This site is dedicated to providing information and support to patients and families dealing with chronic lymphocytic leukemia (CLL). It takes a clearly patient-oriented view of the world. The subject matter is focused on current developments in understanding and treating the disease.
Discussion topics include basic science, therapeutic approaches, clinical trials and analyses of the results of these trials. We are witnessing significant changes in our understanding of the processes involved and in the therapies available to combat the disease. It is hoped that the discussions in our articles will bridge the gap between the professional cancer research community and practicing oncologists on the one hand and patients and their families on the other.
The opinions and analyses presented are those of lay observers of the CLL scene and not those of medical or research professionals. They are not intended to provide clinical guidance or recommendations on the management of the disease. This site draws its strength from a team of dedicated volunteers. None of us has any affiliation with the medical or pharmaceutical industries. Our only interest is patient education and advocacy. We hope our website can help you understand your therapy options better and make you better prepared to discuss these options with your healthcare providers.
You may use the Contents page to review the material in this site organized by major subject area or use the customized site search form in the right column to get quickly to a specific topic of interest.
We welcome your comments about this website or your thoughts about any of the subjects discussed or referenced here. Please use the form on our Feedback page or send your email to us at .
Chaya & P. C. Venkat
CLL Topics.org was the online publication of a patient-operated, non-profit corporation, CLL Topics, Inc.
We have no affiliation with any entity in the health care industry and do not accept any advertising on our publication. Our operating expenses were funded entirely by CLL Topics, Inc. which derives all its revenues from donations from the public. The bulk of funds that were raised from our donors was devoted to supporting clinical trials for therapies in CLL. For details, please use links to financial statements and other corporate documents below.
Please refer to the About Us section on this website for background information on the CLL Topics Team.
Please do remember that the writers of the articles on CLLTopics.org are not medical professionals and do not provide medical advice or recommendations for treatment. Please consult and follow the advice of your own healthcare providers.
Chief Science Writer:
Editor, Publisher and Webmaster:
P. C. Venkat
Board of Directors:
L. Keith Friedlander
P. C. Venkat
Each member of our Board is a CLL patient or family member of a CLL patient. For short biographies of our Board members, please see the About Us page on this website.
According to Mayo
You can read an article about CLL Topics and its founders in the Spring 05 issue of Mayo Magazine: Information Empowers Leukemia Patients
the Wall Street Journal
The Journal, too, has had occasion to publish an article in which CLL Topics figured. You can read the March 2006 article by Journal reporter Rhonda Rundle at: Testing the Power of Green Tea.
the Washington Post
The Washington Post was not far behind in publishing an article in which CLL Topics received positive coverage. You can read read why their reporter says, "For the latest real news specific to the condition, I would find the best stuff on CLL Topics." Here is a link to the Post article, A 10-Year Checkup. If you find this link does not work, write to us and we will help you locate one that does.
Our Non-Discrimination Policy
We Support CLL Patients Everywhere - and Bar None
CLL Topics extends its services to and encourages participation in its activities by all individuals affected by Chronic Lymphocytic Leukemia. It does not discriminate on the basis of race, ethnicity, religion, age, size, national origin, citizenship, geographic location, language, gender, sexual orientation, socioeconomic background or mental or physical handicap. In fact, we are pleased to extend our services to any person who wishes to benefit from them.
An Open Invitation
Exercise Your Pen - or Keyboard
Your Opinion Counts
The CLL Topics Team is happy to hear from you. We value your willingness to share your knowledge, experience and concern for our community. The section titled "Patients' Corner" is intended to provide a forum for your opinions and insights. Of course, your articles can be published in any of the other sections if they fit better there. If you would like us to consider for publication an article you have written, please submit the document by email to the address shown below.
Don't forget to include your name and email address or phone number so that we can contact you if we have any questions. We will entertain full-length articles, announcements or snippets of information or commentary that may be of interest to our readers.
Help to Get the Most Out of This Site
It's Easier Than You Think
The sheer amount of information available on this site may be overwhelming at first. But appearances can be deceptive, especially in this case. Most people find that there are some easy ways of getting around the site, locating topics of interest, printing the material they want as hard copies, downloading material and solving technical problems as they arise. We have paid special attention to browser compatibility, accessibility and ease of use. Many of these subjects are covered in our Navigation Notes article.
Of course, we can always use your help to identify those areas which have still escaped our attention, or simply those that do not work right for you. Just write to us with a clear explanation of the problem and include the basic details of your computer set-up. It is entirely possible that someone else has run into your particular problem and we may already have an off-the-shelf solution. We do not promise to cure all the technical ills of the world wide web. We will, however, listen to your problems politely and at least try to make helpful suggestions. After all, we would like to make our work accessible to as many people as possible. That's why we started Topics in the first place.
The Contents page will provide you with links to all the main subject areas on this website dealing with the disease, its diagnosis, prognosis, therapies, clinical research and the societal aspects of coping with the disease and the medical establishment.
A CLL Primer is directed at newly diagnosed patients (or as a refresher for those desiring to get caught up quickly) and serves to orient the patient or caregiver and highlight some basic facts and considerations. A list of additional articles to read is suggested in Step 5.
You will find spreadsheet templates you can use to keep track of your clinical data in Your Charts.
Our Reference section has links to many important resources on the Web for patients seeking to expand their knowledge of the disease.
For those with a scholastic bent, the Textbooks section provides links to a collection of superb online textbooks that can provide an entire education.
The Search Tools page gives you access to professional search tools to locate abstracts and articles, search scientific databases, medical news and clinical trials.
Donations: Your generous support and encouragement have been terrific. You have indeed shown us that you think what we do is worthwhile. With your help we have exceeded our fundraising goals for the year. As of July 1, 2007 we are temporarily suspending our fundraising. This also happens to be the time when our editor, publisher, webmaster and record keeper is going into a chemoimmunotherapy treatment program - and suspending fundraising will enable us to concentrate our resources on running our publishing operation (this website and Topics Alert). Send us an email () if you would like to volunteer your time and skills to join us in the work of this organization.
