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Encyclopedia > Chronic lymphocytic leukemia
Chronic lymphocytic leukemia
Classification & external resources
Peripheral blood smear showing CLL cells
ICD-10 C91.1
ICD-9 204.9
ICD-O: 9823/3
DiseasesDB 2641
MedlinePlus 000532
eMedicine med/370 
MeSH D015462

Chronic lymphocytic leukemia (also known as "chronic lymphoid leukemia" or "CLL"), is a type of leukemia, or cancer of the white blood cells (lymphocytes). CLL affects a particular lymphocyte, the B cell, which originates in the bone marrow, develops in the lymph nodes, and normally fights infection. In CLL, the DNA of a B cell is damaged, so that it can't fight infection, but it grows out of control and crowds out the healthy blood cells that can fight infection. Image File history File links Download high resolution version (2004x1510, 169 KB) Summary Taken by Mary Ann Thompson. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // C00-D48 - Neoplasms (C00-C14) Malignant neoplasms, lip, oral cavity and pharynx (C00) Malignant neoplasm of lip (C01) Malignant neoplasm of base of tongue (C02) Malignant neoplasm of other and unspecified parts of tongue (C03) Malignant neoplasm of gum (C04) Malignant neoplasm of floor of mouth (C05) Malignant neoplasm of... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The International Classification of Diseases for Oncology (ICD-O) is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... Leukemia or leukaemia (see spelling differences) is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes). ... A lymphocyte is a type of white blood cell involved in the human bodys immune system. ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ...


CLL is an abnormal neoplastic proliferation of B cells. The cells accumulate mainly in the bone marrow and blood. CLL is closely related to a disease called small lymphocytic lymphoma (SLL), a type of non-Hodgkin's lymphoma which presents primarily in the lymph nodes. The World Health Organization considers CLL and SLL to be "one disease at different stages, not two separate entities".[1] Small cell lymphoma (or small lymphocytic lymphoma) is a type of follicular B-cell lymphoma. ... Non-Hodgkins lymphoma is a type of cancer. ... Lymph nodes are components of the lymphatic system. ... “WHO” redirects here. ...


In the past, cases with similar microscopic appearance in the blood but with a T cell phenotype were referred to as T-cell CLL. However, it is now recognized that these so-called T-cell CLLs are in fact a separate disease group and are currently classified as T-cell prolymphocytic leukemias. T-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin involvement. ...


Acute lymphocytic leukemia (ALL) is a disease of children, but CLL is a disease of adults. Most (>75%) people newly diagnosed with CLL are over age 50, and two-thirds are men. In the United States during 2007, it is estimated there will be 15,340 new cases diagnosed and 4,500 deaths[2], but because of prolonged survival, many more people are living with CLL.[citation needed] Acute lymphocytic leukaemia (ALL), also known as acute lymphoblastic leukaemia is a cancer of the white blood cells, characterised by the overproduction and continuous multiplication of malignant and immature white blood cells (referred to as lymphoblasts) in the bone marrow. ...


Most people are diagnosed without symptoms as the result of a routine blood test that returns a high white blood cell count, but as it advances CLL results in swollen lymph nodes, spleen, and liver, and eventually anemia and infections. Early CLL is not treated, and late CLL is treated with chemotherapy and monoclonal antibodies. Survival varies from 5 years to more than 25 years. It is now possible to diagnose patients with short and long survival more precisely by examining the DNA mutations, and patients with slowly-progressing disease can be reassured and may not need any treatment in their lifetimes.[3]

Contents

Classification and prognosis

Clinical staging

Staging is done with the Rai staging system and the Binet classification (see details[4]).


Gene mutation status

Recent publications suggest that two[5] or three[6] prognostic groups of CLL exist based on the maturational state of the cell. This distinction is based on the maturity of the lymphocytes as discerned by the immunoglobulin variable-region heavy chain (IgVH) gene mutation status.[7] High risk patients have an immature cell pattern with few mutations in the DNA in the IgVH antibody gene region whereas low risk patients show considerable mutations of the DNA in the antibody gene region indicating mature lymphocytes. An antibody molecule. ...


Since assessment of the IgVH antibody DNA changes is difficult to perform, the presence of either cluster of differentiation 38 (CD38) or Z-chain–associated protein kinase-70 (ZAP-70) may be surrogate markers of high risk subtype of CLL.[7] Their expression correlates with a more immature cellular state and a more rapid disease course. The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... CD38 (cluster of differentiation 38) is a glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B and natural killer cells. ... CD38 (cluster of differentiation 38) is a glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B and natural killer cells. ... ZAP-70 is an abbrevation for Zeta-chain-associated protein kinase 70 (70 is the molecular weight in kDa). ...


Fluorescent in situ hybridization (FISH)

In addition to the maturational state, the prognosis of patients with CLL is dependent on the genetic changes within the neoplastic cell population. These genetic changes can be identified by fluorescent probes to chromosomal parts using a technique referred to as fluorescent in situ hybridization (FISH).[7] Four main genetic aberrations are recognized in CLL cells that have a major impact on disease behavior. A metaphase cell positive for the bcr/abl rearrangement using FISH. The chromosomes can be seen in blue. ...

  1. Deletions of part of the short arm of chromosome 17 (del 17p) which target the cell cycle regulating protein p53 are particularly deleterious. Patients with this abnormality have significantly short interval before they require therapy and a shorter survival. This abnormality is found in 5-10% of patients with CLL.
  2. Deletions of the long arm on chromosome 11 (del 11q) are also unfavorable although not to the degree seen with del 17p. The abnormality targets the ATM gene and occurs infrequently in CLL (5-10%).
  3. Trisomy 12, an additional chromosome 12, is a relatively frequent finding occurring in 20-25% of patients and imparts an intermediate prognosis.
  4. Deletion of the long arm of chromosome 13 (del 13q) is the most common abnormality in CLL with roughly 50% of patients with cells containing this defect. These patients have the best prognosis and most will live many years, even decades, without the need for therapy. The gene targeted by this deletion is a segment that likely produces small inhibitory RNA molecules that affect expression of important death i

Symptoms and signs

Most people are diagnosed without symptoms as the result of a routine blood test that returns a high white blood cell count, but as it advances CLL results in swollen lymph nodes, spleen, and liver, and eventually anemia and infections.


Uncommonly, CLL presents as enlargement of the lymph nodes without a high white blood cell count or no evidence of the disease in the blood. This is referred to as small lymphocytic lymphoma. Small cell lymphoma (or small lymphocytic lymphoma) is a type of follicular B-cell lymphoma. ...


Diagnosis

CLL is usually first suspected by the presence of a lymphocytosis, an increase in one type of the white blood cell, on a complete blood count (CBC) test. This frequently is an incidental finding on a routine physician visit. Most often the lymphocyte count is greater than 4000 cells per mm3 (microliter) of blood but can be much higher. Lymphocytosis is an increase in the number of lymphocytes in the blood. ...


Determining clonality

The diagnosis of CLL is based on the demonstration of an abnormal population of B lymphocytes in the blood, bone marrow, or tissues that display an unusual but characteristic pattern of molecules on the cell surface. This atypical molecular pattern includes the co-expression of cells surface markers cluster of differentiation 5 (CD5) and cluster of differentiation 23 (CD23). In addition, all the CLL cells within one individual are clonal, that is genetically identical. In practice, this is inferred by the detection of only one of the mutually exclusive antibody light chains, kappa or lambda, on the entire population of the abnormal B cells. Normal B lymphocytes consist of a stew of different antibody producing cells resulting in a mixture of both kappa and lambda expressing cells. The lack of the normal distribution of kappa and lambda producing B cells is one basis for demonstrating clonality, the key element for establishing a diagnosis of any B cell malignancy (B cell Non-Hodgkin lymphoma). The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... CD5 is a cluster of differentiation found on a subset of IgM secreting B cells called B-1 cells. ... CD5 is a cluster of differentiation found on a subset of IgM secreting B cells called B-1 cells. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... CD23 or Fc epsilon RII is the low affinty receptor for IgE, an antibody isotype involved in allergy and (arguably) resistance to parasites and is important in regulation of IgE levels. ... CD23 or Fc epsilon RII is the low affinty receptor for IgE, an antibody isotype involved in allergy and (arguably) resistance to parasites and is important in regulation of IgE levels. ...


Clonality is confirmed by the combination of the microscopic examination of the peripheral blood and analysis of the lymphocytes by flow cytometry. The later is easily accomplished on a small amount of blood. A flow cytometer is an instrument that can examine the marker molecule expression on individual cells in fluids. This is accomplished using antibodies with fluorescent tags recognized by the instrument. In CLL, the lymphocytes are genetically clonal, of the B cell lineage (express marker molecules cluster of differentiation 19 (CD19) and CD20), and characteristically express the marker molecules CD5 and CD23. Morphologically, the cells resemble normal lymphocytes under the microscope, although slightly larger, and are fragile when smeared onto a glass slide giving rise to many broken cells (smudge cells). Analysis of a marine sample of photosynthetic picoplankton by flow cytometry showing three different populations (Prochlorococcus, Synechococcus and picoeukaryotes) Flow cytometry is a technique for counting, examining and sorting microscopic particles suspended in a stream of fluid. ... Flow cytometry is a technique for counting, examining and sorting microscopic particles suspended in a stream of fluid. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... CD20 is a non-glycosylated phosphoprotein expressed on the surface of all mature B-cells. ... CD5 is a cluster of differentiation found on a subset of IgM secreting B cells called B-1 cells. ... CD23 or Fc epsilon RII is the low affinty receptor for IgE, an antibody isotype involved in allergy and (arguably) resistance to parasites and is important in regulation of IgE levels. ...


