The average age of CLL patients is more than 70 years and it should be noted that a complex clinical picture occurs in more than half of the cases due to coexisting diseases. The CLL itself leads to unspecific symptoms such as general malaise and weakness, possibly also to fever, night sweats and weight loss. In the physical examination, generalized lymphadenopathy and hepato- and/or splenomegaly may be noted. The excessive proliferation of the lymphocytes results in immunological insufficiency and the patients are more susceptible to infections. Recurrent infections of the respiratory tract and urogenital tract are regularly described, and in fact pneumonia and sepsis are the most common causes of death associated with CLL. At the same time there are disturbances in the formation of erythrocytes and thrombocytes, leading to symptoms of anemia and hemorrhagic diathesis, patients are pale, their performance is reduced, they complain of headaches and dizziness as well as palpitations. Epistaxis, gastrointestinal bleeding, and to the formation of hematomas are also common. CLL patients also tend to autoimmune reactions. If these are directed against erythrocytes or blood platelets, the aforementioned symptoms are further intensified.

An acute increase in lymphadenopathy or organomegaly, as well as a worsening of the general condition with accentuation of B symptoms point to a Richter's transformation, a progression to an aggressive Non-Hodgkin lymphoma or - more rarely - to Hodgkin's disease.

• Easy Bruising

  CLL or cancer of the lymphatic system Having relatives who are Russian Jews or Eastern European Jews Exposure to Agent Orange Symptoms Symptoms include: Painless swelling in the neck, underarms, stomach or groin Tiredness Paleness (a sign of anemia) Easy [uvahealth.com]

  Symptoms include anemia, fatigue, weight loss, easy bruising, thrombocytopenia, and granulocytopenia that leads to persistent bacterial infections. [medical-dictionary.thefreedictionary.com]

  Thrombocytopenia is a condition when there is a low number of platelets which can cause bleeding and easy bruising with no apparent cause. Low numbers of all three blood cell counts is called pancytopenia. [lls.org]

  A low number of blood platelets ( thrombocytopenia ) can lead to problems with easy bruising and bleeding. Some people have frequent or severe nosebleeds or bleeding from the gums. [aamds.org]

• Anemia

  Anemia and thrombocytopenia are the major adverse prognostic variables. CLL has no standard staging system. [web.archive.org]

  Group C: anemia (Hb less than 10 g) and/or thrombopenia (platelets less than 100,000/mm3); about 15% of the patients; median of 2 years. [ncbi.nlm.nih.gov]

  hepatomegaly, splenomegaly, or anemiaBinet classification Clinical stage A: characterized by no anemia or thrombocytopenia and fewer than three areas of lymphoid involvement (Rai stages 0, I, and II) Clinical stage B: characterized by no anemia or thrombocytopenia [en.wikipedia.org]

  Acute leukemias affect immature cells; the disease develops rapidly, with symptoms including anemia, fever, bleeding, and swelling of the lymph nodes. [britannica.com]

  Stage III: Stage III CLL is characterized by absolute lymphocytosis and anemia (hemoglobin Stage IV: Stage IV CLL is characterized by absolute lymphocytosis and thrombocytopenia ( 3 ) with or without lymphadenopathy, hepatomegaly, splenomegaly, or anemia [cancer.unm.edu]

• Fever

  The symptoms of this infection range from a silent infection to fever, enlargement of the liver and spleen, weight loss, and pancytopenia. [ncbi.nlm.nih.gov]

  Acute leukemias affect immature cells; the disease develops rapidly, with symptoms including anemia, fever, bleeding, and swelling of the lymph nodes. [britannica.com]

  Fever and infection. Weight loss (unexplained). Tests that examine the blood, bone marrow, and lymph nodes are used to detect (find) and diagnose chronic lymphocytic leukemia. [web.archive.org]

  The exact cause of CLL is uncertain. 2 Symptoms generalized Lymphadenopathy Pruritus recurrent Herpes infections Note: Since CLL symptoms are rare, and, when present, largely unspecific (e.g. recurrent infections, fever, flu -like symptoms), the disease [flexikon.doccheck.com]

• Fatigue

  Call a provider if you develop enlarged lymph nodes or unexplained fatigue, bruising, excessive sweating, or weight loss. [nlm.nih.gov]