Please do browse Current Articles and Contents to orient yourself to the resources available on this site. The material presented is based on serious, peer-reviewed articles in professionals and scientific journals, complete with references and links to source materials. However, we have made it a priority to simplify the language and clarify the communication to make it accessible to the lay reader. Most important, we offer critical review form the patient's point of view. We hope you will become familiar with the terminology, our style of presentation and the navigation of this website pretty quickly. If you do experience difficulty with any part of it, please send us your comments so that we may improve this website. You may use the form on our Feedback page or send email to .
CLL Topics becomes a Corporation.
A Short History
This website, CLL Topics.org, has been on the Web for a relatively short time. It was launched on April 4, 2003.
CLL Topics, Inc. was registered as an Arizona non-profit corporation on October 27, 2003. The IRS issued an advance ruling on the Corporation's 501(c)(3) tax-exempt status on June 21, 2004.
On December 16, 2003 the collaboration with Mayo Clinic on Project Alpha was announced. As of December 16, 2003, the Corporation started fundraising to support clinical trials. For more details please see our Donations page.
On February 25, 2008, the IRS confirmed its advance ruling that CLL Topics, Inc. is a public charity, having conformed to all regulatory requirements for this status. As of March 1, 2008, the Corporation has finished five years of regulatory reporting, raised over $300,000 in funds from worldwide donations principally for supporting clinical research in CLL, sponsored and funded four clinical trials with a fifth in the final stages of regulatory approval and maintained an active online publication and bulletin system in the form of CLLTopics.org and Topics Alert. On February 25, 2008, we launched an online journal focusing on the details of a cord blood stem cell transplant for a CLL patient.
As of December 31, 2007 we have received a total of $310,828.34 from 555 donors. For details and a list of donors, please see our Acknowledgements page.
We have fully funded our commitments to three clinical trials that we have sponsored, and another two are pending disbursement. Current fund balances will support investigations of a number of promising new agents. Additional details will be reported as we develop these projects with the research community. You can read the details of past projects we have sponsored on the page on Sponsored Projects. Your donations have enabled us to offer critical financial support to these investigations at a formative stage and demonstrate patient involvement and reflect patient priorities in the process.
We have reached our fundraising goals for the year 2007 and as of July 1, 200 we will temporarily suspend fundraising activities while our publisher, webmaster and chief administrator is undergoing treatment for his CLL. Suspending this labor-intensive activity will lighten up our operational commitments and allow us to concentrate our time and effort on maintaining our publishing and educational activities, including this website and Topics Alerts. We will report on the results from our sponsored projects as and when they become available.
We are grateful to all our generous donors for their support and encouragement.
To see financial statements for the Corporation you may use the following links:
Other Corporate Documents
Additional corporate information may be found through the following links:
P. C. Venkat, 1949-2008
We are deeply saddened to announce the death of our Webmaster, Editor and Publisher.
After a period of mourning, CLL Topics Updates has continued our mission in his honor. (7/3/2008)
Fully Humanized Competition for Rituxan
Another Anti-CD20 Monoclonal in Clinical Trials
Immunomedics is recruiting CLL and NHL patients for a Phase I/II clinical trial of their new anti-CD20 monoclonal at multiple centers across the U.S. Read about how this Mab compares to the gold standard Rituxan in Veltuzumab: Another Anti-CD20 Monoclonal in Clinical Trials. (9/21/2008)
NK-cell Therapy: Better than a transplant?
GVL without GVHD?
Having Your Cake and Eating It Too
New research findings point to NK (Natural Killer) cells as the most potent cell line capable of GVL (graft-versus-leukemia), but these cells do not seem to do as much GVHD (Graft-Versus-Host-Disease). A brand new clinical trial launched at the University of Minnesota uses haplo NK cells in an attempt to get the much desired GVL, while steering clear of the dreaded GVHD. Our review NK-cell Therapy: Better than a transplant? describes the background, rationale and advantages of this approach. (7/28/2008)
Long Term Survival
Are CLL Patients Living Longer?
If Not a Cure, At Least Longer Life?
A new article has been published in Blood Journal on the subject of long term survival of CLL patients. The paper, based on SEER survey data, is reviewed in our article titled Are CLL Patients Living Longer? (3/2/2008)
Single Agent Fludarabine: Definitely Not the Gold Standard
UK CLL4 Clinical Trial Results
AIHA: One More Reason to Shun Single Agent Fludarabine
Fludarabine and chlorambucil as single agents have often been the conventional choice for first line treatment of CLL even while there was ample evidence that combination therapies produced more impressive responses. Now we have results from the UK CLL4 clinical trial, a head-to-head comparison of these same single agents against a combination of fludarabine and cyclophosphamide. In Single Agent Fludarabine: Definitely Not the Gold Standard, we examine the role of fludarabine monotherapy in precipitating potentially life threatening AIHA. (2/09/08)
MUD Transplants at the NCI
NIH Will Pick Up the Tab
Brand New Protocol Makes Its Debut
The NCI has just announced a new mini-allo MUD stem cell transplant clinical trial designed to evaluate the relative efficacy of two different methods of handling GVHD (graft versus host disease). Patients should take additional – and particular – notice of the fact that the NCI will pay for the entire protocol – from cytoreduction to transplant and post-transplant monitoring. Patients with a well matched unrelated donor (MUD) but without adequate insurance will find this trial may open a door that is otherwise closed. To find out more please read MUD Transplants at the NCI. (1/18/08)
Treanda: A Facelift for Bendamustine
Old Drug Recycled as New Therapy
Cephalon Makes a Splash with Orphan Drug for CLL
Recent presentations at the ASH 2007 meeting and a flurry of press releases on Treanda (bendamustine hydrochloride) have raised a considerable level of interest in the drug. While the agent itself has been around for over thirty years, its development as a drug for use in CLL is more recent. In our article, Treanda: A Facelift for Bendamustine, we examine the results of clinical trials reported to date and offer our analysis of the clinical trial results and the potential value of this drug in treating CLL. (12/15/07)
ITP: Immune Thrombocytopenia
Possible Connection to H. pylori
Platelets in Danger
Immune thrombocytopenia (ITP) is a serious complication of CLL that affects a small percentage of patients. It is a condition in which the immune system destroys platelets. Research suggests that a common pathogen, Helicobacter pylori, can sometimes be the cause of ITP and that controlling and eradicating this infection can resolve ITP in its early stage. We discuss this and other characteristics of this condition in ITP: Immune Thrombocytopenia. (12/6/07)
NCI Overview on CLL
Up-to-date and Comprehensive Statement
Official — and Exceptionally Useful
The National Cancer Institute produces a variety of publications that are useful – and generally taken for granted. We would like to alert you to a newly updated document that is on the NCI website: Chronic Lymphocytic Leukemia (PDQ®): Treatment. This is an up-to-date, comprehensive, authoritative reference with an extensive bibliography that should prove useful to professionals and patients. (There is a simplistic patient version and a more businesslike health-professional version.) Highly recommended reading. (10/21/07)
When You Have Been Around the Track a Few Times
Salavge Therapy Produces Grim Statistics
There are not many good therapy choices for CLL patients who become resistant to fludarabine and Campath. While a number of salvage therapies are in use, the results are variable and the survival statistics are grim. We agree with the experts in the field that a wider range of approaches and more effective agents are desperately needed for these patients. Refractory CLL is our review the literature and the latest reported results of salvage treatment for refractory CLL. (10/14/07)
Improving Flu Vaccinations
Launch of Phase II Clinical Trial Sponsored by CLL Topics
Jab & Dab: At Last We Have Liftoff!
