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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-01-0084.
Submitted January 11, 2002
Accepted June 6, 2002
Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia
Stefano Molica*, Angelo Vacca, Domenico Ribatti, Antonio Cuneo, Francesco Cavazzini, Domenico Levato, Gaetano Vitelli, Luigi Tucci, Aldo M Roccaro, and Franco Dammacco
Department of Hematology/Oncology, Azienda Ospedaliera 'Pugliese Ciaccio', Catanzaro, Italy
Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy
Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy
Institute of Hematology, University Ferrara, Ferrara, Italy
Clinical Pathology Service, IRCCS Regina Elena, Roma, Italy
Department of Anatomy and Histopathology, Azienda Ospedaliera 'Pugliese Ciaccio', Catanzaro, Italy
* Corresponding author; email: smolica{at}libero.it.
Since tumor progression is angiogenesis-dependent, angiogenesis density was investigated by immunohistochemistry and computed image analysis in bone marrow (BM) biopsies of 45 newly-diagnosed patients with Binet stage A B-cell chronic lymphocytic leukemia (B-cell CLL) and correlated to upstaging and progression-free survival during a 40-month follow-up. Their microvessel areas and counts were significantly higher than those of patients with anemia due to iron or vitamin B12 deficiencies. A cutoff value of 0.90 mm2 x 10-2 or greater of the microvessel area identified patients with earlier upstaging and shorter progression-free survival. When the cutoff was applied to the Rai subclassification, both Rai 0 and Rai I-II patients who upstaged and shortened the progression-free survival were classified correctly. Information of this type was not given by the microvessel counts. The cutoff did not correlate with other predictors representative of tumor mass or disease progression. The microvessel area correlated with the expression of angiogenic vascular endothelial growth factor (VEGF) by tumor tissue, and serum levels of VEGF were found to be of prognostic value. A causal relationship between risk of progression and BM angiogenesis in B-cell CLL is suggested. A risk stratification inside Rai is proposed. The prognostic usefulness of BM angiogenesis in patients with B-cell CLL is envisaged.
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