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    This section provides links to Internet resources, scholarly articles and other material we have collected on some important aspects of understanding and treating CLL and other cancers. Many of these sources are referenced in the articles on this site. Some of these external links do change occasionally, but they can usually be located again with a simple keyword search with an engine such as Google.

    Information Sources on the Internet

    June 22, 2024

    by: P. C. Venkat

    Reference Material, Key Articles, Educational Websites and Other Resources

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    NYPL lion statue

    Apoptosis

    Discussion of apoptosis mechanisms - from Professor John W. Kimball's online textbook. (The entire document is available under Textbooks.)
    Kimball on Apoptosis

    Angiogenesis

    Collection of four articles addressing different aspects of angiogenesis as it relates to cancer.

    Angiogenesis and Cancer Control: From Concept to Therapeutic Trial. Steven Brem, MD, Moffitt Cancer Center at the University of South Florida.

    Tumor angiogenesis: past, present and the near future, Robert S. Kerbel, Sunnybrook & Womens College.

    NCI tutorial on understanding angiogenesis, National Cancer Institute.

    ASH Education Book

    This is an extremely important resource both for patients and for doctors. The American Society of Hematology publishes an annual CME volume called the ASH Education Book, targeted at practising hematologists. The material, however, is often within the grasp of the well-informed patient. There is usually an overview article that captures the most recent thinking on the subject of CLL and other articles that summarize developments in treatment strategies and new therapies. These are among the presentations usually made at the annual ASH meeting and symposium.

    This link will lead you to the most recent Ash Education Book, http://www.asheducationbook.org/, but previous years' books are also available at the site.

    In the 2024 ASH Education Book (from the Orlando conference) you will find the following three articles of high importance to CLL patients:

    New Prognostic Markers in CLL by Emili Montserrat, Barcelona, Spain;

    Current and Investigational Therapies for Patients with CLL by William Wierda, M. D. Anderson Cancer Center;

    Evolving View of the In-Vivo Kinetics of Chronic Lymphocytic Leukemia B Cells by Nicholas Chiorazzi and Manlio Ferrarini, Feinstein Institute for Medical Research.

    In the 2024 ASH Education Book (from the Atlanta conference) you will find the following three articles of high relevance to CLL patients:

    CLL Biology and Prognosis by Guillaume Dighiero, Institute Pasteur;

    CLL - First Line Treatment by Michael Hallek, German CLL Study Group;

    Salvage Therapy for CLL and the Role of Stem Cell Transplantation by John G. Gribben, Barts & the London School of Medicine.

    Black Box Warnings

    According to Wikipedia, "A black box warning means that medical studies indicate that the drug carries a significant risk of serious or even life-threatening adverse effects. The U.S. Food and Drug Administration (FDA) can require a pharmaceutical company to place a black box warning on the labeling of a prescription drug, or in literature describing it. It is the strongest warning that the FDA requires."

    Formulary Productions, LLC, maintains a searchable database of these black box warnings on all drugs regulated by the FDA. You can even look under therapeutic classification of "antineoplastic drugs" to find all your favorite cancer drugs. Here is the link: Black Box Warnings. While this is a useful compilation, just keep in mind the source: it is a commercial venture marketing to the biotech and pharmaceutical communities. Here are some names you might recognize: alemtuzumab, chlorambucil, cladribine, doxorubicin, fludarabine, mitoxantrone, pentostatin, rituximab. You will note that the names are generic names, not brand names like Fludara, Nipent, Campath or Novantrone. You will also find another familiar name, lenalidomide (generic for Revlimid) parked in the list of hematologic agents and also under immunomodulators.

    See also FDA Warning Letters to Companies, below.

    BSA Calculation

    Some methods of calculating Body Surface Area (BSA) for chemotherapy dosage.

    BSA Formulas: This page from the BC Cancer Agency tells you what the formulas are.
    Formulas to Calculate BSA .

    BSA Calculator: This unofficial site has a handy dandy calculator to do the BSA computations for you. As an additional bonus, it will calculate your dosage and inform you of your body mass index, lean body weight and "ideal body weight". "Ideal", of course, is a matter of opinion.
    Halls.md BSA Calculator.