The clinical trial we first announced in our May 13, 2006 article, Improving Routine Immunizations, has finally cleared all hurdles and the research team at the Royal Bournemouth Hospital is ready to recruit patients for this controlled Phase II clinical trial. The trial is designed to compare the results from imiquimod-enhanced flu shots to results from an age-matched control group. We discuss the science, trial protocol and enrollment criteria in a new article titled Jab & Dab: We Have Liftoff!. The patient community has tremendous “ownership” in this trial: the concept originated at CLL Topics, and it is sponsored with your donation money! (10/6/07)
Quality of Life with CLL
First of Several Articles Published
Results from Mayo Clinic Survey
We would like to thank many of our readers who heeded our call and participated in the Quality of Life survey conducted by the CLL research team at Mayo Clinic, Rochester, MN. The results from this survey continue to be analyzed but some of the early findings have been published in an article which appeared in the British Journal of Haematology in September 2007. For more details, refer to Topics Alert #253: Quality of Life with CLL. (9/29/07)
Campath as Single-Agent Frontline Therapy
FDA Expands Approval
Jumping the Gun
The FDA approved Campath for use in treating relapsed or refractory CLL in May 2001. The drug has since proved useful, especially in those cases with p53 deletions which are otherwise resistant to treatment. However, the antibody produces severe immune suppression and other side effects and its use has been limited. Most recently, based on the results of a clinical trial that compared Campath with chlorambucil, the FDA has expanded the use of the drug to include frontline single-agent treatment of CLL. In this article, Jumping the Gun, we examine the value of the broader use of Campath as frontline single-agent therapy for CLL. (9/24/07)
Opinion: What Say You, Dr. Expert?
Viewpoints from Noted CLL Experts
Making Sensible Decisions About Stem Cell Transplants
The clinical research community is slowly coming to grips with the question of when a stem cell transplant makes sense in CLL. The mortality and GVHD risks associated with transplants are definite deterrents but there are substantial survival risks, too, in not taking definitive action when faced with aggressive, poor-prognostic or refractory disease. Four of our favorite CLL experts from major research centers have been generous in sharing their personal viewpoints on the question. You can read their opinions in our article, "What Say You, Dr. Expert?" (9/10/07)
Radioimmunotherapy: Underappreciated Option?
Hot and Cold Monoclonal Antibodies
A Protocol Waiting for a Trial
There are two approved radioimmunotherapy drugs currently on the market, Bexxar and Zevalin. Unfortunately, both are at risk of becoming unavailable to patients as a result of reimbursement issues. Both drugs have proven effective at producing durable remissions in follicular lymphoma and one, Bexxar, is currently being tested in CLL at the Fred Hutchinson Cancer Research Center. In our article Radioimmunotherapy: Underappreciated Option?, we suggest an approach that may be used in early stage patients to reduce bone marrow involvement and then deliver clean, durable remissions: all in a patient-friendly protocol. We can use your help in getting the research community interested in launching a clinical trial to test the concept.(9/6/07)
Radioimmunotherapy Reimbursement Cuts
Patients Appeal Against Proposed Changes
An Important and Effective Therapy Option May Disappear
We would like to draw your attention to an issue that threatens the availability of a valuable, FDA approved therapy for B-cell malignancies. Proposed modifications to the Medicare/Medicaid reimbursement schedules would make it uneconomic for hospitals to continue offering radioimmunotherapy as an option for treating diseases like the lymphomas and CLL. This comes at a time when a promising new clinical trial is under way at the Hutch to establish a methodology for using radioimmunotherapy agents effectively in CLL. See Radioimmunotherapy Reimbursement Cuts, our announcement on this issue and please take the time to add your endorsement to the patient initiative that has been launched to keep this therapy option alive. (8/31/07)
FISHing in Murky Waters
The Story of Undetected FISH Defects
The Importance of Asking the Meaningful Question
The typical commercially available FISH panel contains four probes which seek to establish the presence or absence of the most common cytogenetic abnormalities in CLL. Results that do not have one of these four common deletions or mutations are labeled “normal” — a misleading label. CLL cells almost certainly suffer from some genetic abnormality that makes them cancer cells to begin with. Even for those patients who have one or more of the known defects, the limited probe set could mask additional defects that may have a bearing on risk assessment and treatment. In FISHing in Murky Waters, we examine the importance of expanding the probe set presently used in the standard CLL FISH panel. (8/29/07)
Cord Blood Transplants
Review of the State of the Art
Greatly Improved Odds: but Transplant Mortality Remains
The state of the art in cord blood transplants has come a long way in the past few years. Originally attempted only with children because of the limited stem cell dose available in umbilical cords, these procedures have evolved to include double cords and are now producing results in adults comparable with those from adult donor transplants. We review the results from the University of Minnesota and elsewhere and explain the concepts involved in our article titled Cord Blood Transplants: State of the Art. For many patients who do not have a matched sibling or unrelated adult donor, cord blood transplants are a lifeline of hope for a durable remission and perhaps a cure. (8/11/07)
Catch 22 – The Transplant Minefield
The Chance of a Real Cure versus Transplant Mortality Risk
Expert Opinions Diverge on Timing
Many CLL patients with adverse prognostic indicators know that sooner or later they will have to face the prospect of a stem cell transplant. Current research shows improving results from mini-allo transplants for CLL patients, especially if they have clean remissions and are otherwise in good health going into the transplants. While this might argue for early, elective transplants for some patients, the mortality risks are still significant and there is as yet no consensus among transplant experts on timing and exhaustion of other therapy options. To understand the issues involved, please read our case study of an anonymous patient volunteer in Catch 22 – The Transplant Minefield. (7/4/07)
Strategy & Tactics
Harvey Chooses to Fight on His Own Terms
Harvey, our purely hypothetical patient with challenging cytogenetics, is not unique in facing a complex and aggressive disease. However, he is determined to be as organized and logical about it as he can and use his resources to the best effect. He has put together a plan that may give him a chance to beat the disease and live to be an old man. Read about his battle plans in Strategy and Tactics. (6/12/07)
Incidentally, we would also like to tell you about future changes in our operations and fundraising efforts here at CLL Topics.
