The Treatment of Chronic Lymphatic Leukemia

Chronic lymphocytic leukemia (CLL) mainly affects older persons and is the commonest form of leukemia, with an incidence of 6 cases per 100 000 per- sons per year. In Germany, approximately 1000 men and 850 women die of CLL each year.

This review is based on pertinent publications retrieved by a selective literature search in PubMed and on the authors' scientific and clinical experience.

The diagnosis of CLL requires the detection of at least 5000 B-lymphocytes per microliter in the peripheral blood. Courses of CLL may be indolent and require no treatment, but may also be aggressive and progress rapidly. Treatment should be initiated when there is marked evidence of bone-marrow suppression or disease- related symptoms such as B symptoms or fatigue. In the past ten years, a number of targeted drugs have been introduced that can achieve a very good, long-lasting response, particularly when used in combination. The combination of chemotherapy with anti-CD20 antibodies (chemoimmunotherapy) is the standard first-line treat- ment. In younger patients without any relevant accompanying illnesses, the combi- nation of fludarabine, cyclophosphamide, and rituximab prolongs survival. Patients with comorbidities should be treated with a combination of chlorambucil and obinutuzumab. In the last few years, ibrutinib, idelalsib, and venetoclax have been approved for clinical use. These substances inhibit cellular signal transduction pathways and are being increasingly used.

Recent progress in the development of novel treatment options gives hope that CLL may soon be a controllable disease. Even at present, chemoimmuno- therapy can achieve a progression-free survival of more than eight years in certain genetically defined subgroups of CLL patients.