and stick to proven regimens).
All three doctors are right. We don't know enough to predict in advance for a
particular patient, which is the "best" course of treatment. They are all good
choices and I respect their reasoning. Reading it over, it is indeed very hard
to pick a winner as all three doctors make an excellent case. But I'm glad I
have 4 great options to choose from!
Also, whatever I choose, I'm going to try to persuade my doctors that taking
20mg simvastatin a day cannot hurt and has the potential to slow or even reduce
my disease. The reason for this is that in my opinion, it is much much better to
keep the disease "in check" while it is relatively small, rather than allow it
grow to be huge.
When IgMs get to be really huge, your options and time get limited very
example, Sharon, who is the same age I am, reports the following:
Dx Feb 2003. Age 51. Treatment R-CVP rendered good results for 18
3/06 Rituxan alone no response, 5/06-10/06 R-CVP no response, 12/06
Gleevec no response, 2/07-6/07 Velcade/Rituxin with partial response but had
Terrible pn, 7/07-9/07 Campath no response, 10/07-11/07 Etopiside,
Matulane, Cyclophosphamide and Prednisone with no response, 11/07-present
Pentostatin, Cytoxin with Rituxin just finished 2nd round.
Latest blood test (12/3) shows things are still haywire. Total protein
6.8, Platelets 7, IGM 9060. CBC low. Current receiving weekly
red blood cell transfusions. Apheresis knocks IGM down to around 4000
jumps back up with in a week. Neulasta following PCR and Aranesp every
Here are some other options that have worked for people:
- Vicki: I'm Vicki (54) from Oregon.... I don't post very often...
I'm mostly a lurker..... anyway, I believe you are right on with starting
that way. I pulled my records from when I started treatment, I started with
Rituxan for 6 months and got no real result until I started CPR month 7 into
- Judy: I also debated for a long time as to what to take for the
initial treatment. I saw Dr. Treon, had one PP and then only rituxin. I am
very glad I only did rituxin. So far it has done well for me. I was
diagnosed in 2002 and first treated in 2005 with IGM at 4000 and 4
viscosity. I have had 3 rounds of 4 rituxins per round. Am on my fourth
right now. Hopefully it will work again. Medicated with one prednisone night
before. Zantac, tylenol, hydrocortisone, benadryl before rituxin - drip only
goes up to 150 speed. I get some flushing, little chills and some fever the
next day and some up tightness from the steroids. I take zyrtec, more home
benadryl and tylenol and that usually works. Each round I have gotten about
a year of good remission. No PN, no hair loss, no nausea, no bad effects. My
IGM gets down in the 1900 to 2000+ range. I get treated at 3000 IGM. I would
not choose chemo as my first option - you can always have that later.
Rituxin is the least damaging that I can see. If you are anemic, procrit in
moderation. I have been able to do most everything. Good luck with your
decision and I wish you the best.
- Ann: Just returned from my appt. and my doctor, who is head of
oncology at Kaiser-Fresno, reviewed (briefly!) the info regarding treatment.
He suggested I let you know what he has been using with much success:
Pentostatin 4 mg/mt + Rituxan 375 mg/mz every 2 wks x 12 courses. (Note:
can't really make out the writing after the slashes (mt...? and mz...?...he
said "squared"...?). It's way over my head...sorry. Hope it makes sense to
- Fionna: My physician suggested Fludarabine - arguing that if 2CdA
had worked in the past, Fludarabine was likely to suit me - but it could be
taken in pill form with no need to be in- - or even out- - patient this
time. However, he also persuaded me to add Cyclophospharmide to the mix.
Between February and August of 2005 I had 7 rounds of Fludarabine (80mgs for
3 days) to which Cyclo was added for the last three rounds(5,000mgs for 3
days) - all taken as pills. Shingles threatened once again, but was quickly
brought under control. Apart from that, no hair loss, no loss of taste,
but, above all, my numbers have continued to go in the right direction.