The Tricky Business of Using Radiation in CLL
Bexxar: An Introduction
A Phase II clinical trial for CLL has been launched by the Fred Hutchinson Cancer Research Center in Seattle, using the radioimmunotherapy agent, Bexxar. By combining a CD20-targeting monoclonal antibody with a radioactive payload, this agent offers the promise of high-precision targeting plus a lethal wallop – which may lead to low MRD and long remissions. But since CLL invariably involves the bone marrow, the partcipants must first go through a course of RF therapy to get B-cell infiltration of the marrow as low as possible and thereby avoid damage to the bone marrow and precious stem cells. Read about how this first-line therapy may work for you in Bexxar: An Introduction to Radioimmunotherapy. (5/15/07)
A New Agent to Improve Chances of Survival
GVHD: A Pebble in the Transplant Shoe
While mini allo stem cell transplants hold the promise of a cure for this disease, the risk of mortality and graft versus host disease have been major deterrents to using this technique in high risk CLL patients. New results from research in managing the worst effects of GVHD point the way to improved survival and transplant related symptoms. We review encouraging results reported by the team at the Fred Hutchinson Cancer Research Center in our article GVHD: A Pebble in the Transplant Shoe and explain why this could be very important to CLL patients with poor prognostics. (5/3/07)
How Much Time Do You Think You Have?
Jenny Tells the Forest Story
Forest Bump is the pen name of a CLL patient who volunteered to share with our readers his experience in the FCR Lite clinical trial. You can read the first installment of this case study in Forest Bump. As it sometimes happens with CLL, what followed next was not something he or his wife, Jenny, or indeed any of his doctors, anticipated. Forest suffered complications brought on by his CLL and died in early March. Jenny bravely picks up the tale here, in the conclusion of the Forest Bump saga titled Jenny Tells the Forest Story. Easy answers are hard to come by but the story may provide you with some serious food for thought. (4/23/07)
Monoclonal Antibodies with Enhanced Firepower
CAT8015 – A Trojan Horse
Investigators at the NCI and NIH are hard at work on another agent that promises to combine sharp targeting and a powerful knockout punch to destroy CLL cells: an immunotoxin called CAT-8015. A new clinical trial with this agent has been announced and is currently recruiting. In our article, CAT8015 – A Trojan Horse, we review the background science and discuss the pros and cons of this approach. (4/12/07)
Antibody in Development
An Antibody Targeted to the CD23 Marker
Lumiliximab: The Next Drug in CLL?
Biogen Idec, the folks that brought us Rituxan, are busy developing a new monoclonal antibody for use in CLL. The drug, Lumiliximab (formerly IDEC 152), has some interesting features that might make it useful in treating CLL. It targets CD23, a marker which is brightly expressed by CLL cells and is in fact a B-cell activation marker. The drug appears to have an enviably low toxicity profile. We review the research literature from early clinical trials, discuss the major features of the agent itself and evaluate a recently launched pivotal Phase III multicenter clinical trial of the drug as an addition to the FCR protocol. For the details, see our review titled Lumiliximab: The Next Drug in CLL? (3/6/07)
Celgene Targets Revlimid as CLL Therapy
Revlimid to the Rescue?
Oncology drug maker, Celgene Corp., sponsored two recent phase II clinical trials for the use of its drug Revlimid, in CLL. The results of these trials were reported in the 2006 ASH annual meeting in Orlando. In our article, Revlimid to the Rescue?, we review the results of these trials and present our commentary on the drug's efficacy, adverse effects and potential value in cases with difficult prognostic factors. Any CLL patient who is asked to consider off label use of this drug or to participate in Celgene's big follow-up phase III clinical trial needs to do his or her homework first — starting by reading this article. (1/30/07)
HuMax-CD20 for Follicular Lymphoma
Phase III Clinical Trial of Single-Agent HuMax-CD20
Seeking Approval on Different Fronts
In mid-2006 Genmab announced the launch of a second pivotal phase III clinical trial of HuMax-CD20 as a single agent: this time for treating follicular lymphoma patients who have failed chemoimmunotherapy combinations incorporating Rituxan or Rituxan given as maintenance therapy. While the trial is interesting in itself as expanding the options for follicular lymphoma patients, it also serves as another clinical platform to demonstrate the possible superior efficacy of HuMax-CD20. The results of this clinical trial should be of interest to CLL patients as well if it results in market entry for this drug. Read the details in HuMax-CD20 Monotherapy in Refractory Follicular Lymphoma. (1/21/07)
HuMax-CD20 plus Fludarabine plus Cyclophosphamide
New Phase II H+FC Clinical Trial
Genmab has recently launched a chemoimmunotherapy combination clinical trial involving its anti-CD20 monoclonal antibody, HuMax-CD20 (generic name ofatumumab). This is a phase II dose comparison trial. The Genmab protocol combines HuMax-CD20 with fludarabine and cyclophosphamide over a 6 month treatment cycle. The trial is currently being offered at four recruitment centers in the United States. There is reason to hope that HuMax-CD20 will be more effective than Rituxan both as a single agent as well as in chemoimmunotherapy combinations such as this. You can find our discussion of this announcement at: HuMax+FC Announcement. (1/9/07)
Rituxan plus Fenretinide
A Match Made in Heaven?
