Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (342 page)

   
Genomic studies
may emerge in the future as the best tools for determining the clinical course of CLL/SLL. Genetic complexity is associated with aggressive disease. Loss or mutation of TP53 (a tumor suppressing gene) places patients in the highest risk prognostic group. Down-regulation of miR-29c and miR-223, and possibly other microRNAs, has been associated with adverse prognosis. MiR-34a indicates resistance to chemotherapy. This is an area that is developing rapidly. The integration of genomic mutations and cytogenetic lesions improves the accuracy of survival prediction in CLL.

   
Serum immunoglobulins
: Hypogammaglobulinemia develops and progresses as the disease becomes more advanced. A monoclonal protein, usually of the same class as the surface membrane immunoglobulin, is found in 5% of patients.

   LDH, β-2 microglobulin, and thymidine kinase are elevated in more than half the patients. Their increase parallels a worsening prognosis.

TABLE 9–3. Differential Immunophenotypic Markers for Four Chronic Lymphoproliferative Diseases

B-PLL, prolymphocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; SLL, small lymphocytic lymphoma; TRAP, tartrate-resistant acid phosphatase.

   Transformation

   The most common transformation is reflected by a progressive increase in prolymphocytes. When ≥55% of the leukemic lymphocytes acquire characteristics of prolymphocytes, the disease becomes known as prolymphocytic leukemia (see below). It connotes a grave prognosis.

   Richter syndrome is an aggressive transformation from CLL/SLL seen in 2–8% of patients. Diffuse large B-cell lymphoma is the most common histology. This lymphoma may arise from the CLL clone, but occasionally it represents an independent clone. It is considered a very aggressive lymphoma, but a large recent study demonstrated genetic heterogeneity and that survival can vary from a few weeks to 15 years.

Suggested Readings

Gribben JG. How I treat chronic lymphocytic leukemia.
Blood.
2010;115:187–197.

Rawstron AC, Bennett FL, O’Connor SJM, et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia.
N Engl J Med.
2008;359:575–583.

Rossi D, Rasi S, Spina V, et al. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia.
Blood.
2013;121:1403–1412.

Rossi D, Spina V, Deambrogy C, et al. The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation.
Blood.
2011;117:3391–3401.

PROLYMPHOCYTIC (PLL) LEUKEMIA OF B- AND T-CELL SUBTYPE

   Definition

B-cell PLL is a rare, aggressive, clonal lymphoproliferative disease composed mainly of B-cell prolymphocytes. It involves peripheral blood, bone marrow, and spleen. T-cell PLL is still rarer and will not be discussed further.

   Who Should Be Suspected?

Patients who present with prominent splenomegaly but no lymphadenopathy, B symptoms and WBC counts of >100,000 comprised nearly exclusively of abnormal appearing lymphocytes and frequently with anemia and thrombocytopenia. Some have a history of CLL/PLL, which occasionally transforms into B-cell PLL (see p. 402).

   Laboratory Findings

   
CBC
: 50% of patients present with anemia and thrombocytopenia.