- Larry: at age 56 i had similar numbers .. asymptomatic except for
my anemia... my course of action was 2cda followed later with rituxan...
have had a four plus year of hibernation with great numbers... because of a
rare condition associated with my wm called fanconi... i just completed 4X
rituxan hoping for at least three plus good years of hibernation.. just wish
i had saved my stem cells before treatment.. as i am having trouble
retrieving them now... will try again this spring at mayo.. good luck with
your decision... in the end you are your own conductor..larry
- Mitch: dx 12/02 with 4,000 IgM, 2.5 SV. Asymptomatic. 9,010 IgM,
6.7 SV, 10.5 HgB by spring of 04 I have always attitudinally been
treatment-reluctant Treatment: solo-Fludarabine, July through December 2004:
[5 infusions/week followed by three weeks off] x 6. Very easy to take.
Results: IgM 3,500, which has held steady since...2.0 SV...13 HgB, which has
declined to 8.6 in last 5 months. Nerw symptoms: drenching night sweats,
some fatigue, though still aim for daily aerobic exercise on rowing machine.
Treatment: Chromagen--iron replacement. My oncologist, John P. Leonard of
Cornell-Weill, believes the HgB decline is secondary to WM.
- Michel (from France): I am 52 years old, male with WM dx in
december 2006. My number are all correct exept IGM 3860. I was on
clhorambucil for 3 months and now I take RFC treatment. Rituxan,
Fludarabine, Endoxan (cyclophosphamide) with Bactrim and Zelitrex versus
side effects. I had 3 cure in september, october and november. I will have 3
more in decembre (tomorrow) , january and february. I saw your link for your
options therapies. The RFC treatment is not on your list. If you need some
infos about this treatment, just let me know, if I can help you for
anything. Sorry for my poor english Michel Avignon Diagnostiqué maladie de
Waldenström :12/06 (âge 51) IGM = 38,6 g/L Traitem. 01/07 : chloraminophène
(3 mois) - pas de résultat Traitem. 09/07 : Rituxan Fludarabine
Cyclophosphamide (en cours pour 6 mois) - résultat vers mi février 2008
- John: I was diagnosed in 1995 age 49 with low Hgb 9.9 eye
involvement and SV at 5,I have taken 2 rounds of Chlorambucil the last
treatment 3 years ago and numbers still OK Hgb 15.7.
- Sharon: You asked about numbers prior to R-CVP. Hgb was 12, Hct
was 34, Igm was 8140, Visc was 4.2, Total Protein was 12.4. I had 7 rounds
of the R-CVP and at the end my numbers were Hgb 8.7, Hct 23.9, Igm 7880,
Visc 3.3, Total protein 12. I had apheresis prior to 4 of the infusions to
help with viscosity and Igm levels. I started with Velcade twice a week but
was changed to one a week due to the pn. During the severe pn my legs were
numb up to my knees and I had trouble lifting my legs to walk and a hard
time sleeping due to the aching. The pn is better now but it never went
away. Treon recommended Gleevac but I had no response. After talks with Dana
Farber, University of Michigan (my onc) and Mayo in Rochester the condenses
was Penostatin, Cytoxin and Rituxin. I haven't tried perifonsine or rad001
but will ask about it. Another PP Friday followed by packed red blood cells
- Robyn: If I did CPR which is what I will do as the next step when
I need it, I would have my bone marrow tested by Rational Therapeutics.
- John: I am now 66 years old. I live in Minneapolis. Diagnosed in
2001. I had two treatments (2002 and 2005) of Rituxan only with some
response. In 2006 my HgB went down to 9 and IgM to 9500, BMB showed 90%
involvement. I had no other symptoms. Mayo recommended R-CVP and I had six
rounds from Nov '06 to April '07. Minimal side effects. No hair loss, no
nausea, no PN. Some loss of appetite and insomnia from prednisone. Most
recent blood test shows HgB 15.3, IgM 2500, Neutrophils 1900. I did have low
WBC and neutrophil count during the treatments. I feel great and am now
working on Scuba certification. Let me know if you need further info.