  The most common side effects of Bruton tyrosine kinase inhibitors include fatigue, nausea, diarrhea, bruising, and cytopenias. [ncbi.nlm.nih.gov]

  Some patients notice fatigue, enlargement of lymph nodes or fullness in the abdomen due to an enlarged spleen. [ucsfhealth.org]

• Weight Loss

  Weight loss (unexplained). Tests that examine the blood, bone marrow, and lymph nodes are used to detect (find) and diagnose chronic lymphocytic leukemia. [web.archive.org]

• Lymphadenopathy

  At 12 months' follow-up, we observed white blood cell normalization, increased hemoglobin and platelet levels, disappearance of lymphadenopathy, and spleen size reduction. Therapy was well-tolerated with no evidence of RS. [ncbi.nlm.nih.gov]

  Chronic lymphocytic leukemia–stages 0 Lymphocytosis in blood, without other Sx of leukemia I Lymphocytosis; lymphadenopathy II Lymphocytosis; lymphadenopathy; hepatosplenomegaly III Lymphocytosis; lymphadenopathy; hepatosplenomegaly, anemia IV Lymphocytosis [medical-dictionary.thefreedictionary.com]

  Complete response was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy. [clinicaltrials.gov]

  The exact cause of CLL is uncertain. 2 Symptoms generalized Lymphadenopathy Pruritus recurrent Herpes infections Note: Since CLL symptoms are rare, and, when present, largely unspecific (e.g. recurrent infections, fever, flu -like symptoms), the disease [flexikon.doccheck.com]

• Splenomegaly

  One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. [ncbi.nlm.nih.gov]

  Imaging may identify various features of the disease such as splenomegaly, hepatomegaly /- lymphadenopathy, although these are not specific for the disease. [radiopaedia.org]

  Staging and Prognosis In 1975, Rai, Sawitsky and colleagues have introduced a CLL staging system : Stage 0 lymphocytosis in the blood and marrow only (survival 120 months) Stage I lymphocytosis and adenopathy (survival 95 months) Stage II lymphocytosis, splenomegaly [flexikon.doccheck.com]

• Generalized Lymphadenopathy

  The exact cause of CLL is uncertain. 2 Symptoms generalized Lymphadenopathy Pruritus recurrent Herpes infections Note: Since CLL symptoms are rare, and, when present, largely unspecific (e.g. recurrent infections, fever, flu -like symptoms), the disease [flexikon.doccheck.com]

  Clinical Information A chronic leukemia characterized by abnormal b-lymphocytes and often generalized lymphadenopathy. [icd9data.com]

  Miranda, Composite Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and T-Prolymphocytic Leukemia Presenting with Lymphocytosis, Skin Lesions, and Generalized Lymphadenopathy, Case Reports in Pathology, 10.1155/2019/4915086, 2019, (1-10), (2019 [doi.org]

  In the physical examination, generalized lymphadenopathy and hepato- and/or splenomegaly may be noted. The excessive proliferation of the lymphocytes results in immunological insufficiency and the patients are more susceptible to infections. [symptoma.com]

• Massive Splenomegaly

  splenomegaly and occasionally lymphadenopathy; prognosis is often poor. [medical-dictionary.thefreedictionary.com]

  Bulky disease was defined as the presence of lymph-nodes more than 5 cm in longest diameter by CT and/or ultrasound examination or the presence of massive splenomegaly (6 cm below the left costal margin). [mjhid.org]

  Massive splenomegaly (  6 cm) resolved in 90% of responders and 25% overall. [doi.org]

• Inguinal Lymphadenopathy

  lymphadenopathy, spleen, liver) B: no anemia, no thrombocytopenia, 3 or more lymphoid areas enlarged C: anemia or thrombocytopenia Reference : U.S. [pathologyoutlines.com]

  Binet staging system takes into consideration five potential sites of involvement: cervical, axillary, and inguinal lymphadenopathy (each area counts as one either unilateral or bilateral), spleen, and liver, in addition to the presence of anemia and/ [intechopen.com]

• Cervical Lymphadenopathy

  An 80-year-old man presented with painless mass of the right parotid gland of 2 years duration with recent ulceration of the overlying skin and right cervical lymphadenopathy underwent a surgical resection of parotid mass and biopsy of the periglandular [ncbi.nlm.nih.gov]

• Pneumonia

  Patient 2 developed atrial fibrillation from ibrutinib prior to admission for presumed health care-associated pneumonia. [ncbi.nlm.nih.gov]

