CD5+ Chronic B-Cell Lymphoproliferative Disorders Could Contain a Novel Disease Entity.
Authors: Dronca Roxana S , Hanson Curtis A. , Jevremovic Dragan , Collins C. Scott , Rabe Kari , Sonbert Jessica , Slager Susan L. , Schwager Susan , Shanafelt Tait D. , Kay Neil E. , Zent Clive S. 
Published: April 2020

Background: The biology, pathology and clinical course of CD5+ chronic B cell lymphoproliferative disorders (CD5+ B-CLPD) excluding chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) and mantle cell lymphoma (MCL) are poorly defined. These patients could either have a leukemic variant of a known B cell malignancy or a novel disease entity.

Objective: To define the clinical features and pathology of CD5+ B-CLPD, compare these features to CLL, and test the hypothesis that at least some of these patients have a unique B cell malignancy.

Methods: The study was conducted with Institutional Review Board permission. We studied 231 patients evaluated in the Division of Hematology at Mayo Clinic Rochester between 1996 and 2008 who had CD5+ monoclonal B cell population in the peripheral blood and/or bone marrow, and in whom CLL and MCL was not diagnosed after flow cytometry, histology and interphase fluorescence in situ hybridization (FISH) examinations. Data were abstracted from patient records and from the Mayo Clinic CLL database. Statistical analysis: To compare differences in characteristics between CD5+ and CLL patients, χ2 statistics were used for qualitative variables (gender, treatment, vital status) and t-tests were used for quantitative variables (age). We performed survival and time to treatment analyses with results displayed using Kaplan-Meier curves and p-values calculated using a log-rank test.

Results: We analyzed data on 231 CD5+ B-CLPD patients diagnosed between 7/1/1976 and 5/2/2008 and 1572 CLL patients diagnosed in the same time period. Median follow-up from diagnosis was 2.5 years (range 0 to 25.1 years) for the CD5+ patients and 5.2 years (range 0 to 29.9 years) for CLL patients. CD5+ B-CLPD patients had a median age at diagnosis of 68 years (range 30–94 years) with male predominance (61.5%). One hundred and nine of 231 (52.4%) patients received treatment for their CD5+ B-CLPD and 162 (70.1%) patients were alive at the time of last follow-up. As a group, CD5+ B-CLPD patients had a similar male predominance to CLL but were older at diagnosis. CD5+ B-CLPD patients required their first treatment significantly sooner than CLL patients (median 2.0 years vs. 6.8 years, (p&lt; 0.001) and a higher percentage of CD5+ B-CLPD patients required treatment (52.4% vs. 37.5%, p&lt;0.0001). In addition, CD5+ B-CLPD patients had a shorter survival from diagnosis than CLL patients (median 8.4 years vs. 12.5 years, p&lt;0.001). In 60 patients the CD5+ B-CLPD disease was the leukemic phase of a known lymphoma (lymphoplasmacytic lymphoma, n=34; nodal marginal zone lymphoma, n=6; splenic marginal zone lymphoma, n=16; MALT lymphoma, n=4), 46 patients had incomplete data, and 125 patients did not have pathological and flow cytometry features of a known lymphoid malignancy. Next we compared clinical outcome among the 125 patients with unclassifiable CD5+ B-CLPD to the CLL patients. The unclassifiable CD5+B-CLPD patients were older at diagnosis (median 69 vs. 65 years, p=0.0003) but there were no significant differences in time to treatment (median 9.0 years vs. 6.8 years, p=0.93) or the proportion of patients receiving treatment (30% vs. 37.5%, p=0.11). The survival from diagnosis was shorter for unclassifiable CD5+ B-CLPD patients (median 6.3 vs. 12.5 years, p&lt;0.001).

Conclusions: In this large series of CD5+ B-CLPD patients we found that a large subset did not meet diagnostic criteria for known B-cell malignancies and could have a novel disease. This will need to be investigated further. We reviewed the pathology of all available archived tissue and intend to examine additional clinical and prognostic information including molecular prognostic markers. Our data provide a clinical rationale for the careful differentiation between patients with CLL and CD5+ B-CLPD.