Chronic lymphocytic leukemia (CLL) is a malignant disease of the lymphatic system associated with increased synthesis of nonfunctional lymphocytes. In this regard, chronic lymphocytic leukemia represents the most common form of leukemia in adults, especially after the age of 70, accounting for more than 30 percent of cases.
What is chronic lymphocytic leukemia?
Chronic lymphocytic leukemia (CLL) is a low-malignancy disease of the lymphatic system (B-cell non-Hodgkin’s lymphoma) with a leukemic course that is due to clonal cell proliferation of lymphocytes (white blood cells). Chronic lymphocytic leukemia is manifested by swelling of the lymph nodes, enlargement of the spleen and liver, fatigue and weakness, anemia, thrombocytopenia (decreased blood platelet count), and specific skin changes (itching, eczema, mycoses, nodular infiltrates, skin bleeding due to an increased bleeding tendency, skin pallor, herpes zoster) and a generally increased susceptibility to infections (recurrent pneumonia, bronchitis). In addition, the clinical picture of chronic lymphocytic leukemia includes parotitis (Mikulicz syndrome), leukocytosis in combination with lymphocytosis, antibody deficiency syndrome, incomplete heat autoantibodies, a decreased antibody concentration accompanied by an increased concentration of lymphocytes in the bone marrow.
Causes
Chronic lymphocytic leukemia is due to clonal proliferation of small-cell and nonfunctional B lymphocytes. The exact causes of the increased synthesis of B lymphocytes have not yet been determined. It is considered certain that CLL is generally (80 percent) caused by acquired genetic changes in the chromosomes, with a deletion (absence of a chromosome sequence) on chromosome 13 in the majority of cases. Similarly, missing sequences on chromosomes 11 and 17 and trisomy 12 (triple presence of chromosome 12) can cause CLL. The triggers for these chromosomal changes are not known, but bacterial, viral, or parasitic infections are ruled out. In addition, chemicals (especially organic solvents) and a genetic predisposition are discussed as triggers.
Symptoms, complaints, and signs
The complaints of this disease have a very negative effect on the quality of life and can thereby considerably restrict and complicate the daily life of the affected person. First and foremost, the patient’s lymph nodes are swollen and may also hurt. There is also an enlargement of the liver and spleen, which is also associated with pain. If the disease is not treated, in the worst case it can lead to liver insufficiency and thus to the death of the affected person. On the skin, there is a rash and severe itching. Likewise, bleeding can occur on the skin and significantly reduce the aesthetics of the patient. In many cases, the disease leads to anemia and thus to severe fatigue and exhaustion of the affected person. As a result, patients no longer actively participate in daily life and require assistance from others in their daily routine. Similarly, nosebleeds and bruising may occur in various parts of the body. If the disease is not treated, the patient’s life expectancy is significantly reduced. As the disease progresses, it also leads to psychological upset or depression in the process.
Diagnosis and course
Initial suspicion of chronic lymphocytic leukemia results from characteristic symptoms (including swelling of the lymph nodes in the neck, armpits, and groin). The diagnosis is confirmed by a blood count or differential blood count and immunophenotyping of the lymphocytes. If an increased lymphocyte count in the serum (over 5000/µl) is detectable for at least 4 weeks and if the lymphocytes characteristic of CLL (deviating surface proteins, Gumprecht’s nuclear shadows) can be detected in the blood smear, chronic lymphocytic leukemia can be assumed. Imaging techniques such as sonography and computed tomography provide information about involvement of the internal organs (splenomegaly, liver enlargement) as well as the extent of the disease. The course of CLL is heterogeneous and depends on the underlying chromosomal alteration.Thus, affected individuals with a deletion on chromosome 13 have a comparatively favorable prognosis with a slow course, whereas chronic lymphocytic leukemia resulting from a deletion on chromosomes 17 and 11 generally has a severe course with an unfavorable prognosis.
Complications
Chronic lymphocytic leukemia can lead to a variety of complications. A fairly common negative side effect of this disease is the so-called antibody deficiency syndrome. The CLL cells characteristic of lymphocytic leukemia displace the functional B cells in the human immune system. As a result, the risk of infection increases immensely. At the same time, the body’s defenses against pathogenic germs are weakened by the absence of functional B cells. In some cases, the amount of granulocytes is reduced. The body needs these to protect itself against bacteria. Affected individuals therefore develop bacterial infections more frequently. The respiratory tract and the organs of the gastrointestinal tract are particularly frequently affected. Infection of the lungs with viruses or bacteria in particular can have serious consequences if not treated promptly. In the worst case, an infestation of the lungs ends fatally. In addition to an antibody deficiency, autoimmune hemolytic anemia may develop. The consequences are pallor, fatigue, shortness of breath and ringing in the ears. In the later course, further complications such as fever, chills, abdominal pain and vomiting may occur. In particularly severe cases, this disease can lead to kidney failure or shock. Another serious complication is the development of malignant lymphoma. This transition is also known as Richter transformation. It has a much worse prognosis than chronic lymphocytic leukemia.
When should you see a doctor?