- JMT: I was diagnosed in December 2002. My first oncologist did a
bmb that showed 99%bone marrow infiltration. He said he didn't think there
was anything he could really do and that I should go home and attend to my
matters. That caught my attention as he was the head of the department and
very experienced. He referred me to another oncologist who doubted the % of
bm infiltration. To his surprise the second bmb came in at 88%. Hg 100 (and
dropping) IgM 2300 (and rising) relatively significant pn in feet. Platelets
low and dropping, IgG low and dropping, SV slightly elevated at 2.5 and
rising I wanted the disease carpet bombed with the strongest chemo possible
( I had just lost my wife of 28 years four weeks before my diagnosis. I had
watch her breast cancer destroy her a neuron at a time over a two year
period and knew first hand the potential savagery of cancer). At the time,
2002, a change was occurring in cancer treatment. The traditional methods of
treating virtually all cancers - high dose, high volume and very strong -
chemo agents was being revised by some doctors of patients with NHL -
particularly indolent forms. My oncologist (also a hematologist and medical
professor) was one such doctor. He told me he was going to try a combination
of drugs at lower dosages to achieve a synergistic response. He hoped to buy
me a year or two but would not make any promises. I received a combination
of Cytoxan and Fludarabine. He would have added Rituxan, but it was not
approved as a first time treatment in 2002. Over the course of six rounds at
three days per month my bmb % of infiltration decreased to10%, while my cbcs
rose: Hg 160 , Igm 200 others near normal. In 2006 my numbers began to
change again albeit slightly. Therefore, I had Rituxan X 4 @ 1/week in July
and again in September. In 2007 I had Rituxan at 1/month Q 3 months. My
numbers are presently good and stable Hg 155+ range, IgM 300 other cbcs
normal range. Therefore I believe in lower dosages of combination drugs to
promote synergy and avoid provoking an indolent disease into transformation.
My second oncologist's novel, at the time, treatment is now widely used.
- Jerry: -I'm surprised that you didn't consult Dr. Gertz of the
Mayo clinic in Minnisota. He and Dr. Treon are our two "mavens", in my
opinion. . He and Dr. Kyle, (also from the Mayo), might have recommended
chlorambucil as your first line treatment, (as would many European doctors).
I've taken it twice, for 10 and 15 months. I just swollowed pills with a
glass of water and had no side effect whatever. My first remission lasted
two years and I'm now in the eleventh month of my second remission, feeling
well, with improving blood counts.. For me, W.M. is a chronic illness..Thus.
I prefer to keep it in check with the least damaging drug. According to Dr.
Tom Hoffmann, there is no complete remission for W.M. (According to Dr.
Treon, this also applies to persons who have received a stem cell
transplant). When I again require treatment, I'll chose rituxan alone,
repeating it as needed, until a better relatively non-damaging.drug appears.
It appears that most WM'ers die from either the side effects of their
treatments, or age related ilnesses..I took 8 gms.daily, (four pills), which
was based upon my weight.When my WBC count went below 2.0, or my neutrofils
below 1.0, treatment was discontinued for a few weeks to permit them to
recover, (which they did). During my second period with chlorambucil, I
alternated between 6 and 8 gms daily in order to better tolerate the effect
upon my WBC and neutrafils. (My platelet count was not affected by the
treatment). Being a relatively mild drug, chlorambucil is slow acting. My
Igm was 6150 in August 2005, when I began the treatment. .In November, it
was 5590. Therafter, it continued to gradually decline. In January, 2007
when I discontinued treatment it was 2440. in October, my last bloodtest, it
was 1780. My Hgb. in August 2005 was 10.7.In February, 2006, 11.6., in May
12.6 , July, 13.7 My blood viscosity in August, 2005 was 4.1, in September,
3.7., May, 2006, 3.1, Nov. 2006, 1.7, Sept. 2007, 1.8. According to Dr.