  High grade pneumonia and neutropenia were seen in significant percentage of patients in previous trials using CAL-101. [web.archive.org]

  With the sequential regimen, there were 14 opportunistic infections, including 2 dermatomal varicella zoster infections, 7 localized herpes simplex infections, and 1 case each of influenza A, cytomegalovirus pneumonia, and pneumocystis carinii pneumonia [dx.doi.org]

• Pleural Effusion

  CD45-gated flow cytometry of the pleural effusion showed elevated numbers of CD5- and CD23-positive lymphocytes and a high serum level of soluble interleukin-2 receptor. [ncbi.nlm.nih.gov]

• Early Satiety

  If the spleen grows in size, a patient might feel bloated and have the sensation of early satiety (filling up with food after eating only a small amount). Learn more about CLL/SLL at cancer.net. [medicine.duke.edu]

  satiety) Weight loss The health care provider will perform a physical exam and ask about your symptoms. [nlm.nih.gov]

  satiety mucocutaneous bleeding from thrombocytopenia Physical exam painful lymphadenopathy hepatosplenomegaly Evaluation Labs – CBC WBC ( 20,000/μL) with 80% lymphocytes RBCs (attacked by CLL cells) PLTs (attacked by CLL cells) IgG in half of patients [step2.medbullets.com]

  Symptoms and signs may be absent or may include lymphadenopathy, splenomegaly, hepatomegaly, fatigue, fevers, night sweats, unintentional weight loss, and early satiety. Diagnosis is by flow cytometry and immunophenotyping of peripheral blood. [merckmanuals.com]

  satiety) Weight loss Exams and Tests The health care provider will perform a physical exam and ask about your symptoms. [mountsinai.org]

• Abdominal Fullness

  As the disease progresses, symptoms can include: enlarged lymph nodes tiredness fever night sweats weight loss frequent infections abdominal fullness Make an appointment with your doctor if you develop any of the above symptoms. [healthline.com]

  fullness with early satiety, increased frequency of infections, and symptoms of an autoimmune cytopenia, as well as enlarged lymph nodes, hepatomegaly, and splenomegaly, which can be detected by palpation. 1 Essential components of the CLL diagnosis [targetedonc.com]

  People may also have enlarged lymph nodes and a sense of abdominal fullness due to enlargement of the spleen. Blood tests are needed for diagnosis. Treatment includes chemotherapy drugs, monoclonal antibodies, and sometimes radiation therapy. [merckmanuals.com]

• Abdominal Distension

  We describe the case of a 75-year-old man with refractory chronic lymphocytic leukemia who presented with multiple growing fatty abdominal masses on computed tomography and vague abdominal distension. [ncbi.nlm.nih.gov]

• Palpitations

  […] any of these symptoms during or after an infusion of RITUXAN: Hives (red itchy welts) or rash Itching Swelling of your lips, tongue, throat, or face Sudden cough Shortness of breath, difficulty breathing, or wheezing Weakness Dizziness or feel faint Palpitations [rituxan.com]

  At the same time there are disturbances in the formation of erythrocytes and thrombocytes, leading to symptoms of anemia and hemorrhagic diathesis, patients are pale, their performance is reduced, they complain of headaches and dizziness as well as palpitations [symptoma.com]

  Infections – due to lack of normal white blood cells Weakness, tiredness, shortness of breath, light-headedness, palpitation Anaemia – due to lack of red blood cells Infections are more frequent, more severe and last longer Fever, malaise (general feeling [leukaemiacare.org.uk]

• Bleeding Gums

  Thrombocytopenia A shortage of platelets, which can cause excess bruising and bleeding, such as frequent or severe nosebleeds or bleeding gums. [uihc.org]

  gums or nosebleeds Excessive bleeding from a small cut, or bleeding that won't stop even after pressure has been applied Dark urine or blood in the urine Blood in stool or from the rectum after a bowel movement; black-colored stools Menstrual bleeding [pennmedicine.org]

  They can include: Pale skin Feeling tired, weak, or cold Dizziness Headaches Shortness of breath, trouble breathing Frequent or long-term infections Fever Easy bruising or bleeding, such as nosebleeds or bleeding gums Bone or joint pain Belly (abdominal [stanfordchildrens.org]

  gums Bleeding and bruising – due to lack of platelets Other signs and symptoms which may occur include: Swollen liver, spleen or lymph nodes (glands) Some patients with CLL develop autoimmune conditions, in which the body produces antibodies against [leukaemiacare.org.uk]

