Long-term follow-up of monoclonal B-cell lymphocytosis detected in environmental health studies.
BACKGROUND
Four individuals in whom Monoclonal B cell Lymphocytosis (MBL) had been previously detected were evaluated for the fourth time after 15-18 years since initial testing. All four were environmental health study participants without hematologic malignancies who had elevated absolute B cell counts at initial testing.


METHODS
The current laboratory evaluation included complete blood counts, lymphocyte immunophenotypes, immunoglobulin heavy-chain variable (IGHV) gene mutation status, and serum tests for monoclonal immunoglobulins and free light chains. Results from this evaluation were compared with those from the three previous evaluations. Clinical status was assessed by reviewing medical records.


RESULTS
B-cell clones with phenotypic characteristics of the original MBL clone were detected in three of the four individuals. Since the last evaluation in 2003, one participant who had a clinical diagnosis of Waldenstrom's Macroglobulinemia had developed a diffuse large cell lymphoma and was treated. Another participant continued to show a decline in lymphocyte and B cell counts, reaching clinical lymphocytopenia and B cell lymphopenia. The MBL clone was still detectable. The remaining two participants had stable blood counts and MBL phenotypes. Neither had been diagnosed with a hematologic malignancy. However, molecular analysis revealed clonal changes in both: one showed a marked decline in the percentage of somatically-mutated B cells, and the other showed a clonal transition from IGHV3-13 to IGHV4-34.


CONCLUSIONS
A diversity of clonal evolution was observed in these MBL cases. These observations suggest that long-term follow-up studies using standardized MBL subcategories are essential to understanding B-cell pathobiology and optimizing clinical management.
Marti
Gerald E
GE
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA.
Shim
Youn K
YK
Albitar
Maher
M
Middleton
Dan
D
Abbasi
Fatima
F
Anderson
Ayana
A
Vogt
Robert F
RF
D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002999:Clone Cells; D004784:Environmental Monitoring; D005260:Female; D005500:Follow-Up Studies; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D006403:Hematologic Tests; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged