Those Aches and Pains
The Effects of a Hidden Deficiency May be Wrongly
Blamed on CLL
This Topics Alert
Identifies an Available Fix for What Possibly Ails You
One of the common mistakes
we (and our doctors!) make is attributing everything that goes wrong to
CLL - such as muscle pains and the aches in our bones.
You could be suffering
from something that can be very easily corrected, a real cheap fix. Not
only does it not cost a lot, it is not even toxic (isn't that a welcome
change from the usual caveats with chemo drugs?), and it might even help
you fight the CLL. But don't do this without medical supervision. What
is this drug? It is called vitamin D3. Read our Alert titled 'Those
Pesky Aches and Pains' for some interesting pointers.
Target Mitochondrion
Promising New Approaches Bypass the Usual Cellular
Control Points and May Level the Playing Field for Bucket C Patients
We Review New Research
Articles that Focus on Attacking Mitochondria in B-CLL Cells
Several recent research articles have
opened up exciting new opportunities in the treatment of CLL. These
feature new small molecule drugs that take an entirely different
approach to targeting CLL cells. In this new approach to treating CLL,
it seems to make no difference if you are IgVH mutated or unmutated,
CD38 positive or not, chemo-naïve or have been through the wars with
every chemotherapy drug known to man. In fact, there are some
indications that heavily pretreated and late Rai stage patients may
respond better to this approach.
To learn more, read 'Exciting
New Drugs on the Horizon'.
Arabella Gets Xcyted
A Case Study in CTL Therapy
A Volunteer Updates Her
Report as She Goes Through the Xcyte Therapies
Protocol
Our intrepid volunteer, Arabella, brings us
up-to-date through her second infusion of expanded T-cells as she
undergoes the cutting-edge
Xcyte Therapies, Inc. protocol, conducted at an anonymous Consortium
Cancer Center. In
Report 4
and
Report 5 she continues the narrative of this case study. If you would rather
start at the beginning, you may go straight to
the top.
ZAP-70 & IgVH Gene Mutation Status
Two Prognostic Indicators Worth Understanding
We Compare the Value of
These Indicators in Identifying a Patient's Risk Category
These two indicators, in combination with FISH
analysis to pinpoint the chromosomal aberration that is at the root of
the CLL, go a long way toward defining the risk category of a given
patient. In
ZAP-70
and IgVH Gene Mutation
we review the current research on the prognostic value of these
two important tests.
Rituxan + HDMP Clinical Trial Update
Correspondence with Dr. Thomas Kipps
Current Status of Trial -
Detailed Inclusion and Exclusion Criteria
We thank Dr. Kipps for responding to our query
regarding the status of this trial. You can read the correspondence in
Rituxan + HDMP Update.
AIHA: Auto-Immune Hemolytic Anemia
Important Insight
We Review the Causes and
Mechanisms of AIHA and Suggest Some Strategies to Deal with It
AIHA affects a significant part of the CLL
population, particularly those with advanced disease. Understanding the
causes of the disorder is critical to dealing with it. In
AIHA: Auto-Immune Hemolytic Anemia, we review the relevant research and make some
suggestions.
Monoclonal Redux
Campath plus Rituxan as Therapy
We Review the M. D.
Anderson Clinical Trial of the R+C Combination Protocol
These two potent monoclonal antibodies in CLL
treatment hold great promise by themselves and in combination with other
agents. The logical question of whether they work well together, or have
synergies in their method of action, are important ones to answer if we
are to make the best use of our options. In
immunotherapy, however, things are not always as they seem, as shown by
this clinical trial conducted by M. D. Anderson. Negative results, while
disappointing, still have value in our understanding of the disease and in
plotting treatment strategies.
Diagnosing Your Doctor
A Patient's Viewpoint
Why Patients Need to Be
Proactive: The Life You Save Could Be Your Own
Former newspaper reporter and editor David Arenson
analyses the weak points in many relationships between CLL patients and
their doctors and makes some constructive suggestions for improvement. In
his article titled "Diagnosing
Your Doctor" he identifies the qualities and approach he feels are
necessary on both sides for CLL patients and their doctors to develop interactive and effective relationships.
Familial CLL
Insight, Advances and Research
Tracking Down Clues in
Population Data
Dr. Tim Call is a
hematologist/oncologist at Mayo Clinic, Rochester, MN and an Assistant
Professor of Medicine at the Mayo Clinic College of Medicine. He has
done much important work in the area of familial CLL and lymphoma, and
is responsible for developing a database at Mayo Clinic on the
familial incidence of B-cell malignancies including CLL, B-cell
lymphomas and a few related diseases. You might recall his name as an
author on the Mayo Best Practices article -
Current Approach to Diagnosis and Management of CLL. More details
about him are provided in his official Mayo Clinic
profile. We are pleased that he has written this article,
Familial CLL, addressed to the patient community. We strongly encourage that our readers
register in one of the recommended databases when appropriate.