    Cancer Drug Manuals

    BC Cancer Agency – Useful data sheets on a list of drugs commonly used in treating various cancers. (Some newly approved drugs may take time to get on the list in Canada.)
    BCCA Drug Database;

    CancerBACUP, a U.K. information site, provides a user-friendly compendium of cancer drugs. (As in Canada, there could be a lag in getting brand new agents onto the list of accepted therapies).
    Chemotherapy Drugs;

    Drug3k, an online drug database launched by the non-profit European Organization of Family Health Research. It aims to provide easily accessible information on the most commonly prescribed drugs.
    Drug3k-Online Drug Encyclopedia;

    US FDA – Current listing of approved oncology drugs with detailed approval information. Click on the trade name of any of the drugs on the list and you will be presented with a long table of technical information on the drug. In addition to the standard view, there are separate views for those who prescribe, prepare and administer the drugs. This is an authoritative source, in some ways the definitive source. While the FDA is chronically underfunded and sometimes subject to political and lobbying pressures, it is nevertheless the pre-eminent regulatory agency in the world for pharmaceuticals and biotechnology. If you want to get the details about a drug, warts and all, this is the place to go. Of course, the FDA cannot tell you about things that have not been reported to it: to some extent it (and the entire world) relies on the drug industry to be self-policing and conscientious in reporting adverse events. There have been some very troubling recent examples where this assumption was not correct.
    FDA Approved Oncology Drugs.

    CancerIndex

    This is a "Guide to Internet Resources for Cancer". Its aim  is to make it easier to find more specific information quickly by providing an directory of some of the key cancer-related sites and pages. Links are sorted into categories (by disease-type, medical specialty country etc.), and where possible annotation is provided to give the reader a brief description of each site / organization. As well as links the site presents basic information about cancer-related topics. Also, the site aims to draw the readers attention to issues about cancer-related information on the Internet, especially those relating to the quality of information . This site is the work product of one individual, Simon Cotterill, who does not have a medical background but does have qualifications in computing and statistics.

    The web address is: http://www.cancerindex.org. A CLL-focused page is at: http://www.cancerindex.org/clinks3y.htm

    CLL Best Practices

    The following articles on best practices in dealing with CLL and its complications will be of interest to CLL patients and their oncologists alike:

    1)   Current Approach to Diagnosis and Management of CLL, Tait Shanafelt and Timothy G. Call, Mayo Clinic Proceedings, March 2024.

    2)   Infectious Complications of CLL, Punit D. Wadhwa and Vicki A. Morrison, Seminars in Oncology, 2024.

    Here is the link to the CLL Topics Best Practices index page, which has links to a collection of our own articles on the subject.

    CLL (PDQ): Treatment

    Entry for CLL in the NCI's PDQ (Physician Data Query) database. You may click on the tab for "health professional" or "patient" to get a tailored presentation. This is the current (11.21.05) official report on staging, symptoms and treatments available for the disease. There is a wealth of links and abstracts attached to the "health professional" version. Required reading for the CLL patient.
    NCI Physician Data Query Database.

    CLL Overview

    CLL Overview articles appear periodically in professional journals or are a part of the annual ASH Education Book. Here are some recent overview articles worth reading.

    1) CLL: Mechanisms of Disease, by Nicholas Chiorazzi, Kanti Rai and Manlio Ferrarini, the New England Journal of Medicine, February 2024;

    2) CLL: Novel Prognostic Factors and Risk Adapted Strategies, by Marco Montillo, Terry Hamblin, Michael Hallek, Emili Montserrat and Enrico Morra, Haematologica, 2024;

    3) CLL: Diagnosis and Treatment, by Karen W. L. Yee and Susan M. O’Brien, Mayo Clinic Proceedings, August 2024.

    CLL Research Consortium

    NCI-sponsored multi-institution CLL research effort with shared infrastructure and resources. 

    The cancer hospitals involved are listed below. Links to all of them may be found at: the CRC website.

    M. D. Anderson,
    Dana Farber,
    Long Island Jewish,
    Ohio State,
    Mayo Clinic,
    The Burnham Institute,
    Bart's Cancer Center in the UK,
    University of California at San Diego.