Gertz, one must allow up to 6 months, for a response. I've observed, on the
talklist, that many gave up after several months.I had to convince my
oncologists to continue, (showing them what Dr. Gertz wrote). I hope this is
helpful. Please feel free in ask any additional questions. Again, I
appreciate your active interest in understanding this rare and strange
- David: Your analysis of the 4 options is interesting. You should
probably take whatever suits you best as they all look OK. I think it's
unlikely you will get a complete response but any one of them should get at
least a decent partial response. I had IgM, HGM and viscosity numbers quite
close to yours (but I am 25 years older). I took light doses of daily oral
chlorambucil and prednisone for 18 months, with the result of a 75% response
and no side effects. I have been w&w for a year. I was taking 4 mg's of
chlorambucil and 10 mg's of prednisone daily. A problem for a younger person
like you in taking any chemicals like chlorambucil would be the negative
effect on future stem cell transplants.
- Betty: I had R + CVP then cut the vincristine in half. Probably
could have done without the V. Anyway, I'm sure you are making the best
choice! As I said before, this is what I did and when it came to R CVP and R
CHOP, CVP meant I could continue on with life as usual (pretty much,
anyway). The first treatment is the hardest. Mine was, but I had very little
side effects from the get go. The reason my first treatment was the hardest
was because I actually had pneumonia and didn't even know it. No hair loss
and every month I felt better because everything improved. I even went on a
ski trip half way through. I agree about getting it right the first time and
I wasn't too thrilled about the toxicity of doxyrubin. I wanted the most
bang for my buck without taking too hard of a hit... and that meant R cvp.
And, I have never looked back. I'll be thinking about you on Thursday. Dress
in layers. You might feel hot or you might feel cold. After my first
treatment, my husband and I went out for lunch!! I kept wondering when I was
going to 'feel' it!
- Bill: For what it is worth, I had CVP-R and even with the
Vincristine added to the mix, I didn't lose any hair. According to my
doctors and the nurses (and as noted by Paul), folks with CVP-R often keep
their hair. Doxorubicin (in CHOP) is what really gets you.
I scheduled my doses for a Friday, and although I would feel a bit lousy
over the weekend, I didn't miss any work (actually the worst time is about 4
or 5 days after treatment). One modification that my doctors and I agreed on
was a 14 day cycle rather than a 21 day cycle, which got me done sooner and
might (no controlled studies) increase the effectiveness. I am about your
age and in good shape, so I am not sure a 14 day cycle is for everyone, and
it means less time feeling "normal" (which takes a while after each round),
but it was nice to be done in 12 weeks rather than 18 (the whole course of
chemo is a little like beating your head against a wall -- it feels so nice
when you stop).
I was IgM 3900 at treatment with Hg 9.7 (the real frustration, as my
recreation is running). I finished treatment in August, IgM is now around
1,000, Hg is up to 13.5, and I ran a half-marathon at Thanksgiving. For what
it is worth, I decided on CVP-R rather than a more conservative route
because I decided that I wanted to hit the WM hard and try to return to full
function as quickly as possible, even if it meant that I would have fewer
"silver bullets" on remission. In bluntest terms, I wanted to be able to
work and exercise at full capacity even if it meant a shorter lifespan,
rather than live longer with constant limits. I put it that boldly because I
think everyone needs to make their own choice, and I think it is entirely
rational (maybe even more rational) to take treatment very slowly,
escalating to more drastic measures only if the early measures prove
- Jacob: I was diagnosed 6 years ago when I was discovered to have
a mild anemia. In the initial workup my internist made the diagnosis of WM,
but also found a slightly low testosterone level. My IgM was 550 and my
Hemoglobin was around 13. After 2 years with WM, my hemoglobin had dropped a
bit to 11.5, and I asked my oncologist and internist about hormone
replacement. This was primarily because one of the side effects of
testosterone is to boost red cell production in the bone marrow (which was
30-40% involved with WM cells at diagnosis). So I started Androgel. Not only
did my hemoglobin go up into the normal range, but my IgM dropped from 670
down to 420. My oncologist at Mayo is still trying to figure out why. He
thinks it is either an effect on the Bcl protein or on the mast cells in the
bone marrow. (he wrote it up as a case report, and I can send you the
reference if you are interested)
- David H.: My husband David was dx with WM in Sept, 2005 at the
age of 45, with Igm of 7500, Sv 2.9, and Hemoglobin around 10. Bone marrow
After consulting a local hemo/onc, then the head of Northwestern's Cancer
Center (Chicago), a doc at Mayo, and Ghobrial, he had Rituxan x8. Got the
flare, plus massive migraines (to the point of ER visits plus a spinal tap),
but no response.