A New Combination Therapy Is on Trial at the Hutch
We announce the launch of a promising Phase II clinical trial at the Fred Hutchinson Cancer Research Center. The trial combines Rituxan with a Vitamin A analogue called fenretinide, already in wide use as a maintenance agent in other cancers. This combination offers the potential of low-toxicity and possible synergy between the two agents — and that could mean an effective therapy for CLL. This trial is sponsored and partly funded by CLL Topics — with your hard-earned donation dollars. That should tell you what we think of this approach. Read and evaluate for yourself the logic behind the protocol and the promise that it offers — Rituxan plus Fenretinide: a Match Made in Heaven? (1/8/07)
Almost Free Stem Cell Transplants
NIH Clinical Trial for Sibling Donor Transplants
A Unique Opportunity
The National Institutes of Health in Bethesda, MD are conducting a clinical trial for sibling donor transplants that may offer a unique therapeutic opportunity for CLL patients with aggressive disease and poor prognostics. In this article, Stem Cell Transplants - Free of Charge (Almost!), we review the background and rationale for this clinical trial, as well as give you contact information. Potential participants both in the US and overseas should carefully consider this unique opportunity that might otherwise be out of their reach for financial reasons. (1/3/07)
ASH 2006 Highlights
Summary of New Research Findings
Latest in Hematology
The American Society of Hematology Annual meeting is the high point in the year for a variety of people dealing with CLL: professional hematologists, research scientists and corporations in the pharmaceutical and biotech industries — and to patients anxiously awaiting the next big development in therapy. Our team of reporters covering this year's ASH annual meeting at Orlando, FL, describes the highlights of the 5-day meeting in this report: ASH 2006 Highlights.
The Road to a Stem Cell Transplant
Greg's Story: A Cautionary Tale
Greg's Story is a case study based on the notes of an anonymous patient. It is a cautionary tale about the dangers inherent in a relapse in the face of poor prognostics. Delaying the decision to seek a mini-allo transplant, the only known cure at this point for poor prognostic disease, can result in that choice being removed suddenly. You will learn why Greg feels poor prognosis CLL should be taken very seriously and why a decision on pursuing a mini-allo should be made early in the process.
The Body's Way of Controlling the Mayhem
Key Players in a Delicate Balancing Act
The human immune system performs a delicate balancing act between safeguarding the body's own vital tissues and aggressively destroying pathogens and cancers. In recent years research has revealed how a key role in this act is performed by immune system cells called Tregs. We review the critical role of these important players in an article titled Tregs Revealed. Understanding how these cells function and their relationship to the rest of the immune system is central to designing effective therapies for CLL — and to controlling the unwanted side effect of autoimmune disease.
Fundraising and Sponsorship Philosophy
How We Select Research Projects to Sponsor and Support
Factoring Patients' Priorities into Clinical Trials
When it comes to spending our donors' money on clinical trials, we try to make every last dollar count. Even more important, we try to get projects launched that have the potential to make a difference to patient survival and quality of life. Please read Our Fundraising and Sponsorship Philosophy to understand objectives and the logic behind our efforts.
Infections: Who Is Most at Risk?
Prognostic Indicators Can Identify Infection Risk
Know Your Enemy
Serious infections account for an alarming proportion of deaths among CLL patients. But are some patients more at risk than others? What are the prognostic indicators which can help you assess the risk of serious infections in your own case? In Who Is Most at Risk? we review a very recent article that looks at the different risk buckets and provides some practical pointers to improve your chances of staying out of the hospital.
An Expert Looks at Therapies for p53 Defective CLL
A Sledgehammer To Be Used Wisely
A defect in the p53 gene is a poor prognostic marker and predicts aggressive disease. Patients who have this defect tend to respond poorly to standard chemotherapy. Finding new and better ways of treating CLL patients with p53 defects is therefore a major priority in CLL clinical research. In his article, Steroid-Campath Combinations, Dr. Andrew Pettitt of the Royal Liverpool University Hospital evaluates agents that have promise in this area and addresses the important questions of when to treat such patients and how far to go with the treatment.
Sponsored Clinical Trial
CD20 Shaving with Rituxan
Are Standard Dosages Way Too Much?
The original dosing scheme for Rituxan was quite arbitrary — but it seemed to do the job. A research team at the University of Virginia is now examining the finer features of how Rituxan works and is asking an important question: when does it make sense to use less of this drug than the dosage standard? In this article we examine the concept of "CD20 shaving" and introduce a research project at UVA that we will be sponsoring and supporting financially. The answers from this research can have an important bearing on the best way to utilize this valuable monoclonal antibody. Details in CD20 Shaving with Rituxan.
Super Bugs: Staph
MRSA Is on the Loose
The Dangers of Drug Resistant Bacterial Infections
Recent reports prove that infections from strains of drug-resistant bacteria are far more prevalent than previously thought, accounting for more than half of all skin infections treated in hospital emergency rooms. Infectious diseases experts are trying hard to get the word out. While this poses a serious threat to public health, CLL patients will do well to pay special attention to this phenomenon and take some precautions — so that they may avoid these difficult and persistent infections which their systems are ill-equipped to fight. Read about these super bugs in The Dangers of Drug Resistant Bacterial Infections.
HuMax-CD20: Risks and Rewards
Belt, Suspenders and Cummerbund
Get to Know Ofatumumab
HuMax-CD20 derives part of its improved efficacy from its capacity to work with a patient's complement system to destroy B-cells. In HuMax-CD20 Risks and Rewards, we examine the potential risks of complement depletion that may accompany intensive treatment with this monoclonal antibody — and suggest a possible precautionary measure for those who are taking part in the Phase III trial of this agent for fludarabine- and Campath-refractory patients.
A Smarter Monoclonal on Trial
What Makes HuMax-CD20 Different from Rituxan?