    Dr. Thomas Kipps at UCSD coordinates the consortium. Dr. Roy S. Wu at the NCI supervises the government funding of the project.

    The list is current as of July 2024. The Burnham Institute is described as involved with CLL basic research only and not a clinical CRC site. Bart's in the UK was added recently after Dr. John Gribben moved from Dana Farber to Barts. You will also note that past members Johns Hopkins and Thomas Jefferson are no longer on the list.

    Current details and a performance summary of this government-sponsored project are available on a database maintained by the National Cancer Institute, the Cancer Research Portfolio. This a database of cancer research projects, funding opportunities and resources and is supposed to be generated on the spot by the NCI database server to be current when you click on the link for any specific project — such as the CLL Research Consortium. However, the server seems to be intermittent in its availability, hence we have provided you with a pdf version of the summary CRC report as a backup, current as of July 29, 2024.

    Other countries have their own CLL research consortia, notably in Europe. Much original research is published by the institutional groups in the U. K., Germany, Sweden, Italy and the other countries of Western Europe..

    CTL Therapy

    Stimulation of cytotoxic T cells against idiotype immunoglobulin of malignant lymphoma with protein-pulsed or idiotype-transduced dendritic cells. Frank Osterroth, Annette Garbe, Paul Fisch, and Hendrik Veelken
    Blood Article on CTL Therapy

    Familial CLL

    If you are aware of multiple instances of CLL or other lymphoproliferative diseases in your own family, you are encouraged to contact one of the research centers to report the details. You can add vital data to the research database which may one day provide us with valuable answers. Here are a couple of contact points for you to get started:

    • The Genetic Epidemiology Branch of the National Cancer Institute has a program for collecting blood and family histories on familial CLL families. Information can be obtained by calling 1-800-518-8474.
    • Mayo Clinic has a research study for families with either CLL or lymphoma. Individuals can either be seen at the clinic, or can fill out questionnaires and submit blood samples from their home facility. Information can be obtained by calling 1-800-610-7093.

    You can also read the following articles published in CLL Topics on the subject:

    Not the Worst Day of Your Life;
    Familial CLL, by Dr. Tim Call of Mayo Clinic.

    FDA Warning Letters to Drug Companies

    The FDA frequently sends warning letters to pharmaceutical and biotech companies regarding false or misleading marketing of their products. The list presented here is organized by company name and drug name. You will find that many of the warnings are related to adverse effects. The list is not limited to oncology drugs but if you know the name of the manufacturer you can easily locate any warning issued on your drug of interest. This link will connect you to the list — PharmCast Warning Letter Index — but you should be aware that the page is maintained by a commercial venture marketing to pharmaceutical and biotech communities. Needless to say, commercial websites are almost always trying to sell something to somebody. Just be aware of the nature of your sources. See also Black Box Warnings, above.

    Gene Delivery Systems

    Article from the Scientist describing multiple approaches to delivering genes. Access to this article requires a free registration to the Scientist, which might be a useful thing to have. You will be asked to register or sign in with your email address before viewing the article.
    Scientist.com Article on gene delivery systems.

    Gene Therapy

    Human Genome Project Information home page on Gene Therapy. Many links.
    Gene Therapy

    Immunotherapy

    Basics of immunotherapy as expounded by the American Cancer Society.
    ACS Immunotherapy Article

    Managing Infections in Immune Compromised Patients

    Extensive multimedia presentation with everything you wanted to know about infections with a special section on CLL. This is a Medscape reference titled "Managing Infections in Patients With Hematological Malignancies". You may access this article with the CLL Topics' sign-in unless you have your own established. (User ID: clltopics; Password: optimist.) There are benefits to registering your own free membership in Medscape, including a free subscription to MedPulse, the weekly email newsletter about what's new on Medscape.
    Medscape Article on managing infections.

    Laboratory Blood Test Results - How to Read and Interpret

    By Joel Gibson, MS. A document published by the Seattle Treatment Education Project, an AIDS education effort.
    Reading Test Results.

    Leukaemia Research Fund

    This UK-based public charity was established in 1960. It is dedicated to "improving treatments, finding cures and learning how to prevent leukaemia and the related blood disorders in both adults and children". Depending entirely on voluntary donations, the LRF annually commits over £ 20,000,000 to the support of research. It also publishes a line of patient education materials.
    Leukaemia Research Fund website.