Went back to Ghobrial, then did the Velcade/Rituxan 2x/week. Completed 1
cycle, got bad PN, IgM declined 35%, but quickly rebounded. PN eventually
resolved after several months with Cymbalta.
Did 3 rounds of CVP-R, no response. Then 2 rounds of CHOP, no response.
Thought about harvesting stem cells, since Fludarabine or Cladribine
seemed the next logical step. Went back to Mayo to confirm plan.
Harvested stem cells at Northwestern in May 2007.
Consulted with Dimopoulos in Greece in August 2007. He didn't think that
Fludarabine would work for David (30-40% chance, he said), and that he has
seen too many patients who have taken it become permanently immuno-
suppressed. Strongly suggested David proceed with stem-cell transplant.
First doctor to really express a strong opinion on a treatment. Up to now,
all of the docs have presented options and maybe mildly favored one
treatment over another. Dimopoulos transplant gives the best option for long
Saw local hemo/onc last week, and going to Northwestern on Tuesday to
discuss having autologous stem-cell transplant in January. Numbers have
remained the same.
Good luck on your decision. I sure wish we knew which treatments would
work ahead of time. That would have saved David a lot of treatment, not to
mention losing his hair twice (CHOP and stem-cell harvest chemo)!
- Ray: Well, I didn't want to get into this conversation about
Rituxan maintenance again (there's plenty in archives) but since you ask I
can only say that it's been effective for me. I am one of the success
stories- I've had 12 Rituxan solo (with benadryl and tylenol only) infusions
since 2002 beginning with treatment (X4)in 2002; re-treatment (X4) in 2005 (
with a 32 month time frame before re-treatment) and 4 R maintenance
infusions. My physican/oncologist has stated that he has not seen refraction
in his practice. I'm feeling great, am excersizing again and doing very
well. I attribute it all to Rituxan maintenance. I'm sure there are others
who can say the same.
Here is some advice I got:
- Maureen: I am glad you got your dilated eye examination. I assume
from your note your had a peripheral retina hemorrhage. These can only be
seen by a dilated examination and this is why I encourage people on the list
to have one. Just be careful whatever treatment you do to watch that your
iGm does not go too high because you could trigger a major bleed in one or
both eyes. One thing I did not get into before and that many
ophthalmologist are not aware is that you can also get maculopathy similar
to a central serous with WM. One dentist on the list whom I reviewed his
record has pertinent loss of vision of the maculopathy in the range of 20/70
and can no longer practice. Good luck on your decision. Personally high IGm
was not an issue. My rituxan flare was from 394 to 675 (post Rituxan). I had
also done Iv iron before my diagnosis.
- Penni: Hi Steve, Starting treatment is a big hurdle and I wish
you the very best, and, of course, the very best possible results. You may
well have some nausea and some sleeplessness. You have so much energy, I
wonder how you tolerate the extra energy dose of steroids! In any case, if
you drink coffee, as I do, and are nauseous, as I was, you may get a
horrible headache from caffeine withdrawal. So here's my antidote that
sounds terrible, probably to anyone not nauseous: flat, room temperature
- Michael: Tips for chemotherapy: drink plenty of water before, to
pump up your veins to make easy to insert the line; make sure to ask for as
much anti-nausea medication as possible, which is administered before the
treatment; take a book on tape; take something to eat, because you can get
hungry; at the first sign of chills or shaking, call the nurse, because you
could be having a reaction to the Rituxan (this happened to me two or three
times and is most likely to happen on the first injection); take some eye
shades of the type distributed on airliners so that you can sleep (I usually
dozed off at some point.)
never take Prednisone on an empty stomach!