Because chronic lymphocytic leukemia is a malignant disease, a physician should be consulted immediately as soon as there is a persistent feeling of illness or a diffuse sense of discord. The course of the disease is insidiously progressive and can be fatal without timely medical attention. Due to the slow progression of leukemia, it is difficult for the affected person to assess at what point the symptoms that occur are triggered by a serious illness. People who are unusually tired over a long period of time or have pale facial coloration over several weeks should already take advantage of these indications and consult a doctor. Swollen lymph nodes in various areas of the body are considered worrisome and must be clarified by a doctor as soon as they are palpable over several weeks. This is especially true if the painless swellings have not developed as a result of influenza illness. General weakness or states of exhaustion with sufficient sleep and without mental or emotional stress should be clarified by a physician. Lack of strength that develops for reasons that cannot be understood must be investigated and treated as soon as possible. If there is a perceived lack of blood, a visit to the doctor is also necessary. If the fingers or toes cool down unusually quickly or are permanently cold despite normal temperature conditions, it is advisable to see a doctor.
Treatment and therapy
In chronic lymphocytic leukemia, the choice of therapeutic measures correlates with the stage of the disease. Thus, in the early stages of CLL (Binet A and B), therapeutic measures are generally not yet required if the patient is symptom-free. In contrast, in the case of advanced chronic lymphocytic leukemia (Binet C) or unfavorable chromosomal changes, an early start of therapy is indicated. In this case, the treatment options primarily include chemotherapy, in which the cell division of the cancer cells is inhibited by drugs and the lymphocyte count in the bone marrow is reduced, and immunotherapy, in which the cancer cells are killed by genetically synthesized immunoglobulins. Chemotherapeutic agents used are the alkylants chlorambucil and bendamustine in combination with rituximab, and the purine analogues deoxycoformycin, chlorodeoxyadenosine or fludarabine. For physically fit patients, a combination of cyclophosphamide, fludarabine and rituximab is usually recommended. Monotherapeutically, synthesized alemtuzumad, an anti-CD52 antibody, is used in the context of immunotherapy.Since chronic lymphocytic leukemia is a systemic disease, radiation therapy is only considered locally for large lymphomas, while bone marrow or stem cell transplantation is performed exclusively for refractory (unmanageable) or early relapsed CLL due to the high mortality rate. In addition, supportive measures (blood cell replacement with transfused red cell or platelet concentrates, antibiotics) may be indicated in chronic lymphocytic leukemia to prevent complications.
Prospect and prognosis
Patients with chronic lymphocytic leukemia can often have several years of symptom-free disease. Leukemia can have a benign course for up to 20 years without any adverse health effects. This leads to a gradual spread of the blood cancer in the organism. The disease often develops over a long time window with only a slight increase in symptoms. Only a few patients have a rapid course of the disease, in which within a few months after the onset of leukemia the lymphocytes increase to such an extent that treatment is initiated. For this reason, it is almost always discovered at a very late stage of development and cannot be treated until then. However, the timing of diagnosis is critical to the course of cure. The later CLL is discovered, the worse the prognosis. In addition, older people over the age of 70 often develop chronic lymphocytic leukemia. Due to their advanced age, the patients usually have other diseases that lead to a general weakening of the immune system and a reduction in the prospect of cure. In addition, if the lymphocytes are already in the bone marrow or if there has already been enlargement of the liver or spleen, the prospects of cure are considerably worsened.
Prevention
Because the causes of the chromosomal abnormalities underlying chronic lymphocytic leukemia have not yet been determined, the disease cannot be prevented. However, organic solvents and a family prevalence (disease frequency) are considered risk factors with regard to the manifestation of CLL.
Follow-up
Chronic lymphocytic leukemia requires follow-up if the patient could be discharged symptom-free. Otherwise, he or she must continue treatment until symptom-free. Symptom-free patients with chronic lymphocytic leukemia should present to the treating physician for blood cell testing at intervals of three to six months. The reason for close monitoring is possible relapses. In order to track and document the effect of treatment, physical examinations for typical signs of relapse are one of the useful things to do during the follow-up of those affected. In addition, blood and bone marrow tests are performed for chronic lymphocytic leukemia. In case of doubt, imaging procedures such as ultrasound and computer tomography can also provide information about the current state of affairs. Indeed, if a relapse occurs, only blood stem cell transplants, cellular immunotherapies and kinase inhibitors can help. A patient who agrees during follow-up to participate in clinical trials for chronic lymphocytic leukemia will be exposed to specific laboratory methods. For example, he or she will experience immunophenotyping or polymerase chain reaction testing. This can detect even the smallest amounts of degenerated blood cells in the organism. The extent and intensity of the aftercare measures also depends on the other diseases the patient had previously suffered from. If the patient is in good general health, the follow-up measures may be less frequent than in the case of previous diseases that affect the general condition.
Here’s what you can do yourself
Chronic lymphocytic leukemia usually causes no symptoms for a long time, so patients can go about their daily activities as usual. Sports activities are also still possible, but individual performance limits should not be exceeded. Due to the increased risk of infection, affected persons should avoid traveling to tropical areas. Protective vaccinations with a live vaccine can have a negative influence on the course of the disease, but the annual flu vaccination with a dead vaccine is recommended.Regular exercise, preferably in the fresh air, and a healthy, vitamin-rich diet strengthen the immune system and reduce susceptibility to infections. Particularly during the cold season, people should avoid crowds and special emphasis should be placed on regular and thorough hand washing. Careful washing of fruit and vegetables can significantly reduce the number of ingested germs, and avoiding unpasteurized dairy products reduces the risk of listeriosis infection. If, despite these precautions, symptoms of an infectious disease such as fever, diarrhea or respiratory problems appear, immediate medical treatment is urgently recommended. During and after chemotherapeutic treatment, protection against infections and their rapid control is particularly important. Chronic lymphocytic leukemia can also affect the psyche: Accurate information, conversation with family and friends, or exchange in a support group can help to accept and better cope with the disease.