Differential diagnosis

Hematologic disorders that may resemble CLL in their clinical presentation, behavior, and microscopic appearance include mantle cell lymphoma, marginal zone lymphoma, B cell prolymphocytic leukemia, and lymphoplasmacytic lymphoma.

  • B cell prolymphocytic leukemia (B PLL), which is a related but more aggressive disorder, has cells with similar phenotype but that are signficantly larger than normal lymphocytes and have a prominent nucleolus suggests a related.
  • Hairy cell leukemia is also a neoplasm of B lymphocytes but differs significantly from CLL by its morphology under the microscope (hairy cell leukemia cells have delicate, hair-like projections on their surface) and marker molecule expression.

All the B cell malignancies of the blood and bone marrow can be differentiated from one another by the combination of cellular microscopic morphology, marker molecule expression, and specific tumor-associated gene defects. This is best accomplished by evaluation of the patient's blood, bone marrow and occasionally lymph node cells by a pathologist with specific training in blood disorders. A sophisticated instrument called a flow cytometer is necessary for cell marker analysis and the detection of genetic problems in the cells may require visualizing the DNA changes with fluorescent probes by fluorescent in situ hybridization (FISH). Hairy cell leukemia is a B cell neoplasm. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Flow cytometry is a technique for counting, examining and sorting microscopic particles suspended in a stream of fluid. ... A metaphase cell positive for the bcr/abl rearrangement using FISH. The chromosomes can be seen in blue. ...


Treatment

Whilst generally considered incurable, CLL progresses slowly in most cases. Many people with CLL lead normal and active lives for many years - in some cases for decades. Because of its slow onset, early-stage CLL is generally not treated since it is believed that early CLL intervention does not improve survival time or quality of life. Instead, the condition is monitored over time.


The decision to start CLL treatment is taken when the patient's clinical symptoms or blood counts indicate that the disease has progressed to a point where it may affect the patient's quality of life.


CLL treatment focuses on controlling the disease and its symptoms rather than on an outright cure. CLL is treated by chemotherapy, radiation therapy, biological therapy, or bone marrow transplantation. Symptoms are sometimes treated surgically (splenectomy removal of enlarged spleen) or by radiation therapy ("de-bulking" swollen lymph nodes). Chemotherapy is the use of chemical substances to treat disease. ... Clinac 2100 C100 accelerator Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ... Immunotherapy is a disease treatment based upon the concept of triggering the bodys own natural defenses to fight off the disease, usually by stimulating the immune system either locally or systemically. ... Bone marrow transplantation is a medical procedure that involves stem cell transplantation. ... A splenectomy is a procedure that involves the removal of the spleen by operative means. ... Clinac 2100 C100 accelerator Radiation therapy (or radiotherapy) is the medical use of ionizing radiation as part of cancer treatment to control malignant cells (not to be confused with radiology, the use of radiation in medical imaging and diagnosis). ...


Clinical "staging systems" such as the Rai 4-stage system and the Binet classification can help to determine when and how to treat the patient.[4]


Determining when to start treatment and by what means is often difficult; studies have shown there is no survival advantage to treating the disease too early. The National Cancer Institute Working Group has issued guidelines for treatment, with specific markers that should be met before it is initiated.[8]


Initial CLL treatments vary depending on the exact diagnosis and the progression of the disease, and even with the preference and experience of the health care practitioner. There are dozens of agents used for CLL therapy, and there is considerable research activity studying them individually or in combination with each other.[9]


Purine analogues

Although the purine analogue fludarabine was shown to give superior response rates than chlorambucil as primary therapy,[10][11] there is no evidence that early use of fludarabine improves overall survival, and some clinicians prefer to reserve fludarabine for relapsed disease. Fludarabine is a chemotherapy drug used in the firstline treatment of chronic lymphocytic leukemia. ... Chlorambucil (marketed as Leukeran by GlaxoSmithKline) is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia. ...


