Generally, prolymphocyte proportion exceeds 90%
Minimal or absence of lymphadenopathy – abnormalities in size, number or consistency of lymph nodes
Splenomegaly - Abnormal enlargement of the spleen
High white blood cell count
B-symptoms – Fever, night sweats and/or weight lossSimilar to other leukemias, B-cell prolymphocytic leukemia is often asymptomatic. The most common signs and symptoms are the result of the inability of the bone marrow to produce normal levels of blood cells:
Anaemia – due to lack of red blood cells
More frequent, severe and prolonged infections – due to lack of normal white blood cells
Bleeding and bruising – due to lack of platelets

Diagnosis
Diagnosis of B-PLL is difficult due to its considerable overlap with other mature B-cell leukemias and lymphomas. It requires integration of morphology with diagnostic tests including immunophenotyping and chromosome analysis (cytogenetics). Morphology
The malignant B cells are larger than average. In order to diagnose a patient with B-PLL, b-prolymphocyte composition of a patients blood cells must exceed 55%. High white blood cell counts – greater than 100 x 109/L  – are also indicative of B-PLL. B-prolymphocytes are characterized by:
Large size – approximately twice the size of a normal small lymphocyte
Round or oval-shaped nuclei
Single prominent nucleolus
Moderately condensed nuclear chromatin
High nuclear-cytoplasmic ratio – indicates more abundant cytoplasm

Immunophenotype
This technique is used to study proteins expressed in cells using immunologic markers. In B-PLL patients there is strong expression of surface immunoglobulin – a membrane-bound form of an antibody, b-lymphocyte surface antigens CD19, CD20, CD22, CD79a and FMC7, and weak expression of CD5 and CD23.
Watchful Waiting
Some patients do not require immediate treatment after diagnosis; these patients include those that do not show overt symptoms or whose cancer has not been observed to be progressing. Regular check-ups with physicians are required to actively monitor the patients condition; once there is evidence of disease progression or patient distress from symptoms, treatment will be implemented. Chemotherapy
B-PLL has a very aggressive clinical course and refractoriness to chemotherapy; it is believed this resistance is the result of mutations to the TP53 gene. Its resistant nature has led to the use of combinations of chemotherapy drugs. Drug regimens recommended and employed by physicians are unique to each patient and are based on previous chemotherapy experience along with potential side effects. In addition to the utilization of combinations of chemotherapeutic drugs, it is most often paired with immunotherapy treatments. Targeted Therapy
Monoclonal Antibodies
A type of targeted therapy that recognizes specific proteins in leukemia cells preventing collateral damage to normal, healthy cells. The following are compounds currently showing promising results in clinical trials and studies:

Rituximab is a widely used monoclonal antibody in treating B-cell malignancies, it is directed against the surface protein CD20. Case studies have documented successful treatment of B-PLL solely with rituximab; additional studies have reported positive activity when rituximab is paired with the chemotherapeutic drugs fludarabine or bendamustine together with the anthracyclines mitoxantrone or epirubicin
Alemtuzumab is a humanized antibody that targets the CD52 antigen which is highly expressed in malignant B-lymphocytes. In vitro tests have demonstrated that it induces cell death.