Rituxan plus Neupogen
Improving Efficacy and Reducing
Neutropenia
New
Information on Neupogen as Booster to Rituxan Monotherapy
In this article,
Neupogen
as Booster to Rituxan Monotherapy, we discuss one method of
getting maximum mileage from Rituxan monotherapy. First we
examine the impressive results of a major Phase 3 study from
Amgen on the use of G-CSF (Neupogen) in moderately
myelosuppressive (breast) cancer therapy, in which the authors
conclude their logic would hold for any cancer therapy with the
risk of neutropenia. We also cover a wide range of abstracts
that point to the important role played by neutrophils in
the depth and duration of remissions produced by Rituxan in CLL
and in the avoidance of resistance to Rituxan therapy. We also
discuss the risks involved and conclude with a plea for the
rapid publication of critical results from clinical trials.
FluCam 106
Combination Therapy with
Fludarabine and Campath
Berlex Labs
Recruiting Participants for Phase 2 Multi-center Clinical Trial
Supervised by John Gribben
We report on our participation in a
Patient Advisory Board Meeting conducted by Berlex Laboratories,
US distributors for Campath and fludarabine.
FluCam 106 is a direct
head-to-head comparison between Campath + fludarabine versus the
better understood Rituxan + fludarabine therapy pioneered by Byrd,
et. al. Campath plus fludarabine is a powerful combination of
agents that has proven effective even in cases refractory to
fludarabine and Campath as single agents. This is an important
clinical trial and we examine the issues involved.
Project Alpha
Drum Rolls and Announcements
We Pass Two
Milestones
We have some important information
to report on our patient-sponsored clinical trial initiative,
Project Alpha. First, we have clearance to announce the agents
that will be used in the trial. Read
Project Alpha Milestones
to learn about the agents and the logic for using them. We also
finally hear from our favorite governmental agency, the IRS, on
our tax-exempt status.
Harvey's Saga
Maintaining a Remission; The
Dangers of Overmedication
An Update on the
Case of the RHK
Harvey, our Round Headed Kid, is
experiencing the benefits of a deep remission after going through
the "RHK protocol" three months ago. He is on an aggressive
regimen of medication, supplements and exercise, a program that he
and Serena negotiated with "Doc" to keep his remission going.
However, nothing is simple for our hero. In this update Harvey and
Serena find out from a blood test that it pays to be vigilant -
you will learn about the dangers of drug interaction and
overmedication in the Latest on
Harvey, the next installment of our continuing case study.
Vitamin D3
Essential for Health
Effective
Supplementation Can Help Fight Cancer
Vitamin D is a very potent
regulator of cellular biochemistry. We review the research
literature on the value of an adequate intake of Vitamin D3 in
maintaining general health and in fighting cancer. The literature
indicates that the officially recommended dosage (RDA) of the
vitamin is barely enough to avoid deficiency diseases and woefully
inadequate to provide the multiple health benefits available from
this supplement. However, any aggressive supplementation regimen
must be carefully monitored and medically supervised since high
dosages can lead to systemic toxicity (hypercalcemia) and even
death. Our review article, "Vitamin
D3: Essential for Health" explores the benefits, raises the
caution flags and explains how to benefit from the vitamin without
the risk of sun exposure.
Chemotherapy
NCI Develops Experimental Drug
Flavopiridol: a
Drug that May Save Lives
We review preclinical data and
early results from clinical trials with flavopiridol, an important
new experimental drug. Flavopiridol is being developed by Aventis Oncology in collaboration
with the National Cancer Institute. Its use is presently under
investigation for a variety of solid tumors as well as hematological cancers. It
offers the possibility of p53- and ATM-independent cell kill in CLL, thereby opening an important therapeutic path for
patients with poor-prognosis cytogenetics. While there are issues
related to the drug's toxicity, there is also hope that it could survive the early phase optimization trials to become a
major drug for the treatment of CLL. Read about the potential value and possible
drawbacks of this agent in "Flavopiridol:
a Drug that May Save Lives".