• Hepatomegaly

  1975, Rai, Sawitsky and colleagues have introduced a CLL staging system : Stage 0 lymphocytosis in the blood and marrow only (survival 120 months) Stage I lymphocytosis and adenopathy (survival 95 months) Stage II lymphocytosis, splenomegaly and/or hepatomegaly [flexikon.doccheck.com]

  Imaging may identify various features of the disease such as splenomegaly, hepatomegaly /- lymphadenopathy, although these are not specific for the disease. [radiopaedia.org]

  […] swelling of the left region of the eyehole, of the base of the nasal pyramid, and of the left zygomatic region; anterior nasal bleeding; pustulous non-itching lesions at the cervical region and posterior thorax; enlarged bilateral axillary lymph nodes; hepatomegaly [ncbi.nlm.nih.gov]

  Splenomegaly and hepatomegaly are less common than lymphadenopathy. Skin involvement (leukemia cutis) is rare. [merckmanuals.com]

• Hepatosplenomegaly

  Chronic lymphocytic leukemia–stages 0 Lymphocytosis in blood, without other Sx of leukemia I Lymphocytosis; lymphadenopathy II Lymphocytosis; lymphadenopathy; hepatosplenomegaly III Lymphocytosis; lymphadenopathy; hepatosplenomegaly, anemia IV Lymphocytosis [medical-dictionary.thefreedictionary.com]

  Stage I : Stage I CLL is characterized by absolute lymphocytosis with lymphadenopathy without hepatosplenomegaly, anemia, or thrombocytopenia. [cancer.unm.edu]

  Stage I Stage I CLL is characterized by absolute lymphocytosis with lymphadenopathy without hepatosplenomegaly, anemia, or thrombocytopenia. [web.archive.org]

  Presentation Symptoms many are asymptomatic at presentation most common symptom is fatigue recurring infections from incompetent lymphocytes pneumonia zoster early satiety mucocutaneous bleeding from thrombocytopenia Physical exam painful lymphadenopathy hepatosplenomegaly [step2.medbullets.com]

• Night Sweats

  Symptoms of CLL may include: Abnormal bruising (if platelets are low) Enlarged lymph nodes, liver, or spleen Excessive sweating, night sweats Fatigue Fever Infections that keep coming back (recur) despite treatment Loss of appetite or becoming full too [nlm.nih.gov]

  Symptoms and signs may be absent or may include lymphadenopathy, splenomegaly, hepatomegaly, fatigue, fevers, night sweats, unintentional weight loss, and early satiety. Diagnosis is by flow cytometry and immunophenotyping of peripheral blood. [merckmanuals.com]

  Other signs of CLL include: Fatigue Lethargy Night sweats Unexplained weight loss Unusual fullness after a meal Abdominal pain or swelling Fever and/or infection Bleeding Bruising [pennmedicine.org]

  If you do exhibit symptoms, they typically include: fatigue fever frequent infections or illness unexplained or unintended weight loss night sweats During a physical examination, your doctor may also find that your spleen, liver, or lymph nodes are enlarged [healthline.com]

• Petechiae

  Mucocutaneous bleeding and/or petechiae may be due to thrombocytopenia. Tiredness and fatigue may be present secondary to anemia; 10% of patients with CLL will present with an autoimmune hemolytic anemia. [emedicine.medscape.com]

  The most common treatment-related AEs (reported in at least 5 percent of patients) were headache (20 percent), an increased tendency to bruise (12 percent) and petechiae (12 percent). [curetoday.com]

  Common leukemia symptoms are: persistent fatigue, weakness; frequent infections; weight loss without trying; swollen lymph nodes, enlarged liver or spleen; easy bleeding or bruising; tiny red spots in the skin (petechiae); and bone pain or tenderness. [publichealth.va.gov]

  They may also develop petechiae, which are small red and purple spots on the body. These indicate that blood is not clotting properly. Petechiae develop when immature white blood cells crowd out platelets, which are crucial for blood clotting. [medicalnewstoday.com]

