These immature lymphocytes are not normally found in the blood; part of their maturation process is being programmed to produce antibodies against foreign material prior to their departure from the bone marrow.

The most common signs and symptoms are the result of the inability of the bone marrow to produce normal levels of blood cells:[7] Diagnosis of B-PLL is difficult due to its considerable overlap with other mature B-cell leukemias and lymphomas.

Immunophenotyping helps distinguish B-PLL from similar diseases, one of its key identifiers is the absence in expression of the surface antigens CD10, CD11c, CD25, CD103 and cyclin D1 – an important regulator of cell-cycle progression.

Amplification of c-MYC has been reported in B-PLL patients and while the consequences are unclear, it is generally associated with poor clinical outcome.

[18] After physicians have identified an abnormality in the composition of the peripheral blood, biopsies (tissue samples) from a patient's bone marrow and/or spleen are often recommended for confirmation.

[20] The rarity of B-PLL paired with its considerably fast progression compared to other leukemias has resulted in difficult production of effective treatments.

This disease is currently incurable, treatments and therapy are guided to reduce prolymphocyte abundance in the blood and production by the bone marrow, treating symptoms and controlling progression.

Drug regimens recommended and employed by physicians are unique to each patient and are based on previous chemotherapy experience along with potential side effects.

[19] The following are compounds currently showing promising results in clinical trials and studies: Ibrutinib is a targeted therapy known as a Bruton's tyrosine kinase (BTK) inhibitor.

[23] Patients with splenomegaly (enlarged spleen), unfit for systemic treatment or refractive to chemotherapy may have their spleens removed via splenectomy or undergo splenic irradiation in order to relieve pain, control their symptoms, and allow removal of a major proliferative focus and tumour bulk in this disease.

[8][19] Despite advancements in treatments and deeper understanding of pathogenesis, the prognosis for B-PLL patients is poor,[25] with early relapse and median survival time between 3–5 years.

[26][27] B-PLL represents less than 1% of all leukemia cases worldwide,[28] mainly affecting the elderly population with a mean age of presentation between 65 and 70[29] years.