    The Leukemia and Lymphoma Society

    The LLS provides disease information and patient services. It grew out of a volunteer effort launched in 1944 by a patient's family. Today, the Society is supported by annual donations of over $150,000,000, a professional staff and many volunteers. It supports a wide array of research and scholarship in the search for cures for leukemia, lymphoma, Hodgkin's disease and myeloma, and is dedicated to improve the quality of life of patients and their families.
    Website of the Leukemia and Lymphoma Society.

    Martindale's Health Science Guide

    Online "virtual medical center" with everything from medical texts, courses, modules and cases on topics from bacteriology to urology. This site has a wealth of links to live information on the web. Courtesy University of California, Irvine.
    The link: Martindale Health Science Guide.

    M.D. Anderson - Leukemia Insights Newsletter

    Published by the Leukemia Department 3-4 times annually. Thorough discussion of important new therapies and pivotal clinical trials from the #1 cancer center in the country. Extensive archives. This publication is available in HTML and PDF formats.
    The link: Leukemia Insights.

    Monoclonals

    Very useful introduction to monoclonal antibodies from Kimball's Biology Pages. (A link to Professor Kimball's online text is provided on our Textbooks page.)
    Kimball's Introduction to Monoclonal Antibodies.

    NCI Working Group Guidelines

    Many important definitions are contained in a document titled "National Cancer Institute-Sponsored Working Group Guidelines for CLL: Revised Guidelines for Diagnosis and Treatment". This document, although quite ancient by cancer therapy standards (it was submitted in November 1995 and published in the June 1996 issue of Blood), is nevertherless the authority for what constitutes a CR, PR, Stable or Progressive Disease, besides defining the Rai and Binet staging systems, grading of hematological toxicity, eligibility for clinical trials, and a variety of other related matters. This document's authors' list might explain why it reflects so much authority: Bruce D. Cheson, John M. Bennett, Michael Grever, Neil Kay, Michael J. Keating, Susan O'Brien, and Kanti R. Rai. Here is the link to a pdf version of this document: NCI WG Guidelines.

    The International Workshop on CLL, a biennial professional gathering of CLL specialists from around the world, has come out with its own guidelines and definitions in treating CLL. You might see references in the research literature to the IWCLL criteria or guidelines - while the specific definitions might vary somewhat from the NCI guidelines, being somewhat more "Euro" flavored, they are not fundamentally different from the NCI versions.

    Neutropenia

    Two informative links on the subject of fever and neutropenia.

    Concise presentation on neutropenia, its causes, effects and treatment presented by Cyndi Cramer of RealNurseEd.com. This is an educational module meant for professional nurses.
    Neutropenia Educational Article.

    Comprehensive neutropenia and fever treatment guidelines for cancer patients. Joint publication of the American Cancer Society and the National Comprehensive Cancer Network. This is a 39 page document dated May 2024.
    Neutropenia & Fever Treatment Guidelines.

    NSAIDS

    COX-2 Inhibition, Apoptosis and Chemoprevention by Nonsteroidal Anti-inflammatory Drugs. Overview article by B. C. Moore and D. L. Simmons at BYU. Source: Current Medicinal Chemistry, Volume 7, Number 11, November 2024, pp. 1131-1144(14)
    Link to article in pdf form: Moore/Simmons NSAIDS Article.

    NF-κB

    NF-kB Primer - comprehensive background presentation at this website. 
    This link tends to change, so you may have to run a Google search by the author's name to get to this page: Dr. Thomas D Gilmore, Biology Department, Boston University.
    Gilmore's NF-kB Primer.

    NF-kB in Therapy - Therapeutic potential of inhibition of the NF-B pathway in the treatment of inflammation and cancer.
    Yumi Yamamoto & Richard B. Gaynor, UT Southwestern Medical Center, Dallas.
    NF-kB Inhibition as Therapy.

    Patient Run Support Groups

    Here are a few online volunteer groups that assist patients and families dealing with CLL and related diseases. These support groups are a godsend to the newly diagnosed patient or family member and a source of continuing strength for the battle-weary.

