Chronic Lymphocytic Leukemia (Cll)

(Chronic lymphocytic leukemia)

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western world. It is revealed by appearing ripe, but non-functional neoplastic lymphocytes (almost always B cells) with an abnormally long life. be infiltrated not only the peripheral blood and bone marrow, but also the spleen and the lymph nodes. Patients may be asymptomatic or clinical signs of lymphadenopathy, splenomegaly, hepatomegaly, or nonspecific symptoms associated with anemia (fatigue, performance limitations) and immunosuppression (eg., Fever) have. The diagnosis is made based on peripheral blood smears and bone marrow examination. The therapeutic measures are only used when symptoms persist, are aimed at prolonging life and a reduction in symptoms. Here, substances such as chlorambucil or fludarabine, prednisone come (Editor’s Addition: also bendamustine), cyclophosphamide or doxorubicin used. Monoclonal antibodies (. Eg alemtuzumab, rituximab or obinutuzumab) (Editor’s note: and new drugs like Ibrutinib and Idelalisib) are becoming increasingly important. In patients with severe lymphadenopathy or splenomegaly, palliative radiotherapy can be used.

Incidence of CLL increases with age. 75% of all cases are diagnosed> 60 years in patients. CLL is twice as likely as women in men. The etiology is unknown, but a hereditary component is assumed. In Japan and China, the disease is rare. Since there will be no increase in the incidence among Japanese emigrated to the USA, genetic factors appear to play a role. The CLL is more common in eastern Europeans of Jewish origin.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western world. It is revealed by appearing ripe, but non-functional neoplastic lymphocytes (almost always B cells) with an abnormally long life. be infiltrated not only the peripheral blood and bone marrow, but also the spleen and the lymph nodes. Patients may be asymptomatic or clinical signs of lymphadenopathy, splenomegaly, hepatomegaly, or nonspecific symptoms associated with anemia (fatigue, performance limitations) and immunosuppression (eg., Fever) have. The diagnosis is made based on peripheral blood smears and bone marrow examination. The therapeutic measures are only used when symptoms persist, are aimed at prolonging life and a reduction in symptoms. Here, substances such as chlorambucil or fludarabine, prednisone come (Editor’s Addition: also bendamustine), cyclophosphamide or doxorubicin used. Monoclonal antibodies (. Eg alemtuzumab, rituximab or obinutuzumab) (Editor’s note: and new drugs like Ibrutinib and Idelalisib) are becoming increasingly important. In patients with severe lymphadenopathy or splenomegaly, palliative radiotherapy can be used. Incidence of CLL increases with age. 75% of all cases are diagnosed> 60 years in patients. CLL is twice as likely as women in men. The etiology is unknown, but a hereditary component is assumed. In Japan and China, the disease is rare. Since there will be no increase in the incidence among Japanese emigrated to the USA, genetic factors appear to play a role. The CLL is more common in eastern Europeans of Jewish origin. Pathophysiology In about 98% of the cases transform CD5 + B cells, thereby initially to an accumulation in the bone marrow and later comes in the lymph nodes and other lymphatic tissues. As a result, a splenomegaly and hepatomegaly may occur. In the course of CLL, the displacement of normal hematopoiesis in anemia, neutropenia, thrombocytopenia and decreased production of immunoglobulin leads. Many patients develop hypogammaglobulinemia and show an impaired antibody response that seems to be associated with an increased activity of T suppressor cells. In addition, patients have an increased susceptibility to autoimmune diseases such. As autoimmune hemolytic anemia (the Coombs test is usually positive) or thrombocytopenia as well as a slightly increased risk of a second malignancy on. In 2-3% of cases the disease is based on the clonal expansion of T cells. Here, too subtypes are distinguished (eg. As large granular lymphocytes with cytopenias). Partial CLL also be associated with other chronic leukemias: prolymphocytic leukemic phases of cutaneous T-cell lymphomas (. E.g., Sezary syndrome), hairy cell leukemia lymphoma, the progress (. For example, in advanced stages of malignant lymphoma) leukemia These subtypes may are usually easily distinguished from the typical CLL by light microscopy and immunophenotyping. Diagnostic blood count and peripheral blood smear examination of the bone marrow Immunophenotyping CLL is diagnosed by peripheral smear and bone marrow tests. The main finding is an ongoing peripheral absolute lymphocytosis (> 5,000 / ul), and an increased lymphocyte percentage (> 30%) in bone marrow. Because of immunophenotyping differential diagnoses can be more easily detected. Further findings at diagnosis may (<15% of cases) and hypogammaglobulinemia - be increased LDH - but very rare. About 10% of patients have a moderate anemia at diagnosis (sometimes autoimmunhämolytisch) and / or thrombocytopenia. In 2-4% of cases is found in serum, a monoclonal immunoglobulin, which corresponds to the on the surface of leukemic cells. Important for prognosis and treatment is the clinical staging. Staging is often done by Rai and Binet. Both systems are based on hematological changes and the spread of the disease (s. Clinical staging of chronic lymphocytic leukemia *). Clinical staging of chronic lymphocytic leukemia and * Classification Stage Description Rai stage 0 Absolute lymphocytosis> 10,000 / ul in the blood and ? 30% lymphocytes in the bone marrow Stage I Stage 0 and Stage II Stage 0 enlarged lymph nodes and hepatomegaly or splenomegaly Stage III Stage 0 and anemia with hemoglobin <11 g / dl Stage IV Stage 0 and thrombocytopenia with platelet counts <100,000 / ul Binet stage A Absolute lymphocytosis> 10,000 / ul in the blood and ? 30% lymphocytes in the bone marrow Hb ? 10 g / dl Platelet ? 100,000 / ul ? 