B-cell chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL ) is a low-grade, leukemic extending B- cell non- Hodgkin 's lymphoma (B- NHL). It is in the Western world, the most common form of leukemia and occurs mainly in older age (the average age at diagnosis is over 50 years, which is why the disease is sometimes referred to as "Old leukemia "). The WHO classification of hematological diseases differs in addition to the CLL have a sub-form, the small lymphocytic lymphoma (B- SLL, Small cell B -cell lymphoma ), which essentially corresponds to a CLL in which the lymph node involvement is in the foreground, without it to a higher grade manifestation in the blood ( leukemia) is (sort of a non- leukemic running CLL).

Epidemiology

The incidence ( number of new cases ) per year is approximately 4 per 100,000 inhabitants, making it the most common leukemia in the Western world. Men are affected more often than women ( M: F = 1.7: 1). The median age is 70 to 75 years at diagnosis.

Pathogenesis

In the disease there is a clonal proliferation of mature, small cell, but non-functional B lymphocytes. The exact reason for this is not known. However, it is now believed that genetic changes that have been acquired in the course of life, crucial trigger for the disease. Notes for an infectious cause, such as viruses, does not yet exist.

The molecular genetic analysis using fluorescence in situ hybridization (FISH) is more than 80 % genetic modification of chromosomes. The most common abnormality is a deletion on chromosome 13 ( del ( 13q ) ). Further changes are deletions of chromosome 11 ( del ( 11q ) ) and 17 ( del ( 17p ) ) and trisomy 12 These chromosomal changes have prognostic significance. Patients who have a del ( 17p ), typically have a less favorable prognosis. Patients with del ( 13q ) have a relatively favorable prognosis.

In general, the CLL is a very heterogeneous extending disease. There are patients in whom the disease takes a very benign course and does not require treatment over several years or even decades. There are also patients in which the disease shows a more aggressive course. These differences are partly the consequence of different genetic changes in different patients.

Diagnosis

The diagnosis of CLL is generally provided by two simple tests:

Further studies are used to detect the spread of CLL ( chest X-ray, ultrasound examination of the abdomen ).

Symptoms

Often the discovery of the disease an incidental finding during a blood test in the diagnosis of other diseases. The following symptoms occur in the course of the disease:

  • Lymph node swelling
  • Spleen / liver enlargement
  • Skin symptoms (30 percent of cases) itching
  • Eczema
  • Mycoses
  • Herpes zoster
  • Skin bleeding
  • Nodular infiltrates
  • Pale skin and mucous

Differential Diagnosis

  • Leukemic non-Hodgkin's lymphoma
  • Hairy cell leukemia
  • Prolymphocytic

Therapy

The treatment depends on the stage of the disease. The clinical classification according to Binet distinguishes three stages:

In early stages ( Binet stage A and B) is not usually treated unless the disease causes discomfort or is moving very fast. These symptoms may include:

  • Splenomegaly with symptoms
  • Complaints by increasing lymph nodes
  • Severe, life -disfiguring general symptoms ( night sweats, repeated infections, fever, weight loss )

A treatment is also usually displayed from the stage Binet C ( severe anemia or thrombocytopenia).

It is treated with the chemotherapeutic drugs chlorambucil ( an alkylating agent ), Chlorodeoxyadenosin and Deoxyformycin or fludarabine (all three purine analogues ). Since recently, the alkylating agent bendamustine for the treatment of CLL is approved. It is very popular in Germany and has recently been used in combination with rituximab (BR ) scheme. Among these substances, chlorambucil and fludarabine are the best studied. Recent results from the CLL8 protocol of the German CLL Study Group ( GCLLSG ) have shown that the combination of chemotherapy with fludarabine and cyclophosphamide ( FC ) and the CD20 antibody rituximab ( R) representing the currently effective therapy. Compared to FC alone FCR achieves twice the rate of complete remissions, longer progression - free time and a prolonged overall survival. Therefore, the German CLL Study Group recommends since 2009 as a standard therapy for physically fit patients with CLL, a combination of fludarabine, cyclophosphamide and rituximab ( FCR ).

An evidence-based, that is proven effective therapy for patients who suffer a relapse after initial therapy, it does not exist yet. In patients who fail to respond to fludarabine, the anti - CD52 antibody alemtuzumab is employed. It is now possible, under certain conditions, a therapy with ofatumumab. Soon could gain GA101 therapeutic importance, the new CD20 monoclonal antibody. In addition comes a bone marrow or stem cell transplantation into consideration. However, allogeneic transplantation strategies in CLL are associated with high treatment-related mortality rates and are only for use in selected patients. Meanwhile, stem cell transplantation with reduced-intensity conditioning also be used in older patients. For the treatment of larger lymphomas can be used irradiation.

International Classification of Diseases for Oncology World Health Organization Cluster of differentiation Leukocytosis Lymphocytosis Evans syndrome Thymidine kinase Cladribine Pentostatin
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