    The ACOR (Association of Cancer On-line Resources) CLL List is like a cyber village, where you go to meet friends, exchange anecdotal information, welcome newcomers, provide solace and comfort to those in need, and raise general awareness of CLL-related issues. There is a tremendous amount of information available in the List’s archives. The membership is large and varied and discussions sometimes wander far afield. The web address is: ACOR CLL List. ACOR also maintains a list of CLL-specific links at ACOR Leukemia Links: CLL

    The CLL Information Group is a recently established patient organization that maintains a web site at http://www.cllinfogroup.org. The mission of the group is to provide disease-specific information to CLL patients and caregivers, to increase awareness about the disease and to gain increased visibility in order to achieve greater support from the medical community. They also have a discussion group: cllsll@yahoogroups.com. This group is associated with the Lymphoma Research Foundation.

    The CLL Research Discussion Group is hosted on Yahoo! Groups. Posts are generally restricted to citations of research papers or abstracts published in various medical journals, or news accounts of significant interest to the CLL community. Members have access to the archives and Yahoo's search engine makes it easy to look for specific posts. The web address is: Yahoo CLL Research Group.

    Lymphomation.org  is a large, well-organized patient support group for Non-Hodgkins Lymphoma. According to their mission statement, "We provide a helping hand by linking patients and caregivers to reputable evidence-based information, and voicing patient perspectives in the fight against non-Hodgkin's lymphomas." The affiliated online support group, NHL-Info, is hosted on Yahoo! Groups. There is much material of interest to CLL patients at these sites.  Here is the address for the website: lymphomation.org, and that for the online support group is: NHL Info on Yahoo Groups.

    NHL Cyberfamily  is a support group for NHL patients. The group is run by an NHL survivor, Greg Dafoe, who lives in Canada. It supports an informative website, nhlcyberfamily.org, and a very active, well-moderated discussion group hosted on Yahoo Groups, NHL. National boundaries are of little consequence in CLL or NHL: you might find your perfect match of helpful friends with this group. As with Lymphomation.org, there is much of interest at these sites to CLL patients.

    Leukämie-Online.de is one of the largest online communities of leukemia patients in German-speaking countries. Among the major objectives of the group are patient education and the rapid  dissemination of information about new treatment options and the progress in research and therapies. Like CLL Topics, this organization has been launched and is run by volunteers and is entirely patient funded. The community was founded and its website created by Jan, a CML patient. Some articles that appeared in CLL Topics have been translated into German for publication on this website by Topics volunteer Roland Keilwerth. Here is the link to: leukaemie-online.de.

    UK CLL Support Association is a community of leukemia patients in the United Kingdom. This group provides UK-specific support to patients and their care-givers. It is run by volunteers and conducts regular patient meetings, facilitates conferences with expert speakers, delivers literature through the hospital network and also has a web presence available to the public. This group has an interest in promoting targeted clinical research and does its own fundraising as a registered charity. The website is at: UK CLLSA.

    Performance Status

    A performance status scale is one which doctors use to describe how well you are — it is an attempt to quantify a cancer patients general state of well-being.

    ECOG: The Eastern Cooperative Oncology Group has come up with operational performance standards that are often quoted in inclusion or exclusion criteria for clinical trials. These ratings go all the way from '0' for 'Fully Active' to '5' for 'Dead'. (As a patient I am sure you can see how much easier these things are to understand when presented in these eloquent technical terms.) For details see ECOG Performance Status. ECOG Performance status is also sometimes called the Zubrod Score. The WHO Performance Scale is similar if not identical. .

    Karnofsky Score: The Karnofsky score is another method which measures patient performance of activities of daily living. The score has proven useful not only to follow the course of the illness (usually progressive deficit and ultimately death), but also a prognosticator: patients with the highest (best) Karnofsky scores at the time of tumor diagnosis have the best survival and quality of life over the course of their illness. For details, see Karnofsky Score Definitions.

    See also Wikipedia entry on Performance Status.