What I decided
- At ASH, there was talk that physicians should "get it right the first
time." That means, your best "shot" is your first shot. In other words,
doing R first, then CPR later might not produce as good a result as CPR
first. Nobody knows. It is safest to assume that the speaker is correct.
When in doubt, that would be the most conservative approach.
- There really seems to be no downside to CPR. Sure, there are more drugs
and thus additional risk, but the side effects of CPR seem very well
tolerated (e.g., most people never lose their hair) and the downstream risk
appears to be small as far as we know. But the upside is dramatically
different with CPR with a 80% partial response rate and up to 20% that will
get CRs (compared to 45% PRR and 0% CR for Rituxan only).
- NOTE ON STATINS: it is a bad idea to take statins within the
first 30 days after a ritxan infusion. There was a paper at the 2007 ASH
that suggested it reduces the capacity for Rituxan to bind to CD-20.
- Therefore, on an effectiveness point of view, CPR is clearly superior.
And from a downside point of view, CPR seems pretty negligible. So it's the
- Also, Treon said to do 3X PP before therapy. Why not 2X? The answer is
that a PP will get 50% of circulating IgM but 20% to 30% isn't (see
Treatment for Waldenstrom's macroglobulinemia). Therefore, you are
removing 35% to 40% of your total IgM on each PP. So after 3 PPs, you should be
down at least 72% from your original level. What happens typically is your
IgM should go from 4000 to 2000 immediately after PP, and then be at,
say 2500 before next PP, down to 1250 after the second one, etc ... Well it
turns out that was wrong. I was down to SV 1.6 after 2 PP's and the third PP
- December 18, less than a week after the first CPR. I'm running a
fever of 101.2 and my red blood cells and hgb and hct are very low. Going in
for 2 units of red blood. My mouth is dry, my tongue is chewed up by chemo.
Research I did shows pretty consistent evidence of permanent brain "slow
down" as well as permanent alteration of taste (especially for wine). And who knows what else? I
had never assumed I'd also have the risk of a blood infusion too. My
original assumptions were wrong. The more treatments, the more the side
effects. I've re-considered my decision and I'm now going to start with
targeted therapies and see how they go. If they don't work, I'll try other
targeted agents. Mass attacks where everything is destroyed (chemo) should
be a last resort if the surgical strikes fail. After all, if I can get the
disease under control with a targeted therapy, what's the point in the
risking therapy with additional risks. In WM, it is more often other things
that kill us, because we've weakened our bodies from the chemo treatments to
get the WM. There is some evidence that chemo therapy patient age 10 years
over the course of a year.
- If I get a good response, I'll try to keep it from getting worse either
via statin or perifosine or preferably Rituxan (a regular dose every
3 months at a slow infusion rate is proven by the Patient from Hell to keep
your B cell counts in your circulating blood to near zero) or something else. The
idea is to find something that keeps things from getting worse as soon as I
get my peak response and not waste a lot of time doing that. After all the
needles, pills are nice! There is some thinking that low-dose more frequent
administration of existing drugs may be a lot more effective than slamming
the patient with near toxic doses at discrete times, e.g., one rituxan a
month instead of 4X and then wait till progression. For example, a paper at
the 2007 ASH conference reported that reducing the standard dose of
Dexamethasone significantly improved the duration and effectiveness of this
Comments on my decision
- Brian: If I were at your position it would be my choice as well. I was
very sick at diagnosis (age 42) and so opted for PP + 2Cda, Cytoxin and
Rituxin which turned out to be a very good combination for me (it was
experimental at the time and I had to sign multiple wavers). I got about 7
years off and then had to repeat. Being mentally ready is as, if not more,
important than the physical aspect. You'll do great. Good luck. As a p.s. I
am in the minority of people who found cytoxin actually stimulating (akin to
very mild amphetamine). I confess to enjoying the effect although drinking
large amounts of fluids while taking it was a drawback :)
- Ron: Unless you have some rare first time allergy, you will love
CPR. For me it has been a gift that keeps on giving. I slept through
infusions 2 thru 6, once the diphenhydramine hit, and while my first two
month drop was only 400 points to 1850, over the last ten months I've gone
steadily down to 1350. I'm seriously looking at statin trial, expecting
clearance from my hematologist when I get home from FL. It is my cholesterol
that is high, and any IgM reduction would be a bonus CPR is cheap, too --
being on SSDI, I paid only $400 for "supplies." If you are self insured, I
have no idea. Blessings. Be glad and confident now your decision is made!
