Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Leukemia and Lymphoma Phenotyping AlgorithmClinical Background
Chronic lymphocytic leukemia (CLL) is characterized by small lymphocytes in the bone marrow, blood and lymphoid tissues. It is the most common form of leukemia in adults in the United States.
Epidemiology
- Incidence - 2-3/100,000
- Age - median 70 years
- 80% diagnosed greater than or equal to 60 years
- Sex - M:F; 2.8:1
Risk Factors
- Family member with CLL
Clinical Presentation
- 25-50% are asymptomatic - found to have lymphocytosis on complete blood count
- Constitutional symptoms - night sweats, weight loss, fatigue
- Adenopathy
- Hepatomegaly
- Lymph nodes - most commonly cervical, supraclavicular, axillary
- Splenomegaly
- Extranodal disease - uncommon
- Central nervous system
- Gastrointestinal tract
- Lungs
- Renal
- Complications - large-cell transformation (Richter syndrome)
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Leukemia and Lymphoma Phenotyping AlgorithmDiagnosis
Diagnosis
- Based on modification of National Cancer Institute (NCI) information; bone marrow is not necessary if characteristic phenotype is present
| Criteria for the Diagnosis of Chronic Lymphocytic Leukemia* | ||
| Criteria | NCI-WG 1996 | WCLL 2005 |
| Peripheral blood lymphocytes (x10^9/L) | >5 | Not specified ** |
| Morphology | Not specified | Small, mature lymphocytes without visible nucleoli; smudge cells are characteristic |
| Immunophenotype of lymphocytes | greater than or equal to 1 B-cell marker (CD19, CD20 or CD23) and CD5 positivity in the absence of other pan-T-cell marker Monoclonal expression of either kappa or gamma chain Low-density surface Ig | greater than or equal to 1 B-cell marker (CD19, CD20 or CD23) and CD5 positivity in the absence of other pan-T-cell marker Monoclonal expression of either kappa or gamma chain Low-density surface Ig |
| Atypical cells (e.g., prolymphocytes) | <55% and/or <15 x 10^9/L | <55% and/or <15 x 10^9/L |
| Duration of lymphocytosis | None required | Not specified but needs to be chronic |
| Bone marrow lymphocytes (%) | greater than or equal to 30 | Bone marrow evaluation not required*** |
| * IWCLL = International Workshop on Chronic Lymphocytic Leukemia; NCI-WG = National Cancer Institute-sponsored Working Group **A lower value than 5x10^9/L is acceptable provided there is a chronic, absolute increase in blood lymphocytes with the characteristic morphology and immunophenotype *** Bone marrow evaluation is no longer required for diagnosis but useful to determine the extent and pattern of involvement and clarification of the etiology of cytopenias | ||
| (Used with permission from Mayo Clin Prc. Yee and O'Brien, 2006, 1106) | ||
Disease Monitoring and Staging
- IgVH mutation analysis - unmutated VH genes correlated with poor prognosis
- ZAP-70 - correlated with poor outcome if present
- Highly correlated to the immunoglobulin variable heavy chain (IgVH) gene mutation
- Flow cytometry followup - to detect minimal residual disease
- CD38 >30% expression - poor outcome
- Beta 2-microglobulin - elevation associated with poor prognosis
- Chromosome analysis - complex and unbalanced translocations associated with poor prognosis
- FISH panel for prognostic stratification
- p53 (17p) deletion - unfavorable and associated with resistance to fludarabine, alkylator, and possibly rituximab
- ATM (11q) deletion - unfavorable
- Trisomy 12 - neutral
- 13q14 deletion - favorable
Differential Diagnosis
- Benign causes - infections, thyrotoxicosis, Addison disease, postsplenectomy
- Malignant - non-Hodgkin lymphoma transformed, plasma cell dyscrasias, Sézary syndrome, other leukemias
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Leukemia and Lymphoma Phenotyping Algorithm| Tests |
Tests generally appear in the order most useful for common clinical situations
| Test name: Chronic Lymphocytic Leukemia Follow up Phenotyping by Flow Cytometry |
| ARUP #: 0093194 |
| Methodology: Flow Cytometry |
| Use: Monitor disease status after CLL has been established by previous flow cytometry immunophenotyping |
| Test name: Chromosome Analysis, Chronic Lymphocytic Leukemia (CLL) Panel by FISH |
| ARUP #: 0092616 |
| Methodology: Fluorescence in situ Hybridization |
| Use: Fluorescence in situ hybridization panel is performed for CLL prognosis Specific genomic abnormalities tested for are: ATM, D13S25, p53, and trisomy 12 |
| Test name: Chromosome Analysis, Bone Marrow |
| ARUP #: 0097605 |
| Methodology: Giemsa-Band Analysis |
| Use: Detect chromosome abnormalities in bone marrow Complex abnormalities and unbalanced translocations are associated with a poorer prognosis |
| Limitations: CLL cells can grow slowly in culture and may not be present in the cells analyzed. Therefore, it is recommended this test be done in conjunction with the CLL FISH panel for increased sensitivity (0092616) |
| Follow-up: Repeat testing as clinically indicated to monitor disease progression |
| Test name: Chromosome Analysis, Leukemic Blood |
| ARUP #: 0097635 |
| Methodology: Giemsa-Band Analysis |
| Use: Detect chromosome abnormalities in peripheral blood Complex abnormalities and unbalanced translocations are associated with a poorer prognosis |
| Limitations: CLL cells can grow slowly in culture and may not be present in the cells analyzed. Therefore, it is recommended this test be done in conjunction with the CLL FISH panel for increased sensitivity (0092616) |
| Follow-up: Repeat testing as clinically indicated to monitor disease progression |
| Test name: IgVH Mutation Analysis by Sequencing |
| ARUP #: 0040227 |
| Methodology: Polymerase Chain Reaction/Sequencing |
| Use: Prognostication of outcome |
| Limitations: Time-sensitive test |
| Test name: ZAP-70 Analysis by Flow Cytometry |
| ARUP #: 0092392 |
| Methodology: Flow Cytometry |
| Use: Prognostication of outcome |
| Limitations: ZAP-70 results should not be used for diagnostic purposes, but may help in the clinical management of patients with established diagnoses of chronic lymphocytic leukemia. Results of this test should always be correlated with morphologic and clinical information |
| Test name: Immunohistochemistry Stain Offering |
| ARUP #: arup005 |
| Methodology: Immunohistochemistry |
| Use: For fixed tissue samples, consultative services as well as immunohistochemical staining for p53 are available |
References
Cited References
General References
Medical Reviewers
Bahler, David W., M.D., Ph.D. Medical Director, Hematologic Flow Cytometry, and Acting Medical Director, Molecular Hematopathology at ARUP Laboratories; Associate Professor, Pathology, University of Utah
Lamb, Allen N., Ph.D. Medical Director, Cytogenetics, ARUP Laboratories; Associate Professor, Department of Pathology, University of Utah
South, Sarah T. , Ph.D. Medical Director, Cytogenetics at ARUP Laboratories; Assistant Medical Director, CGH Microarray Laboratory, and Assistant Professor, Department of Pediatrics, University of Utah
Comprehensive Review: March 2008
Last Update: September 2008