  These are due to small superficial capillary bleeds known as petechiae (pronounced: pe-tee-chi-a), due to a very low platelet count. frequent or repeated infections and slow healing, due to a lack of normal white blood cells pain or discomfort under the [leukaemia.org.au]

• Pruritus

  The exact cause of CLL is uncertain. 2 Symptoms generalized Lymphadenopathy Pruritus recurrent Herpes infections Note: Since CLL symptoms are rare, and, when present, largely unspecific (e.g. recurrent infections, fever, flu -like symptoms), the disease [flexikon.doccheck.com]

  The patient complained of painless erythema with pruritus in the pocket area. Inflammatory blood parameters were C-reactive protein 17.3 mg/L and leucocytes 29.0   109/L. [ncbi.nlm.nih.gov]

  CLL can also become apparent on the skin in the form of pruritus, chronic urticarial, mycosis and herpes zoster. Such dermatological symptoms in older patients should always let oneself keep in mind a possible CLL. [lecturio.com]

  Symptoms include fever, chills, pruritus, and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. [treanda.com]

• Epistaxis

  Epistaxis, gastrointestinal bleeding, and to the formation of hematomas are also common. CLL patients also tend to autoimmune reactions. [symptoma.com]

• Headache

  We present the case of a 73-year-old Caucasian patient, a rare case in which Wegener's granulomatosis is associated in a patient with chronic lymphocytic leukemia, who is admitted in the Infectious Disease Department for fever, diplopia, headache, purulent [ncbi.nlm.nih.gov]

  The most common treatment-emergent AEs (reported in at least 20 percent of patients) were headache (43 percent), diarrhea (38 percent) and increased weight (25 percent). [curetoday.com]

  Side Effects Side effects of medications used to treat chronic lymphocytic leukemia may include nausea, vomiting, diarrhea, mouth sores, headache, fever, or stomach pain. [nyulangone.org]

  […] or brown urine, unexpected bleeding, or bleeding that is severe or that you cannot control, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, dizziness, weakness, confusion, change in your speech, or a headache [imbruvica.com]

  The most common short-term side effects of chemotherapy include: Loss of appetite Easy bruising or bleeding, from low levels of blood platelets Diarrhea Tiredness (fatigue), from having low levels of red blood cells Hair loss Headaches Increased chance [urmc.rochester.edu]

• Dizziness

  Tell your healthcare provider if you get any symptoms of heart rhythm problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, chest discomfort, or you faint. [imbruvica.com]

  […] nodes (glands) in the neck, under the arms or in the groin, due to collections of lymphocytes in these areas pain or discomfort under the ribs on the left side, due to an enlarged spleen anaemia, due to a lack of red cells, causing persistent tiredness, dizziness [melbournehaematology.com.au]

  Tell your healthcare provider right away if you have new or worsening symptoms or if anyone close to you notices these symptoms: Confusion Dizziness or loss of balance Difficulty walking or talking Decreased strength or weakness on one side of your body [rituxan.com]

  This shortage can cause the following symptoms: Fatigue Feeling week, or low energy Dizziness or lightheadedness Fever Enlarged lymph nodes Enlarged spleen, often feeling like pain or “fullness” in the belly Weight loss Night sweats Many signs of CLL [uihc.org]

  At the same time there are disturbances in the formation of erythrocytes and thrombocytes, leading to symptoms of anemia and hemorrhagic diathesis, patients are pale, their performance is reduced, they complain of headaches and dizziness as well as palpitations [symptoma.com]

• Peripheral Neuropathy

  I had bad peripheral neuropathy of the legs after using a small dose of vincristine in 2007; Dr. Droll said it was not an especially important part of the protocol and left it out. [clldiary.blogspot.com]

Work up includes a detailed history and physical examination.

Laboratory tests

• Complete blood count
• Blood profile
• Lymph node aspiration
• FISH
• Array-based karyotyping
• Matute's CLL Score
• Flow cytometry

Imaging

• Presence of characteristic 'smudge cells' on microscopic view
• Bone marrow biopsy
• CT scan/radiography to stage the disease
• MRI

Test results

CLL is a diagnosed most commonly during routine physical examination and blood work. If the blood work points towards a leukemia, biopsy, cytometry and other such laboratory tests along with imaging studies should be performed to identify and stage the cancer.