Monoclonal antibodies

Monoclonal antibodies are alemtuzumab (directed against CD52) and rituximab (directed against CD20). // Monoclonal antibodies (mAb) are antibodies that are identical because they were produced by one type of immune cell and are all clones of a single parent cell. ... Alemtuzumab (marketed as Campath or Campath-1H) is a monoclonal antibody used in the treatment of chronic lymphocytic leukemia (CLL) and T-cell lymphoma. ... CD52 is a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes were derived. ... Rituximab, sold under the trade names Rituxan® and MabThera®, is a monoclonal antibody used in the treatment of B cell non-Hodgkins lymphoma, B cell leukemia, and some autoimmune disorders. ... CD20 is a non-glycosylated phosphoprotein expressed on the surface of all mature B-cells. ...


Combination chemotherapy

Combination chemotherapy options are effective in both newly-diagnosed and relapsed CLL:

Fludarabine is a chemotherapy drug used in the firstline treatment of chronic lymphocytic leukemia. ... Cyclophosphamide (the generic name for Cytoxan, Neosar) is a nitrogen mustard alkylating agent, used to treat various types of cancer and some autoimmune disorders. ... Fludarabine is a chemotherapy drug used in the firstline treatment of chronic lymphocytic leukemia. ... Rituximab, sold under the trade names Rituxan® and MabThera®, is a monoclonal antibody used in the treatment of B cell non-Hodgkins lymphoma, B cell leukemia, and some autoimmune disorders. ... Fludarabine is a chemotherapy drug used in the firstline treatment of chronic lymphocytic leukemia. ... Cyclophosphamide (the generic name for Cytoxan, Neosar) is a nitrogen mustard alkylating agent, used to treat various types of cancer and some autoimmune disorders. ... Rituximab, sold under the trade names Rituxan® and MabThera®, is a monoclonal antibody used in the treatment of B cell non-Hodgkins lymphoma, B cell leukemia, and some autoimmune disorders. ... Cyclophosphamide (the generic name for Cytoxan, Neosar) is a nitrogen mustard alkylating agent, used to treat various types of cancer and some autoimmune disorders. ... Doxorubicin or Adriamycin® or hydroxyldaunorubicin is a DNA-interacting drug widely used in chemotherapy. ... Vincristine (Oncovin®), also known as leurocristine, is a vinca alkaloid from the Madagascar periwinkle (Catharanthus roseus, formerly Vinca rosea and hence its name). ... Prednisolone is the active metabolite of prednisone. ...

Stem cell transplantion

Allogeneic bone marrow (stem cell) transplantation is rarely used as a first-line treatment for CLL due to its risk. There is increasing interest in the use of reduced intensity allogeneic stem cell transplantion, which offers the prospect of cure for selected patients with a suitable donor.[14] Hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ...


Refractory CLL

"Refractory" CLL is a disease that no longer responds favorably to treatment. In this case more aggressive therapies, including lenalidomide, flavopiridol, and bone marrow (stem cell) transplantation, are considered.[15] The monoclonal antibody, alemtuzumab (directed against CD52), may be used in patients with refractory, bone marrow-based disease.[16] Lenalidomide (initially known as CC-5013 and marketed as Revlimid® by Celgene) is a derivative of thalidomide introduced in 2004. ... Alemtuzumab (marketed as Campath or Campath-1H) is a monoclonal antibody used in the treatment of chronic lymphocytic leukemia (CLL) and T-cell lymphoma. ... CD52 is a protein present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes were derived. ...


Epidemiology

CLL is a disease of the elderly and is rarely encountered in individuals under the age of 40. Thereafter the disease incidence increases with age. Of note, subclinical "disease" can be identified in up to 7-8% of individuals over the age of 70. That is, small clones of B cells with the characteristic CLL phenotype can be identified in many healthy elderly persons. The clinical significance of these cells is unknown.


