Welcome to CLL CANADA

CLL CANADA.ca is for patients, caregivers, families and companions of CLL/SLL patients. The information contained here is from the experiences of CLL patients and should never be considered expert medical information or opinion.

CLL and SLL are used interchangeably on this website. To learn more about SLL: Click Here

The best place to start is to select the "The Basics" menu above, or jump right into some of the articles below.

For many more CLL specific links: Click Here

We welcome you comments and suggestions: Email Link

~chris
CLL patient since 2000 - W&W Stage 1, WBC 47K


Excellent Resources:

CLL/SLL Overview: Understanding CLL/SLL: A Guide for Patients, Survivors and Loved Ones

Important Treatment Guidelines: 2008 CLL Treatment Guidelines (.pdf file) by Michael Hallek et al.

General Overview of White Blood Cell (WBC) disorders: Merck Manuals

CLL Researchers' Overview: CLL Treatment Options from 2006.

British Journal of Haematology, 2004: Guidelines on the diagnosis and management of CLL

General Canadian Cancer Resources Info: Cancer View Canada


headtohead

Cladribine and Fludarabine - compared head to head in major randomized clinical trial

Research just published in the Journal of Clinical Oncology reports on a large randomized clinical trial of 423 patients in the Polish Adult Leukemia Group, PALG-CLL3 Study.

This study compared the purine analog Cladribine (2CDA) combined with Cyclophosphimide with the first line treatment for CLL, Fludarabine and Cyclophosphimide.

Up until this point Cladribine (Leustatin) has been used to treat hairy cell leukemia (leukemic reticuloendotheliosis) and multiple sclerosis.

While Cladribine is a purine analogue and in the same family as Fludarabine it works in a different manner. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. Cladribine has similar side effects to Fludarabine, like T4 cell reductions, a decline in blood cell counts, increases the risk of herpes virus infections and so on.

This study reported: "Of 423 randomly assigned patients (211 to CC and 212 to FC), 395 were evaluated in the final analysis. The CR and ORR reached 47% and 88% in the CC arm and 46% and 82% in the FC arm (P = .25 and P = .11, respectively). The median PFS was 2.34 years with CC and 2.27 years with FC (P = .51). OS and grade 3/4 treatment-related toxicity were also comparable. Moreover, we did not observe any significant differences in CC and FC efficacy across different patient prognostic subgroups that included patients with 17p13 (TP53 gene) deletion who had poor survival in both study arms."

This study concluded: "Cladribine and fludarabine in combination with cyclophosphamide are equally effective and safe first-line regimens for progressive CLL. Both combinations have unsatisfactory activity in patients with 17p13 (TP53 gene) deletion."

Abstract: Click Here

March 10th, 2010

Are CLL patients exposed to too much radiation?

A recent paper published by the FDA's Center for Devices and Radiological Health has started an initiative to reduce unnecessary radiation exposure from medical imaging. The two largest emitters of radiation currently are from computed tomography (CT) 'CAT' scan and fluoroscopy.

Medical imaging procedures are vital for modern medicine and offer important clinical information to the physician. In CLL, CT scans can provide information on node and spleen involvement with the disease. But it must ask if the same or similar information can not be obtained by simple 'hands on' palpation of the spleen and lymph nodes? ct_scanner

Certainly, palpation does not offer a high tech image of the node system or spleen, but this is not needed for most CLL patients at diagnosis. What is needed to be known is by how much the nodes and spleen are swollen.

Even in treated of relapsed patients CT scans may not be of added benefit.

A report in relapsed CLL patients in The Journal of Clinical Oncology, 2007, stated;
"Current CLL response criteria are a significant predictor of PFS in previously treated CLL patients, with no additional benefit from the inclusion of CT scans. Although retrospective, these results highlight the importance of prospective validation of CT scans before routine inclusion in CLL response criteria." Read More Here

The 2008 revision National Cancer Institute–Working Group's CLL Treatment Guidelines by Michael Hallek states;

3.5.2.2. CT scans generally are not required for the initial evaluation or follow-up. Moreover, the staging of CLL does not use CT scans but relies on physical examination and blood counts.