    Phytochemicals — Herbs, Botanicals, Neutraceuticals and "Alternative" Medicines

    Patients suffering from incurable chronic conditions are always interested in "complementary", "alternative" and non-medical agents they can use to improve or stabilize their conditions. While the Internet is a rich source of information on these subjects, unfortunately much of the available information is unreliable or commercially motivated. It is therefore important that patients pay attention to the nature and motivations of the source of the information they consider.

    Here are a few high quality references that may help you get started.

    Memorial Sloan Kettering Cancer Center - Very useful reference on a broad range of products. This site provides objective information for oncologists and healthcare professionals, including a clinical summary for each agent and details about constituents, adverse effects, interactions, and potential benefits or problems. Evaluations of alternative or unproved cancer therapies also are given. Comprehensive, authoritative and replete with references to scholarly work. If you find this material hard to digest, each entry has a tab to display a consumer version of the information. 
    MSKCC Herbs & Botanicals Reference

    U. S. FDA Center for Food Safety and Applied Nutrition - Website on Dietary Supplements maintained by the FDA, including advisories and alerts on unsafe supplements.
    FDA Website on Dietary Supplements

    National Institutes of Health - Office of Dietary Supplements - Website provides dietary supplement fact sheets. It is important not to place too much reliance on "educational information" provided by the vendors of various supplements on the market, all claiming numerous virtues for their product - at a price. These articles, in pdf format, address the value, use and abuse of supplements.
    NIH Dietary Supplement Fact Sheets

    Prognostic Indicators

    Two articles on IgVH gene mutation and CD 38 as prognostic indicators in CLL. Both articles appeared in Blood Journal.

    Unmutated Ig VH Genes Are Associated With a More Aggressive Form of Chronic Lymphocytic Leukemia. By Terry J. Hamblin, Zadie Davis, Anne Gardiner, David G. Oscier, and Freda K. Stevenson
    Blood Journal Article on VH Gene Mutation Status.

    Ig V Gene Mutation Status and CD38 Expression As Novel Prognostic Indicators in Chronic Lymphocytic Leukemia. By Rajendra N. Damle, et al.
    Blood Journal Article on Gene Mutation Status and CD38 Expression.

    The following articles by Chaya Venkat in CLL Topics summarize the prognostic tools available to understand the prospects for CLL patients.

    What Type of CLL Do You Have?

    Prognosis at Diagnosis

    Prognostic Indicators for Infection Risk

    FISH-ing for Answers

    ZAP-70 and IgVH Gene Mutation Status

    Prognostic and Monitoring Test Packages Now Available

    Science Behind Cancer

    NCI's overview of cancer related science. Introductory treatment supported by numerous illustrations.
    Here's the link: Understanding Cancer.

    Stem Cell Transplants

    The BMTInfonet offers much useful information and support to patients who are considering stem cell, bone marrow or cord blood transplants. It is a non-profit effort that has been supporting patients since 1990.
    The link: www.bmtinfonet.org

    The Body

    Multifaceted website with a wealth of information AIDS, blood diseases, immunology and related subjects. Rated one of the best health websites. Much of the information is relevant to hematological cancers.
    The link: http://www.thebody.com 

    Understanding the Immune System

    NCI's excellent basic introduction to the immune system. Introductory treatment supported by numerous illustrations.
    Understanding Cancer - The Immune System.

    Vitamin D3

    Vitamin D3 or cholecalciferol has multiple functions in human physiology. Some of these functions are critically important in preventing and fighting infections, inflammation and even cancers. Traditionally, the value of this vitamin has been greatly underappreciated — and traditional dosage guidelines are now viewed by experts as seriously inadequate. The risk of hypercalcemia (a serious and even fatal condition) comes into play at high dosage rates: an issue to be carefully considered. There is an impressive body of credible research supporting the new viewpoint.

    Vitamin D Council: The Vitamin D Council is a well-organized website with comprehensive information on the topic, presented in a straightforward way that patients can understand. The experts behind this organization have impressive credentials.

    CLL Topics: Of course, we have our own collection of articles and Alerts on the subject of Vitamin D3 and its importance in CLL. You can find links to the entire collection on our Vitamin D3 page.

    Vitamin D Dosage: Peer reviewed paper from the American Journal of Clinical Nutrition on a tolerable upper limit for vitamin D dosage — Risk Assessment for Vitamin D.

     

    New York Public Library

     

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