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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-06-1801.
Submitted June 19, 2002
Accepted September 29, 2002
The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression
Paolo Ghia, Giuseppe Guida, Stefania Stella, Daniela Gottardi, Massimo Geuna, Giuliana Strola, Cristina Scielzo, and Federico Caligaris-Cappio*
Department of Oncological Sciences, University of Turin, Turin, Italy
Laboratory of Cancer Immunology, Institute for Cancer Research and Treatment, Turin, Italy
Divisione Universitaria di Immunologia Clinica e Ematologia, Ospedale Mauriziano Umberto I, Turin, Italy
* Corresponding author; email: fcaligaris{at}mauriziano.it.
CLL has a variable clinical course. CD38 expression and IgVH gene mutational status are independent prognosis predictors, but their relationships and the CD38 cut-off level are unknown. We cytofluorographically analysed CD38 in 148 patients: 108/148 were eligible to evaluate IgVH mutations, correlations with disease history and cumulative survival. Three different patient groups were identified by the CD38 expression pattern: a group homogeneously CD38-, a group homogeneously CD38+ and a group characterised by a bimodal profile, because of the concomitant presence of variable proportions of two distinct populations, one CD38+ and one CD38-. In bimodal patients the CD38+ subset was significantly more represented in the bone marrow than in the peripheral blood. As for IgVH mutations, 11.4% of CD38-, 84.6% of CD38+ and 68.0% of bimodal patients were unmutated. CD38 expression, IgVH mutational status and traditional prognostic factors were concordant. The progression rate was 12.9% for CD38-, 75.0% for CD38+ and 63.3% for bimodal patients. Only 25.8% CD38-, but 63.3% bimodal and 75.0% CD38+ patients were treated. The presence of a CD38+ population albeit small correlated with the development of autoimmune manifestations. The CD38- group has not yet reached the median survival, which is 183 months in the CD38+ and 156 months in the bimodal group, regardless of the size of the CD38+ population. The presence of a distinct CD38+ population within the leukemic clone, rather than a numerical cut-off definition, correlates with IgVH genes mutational status and, irrespective of its size, identifies CLL patients who will have a progressive disease.
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