Therapy Choices
Fludarabine Monotherapy No Longer
the Gold Standard
Addition of
Rituxan Results in Longer Survival
We review two research papers that
have just been published in Blood online. The first, authored by a
panel of top CLL experts, presents persuasive data that a
combination of Rituxan and Fludarabine is superior to Fludarabine
monotherapy in both response rate and survival. The companion
paper, authored by researchers at the NCI, concludes that
Fludarabine monotherapy in CLL relies on a p53-dependent mechanism
for cell kill and that this therapy has the potential to
select for p53-mutant cells, leading to more aggressive and
resistant disease. These are very important conclusions that need
wide dissemination among patients and practicing oncologists.
Please read our article
Fludarabine Monotherapy No Longer the Gold Standard.
Harvey's Chocolates
The Round-Headed Kid Has a Sweet
Experience
Porting EGCG to
the System
We present one possible way of
improving the bioavailability of EGCG through oral and mucosal
absorption of the potent phytochemical. Read
Harvey's Chocolates to discover the formula, the sweetest way
yet to get the phytochemical into your system.
Campath Consolidation
German Clinical Trial Was
Terminated Early Due to an Unacceptable Incidence of Severe
Infections
Hitting a Home Run
Is Not Easy
Campath is a promising agent in CLL
(see our recent article
Campath - Looking Better and Better) but it does have
significant immunosuppressive effects. There is a great deal of
interest in using Campath as a cleanup agent after more
traditional chemotherapy or chemo-immunotherapy to eliminate
minimum residual disease (MRD). Recently published results from a
German CLL research group are revealing. The study was halted
early as the consequence of an unacceptably high level of severe
infections. We compare these results with those reported by M. D.
Anderson and comment on the possible sources of variance between
the two sets of clinical results in the article titled "Hitting
a Home Run with Campath Consolidation?".
New
Drug in Clinical Trial
Novel Application of a New
Anti-CD25 Immunotoxin Offers Prospects of Highly Targeted and
Effective Therapy
LMB-2 in Phase -II
Trial Sponsored by NCI
We report on the recently announced
clinical trial of a new immunotoxin, LMB-2, which shows
early promise in attacking CLL cells. The technology has great
potential if it is used in combination with immunomodulators such
as bacterial-DNA derived CpG-ODN to up-regulate CD25, improving
targeting of B-CLL cells. We discuss the background, results from
early trials and the potential for effective treatment with low
toxicity using this agent. Read about it in
LMB-2.
ASH Meeting
Notes
Patient's Eye View of the
Forty-fifth Annual Meeting and Exposition of the American Society
of Hematology
Review of Papers
and Presentations
Topics' volunteer Suzanne Burr
jumped at the chance to attend the annual ASH meeting. This is
entirely understandable given her experience as a medical
technologist with over twenty years background in hematology and
related fields. In this report, she provides us with synopses of a
number of papers that were presented at the meeting. Click here to
read her ASH Meeting Notes.
CLL
Complications
The Danger of Squamous Cell
Carcinoma in CLL Patients
Dying to Get a
Tan?
If you have CLL, you have a much
higher chance of getting squamous cell carcinoma (SCC), the
second most common skin cancer. Further, CLL patients who
contract this disease are more likely to have an aggressive form
of the disease. We examine some of the possible mechanisms for
the onset of this cancer and review a number of steps you can
take to protect yourself including a few things you can discuss
with your doctor that may help.
Click here to read "Dying
to Get a Tan?".
Making
Therapy Choices
Current Approach to Diagnosis and
Management of CLL
What You and
Your Oncologist Need to Know about CLL
We review and comment on an
important new paper from the Mayo Clinic Hematology Team.
Authors Shanafelt and Call provide an extremely useful review of
recent changes in diagnostic methods and risk assessment and
their therapeutic implications for various cytogenetic
sub-categories of CLL. This is a must-read paper for both you
and your local oncologist. Our editorial comment examines areas
in which they could have gone farther in their recommendations.
Click here to read "Need
to Know".
FISH-ing
for Answers
Chromosomal Aberrations Rule the
Game
A Review of the
Importance of Cytogenetics and Some Practical Information on
Getting Your FISH Test Done
We have previously discussed the
significance of various chromosomal
aberrations in the progression and treatment of CLL ("What
Type of CLL Do You Have?" and the case studies,
RHK-I and
RHK-II).
We now turn to what this implies to any CLL patient considering
his or her alternatives: watch-and-wait, chemotherapy,
immunotherapy, combinations, vaccines, etc. FISH (fluorescence
in-situ hybridization) testing can provide key information in
making these decisions. In "FISH-ing
for Answers" we provide some critical information that may
be useful in getting your very own FISH test done.
RHK- II
The Continuing Saga of Harvey,
the Round-headed Kid
An Update on How
the RHK Protocol Worked Out for Harvey; and Some New Choices He
Now Faces.
