Depending on the individual’s age, physical condition, and whether they have the del(17p) or TP53 mutation, different first line treatments may be offered. As of 2021, BTK inhibitors such as ibrutinib and acalabrutinib are often recommended for first line treatment of CLL. The medications fludarabine, cyclophosphamide, and rituximab were previously the initial treatment in those who are otherwise healthy.CLL affected about 904,000 people globally in 2015 and resulted in 60,700 deaths. In 2021, the estimated incidence of CLL in the United States is 21, 250 new cases and 4,320 deaths. The disease most commonly occurs in people over the age of 65 due to the accumulation of genetic mutations that occurs over time. Men are diagnosed around twice as often as women (6.8 to 3.5 ratio). It is much less common in people from Asia. Five-year survival following diagnosis is approximately 83% in the United States. It represents less than 1% of deaths from cancer. Signs and symptoms
Most people are diagnosed as having CLL based on the result of a routine blood test that shows a high white blood cell count, specifically a large increase in the number of circulating lymphocytes. These people generally have no symptoms. Less commonly, CLL may present with enlarged lymph nodes. If enlarged lymph nodes are caused by infiltrating CLL-type cells, a diagnosis of small lymphocytic lymphoma (SLL) is made. Less commonly the disease comes to light only after the cancerous cells overwhelm the bone marrow resulting in low red blood cells, neutrophils, or platelets.
Malum perforans is a long-lasting, usually painless ulcer that penetrates deep into or through the skin, usually on the sole of the foot (in which case it may be called malum perforans pedis). It is often a complication in diabetes mellitus and other conditions affecting the nerves. Presentation
These ulcers have punched-out edge and slough in floor, resembling gummatous ulcer. Surrounding area might have loss of sensation. Cause
This condition results from denervation of areas exposed to day-to-day friction of bony prominences. The denervation may be result of any of the following diseases:
Spinal injuries
Leprosy
Peripheral nerve injury
Diabetic neuropathy
Tabes dorsalis
Transverse myelitis
Meningomyelocele
Syringomyelia

Pathophysiology
Normal pressure and pain sensations are essential for protecting the foot from excessive and prolonged pressures over bony prominences. In insensitive foot, such as in diabetic neuropathy, soft tissues are exposed to excessive pressures without knowledge of the individual. In other words, by nerve damage in the feet, the patients get no feedback on the impact of the feet when walking. These ulcers start with callosity under which suppuration takes place. The pus comes out and a hole forms under which the lesion grows deeper. This leads to punched-out, painless ulcers usually under metatarsal heads, tip of toe, or proximal interphalangeal joint of a hammertoe or on the heel. In non-ambulatory patients, these ulcers are found on buttocks and back of the heel. Diagnosis
Diagnosis is clinical. Sensation is tested using graded monofilament. Treatment
The underlying cause of the neuropathy is first treated. Necrotic portions of the wound are removed and the wound is kept moist at all occasions.