In clinical trials, in which the treatment intent is to maximize complete remission (CR), chest, abdominal, and pelvic CT scans are recommended to evaluate the response to therapy. One CT scan should be performed before the start of therapy and another CT scan at the first re-staging after therapy if previously abnormal.


radiation It is important to look at the dose of radiation CLL patients get during each scan. According to the FDA report "The adult effective dose from a CT exam of the abdomen is roughly equivalent to the adult effective dose from roughly 400 chest x-rays". (8 mSv) (Mettler, Jr. FA, et al., July 2008.)

Considering this dosage, would you have 400 chest x-rays in a row?

The American National Council on Radiation Protection and Measurements (NCRP) states that the U.S. population’s total exposure to ionizing radiation has nearly doubled over the past two decades. NCRP estimates that 67 million CT scans, 18 million nuclear medicine procedures, and 17 million interventional fluoroscopy procedures were performed in the U.S. in 2006, and the authors predict that these figures will continue to grow.

Clearly, CT Scans have a benefit and a risk. It is a personal decision between you and your doctor, but it may make very good sense to have one CT scan shortly after diagnosis to set a baseline of the spleen and node involvement and a second after treatment.

However, since CLL patients are at a 2.2 times greater risk for all secondary cancers according to a MD Anderson Study (2009) each patient must question the over use of diagnostic radiation, particularly CT scans, which may increase risk of cancer.

Like most diagnostics, CT scans are an important medical tool, but many feel they are over used. The FDA recognizes the importance of empowering patients with information and tools to help them and their physicians manage their exposure to radiation from medical imaging in the short term, even before longer-term changes take effect.

It is highly recommended that CLL patients keep a record of your radiation exposure.
To this end, an X-ray Report Card is available in .pdf format: HERE

FDA Paper - Initiative to Reduce Unnecessary Radiation Exposure from Medical Imaging

More Information on CT Scans:

Click Here
and
Click Here
March 6th, 2010

Transgenic goats make a better anti-CD20 monoclonal antibody

transgoat An announcement today from GTC Biotherapeutics states that it has achieved high-level production of TG20; an anti-CD20 monoclonal antibody (MAb). The TG20 MAb, which is produced in the milk of transgenic goats, is being co-developed by GTC and LFB (a French Company) as part of the LFB-GTC joint venture. (The LFB Group is the leading manufacturer of plasma-derived medicinal products in France and 6th worldwide and is also among the leading European companies for the development of monoclonal antibodies and new-generation proteins based on biotechnologies.)

TG20 has enhanced antibody-dependent cell-mediated cytotoxicity (ADCC), a key feature useful in the treatment of cancer and auto-immune diseases, and it has been shown to have 10-fold enhanced ADCC when compared side by side with rituximab in assays performed with B-cell chronic lymphocytic leukemia, or B-CLL, patient cancer cell isolates.

Under their joint venture, GTC and LFB are developing TG20, a MAb that targets the CD20 receptor of the immune system with target specificity similar to the rituximab MAb (Rituxan®, MabThera®). This antibody has demonstrated a significantly higher ADCC than rituximab. ADCC is one of the mechanisms that the immune system uses to kill cells targeted by a specific antibody. Therapeutic MAbs with increased ADCC are believed to offer more potent treatments for oncology indications. Rituximab has received marketing approval in both the EU and the U.S. for rheumatoid arthritis. Worldwide sales of rituximab were approximately $5.6 billion in 2009.

Article

March 1st, 2010

ATM gene - not the machine

DNA makes RNA, RNA makes protein, and proteins make us. Francis Crick

atm The genetic basis for CLL is partly known. It has been demonstrated by FISH test that the ATM gene is mutant in approximately 20% of samples from CLL patients and that some patients have heterozygous germ line mutations.
The ataxia telangiectasia-mutated gene (ATM) encodes a protein kinase that acts as a tumour suppressor. (Kinase enzymes modify other proteins by chemically adding phosphate groups to them). The ATM protein coordinates DNA repair by activating enzymes that fix the broken double strand breaks (DSBs) of DNA that it finds, rather like glue. The ATM protein is found to be missing on the long arm of 11q chromosome at position 22.3 (aka - 11q:22.3) of CLL patients and is also associated with many other types of cancers as well, like breast cancer. The ATM gene is extremely important to cell repair and survival and it works in conjunction with TP53, found of 17p chromosome (17p:13), to achieve cell death (apoptosis).