In this article we take a closer look at the new agent starring in Genmab's recently announced Phase III clinical trial for fludarabine and Campath refractory CLL patients. This well-designed trial keys in on HuMax-CD20's strengths which we hope will provide significantly better results than singe-agent Rituxan, especially in this difficult patient cohort. To learn more about this pivotal trial and to understand how this important new monoclonal antibody works, read A Smarter Monoclonal on Trial.
The Kiss that Can Kill
The Enemy Within
The Epstein-Barr Virus (EBV) has long been known as a complicating factor in many cancers. Recent research has shown just how serious is the threat posed by this virus in CLL. EBV is estimated to be present in over 90% of adults in the western world but is normally kept in dormancy by active T-cells. Read The Enemy Within to learn how EBV can interfere with normal T-cell function and how T-cell damaging therapy with agents such as fludarabine and Campath can unleash EBV with life-threatening consequences. We also discuss how patients may be able to use a common statin to improve their defenses against this virus.
How to Treat and Manage Infections in CLL
Infectious complications are the major cause of mortality in CLL and affect the quality of life of most patients. The best practices in managing infections have changed over time, tracking our knowledge of the molecular mechanisms at work and reflecting the nature of the therapies used to treat the CLL itself. In our article Infectious Complications of CLL, we review the latest expert findings. We also highlight the need for patients to be actively involved in discussing these best practices with their local oncologists, to ensure that they receive appropriate care.
Caution on EPO
The Dark Side of Epoetin - Getting Darker
Be Careful What You Ask For !
The results of a new meta study have been published in the Journal of the National Cancer Institute. The authors find additional reasons to question the usage of high doses of epoetin drugs to achieve "normal" levels of hemoglobin. Biases in earlier studies may have understated the problems. We present our review in The Dark Side of EPO - Getting Darker.
Genmab in the News
HuMax-CD20 in Action
Harvey is Back!
We have an opportunity to see HuMax-CD20 in action when Harvey and Serena pack their bags and travel to England in pursuit of therapy with this new agent. To learn more, read: Genmab in the News.
Sponsored Clinical Trial
Low Hanging Fruit
Improving Routine Immunizations
Sometimes, when luck is running our way and all the stars are in their correct positions in the heavens, everything comes together just so and we have an opportunity to do ourselves a favor as a community. In our new article, Improving Immunizations, we present a clinical trial to test a method that may boost the efficacy of routine immunizations for CLL patients. We are happy to report that Prof. Terry Hamblin is now working on making this trial a reality.
A Direct Comparison of F+C vs F
Is More Necessarily Better?
The latest issue of Blood carries an article from the German CLL Study Group comparing single-agent fludarabine against a combination of fludarabine plus cyclophosphamide. This is a well-structured, rigorous study and the study group comes to some surprising conclusions. Read F+C vs F for our analysis of the study and comments from an editorial in Blood by Dr. Neil Kay.
A Vaccine Trial for CLL Patients
Finally, It's Our Turn ...
Genitope Corp. has announced a clinical trial of their MyVax proprietary vaccine technology for untreated, early stage CLL patients. We examine this promising technology and the structure of the Genitope clinical trial in our new article, A Vaccine Trial for CLL Patients.
Forest Bump on His Experience in FCR Lite Trial
The Road Turns Less Bumpy for Our Hero
Our intrepid volunteer, thinly disguised as "Forest Bump", reports on his experience as a participant in the "FCR Lite" clinical trial being conducted at the University of Pittsburgh Cancer Institute. Forest, you will discover, has a unique personality and view of life. We hope his tale, Forest Bump, will be useful to those interested in a "lighter" version of the widely used FCR protocol.
Update on New Adverse Effects
Harvey Runs into a Road-block
Since our hypothetical patient Harvey has developed a modest following of his own, our readers will be interested in some new developments. Harvey’s experience coincides with recently published reports on new adverse effects of Rituxan therapy. While the post-marketing surveillance of Rituxan has so far identified only a small percentage of patients having these serious adverse effects, the danger is high and very real for these patients and therefore worth discussing. Find the details in our next installment of the Harvey Saga, Harvey Runs into a Road-block.
The Price of Collateral Damage
Winning the Battle but Losing the War?
Treating CLL needs a different approach from treating more familiar solid cancers. In this article we discuss the costs and benefits of different strategies. If you are considering therapy this article may help you understand your options a little better: Winning the Battle but Losing the War?
The Latest on Green Tea
Details Make a Difference
We report on some recent information that has come to light on green tea extracts and EGCG in cancer treatment and prevention and provide an update on Project Alpha. Read the details in Latest on Green Tea.
Clinical Trial Updates
The Search for Consistency in Reporting Results
Comparing Apples to Kumquats and One Small Victory
We revisit two clinical trials discussed in past articles - FCR and PCR. Comparing the results of these two trials is not easy but we nevertheless make a brave attempt. We also discuss new trials in the offing and report a welcome change in the design of the FCR + M clinical trial. Sometimes it helps to tilt with windmills! Read all about these things in Clinical Trial Updates.
The Search for Efficacy with Lower Toxicity
New Clinical Trial Seeks the Goldilocks Solution
A new chemoimmunotherapy combination employing a higher dosage of Rituxan with reduced dosages of fludarabine and cyclophosphamide, is being tested in a clinical trial at the University of Pittsburgh Cancer Institute. The investigators would like to achieve high response rates with lower toxicity compared to FCR "Classic" pioneered at M. D. Anderson Cancer Center. We review the protocol and comment on the clinical trial design in our article on FCR Lite. We also interviewed Dr. Kenneth Foon, the principal investigator for this clinical trial at UPMC.
RF Risks & Benefits
High Risk Groups Relapse Sooner
Further Analysis from Ohio State
As patients it is important to us that our remissions be long and that we maximize survival. These objectives are not always captured by response statistics typically reported in cutting-edge phase II clinical trials of new agents. In our new article on RF Therapy, we focus on a follow-up paper published by Drs. John Byrd, et. al., that goes straight to the point – CRs and PRs don't mean the same thing to different prognostic risk groups, unlike the proverbial rose that smells just as sweet to anyone who cares to sniff.