- Geta: I have just started the same treatment that Treon has
recommended for you. I had plasmapheresis 2x on Wed. and Thurs. of last
week and CPR on Friday. Pleased to say I had no side effects and am feeling
fine. Treon is my consulting doctor while I am receiving treatment down in
Florida for the winter. I am really a Michigander. Good luck. It sounds
like a good protocol to me. If you have any questions about my stats or
anything, please ask. I read all your comments with interest.
- Dan: Cytoxan/Prednisone/Rituxan. this a well used treatment with
an alkylater, a steroid and a monoclonal antibody. I think this is a good
enough choice and you were right about the first treatment giving you the
best and longest response. You may want to ask the onc for a prescription to
Ativan to take at bedtime to counteract the Prednisone side effect of not
letting you fall off to sleep.
- Robyn: Good luck Steve. I think it is a great choice and one that
I will choose the next time I need treatment. I kind of wish I did it when I
first chose Rituxan alone..but I am responding to the Rituxan now. But next
time, it is the big guns!
- Rinat: I was diagnosed in August with IgM 9200 Hgb 8.1 and total
protein 10.5. Symptoms: fatigue, dizziness, blurred vision and nose
bleedings. The treatment choice was CVP-R. My doc decided not to give me the
regular dose of the Cyclophospharmide (1000/m2) but a lower dosage of 750/m2
because of the chance of developing a different kind of cancer in the future
(one of the side effects of C). After the 3rd treatment my IgM was down to
3900 and Hgb up to 10.0 she decided to reduced the Vincristine by 50%. After
the 5th treatment IgM is down to 1900, Hgb up to 11.7. Now, after the 6th
treatment she is considering to stop the chemo and continue only with the
Rituximab. She is not sure and didn't give me a final answer yet. I know she
will consult with Dr. Treon about my case. Here in Israel they don't have
much experience with WM. As to side effects, the first two treatments are
the worse: headaches, extreme weakness and light nausea for 2 days. After
that it gets a bit better with every treatment. After the first 3 treatments
I needed Neupogen but after that your bone marrow gets "clean" of the
cancerous cells and able to recover by itself. As to hair loss, from the
beginning my doc said there's only 30% chance for it. I didn't lose
completely my hair although my hair thinned. As I see it, the main problem
is the side effects of 100 mg of Prednisone: insomnia (sleeping pills help),
weight gain, nervousness (my husband suffers this one...), and swelling of
the stomach (never take Prednisone on an empty stomach!)
In the beginning my doc defined this treatment as "light chemo" and I
think she is right. Although all of the above it's bearable and the positive
blood test results give you strength to continue with the chemo.
- Peter: Given your condition and the options available to
you...I'd probably opt for the same thing. Just make sure they give you the
appropriate "ancillary" meds to counter any problems with the treatment
process (infections, rituxan reactions, etc.).
I was treated at age 43 first with 2CDA (no effect) then a few months
later with FCR (at the time - in 2005 - it was still felt that FCR was a
good approach to take).
Didn't have tremendous hair loss with FCR (had some but it was more a
thinning that a loss)....and most days, I was able to drive the hour to the
hospital and then drive home afterwards, although they counsel against doing
Will you have a port, or will your treatments be via IV/pill? If going
for IV, always make sure that the nurse/phlebotomist knows what they're
doing when they stick you - I've had some wonderful adventures with them. If
you're not comfortable with the nurse doing it - ask for the IV team .
