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.

• Splenomegaly

  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. [symptoma.com]

  Over half of patients are diagnosed at an early, asymptomatic stage, without lymphadenopathy, splenomegaly, cytopenias, or autoimmune phenomena. With counts >10,000/microliter, progression and severity of CLL become more likely. [library.med.utah.edu]

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

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

• 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]

  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. [symptoma.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]

• 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]

• Axillary Lymphadenopathy

  Regression of axillary lymphadenopathy occurred within 1 month after infusion and was sustained. Arrows highlight various enlarged lymph nodes before therapy and lymph-node responses on comparable CT scans after therapy. [doi.org]

• Anemia

  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. [symptoma.com]

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

  Antibody deficiency syndrome Anemia Transition into a highly malignant, diffuse B-cell lymphoma Severe bacterial infections Myeloic blast crisis [lecturio.com]

  Anemia can affect a wide variety of organs and body functions, and each is treated separately for purposes of determining disability. Chronic Granulocytopenia. [disability-benefits-help.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]

• Fever

  Common symptoms are enlarged lymph nodes, fever, night sweats, fatigue, weight loss and frequent infections. [symptoma.com]

  If you have symptoms, they may include Painless swelling of the lymph nodes in the neck, underarm, stomach, or groin Fatigue Pain or a feeling of fullness below the ribs Fever and infection Weight loss Tests that examine the blood, bone marrow, and lymph [medlineplus.gov]

  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]

• Fatigue

  Other symptoms can include fatigue A decreased capacity for activity that is often accompanied by feelings of weariness, sleepiness or irritability., shortness of breath, anemia A shortage of red blood cells, causing weakness and fatigue., bruising easily [lymphoma.org]

  When to Contact a Medical Professional Call a provider if you develop enlarged lymph nodes or unexplained fatigue, bruising, excessive sweating, or weight loss. [mountsinai.org]

  Snapshot A 62-year-old Caucasian man complains of months of fatigue. He notices that his skin seems abnormally yellow. On physical exam, he has notable tender lymphadenopathy. Peripheral smear reveals some spherocytes and lymphocytosis. [step2.medbullets.com]

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

  If you have symptoms, they may include Painless swelling of the lymph nodes in the neck, underarm, stomach, or groin Fatigue Pain or a feeling of fullness below the ribs Fever and infection Weight loss Tests that examine the blood, bone marrow, and lymph [medlineplus.gov]

• Weight Loss

  Common symptoms are enlarged lymph nodes, fever, night sweats, fatigue, weight loss and frequent infections. [symptoma.com]

  If you have symptoms, they may include Painless swelling of the lymph nodes in the neck, underarm, stomach, or groin Fatigue Pain or a feeling of fullness below the ribs Fever and infection Weight loss Tests that examine the blood, bone marrow, and lymph [medlineplus.gov]

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

• Lymphadenopathy

  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. [symptoma.com]

  On physical exam, he has notable tender lymphadenopathy. Peripheral smear reveals some spherocytes and lymphocytosis. His leukocyte count is 35,000/μL with 95% lymphocytes and a Hb of 7 g/dL. His direct Coombs test is positive with anti-IgG. [step2.medbullets.com]

  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]

  Over half of patients are diagnosed at an early, asymptomatic stage, without lymphadenopathy, splenomegaly, cytopenias, or autoimmune phenomena. With counts >10,000/microliter, progression and severity of CLL become more likely. [library.med.utah.edu]

• 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]

  This can cause the symptoms of fatigue, recurring infection, anemia, and easy bruising. Chronic lymphocytic leukemia usually does not produce symptoms in the early stages. Treatment and prognosis depend on the stage and extent of the disease. [msdmanuals.com]

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

• Pneumonia

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

  […] markedly elevated WBC Insidious onset of symptoms Associated conditions warm autoimmune hemolytic anemia (IgG) Presentation Symptoms many are asymptomatic at presentation most common symptom is fatigue recurring infections from incompetent lymphocytes pneumonia [step2.medbullets.com]

• Pleural Effusion

  An 80-year-old man who had suffered from chronic lymphocytic leukemia (CLL) and achieved complete remission was admitted to our hospital due to right pleural effusion. Thoracentesis revealed that the effusion was chyle. [ncbi.nlm.nih.gov]

• Early Satiety

  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 [step2.medbullets.com]

  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]

  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. [msdmanuals.com]

• Abdominal Fullness

  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. [msdmanuals.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]

  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]

• 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

  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]