HuMax Clinical Trial
Early Results from GenMab's Anti-CD20 Monoclonal Antibody
The Half-Full Glass
We have high hopes for the new generation of monoclonal antibodies that are under development and have discussed new trials under way to test these agents in the clinic. Early results form one such trial, involving GenMab's HuMax, were highlighted at the 2005 ASH conference in Atlanta. We offer our analysis of the published results in Results from GenMab's HuMax Clinical Trial.
Avian Flu and CLL
Recognizing Vulnerabilities and Taking Precautions
A Cave Is No Place to Live
You cannot have missed all the references to "bird flu", "avian influenza", "H5N1" and "pandemic flu" in the mainstream media. There are as many opinions about bird flu as there are chickens in China. We would like to add our two cents, but strictly focused on issues as they pertain to CLL patients, the special risks we face as immune compromised individuals. We also attach some up-to-date reference material that you might find useful, especially when you talk to your doctors about your needs. Read our article on Avian Flu and CLL.
MCL - a Wolf in CLL Clothing
Accurate Diagnosis Leads to Better Treatment
Know the Name of Your Enemy
FISH analysis is one of the key prognostic tests used to identify the type of CLL a patient has. However, the usual FISH panels contain probes for only the most common cytogenetic abnormalities. Rarer aberrations all get lumped together in a basket labeled "normal". In this article, MCL - a Wolf in CLL Clothing, we examine how a probe for one such rare aberration, the "t(11:14)" translocation, can yield valuable information in distinguishing CLL from the more aggressive Mantle Cell Lymphoma, for which treatment choices are not the same. Having this additional probe included in your FISH test may well depend upon your negotiating skills.
Anti-death Protein Protects Cancer Cells
We Review Clinical Trials of Three Different Drugs
Clinical trials are currently under way testing three different drugs to suppress or attack a family of proteins that confers longevity to CLL cells. We review the science behind this approach — and give you our take on the drugs and the clinical trials — in Targeting Bcl-2.
Pneumonia Is the Single Biggest Killer of CLL Patients
Some Pointers to Resources and Education
The annual influenza season will soon be upon us. In Flu Preparedness we offer some research findings and practical advice on making it through this season, whether we are faced with the common or garden variety of flu - or a more ominous humanized version of the avian flu.
Clinical Trial at the Hutch Now to Recruit CLL Patients
Trained CD-20 Targeted Killer T-Cells to the Rescue
Another interesting clinical trial will soon be open to CLL patients. T-cells collected from patients are grown into large armies and targeted to kill only cells with the CD-20 marker. These activated and targeted killer T-cells will be used in the clean-up of minimum residual disease left after more traditional therapies. This innovative approach is the basis for a Phase I clinical trial at the Fred Hutchinson Cancer Research Center in Seattle. Read our review of this latest evolution in using CTLs in Autologous CD-20 Targeted T-Cell Therapy.
A Patient Sponsored Clinical Trial
Project Alpha Kickoff
It has taken longer than we thought it would, but we are pleased to announce Project Alpha is finally ready to start recruiting patients. It represents a first of its kind collaboration between patients and the research community. Your hard earned money went into making this "EGCG trial" a reality. You can read all the details of this newly announced clinical trial at Mayo Clinic, Rochester MN, in our new article, Project Alpha Kickoff.
A Few Short Years Can Change Some Important Things
Death by Conventional Wisdom
The conventional wisdom of a few years ago can prove dangerous when doctors treat patients by outdated rules of thumb. In our (2005) critique of this case study reported by a professional journal in 1999, we identify the necessity for both physicians and patients to understand and employ modern risk-based strategies in dealing with this varied disease. Read " Death by Conventional Wisdom" to understand why staying on top of new developments is critical for your doctor — and even more so for you.
Experts Summarize the State of CLL Therapy
Where Are We?
Drawing from a group of top-rated experts, Dr Marco Montillo in Milan has produced an overview of where we are in understanding and treating CLL. Patients and their oncologists should pay close attention to the historical evidence and conclusions presented by this group. Read about it in Risk-adapted Strategies.
Graft versus Host Disease
Controlling this Killer is the Holy Grail of Transplants
GVHD in Allogeneic Transplants
Graft-versus-host-disease (GVHD) is an example of systemic and potentially life threatening inflammation. It is one of the major causes of death in stem cell transplants. Controlling GVHD is the holy grail of all transplant researchers. This article discusses the causes GVHD, and some commonsense things you can do to protect yourself.
Stem Cell Transplants
The Only Real Cure Out There, for Now
New Papers Spell Out the Chances for Success
As the years go by, survival statistics from stem cell transplants performed in the past have been accumulating. We review the surprising results reported in two newly published papers from the Hutch in our article, The Only Real Cure Out There, for Now.
Hsp 90 and Its Inhibition by 17-AAG
An Important New Trial Has Been Announced
17-AAG may turn out to be an important therapeutic drug for CLL. It has an interesting mechanism of action and should in theory work well in poor prognostic cases. An important new phase I trial of 17-AAG has been announced and is recruiting patients at OSU, soon to be followed by Dana Farber. You can read all about it in our article 17-AAG - An Important New Trial Has Been Announced.
Latest on Candidate 17-AAG
Hope Springs Eternal
The patient community is ever hopeful about new drug candidates that appear to have potential in the lab. In 17-AAG we examine a new agent that is receiving attention, 17-AAG, which is on its way to starring in a clinical trial at Ohio State under the orchestration of Dr. John Byrd.
Campath plus G-CSF Can Be Dangerous
A Scary Story: Telling It Like It Is
The combination of Campath and G-CSF appears logical enough as an approach to reaping the benefits of Campath therapy while keeping the immune suppression and infections typically associated with it under control. However, the co-administration of G-CSF with intravenous Campath to patients enrolled in a phase II trial at Ohio State produced unexpected and discouraging results. The prompt publication of the results is a credit to the Ohio State team. It is important that we understand the results of this trial as we consider our therapy alternatives. Read about it in Campath plus G-CSF.
Restoring Humoral Functions in B-CLL
Possible Benefits of IVIg
Most CLL patients have reduced immunoglobulin (Ig), the levels dropping gradually over time. Lack of proper B-cell function in generating a wide repertoire of Ig needed is one of the reasons why CLL patients get so many infections. This article, Possible Benefits of IVIg, describes what happens when B-cell function is compromised by cancer or therapies used to control the cancer, causing sub-normal Ig levels. One possible solution for this defect is, of course, IVIg. Recent research suggests there may be even more important and unexpected benefits to be gained from IVIg.