You'll come to know right away from their behavior whether they know what
And make sure they follow the rituxan flow process correctly. At the
slightest hint of flushing of face/neck, etc get to the nurses and have them
stop and start slowly again - even if it has to take many more hours....I
didn't have a reaction during my first infusion, but did on my second, and
did not on any other infusions - go figure! (again, we're all different in
our tolerance of treatments).
Make sure to keep an eye out for any odd feelings you may have throughout
the process...I also somehow came down with a urinary tract infection - I
began to urinate fairly frequently, but thought nothing of it until the urge
to urinate became trememdous during my hour drive to the hospital (made even
worse by the fact that I noticed every drop of rain that was falling, every
person drinking from water bottles on the sidewalks, every dog urinating on
a fire hydrant....) - a quick dose of antibiotics took care of it in short
order. Bottom line - don't hesitate to discuss all the odd aches and
Also, even though you shouldn't see dramatic results immediately - make
sure to ask the nurses for copies of the lab reports (at my hospital they
generally don't give them to you unless you ask), so you can track your
progress and be better prepared to ask the doctor some pointed questions as
time goes on.
Dave: Steve, I don't know enough about your situation to "pick a
drug", but chlorambucil's best use is for older patients with mild
symptoms that do not need immediate attention. In younger WM, the risk
is that some future date will show damage to the DNA as a result of the
prior use- like me 20 years later. The CP-R or CHOP- R regimens give a
high rate of remission with little major damage and gives a young person
the later option of a stem cell transplant - freezing stem cells for
later "reset" option.
Jerry's advice is fine for the typical older patient of 65+ years, the
CPR better advice for a younger WM which I must have assumed that you
were. Of course, I have assumed a lot here! Always bad! The Velcade
option has been effective while in use, but there is not enough evidence
to show that it can be successfully discontinued, and the effects can be
brutal. I would save that option until it has been better refined in WM
because of the fine options that have been shown to be successful in WM
now in use.
We often try to jump to the newest and "hottest" new drugs prior to
gaining the best use of existing drugs and treatments. Hope this
helps! Just finished a rapid infusion Rituxan, and am seeing good
results so far! Plain vanilla! Hope you are well!
- Don: My first line treatment was PP (18 times in 4 months) with
Rituxan/Fludara in April 2002 for 4 months (one Rituxan per month with 5
days of Fludara) and added Cytoxan later for months 5 and 6. At that time
most popular first line treatment was deciding between Ritux/Flud or Rituxan
and Cladribine. It wasn't until I added the Cytoxan that my hyperviscosity
stopped with my viscosity staying under 4.0 - never had a PP since. I will
never know for sure if Cytoxan/Ritux would have done the trick alone with a
little Prednisone added. My numbers didn't start coming down dramatically
until Christmas 2002 when the doctor and I decided to added Dexamethasone
(strong steriod) to my low dose Thalidomide protocol. I felt that the
residual Rituxan and Dex were key drugs for me or maybe it was just a
Christmas blessing?? Be a patient patient! Sounds to me that you are making
a wise decision with many unknowns after considering many options. I will
add you to my prayer list.
- Mike: DX 1985 Chlorambucil (10 years), CHOP, COP plus Vinblastine,
Phase 3 trialist Fludara and Rituxan combo (3.25 yrs remission), Rituxan x3
cycles 2 plus years remission each time Very fit and well play 3-5 sets
competitive doubles twice or more per week You and your oncologists no doubt
discounted Fludara/Rituxan combo--its still possible to do stem cell harvest
after Fludara ,and this combo is not really first line treatment It would be
the aim to get it right first shot ,and Steve Treon is the expert in this
field and we seem to be different responders ,WM being a fairly unique
orphan lymphoma 3xpp first --logical Best to go chemo route first probably
and certainly from my personal "anecdotal "experience CPR--- good choice---
hopefully it will be successful and I wish you well and that you get a great
response and a long /complete remission which is what we all deserve Stay
Waldenstrom's macroglobulinemia: A new approach
Waldenstrom's macroglobulinemia: CPR treatment
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