The primary function of ATM is to check cells for defects due to radiation damage and repair them if it can be done. Without any functional ATM protein cells are hypersensitive to radiation and do not respond normally to DNA damage. Instead of activating DNA repair, the defective ATM protein allows mutations to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way.

ATM tries its best to repair cell damage but at some point p53 (protein) assesses the repair process and if it is not going as expected, then TP53 actually sets up the cell death.

In some CLL patients parts of the 11q:22.3 chromosome and the 17p:13 chromosome are damaged or missing. This prevents two important things from occurring. The first failure is the inability to repair damaged genes with ATM, and second failure is to kill defective cells with TP53 (the gene).

Both 11q and 17p deletions are considered the most aggressive forms of CLL, probably because cell repair is blocked by no ATM and cell death fails without the TP53 gene.

ATM Genetics: ATM

More than you ever want to know about ATM: Venture Here

More Information of CLL Genetics (.pdf): Click Here

March 1st, 2010

Familial CLL study in Norway & Denmark

Norden This is a new study looking at approximately 800 cases of CLL. In 56 (7%) out of 800 CLL patients with hematological diseases of all kinds, 51 families and 141 cases of CLL were determined.

Of the total 141 cases of all malignant hematological disease, 107 or 75% were CLL.

Researchers in this study found that paternal (father's side) CLL disease, was transmitted primarily to the youngest sons, but maternal (mother's family side) showed equal distribution of CLL to all siblings. This was demonstrated by means of matrix conjugation and confirmed with Cox regression on parity and birth order.

In this study, researchers found that B-cell expression was exactly the same in familial CLL and sporadic CLL. They also concluded that paternal genomic imprinting is pointed out as one possible mechanism behind this non-Mendelian genomic output.

Source: In Vivo. 2010 Jan-Feb;24(1):85-95., Pay Per View Article
Feb 24th, 2010

Cutaneous Richter’s syndrome ~ Extremely Rare

This study comes from France and concerns 4 cases of cutaneous Richter's syndrome (Transformation)

Richter’s syndrome (RS) corresponds to the transformation of chronic lymphocytic leukemia (CLL) into high-grade lymphoma. RS can involve extranodal sites including the gastrointestinal tract, lungs and skin. Cutaneous RS is rare. In this study researchers describe 4 cases with clinical manifestations, histological and immunohistological patterns, and outcome.

Methods: Clinical data was analyzed and all patients’ skin biopsy samples stained with HE for the CD20, CD5, CD3 and CD30 antigens. Epstein-Barr-virus (EBV)-encoded early RNA and clonal rearrangements were also analyzed.

Results: The patients’ mean age at CLL diagnosis was 57 years (53–62 years), with a male/female sex ratio of 3:1. The transformation to cutaneous RS occurred between 8 and 75 months after initial diagnosis and progressed to a fatal systemic disease in 3 cases, between 24 and 129 months. Cutaneous CLL was associated with earlier transformation in our series and could not be distinguished from RS on clinical grounds alone. All patients in the study had a large-cell infiltrate and clonal rearrangements.

Conclusions: The precise mechanism of RS is unclear, but a role of EBV has been suggested in fludarabine-treated CLL. For all patients, the diagnosis of transformation was made on the basis of cutaneous localizations and led to intensified CLL treatment.

Abstract Link: Dermatology (DOI: 10.1159/000269737)
Feb 23rd, 2010

CLL Research News - moved to main menu 'Research'



CLL Canada News

Canadian Blood Agency
Canadian CLL Clinical Trials

Reovirus studied for CLL too!

Recent news from researchers in Canada, found that the live reovirus was able to infect human prostate cancer cells and kill them.

A ‘reovirus’ (short for respiratory, enteric, orphan virus) is common and usually causes very minor flu symptoms, and often no symptoms at all, in humans. The virus appears to kill cancerous cells over healthy cells. It has already been shown to have potential for treating other cancers such as bowel, colon, ovarian, breast, and bladder cancer.

Reovirus is also being studied for possible use with CLL.

See Here: Reovirus therapy of lymphoid malignancies

CytRx announces CLL trial for Bafetinib

CytRx announced today that they will be proceeding with a phase 2 proof-of-concept clinical trial with Bafetinib in patients with high-risk B-CLL. Trial locations will be given at a later date.