Prognostic Test Packages are Now Available
Quest Diagnostics Is First to the Table
Your doctor can now order a package of CLL-specific prognostic tests from the largest company in the medical test industry, Quest Diagnostics, Inc. Doctors can now get the tests done as a package deal - and at a reasonable cost to the patient. It has been our crusade to take out some of the road blocks to make prognostic testing accessible to local healthcare providers who guide the therapy choices of their CLL patients every day. Read about this important and very useful development in our article on Prognostic and Monitoring Tests. We provide all the details of how to get the tests done and the logic you may need to convince your doctor to order them.
New Clinical Trial at Mayo
Protocol for Previously Untreated Patients
Short Duration Campath plus Rituxan
A new protocol combining short duration subcutaneous Campath with standard dose Rituxan has been launched at the Mayo Clinic, Rochester, MN. It targets previously untreated Rai Stage 0-II patients. Read our review of the protocol and the relevant detail and background in Clinical Trial to Test Rituxan plus Short Duration Campath.
Good News for the Tough Cases
The Half-full Glass
Another piece of solid clinical research with important implications has just been published online in the Journal of Clinical Oncology. In it, Paul Moreton, et al., report on the results of a 7-year phase II study involving late stage and refractory patients. The British team concludes that eradication of minimum residual disease with Campath has a surprisingly good effect on survival in this cohort of tough cases. We review the Moreton article and offer our analysis in Good News for the Tough Cases.
Staging is Superseded
The New Think on CLL Is Finally Here
The Dawn of a New Era
An important new review article has been published in the New England Journal of Medicine. The Rai/Binet staging systems have been important in triggering therapy decisions. In this article the authors, who include Dr. Kanti Rai himself, bluntly state that the staging system with its emphasis on watch & wait should be replaced by better methods using modern prognostic indicators. We cover this important article as well as several other related works in The Dawn of a New Era.
Progress in Getting the Tests Made Accessible
Our Quest For Solutions
The value of getting the right prognostic tests done is slowly gaining acceptance in the patient community. However, the practical difficulties involved are numerous and each patient has to deal with his or her providers as well as he or she can. In this article, Progress on Prognostics, we review our own progress in de-tangling the logistical and communication nightmare for the patient community. In CLL, as in life, what you get is what you negotiate - and we have been busy.
Progress in Finding a Cure
Are We There Yet?
Professor Terry Hamblin needs no introduction to CLL patients. His seminal work on the prognostic value of the IgVH gene mutation status has become a cornerstone in the risk stratification of CLL patients. In his article, Are We There Yet?, Dr. Hamblin discusses criteria for initiating treatment as well as what treatment can and cannot do for the patient. He goes on to review the current status of combination chemo-immunotherapy clinical trials. Read this article for a candid assessment of where we are in the campaign to cure CLL.
Nutrition and Chemoprevention
Omega-3 Fatty Acids
A Fishy Tale
Much current research is focused on the role played by polyunsaturated fatty acids (PUFAs) in a very broad range of cellular functions in humans. Our modern diet and agricultural technology have created a substantial imbalance between the two major groups PUFAs that we consume. Restoring that balance is critical to our ability to avoid and fight cancer and other diseases. In Omega-3 Fatty Acids we review current scientific thought on the importance of increasing our consumption of Omega-3 oils, derived mainly from fish.
Oral Mucositis Can Be Deadly
A Real Pain in the Mouth
Many CLL patients experience painful sores and infections in their mouths, especially when they go through chemotherapy. This incidence of 'oral mucositis' can have serious consequences to the quality of life and even survival of these patients. There may be a few things you can do to help yourself - read about them in A Real Pain in the Mouth.
Matching Made Simple
Is a Bone Marrow Transplant in Your Future?
Allogeneic Stem Cell Transplants Work Better with Closer Matches
HLA matching of the potential donor with the recipient is the first step in allogeneic stem cell transplants, whether the stem cells are obtained from an adult donor or from umbilical cord blood. With increasing frequency, stem cell transplantation is viewed as an early alternative for those with aggressive disease or high risk profiles, especially for younger patients. Familiarity with the concept of tissue typing will be useful as you embark upon the transplant journey. To take some of the mystery out of this process we present Matching Made Simple.
Sons of Rituxan and Campath
A New Generation of More Effective Antibodies Makes It into the Clinic
The monoclonal antibodies Rituxan and Campath have changed the landscape for CLL and a whole range of hematological conditions. New improved versions of these monoclonal antibodies are now coming out of the lab and into the clinic. In our article Sons of Rituxan and Campath, we examine the mechanisms by which these agents achieve their effects - and the methods for increasing their efficacy. Read about a new CD20 monoclonal antibody, HuMax from GenMab, now in clinical trials in Europe and in the US and, incidentally, satisfy your curiosity about why we have a picture of a lobster gracing this paragraph.
Genes Sleeping on the Job
New Therapies Based on a Better Understanding of Cell Biology
An interesting new clinical trial has opened up for CLL patients, one that may have potential for low toxicity as well as good efficacy. As a refreshing change from the usual heavy doses of chemotherapy, this trial is based on using very low doses of drugs, often as little as ten times lower than the amounts used under standard regimens. The rationale for this approach is equally interesting. The DNA in a cell's nucleus is a vast library of information which normally defines and regulates how the cell functions. In cancer cells, however, the information retrieval mechanism is often at fault. The idea here is to use just enough drugs to correct this fault, and thereby allow the cancer cell to kill itself. Click here to read Epigenetics.
Trust but Verify
Shopping for the Therapy that Is Right for You
Picking your therapy based on the results reported from clinical trials is not easy. You have to read the results carefully - the devil is indeed in the detail. Comparing trial results is only valid if the patient groups are well matched between the trials - and sometimes the focus is on the wrong result statistic. Unbiased, timely and complete reporting of the results of human clinical trials is critical to understanding the therapies out there - and your therapy choices. Click here to read Shopping for the Therapy that is Right for You.
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