  […] 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]

  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]

  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 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]

  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

  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. [symptoma.com]

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

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

• Hepatosplenomegaly

  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. [symptoma.com]

  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]

  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]

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

• Night Sweats

  Common symptoms are enlarged lymph nodes, fever, night sweats, fatigue, weight loss and frequent infections. [symptoma.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]

  sweats, weight loss, and frequent infections. [lymphoma.org]

  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]

• Petechiae

  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]

  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]

  “night sweats”) fatigue and weakness that don’t go away with rest unintentional weight loss bone pain and tenderness painless, swollen lymph nodes (especially in the neck and armpits) enlargement of the liver or spleen red spots on the skin, called petechiae [healthline.com]

• 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]

  Headaches and Other Neurological Symptoms Headaches and other neurologic symptoms such as seizures, dizziness, visual changes, nausea, and vomiting may occur when leukemia cells invade the fluid surrounding the brain and spinal cord (cerebrospinal fluid [verywellhealth.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]

  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]

• Dizziness

  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]

  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]

  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]

  If ALL spreads to the central nervous system, symptoms such as headaches, blurry vision, dizziness, and sometimes seizures may occur. When ALL spreads to the chest, shortness of breath and a cough may occur. [verywellhealth.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]

• 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.

• Enlargement of the Spleen

  Cancerous lymphocytes then spread to the liver and spleen, both of which begin to enlarge. [msdmanuals.com]

  CLL leads to unspecific symptoms such as general malaise and weakness, fever, night sweats, weight loss and enlarged lymph nodes, spleen or liver. [symptoma.com]

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

• Enlargement of the Liver

  […] nodes; stage II, lymphocytosis with enlarged spleen or liver or both; stage III, lymphocytosis with anemia; and stage IV:lymphocytosis with thrombocytopenia. [ncbi.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]

  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]

• Lymphocytosis

  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. [symptoma.com]

  […] in the blood and marrow only (survival > 120 months) Stage I lymphocytosis and adenopathy (survival ~ 95 months) Stage II lymphocytosis, splenomegaly and/or hepatomegaly (survival ~ 72 months) Stage III lymphocytosis, anemia (hb < 10) (survival ~ 30 [flexikon.doccheck.com]

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

  Binet Staging System Stage A Lymphocytosis and less than 3 affected lymphoid areas Stage B Lymphocytosis and 3 or more affected lymphoid areas Stage C Anemia (Hb < 10 g/dL) or thrombocytopenia (thrombocytes < 100/nl) Rai Staging System Stage 0 Lymphocytosis [lecturio.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]

• Neutropenia

  AIM: We report an unusual case of early gastric cancer and T-cell-type chronic lymphocytic leukemia accompanied by severe neutropenia that was successfully treated by laparoscopic gastrectomy. [ncbi.nlm.nih.gov]

  Based on available laboratory assessments, grade 3 or 4 neutropenia occurred in 87% of patients in each cohort, suggesting that the incidence of neutropenia was likely independent of the ofatumumab dose level ( Figure 4 ). [bloodjournal.hematologylibrary.org]

  The most common side effects of Venclexta include low white blood cell count (neutropenia), diarrhea, nausea, anemia, upper respiratory tract infection, low platelet count (thrombocytopenia) and fatigue. [fda.gov]

  Grade 4 neutropenia developed in 5% of patients. The data indicate that combination therapy with rituximab and cladribine is a valuable and safe treatment for patients with CLL. [dx.doi.org]

• Hypogammaglobulinemia

  He developed profound lymphopenia and hypogammaglobulinemia. While the risk of MCC is increased in CLL, its rapid dissemination has not been previously reported with fludarabine alone. [ncbi.nlm.nih.gov]

  Hypogammaglobulinemia can develop in up to two thirds of patients, increasing risk for infectious complications. [msdmanuals.com]

• Lymphocytes Increased

  In CLL, the lymphocytes produced are abnormal and are not able to fight infection. 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. [msdmanuals.com]

  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]

• Decreased Platelet Count

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

• Pleural Effusion

  An 80-year-old man who had suffered from chronic lymphocytic leukemia (CLL) and achieved complete remission was admitted to our hospital due to right pleural effusion. Thoracentesis revealed that the effusion was chyle. [ncbi.nlm.nih.gov]

• Leukocytosis

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

  License: CC BY-SA 2.0 In the diagnostic investigation of the CLL, the first suspicion is made by often an accidental finding of a leukocytosis. [lecturio.com]

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
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