Bafetinib (INNO-406, NS-187) is a dual ABL/Lyn inhibitor developed by a team at Kyoto University Hospital in collaboration with Nippon Shinyaku. Bafetinib was 25-55 times more potent than imatinib in blocking BCR/ABL autophosphorylation, while otherwise retaining specificity for ABL and Lyn.

Bafetinib had antiproliferative effects against cells bearing wild-type or most mutated BCR/ABL proteins, except T315I, and also inhibited BCR/ABL-positive leukemic cell growth in the central nervous system. A phase I study on bafetinib was completed and the agent was well tolerated and demonstrated clinical activity across a range of doses, for the treatment of chronic myeloid leukemia (CML).

March 8th, 2010

Gabrielle's Angel Foundation Scholar Award

The Gabrielle's Angel Foundation for Cancer Research is named for Gabrielle Rich Aouad, who passed away in 1996 at the age of 27 after a long struggle against acute myelogenous leukemia. It was Gabrielle's wish that a Foundation be created to help spare others the suffering that she endured. Upon her passing, her mother, Denise Rich established the Foundation to support blood cancer research.

The Foundation has joined ASH in support of research by funding a 2010 Junior Faculty Scholar Award.

This year's recipient is Dr. Jennifer R. Brown, MD. Ph.d. from the Dana-Farber Cancer Institute, whose research will focus on using genomic technology to explore the pathogenesis of familial and sporadic chronic lymphocytic leukemia (CLL) and, ultimately, to identify genes that predispose a patient to acquiring CLL.

March 8th, 2010

Connect™ - Observational CLL Clinical Trial

The purpose of the Connect™ Chronic Lymphocytic Leukemia (CLL) Disease Registry is to explore the history and real world management of patients diagnosed with CLL,connect provide insight into the management of CLL, and evaluate the effectiveness of first, second and subsequent therapeutic strategies employed in both the community and academic settings.

Clinical Trial Info

March 5th, 2010

CD20 antibodies - current crop

Monoclonal antibody (mAb) therapy with the anti-CD20 mAb Rituximab represents one of the most important advances in the treatment of CLL in the last 30 years.

This paper is a review from the Southampton University School of Medicine, about CD20 monoclonals both in the clinic, trials and the lab.

Rather technical read, but worth the effort...

Read More Here .pdf

March 4th, 2010

UK to pay for Rituxan

The U.K.'s National Institute for Health and Clinical Excellence, or NICE, Thursday recommended publicly funded use of drug MabThera (Rituxan) for treating certain patients with relapsed or refractory chronic lymphocytic leukemia.

NICE said its draft guidance recommends rituximab, in combination with fludarabine and cyclophosphamide, for the treatment of this disease except when the condition hasn't previously responded to fludarabine or has relapsed within six months of treatment, or has previously been treated with rituximab.

Professor Peter Littlejohns, clinical and public health director at NICE, said: "Treatment for chronic lymphocytic leukemia can differ from patient to patient depending on factors such as whether a patient has any genetic abnormalities or received any previous treatment. Rituximab, in combination with fludarabine and cyclophosphamide, will offer another treatment option for those patients with relapsed or refractory disease who may benefit most from the drug."

NICE said the recommendations are preliminary and subject to a second round of consultations. NICE's views are closely watched by governments and health insurers worldwide.

Source: Wall Street Journal

March 2nd, 2010

Recent CLL News

Click Here
CLL Flowchart

Many people have asked me for a visual 'Treatment Flowchart' dealing with CLL so they can get the big picture. CLL%20Flowchart This chart is based on work from 2004 and applies generally in most countries. The U.S. experience may be a bit different. This chart is available free to you in .pdf format GET IT HERE

Conferences ~ Meetings

EBMT Conference

36th Annual Meeting of the European Group for Blood and Marrow Transplantation

Vienna • Austria • 21 – 24 March 2010 MORE HERE

ASCO Annual Meeting 2010 - American Society of Clinical Oncology

June 4-8th, McCormick Place, Chicago, Illinois MORE HERE

XIII International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2010

October 15th Fira Barcelona Hall 4, Av Reina Maria Cristina s/n Barcelona, , Spain