Monoclonal B-Cell Lymphocytosis and Chronic Lymphocytic Leukemia
Andy C. Rawstron, Ph.D., Fiona L. Bennett, M.Sc., Sheila J.M. O'Connor, Ph.D., Marwan Kwok, B.Sc., James A.L. Fenton, D.Phil., Marieth Plummer, B.Sc., Ruth de Tute, M.Sc., Roger G. Owen, M.D., Stephen J. Richards, Ph.D., Andrew S. Jack, Ph.D., and Peter Hillmen, Ph.D.
Background A diagnosis of chronic lymphocytic leukemia (CLL)requires a count of over 5000 circulating CLL-phenotype cellsper cubic millimeter. Asymptomatic persons with fewer CLL-phenotypecells have monoclonal B-cell lymphocytosis (MBL). The goal ofthis study was to investigate the relation between MBL and CLL.
Methods We investigated 1520 subjects who were 62 to 80 yearsof age with a normal blood count and 2228 subjects with lymphocytosis(>4000 lymphocytes per cubic millimeter) for the presenceof MBL, using flow cytometry. Monoclonal B cells were furthercharacterized by means of cytogenetic and molecular analyses.A representative cohort of 185 subjects with CLL-phenotype MBLand lymphocytosis were monitored for a median of 6.7 years (range,0.2 to 11.8).
Results Monoclonal CLL-phenotype B cells were detected in 5.1%of subjects (78 of 1520) with a normal blood count and 13.9%(309 of 2228) with lymphocytosis. CLL-phenotype MBL had a frequencyof 13q14 deletion and trisomy 12 similar to that of CLL andshowed a skewed repertoire of the immunoglobulin heavy variablegroup (IGHV) genes. Among 185 subjects presenting with lymphocytosis,progressive lymphocytosis occurred in 51 (28%), progressiveCLL developed in 28 (15%), and chemotherapy was required in13 (7%). The absolute B-cell count was the only independentprognostic factor associated with progressive lymphocytosis.During follow-up over a median of 6.7 years, 34% of subjects(62 of 185) died, but only 4 of these deaths were due to CLL.Age above 68 years and hemoglobin level below 12.5 g per deciliterwere the only independent prognostic factors for death.
Conclusions The CLL-phenotype cells found in the general populationand in subjects with lymphocytosis have features in common withCLL cells. CLL requiring treatment develops in subjects withCLL-phenotype MBL and with lymphocytosis at the rate of 1.1%per year.
Source Information
From the Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Leeds, United Kingdom.
Address reprint requests to Dr. Rawstron at HMDS, Department of Haematology, St. James's Institute of Oncology, Bexley Wing, Beckett St., Leeds LS9 7TF, United Kingdom, or at andy.rawstron{at}hmds.org.uk.
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