References

  1. ^ Harris NL, Jaffe ES, Diebold J, et al (1999). "World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997". J. Clin. Oncol. 17 (12): 3835-49. PMID 10577857. 
  2. ^ National Cancer Institute. Chronic Lymphocytic Leukemia (PDQ®) Treatment: General Information. Retrieved on 2007-09-04.
  3. ^ Chiorazzi N, Rai KR, Ferrarini M (2005). "Chronic lymphocytic leukemia". N. Engl. J. Med. 352 (8): 804-15. DOI:10.1056/NEJMra041720. PMID 15728813. 
  4. ^ a b National Cancer Institute. Chronic Lymphocytic Leukemia (PDQ®) Treatment: Stage Information. Retrieved on 2007-09-04.
  5. ^ Rosenwald A, Alizadeh AA, Widhopf G, et al (2001). "Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia". J. Exp. Med. 194 (11): 1639-47. PMID 11733578. 
  6. ^ Ghia P, Guida G, Stella S, et al (2003). "The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression". Blood 101 (4): 1262-9. DOI:10.1182/blood-2002-06-1801. PMID 12406914. 
  7. ^ a b c Shanafelt TD, Byrd JC, Call TG, Zent CS, Kay NE (2006). "Narrative review: initial management of newly diagnosed, early-stage chronic lymphocytic leukemia". Ann. Intern. Med. 145 (6): 435-47. PMID 16983131. 
  8. ^ Cheson BD, Bennett JM, Grever M, et al (1996). "National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment". Blood 87 (12): 4990-7. PMID 8652811. 
  9. ^ National Cancer Institute. Chronic Lymphocytic Leukemia (PDQ®) Treatment: Stage I, II, III, and IV Chronic Lymphocytic Leukemia. Retrieved on 2007-09-04.
  10. ^ Rai KR, Peterson BL, Appelbaum FR, et al (2000). "Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia". N. Engl. J. Med. 343 (24): 1750-7. PMID 11114313. 
  11. ^ Steurer M, Pall G, Richards S, Schwarzer G, Bohlius J, Greil R (2006). "Purine antagonists for chronic lymphocytic leukaemia". Cochrane database of systematic reviews (Online) 3: CD004270. DOI:10.1002/14651858.CD004270.pub2. PMID 16856041. 
  12. ^ Byrd JC, Peterson BL, Morrison VA, et al (2003). "Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712)". Blood 101 (1): 6-14. DOI:10.1182/blood-2002-04-1258. PMID 12393429. 
  13. ^ Keating MJ, O'Brien S, Albitar M, et al (2005). "Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia". J. Clin. Oncol. 23 (18): 4079-88. DOI:10.1200/JCO.2005.12.051. PMID 15767648. 
  14. ^ Dreger P, Brand R, Hansz J, Milligan D, Corradini P, Finke J, Deliliers GL, Martino R, Russell N, Van Biezen A, Michallet M, Niederwieser D; Chronic Leukemia Working Party of the EBMT (2003). "Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning". Leukemia 17 (5): 841-8. PMID 12750695. 
  15. ^ National Cancer Institute. Chronic Lymphocytic Leukemia (PDQ®) Treatment: Refractory Chronic Lymphocytic Leukemia. Retrieved on 2007-09-04.
  16. ^ Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, Albitar M, Brettman L, Santabarbara P, Wacker B, Rai KR (2002). "Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study". Blood 99 (10): 3554-61. PMID 11986207. 

Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st Century. ... is the 247th day of the year (248th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st Century. ... is the 247th day of the year (248th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st Century. ... is the 247th day of the year (248th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st Century. ... is the 247th day of the year (248th in leap years) in the Gregorian calendar. ...

External links

Blogs:

  • David Arenson's CLL Diary

Forums:

  • CLL Forum - Member supported, moderated, forum-based global community that provides friendly support, information and resources to people living with CLL and their caregivers.
  • UK CLL Support Association - Registered charity that provides UK specific support to patients and caregivers.

Information Resources:

  • CLL Topics - Non-profit educational and patient-advocacy organization (excellent resource.)
  • CLL Research Consortium - NCI funded program project of leading clinician and scientists trying to cure CLL.
  • CLL Canada - Repository of CLL research in laymen's terms.

Listservs and Groups:

  • ACOR Homepage - Non-profit ACOR (Association of Cancer Online Resources) mailing list. Sign-up and receive email messages from other members of the mailing list.
  • CLLResearch - Group dedicated to CLL research and advocacy. Find research papers from various medical journals, CLL news and advocacy information.

  Results from FactBites:
 
Chronic lymphocytic leukemia - Wikipedia, the free encyclopedia (1623 words)
Chronic lymphocytic leukemia (or "chronic lymphoid leukemia"), known for short as CLL, is a type of leukemia in which too many lymphocytes are produced.
CLL is an abnormal neoplastic proliferation of B cells.
CLL is closely related to (and most consider it the same as) a disease called small lymphocytic lymphoma (SLL), a type of non-Hodgkin's lymphoma which presents primarily in the lymph nodes.
Leukemia: Chronic Lymphocytic | AHealthyMe.com (2217 words)
Chronic leukemia is a disease in which too many white blood cells are made in the bone marrow.
Chronic leukemia is a cancer that starts in the blood cells made in the bone marrow.
Unlike acute leukemias, in which the process of maturation of the blast cells is interrupted, in chronic leukemias, the cells do mature and only a few remain as immature cells.
  More results at FactBites »

 
 

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