Correspondence
The Precursor of Chronic Lymphocytic Leukemia
N Engl J Med 2009; 360:2575-2576June 11, 2009
- Article
To the Editor:
Landgren and colleagues (Feb. 12 issue)1 present data that cannot be used to differentiate monoclonal B-cell lymphocytosis (MBL) from chronic lymphocytic leukemia (CLL). The findings of clonal B-cell populations are based on flow-cytometric and molecular analyses, but these approaches do not measure the B-cell count in the prediagnostic blood sample. In Table 2 of the article, the values for “lymphocytes” are percentages of lymphocytes among all cells in the thawed samples measured by means of flow cytometric analysis. Both the absolute lymphocyte count and the percentage of B cells as measured by flow cytometry are mandatory for calculating the B-cell count.2 Without a blood count, unrecognized CLL is the likely explanation for their findings, since it is asymptomatic in its early stage. The primary conclusion of Landgren et al. that MBL is a “precursor state” is not scientifically valid on the basis of the data presented. The issue of whether MBL has a precursor or concurrent3 relationship with CLL remains unresolved.
3 ReferencesChristopher S. Mulligan
University of New South Wales, Sydney, NSW 2052, AustraliaO. Giles Best, B.Sc., Ph.D.
Stephen P. Mulligan, M.B., B.S., Ph.D.
Royal North Shore Hospital, Sydney, NSW 2065, Australiafor the Chronic Lymphocytic Leukaemia Australian Research Consortium
1
Landgren O ,Albitar M ,Ma W , et al. B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med 2009;360:659-667
Full Text | Web of Science | Medline2
Mulligan CS, Thomas ME, Mulligan SP. Lymphocytes, B-lymphocytes and clonal CLL cells: impact of the new diagnostic criteria in the 2008 guidelines for chronic lymphocytic leukemia (CLL). Blood (in press).
3
Mulligan CS ,Thomas ME ,Mulligan SP . Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med 2008;359:2065-2066
Full Text | Web of Science | Medline
Author/Editor Response
The point that Mulligan and colleagues raise is addressed in our article. Although a complete blood count was not included in the baseline blood-test panel in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we are confident of our results, for several reasons. First, in 16 of 45 patients (36%), the number of circulating lymphocytes (CD19+ and CD5+ B cells) was negligible (≤1%) or low (>1 to 20%), accounting for 6% or less of all lymphocytes; this makes it very unlikely that a diagnostic B-cell lymphocytosis was already present. Second, about 90% of the cases of CLL that we detected were as early as Rai stage 0 or I, which is consistent with regular health evaluations in these patients (in the 3 years before enrollment, 38 of 45 patients [84%] underwent some screening study). Third, our study population is a health-conscious group that volunteered for annual screening; the compliance of these patients was in accordance with the requirements of the PLCO trial.1
Although we cannot totally exclude the possibility that CLL existed before the date of diagnosis in a few patients, it is highly unlikely that CLL would remain undiscovered for years in this intensively screened group. The data are entirely consistent with our contention that CLL often has a precursor state.
1 ReferencesOla Landgren, M.D., Ph.D.
National Cancer Institute, Bethesda, MD 20892
landgreo@mail.nih. gov Paolo Ghia, M.D., Ph.D.
Università Vita-Salute San Raffaele, 20132 Milan, ItalyNeil E. Caporaso, M.D.
National Cancer Institute, Bethesda, MD 20892- Citing Articles (1)
Citing Articles
1
Christopher S. Mulligan, Miriam E. Thomas, Stephen P. Mulligan. (2011) Monoclonal B-lymphocytosis: demographics, nature and subclassification in 414 community patients. Leukemia & Lymphoma 52:12, 2293-2298
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