• Lymphocytes Increased

  Also, as the amount of lymphocytes increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may result in infection, anemia, and easy bleeding. [web.archive.org]

  As the number of these abnormal lymphocytes increases, they interfere with the production of other important blood cells, leading to multiple complications, including infection, easy bleeding and swollen lymph nodes. [fredhutch.org]

  As the number of these abnormal lymphocytes increase in the blood and bone marrow, fewer healthy white blood cells, red blood cells, and platelets are produced. This can cause the symptoms of fatigue, recurring infection, anemia, and easy bruising. [merckmanuals.com]

  Treatment may not be needed for years, and then only if the number of lymphocytes increases, the lymph nodes enlarge, or the number of red blood cells or platelets decreases. [medbroadcast.com]

• Decreased Platelet Count

  platelet count, and anemia due to decreased erythrocyte count. [medical-dictionary.thefreedictionary.com]

• Enlargement of the Spleen

  The disease often involves enlargement of lymph nodes in various parts of the body as well as enlargement of the spleen. [cancer.unm.edu]

  An enlarged spleen. The spleen can press on the stomach causing early fullness (satiety) while eating food and also discomfort in the left upper part of the abdomen. [lls.org]

  Full medical history by your doctor Full physical exam with attention paid to enlarged liver and spleen Blood tests: Complete Blood Count (CBC) to check the number of white blood cells, red blood cells and platelets in your blood. [massgeneral.org]

• Enlargement of the Liver

  […] spleen or liver or both; stage III, lymphocytosis with anemia; and stage IV:lymphocytosis with thrombocytopenia. [ncbi.nlm.nih.gov]

  Symptoms of CLL may include: Abnormal bruising (if platelets are low) Enlarged lymph nodes, liver, or spleen Excessive sweating, night sweats Fatigue Fever Infections that keep coming back (recur) despite treatment Loss of appetite or becoming full too [nlm.nih.gov]

  Chronic lymphoblastic leukemias (CLL) often cause an enlargement of the liver and spleen. Involvement of the lymph nodes in CLL is often called small lymphocytic lymphoma. [youtube.com]

• Pleural Effusion

  CD45-gated flow cytometry of the pleural effusion showed elevated numbers of CD5- and CD23-positive lymphocytes and a high serum level of soluble interleukin-2 receptor. [ncbi.nlm.nih.gov]

Treatment is subjective to the stage of the disease. Since it does not have any definite cure, treatment focuses on improving the quality and quantity of life. Optimum therapy includes a combination of radiotherapy and chemotherapy, which may or may not be accompanied with surgery for existing complications such as a splenomegaly or hepatomegaly. Immunotherapy with antibodies against proteins found on the surface of CLL/SLL cells, such as CD20 and CD52, is finding increasing use [8].

Bone marrow transplant can be a potential cure but success rate is not a 100%. There is increasing interest in the use of reduced-intensity allogenic stem cell transplantation, which offers the prospect of cure for selective patients with a suitable donor [9].

Target therapy

Monoclonal antibody therapy and tyrosine-kinase inhibitor therapy are types of targeted therapy used in the treatment of chronic lymphocytic leukemia.

The overall median survival is about 6 years [3]. Prognosis depends upon the stage of cancer. If the patient is at Stage A/0, prognosis is the best, i.e 12-15 years with treatment. As the stage increases, prognosis of this disease worsens. In case of transformation of CLL into other, more aggressive cancers, prognosis is the worst. Both prolymphocytic and large-cell transformation are ominous events, with most patients surviving less than 1 year [7].

CLL is a type of B cell lymphoma which presents primarily in the lymph nodes [3]. Much like other types of cancers, CLL has no definite known cause. It is an acquired disorder, and reports of truly familial cases are exceedingly rare [4]. However, genetic mutations and more commonly, deletions, may he held the culprit behind this disease.

4 main genetic aberrations are recognised in CLL cells that have a major impact on disease behaviour [5]. These include:

• Deletion of 17p
• Deletion of 13q (most common finding)
• Trisomy 12 
• Deletion of 11q

Occurrence of any one or more of the above 4 aberrations may result in abnormally high rate of development and proliferation of B-cells in the bone marrow and other hematopoietic tissue. This results in crowding of normally developing cells in the marrow as well as crowding of normally maturing cells in the lymph nodes. As a result, the B-cells develop impaired functioning even though the lymphocytic count keeps on increasing.

Incidence

CLL is the most common leukemia of adults in the Western world. There are about 15,000 new cases of CLL each year in the United States [1].