When Harvey learned that his
hitherto indolent CLL had evolved to include a 11q deletion, he
decided to learn what the bad news meant. Based on extensive
reading and with the help of a doctor who knew how to listen, he
came up with the RHK protocol. In this continuation of
our hypothetical case study, we follow Harvey's progress on the
protocol. Our hero's hard work produces great results but now he
and his doctor have to decide if and what additional treatment
will further reduce the remaining disease. You can read about
this sequel in "The
Continuing Saga of Harvey, the Round-headed Kid" or perhaps
you prefer to start at the beginning of the case study in "The
Difficult Case of the Round-headed Kid".
Journey of a
Newly Diagnosed CLL Patient
Application of Peter's Principles
A Patient Talks
About His Experience and the Lessons Learned
"Journey
of a Newly Diagnosed CLL Patient" is both a
personal narrative as well as a collection of important
principles directed at helping newly diagnosed patients. The
author, Peter Carpenter, is uniquely qualified to provide this
perspective. He is a patient who has gone through his own
battles to come to terms with the disease, armed with a
multifaceted background in the sciences and the medical research
arena. He provides insight on how things work in the practice of
medicine and some useful practical guidance in dealing with
important issues.
Familial CLL
Genetic Predisposition and
Anticipation
To Know or Not
to Know: That Is the Question
"Not
the Worst Day of Your Life" is a review of the
research findings on the familial aspects of CLL. It is well
documented that CLL strikes more than one person in some
families, there is clearly a predisposition to the disease that
has been passed on from one generation to the next in these
families. Some day, this type of research may prove to be the
key that unlocks the CLL puzzle. In addition the data show that
in families where the disease strikes several generations, the
children of a CLL patient are likely to be diagnosed with the
disease at an younger age compared to the parent. Finally, we
discuss some of the difficult issues involved in testing
children for potential problems down the road that may never
materialize.
Campath - Looking
Better and Better
Campath Proves Effective in Early Stage
and Difficult Cases
Experts Get
Better at Using the Anti-CD 52
Monoclonal
We review the current status of
research and clinical trials involving Campath-1H. This fully
humanized monoclonal antibody has been approved by the FDA
for use in relapsed CLL but current research reveals that it
could have critical application as a frontline therapy in a
subset of high risk cases. It is a powerful therapeutic agent
that is slowly finding wider applicability in early stage
patients. The techniques of administration have improved and so
have the techniques of managing the serious immune suppression
attendant to its use. Our review article,
Campath - Looking Better and Better, explores these and
other aspects of Campath therapy.
Idiotype Vaccine for CLL
Genitope Corporation May Be
Preparing Idiotype Vaccine Trial for CLL
We Look for
Answers at Advocacy Summit
The early promise of idiotype
vaccines has been long held back by the difficulties of applying
vaccine techniques to CLL. But our understanding of the science
and the capabilities of the vaccine production technology have
nevertheless made progress. Now Genitope Corporation may be in a
position to try this approach for CLL, leveraging off what has
been learned in their work with follicular lymphoma. Read about
idiotype vaccines, the difficulties in applying them to CLL, and
the possibility of a Genitope vaccine clinical trial in the
January 9 article, "An
Idiotype Vaccine for CLL?"
Combination Immunotherapy for a Difficult Case
The Round-Headed Kid May Finally
Get to Kick One Between the Goal Posts.
(With apologies and appreciation to Charles M. Schulz)
A Poor
Cytogenetic Aberration Is Not Necessarily a Guarantee of a Poor
Clinical Outcome -
but Choices Are Trickier.
Lucy may have never given Charlie Brown
that perfect opportunity to kick a field goal, but we give our
own round-headed hero, Harvey, a hand in figuring out what to do when he gets
some bad news on the cytogenetics front. Faced with a
11q
deletion event, our hero gets down to facing the facts and
grappling with some thorny questions. Read about Harvey's
problems and his approach to a solution. A long list of
abstracts points the way to a possible therapeutic strategy in
The Difficult Case of the Round-headed Kid.
New Agent in Clinical Trial
Autologous Bone Marrow
Transplants Could Achieve a Higher Success Rate if Adequate Stem
Cells Can be Harvested.
AMD3100: Use in
Stem Cell Mobilization for Transplants
The techniques of stem cell
transplantation have been improving over the years. AMD3100, a
new CXCR4 blocker originally developed for AIDS treatment, shows
promise in mobilizing stem cells for harvesting in both
autologous and allogeneic stem cell transplantation procedures.
Read about this new agent in the article,
AMD3100:
Use in Stem Cell Mobilization for Transplants.
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