2 * affected regions B stage such as stage A, but affected regions 3-5 Stage C as stage A or B, but Hb * are <10 g / dl or platelets <100,000 / ul When regions: cervical, axillary, inguinal lymph nodes, liver, spleen. Prognosis The median survival of patients with B-cell leukemia is about 7-10 years. Is a diagnostic Rai stage 0-II before, patients can survive without treatment 5-20 years. In patients of the Rai stages III and IV at diagnosis, it is likely that these die within 3-4 years. Short survival times observed in patients with progression to bone marrow failure. CLL patients who develop an increased risk of second malignancies, particularly skin tumors. Therapy alleviating the symptoms Supportive treatment Specific treatment The indication for treatment exists only if a significant progression or onset of symptoms. Although CLL is progressive, patients can remain asymptomatic for years. As a cure is usually not possible, the therapy focuses on alleviating the symptoms and prolonging life. The supportive care includes transfusion of packed red blood cells or erythropoietin injection at anemia platelet transfusions for bleeding associated with thrombocytopenia Antimicrobial drugs in bacterial, fungal or viral infections As a result of neutropenia and agammaglobulinemia the defense is reduced against bacteria, antibiotic therapy should consist of bactericidal substances. In patients with hypogammaglobulinemia and repeated or refractory infections therapeutic infusions of ?-globulin should be considered. They can be used as a prophylactic when severe infections have occurred within 6 months of 2 or more. As specific therapeutic measures considered chemotherapy come corticosteroids monoclonal antibody therapy radiotherapy result, the symptoms are reduced and prolongs life. Overtreatment is more dangerous than a less intensive treatment. Chemotherapy The indications for chemotherapy can be given by the appearance of symptoms. Symptoms with umgehendem start of treatment include general symptoms (fever, night sweats, extreme fatigue, weight loss), massive hepatomegaly, splenomegaly or lymphadenopathy and lymphocytosis> 100,000 / ul and infections accompanied by anemia, neutropenia or thrombocytopenia. Alkylating agents, particularly chlorambucil, alone or in combination with corticosteroids, are used as standard treatment for B-cell CLL long time. However, fludarabine has been shown to be effective. A combination therapy of fludarabine, cyclophosphamide and rituximab often induces a complete remission. It also extends the duration of remission and survival time. When hairy cell leukemia in particular 2-Chlorodesoxyadenosin are (cladribine), deoxycoformycin (pentostatin) and interferon alpha highly effective substances. Patients with prolymphocytic and leukemic running lymphomas usually require chemotherapy, often speak out, though very little of. Ibrutinib is a novel investigational oral inhibitor of Bruton’s tyrosine kinase. The enzyme Bruton’s tyrosine kinase plays a crucial role in the activation of several downstream, B-cell mediated signaling pathways that extend the life of CLL cells. In CLL Ibrutinib seems to be very active; it has induced durable remissions in some patients with relapsed or refractory CLL. His role as a single agent or as part of combination therapy is gaining Bedeutung.Corticosteroide indications for corticosteroids are an immunologically induced hemolytic anemia and thrombocytopenia. Prednisone at a dose of 1 mg / kg p.o. once a day can sometimes lead with advanced CLL to an impressive, but usually only short-term improvement in patients. For long-term applications particularly metabolic complications and the increased risk and severity of infections are observed. Prednisone increased in combination with fludarabine the risk of infection with Pneumocystis jirovecii and Listerien.Therapie with monoclonal antibodies Rituximab is the first monoclonal antibody, which has been successfully used in the treatment of lymphoid tumors. In treatment-naïve patients, the response rate is as high as 75%, with 20% of these patients achieve a complete remission. Alemtuzumab is a similar response rate of 75-80% in treatment-naïve patients and a response rate of 33% at the pre-treated with fludarabine patients. Under Alemtuzumab the complications of immunosuppression are significantly larger than rituximab. The combination of rituximab with fludarabine or fludarabine and cyclophosphamide the complete remission rates were increased significantly, both in treatment and in treatment-naïve patients. For the treatment of minimal residual disease alemtuzumab is currently combined with rituximab or chemotherapy. The success of this therapy has been demonstrated. but with alemtuzumab can cause reactivation of cytomegalovirus and other opportunistic infections. Reactivation of hepatitis B infection can occur with rituximab. Obinutuzumab is a newer monoclonal antibody that targets the same CLL cell surface protein such as rituximab. It has recently been discovered that the combination of obinutuzumab and chlorambucil is superior to the extension of a progression-free survival and the achievement of a complete response to treatment compared to rituximab. In general, monoclonal antibodies are well tolerated, although they can cause allergic reactions and a significant immunosuppression. This favorable toxicity profile allows these resources to be combined with conventional chemotherapy, wird.Strahlentherapie which often achieves excellent clinical efficacy For temporary palliation enlarged lymph nodes or liver, or Milzbefall can be irradiated in patients who do not respond to chemotherapy. Occasionally, a whole-body irradiation improved the symptoms temporarily in low doses. Important Points When occurring mostly in the elderly CLL, a slowly progressing leukemia, mature appearing lymphocytes are affected. The treatment is not curative and is usually initiated only when symptoms develop. Chemotherapy with or without monoclonal antibody therapy improves symptoms and survival.

Health Life Media Team

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