Age and sex

The median age at diagnosis is 60 years, and there is a 2:1 male predominance [1].

Race

This disease is very rare in the Chinese and related races [2].

Certain bio-markers may be present in CLL. Most common such markers are B-cell CD19 and B-cell CD20. CD23 and CD5 may also be found.

Morphology

Electron microscopy of blood smears show diffuse effacement of lymph node architecture, with the presence of proliferation centres. Stromal cells in proliferation centres seem to express a variety of factors that stimulate the activity of the transcription factor NK-kB, [6], which promote cell growth and survival. This factor, along with others, result in uncontrolled proliferation of B cells.

The leukemic cells have fragile nuclei, so during slide preparation, insertion of a cover slip on top of the sample on the slide crushes the fragile nuclei, resulting in characteristic 'smudge cells' or 'parachute cells'.

Staging

Binet classification

• Clinical stage A: This stage is characterised by less than 3 areas of lymphoid enlargement. There is no anemia or thrombocytopenia.
• Clinical stage B: In this stage, 3 or more than 3 areas of lymphoid enlargement are found. There is no or little evidence of anemia or thrombocytopenia.
• Clinical stage C: In this most serious stage, there is anemia and/or thrombocytopenia regardless of how many areas of lymphoid enlargement are present.

Rai classification

• Stage 0: Only lymphocytosis is present i.e >15,000 mm3.
• Stage I: Lymphocytosis along with lymphadenopathy is present.
• Stage II: Lymphocytosis along with either splenomegaly or hepatomegaly is present. Lymphadenopathy may or may not be present.
• Stage III: Absolute lymphocytosis with anemia is present. Hepatosplenomegaly and lymphadenopathy may or may not be present.
• Stage IV: Absolute lymphocytosis with thrombocytopenia (<100,000/mm3). Lymphadenopathy, hepatosplenomegaly and anemia may or may not be present.

There is no known prevention of this disease. However, routine check ups and examinations may help in preventing the disease from reaching an advanced stage.

Chronic lymphocytic leukemia (chronic lymphoid leukemia, CLL) belongs to the lymphoproliferative disorders and according to the classification of the World Health Organization to the Non-Hodgkin lymphomas and neoplasias of the B lymphocytes. CLL is the most common form of leukemia in the Western world and affects mainly people of advanced age. CLL leads to unspecific symptoms such as general malaise and weakness, fever, night sweats, weight loss and enlarged lymph nodes, spleen or liver. The onset of these symptoms is often insidious and CLL is frequently diagnosed in routine examinations.

CLL is the most common white blood cell cancer in US adults. It is more common in males and occurs most commonly in the late 5th or early 6th decade of life. Common symptoms are enlarged lymph nodes, fever, night sweats, fatigue, weight loss and frequent infections.

1. Robbins and Cotran, Pathological Basis of Disease. 8th ed. Chap 13, 596-638.
2. Davidson's Principles and Practice of Medicine. 16th ed. Chap 14,737-39.
3. Harris NL, Jaffe ES, Diebold J, et al. WHO Classification of neoplasticism disease of the hematopoietic and lymphoid tissues:a report of the Clinical Advisory Committee meeting Airlie-house, Virginia, Nov 1997. J Clin Oncol. 17(12):3835-49
4. Slager SL, Kay NE. Familial chronic lymphocytic leukemia: What does it mean to me? Clin Lymphoma Myeloma. Sep 1,2009;9:S194-S197
5. Dohner H, Stilgenbauer S, Benner A, et al. Genomic Aberrations and survival in chronic lymphocytic leukemia. NEJM 2000 343(26):1910-6
6. Endo T, et al. BAFF and APRIL support chronic lymphocytic leukemia B-cell survival through activation of the canonical NF- kappaB pathway. Blood 109:703, 2007
7. Tsimberiou AM, Keating MJ. Richter's transformation in chronic lymphocytic leukemia. Semin Oncol 33:250, 2006
8. Alinari L, et al. Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic Leukemia. Oncogene 26:3644, 2007
9. Dreger P, Brand R, Hansz J, et al. Chronic leukemia working party of EBMT 2003. Treatment related mortality and graft versus-leukemia activity after allogenic stem cell transplantation for CLL using intensity-reduced conditioning. Leukemia 17(5);841-8