Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia

• Published in: Blood 2002-11, Vol.100 (9), p.3344-3351
• Main Authors: Molica, Stefano, Vacca, Angelo, Ribatti, Domenico, Cuneo, Antonio, Cavazzini, Francesco, Levato, Domenico, Vitelli, Gaetano, Tucci, Luigi, Roccaro, Aldo M., Dammacco, Franco
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anemia - pathology; Biological and medical sciences; Bone Marrow - blood supply; Capillaries - pathology; Chromosome Aberrations; Disease Progression; Disease-Free Survival; Endothelial Growth Factors - blood; Female; Fibroblast Growth Factor 2 - blood; Follow-Up Studies; Hematologic and hematopoietic diseases; Humans; In Situ Hybridization, Fluorescence; Intercellular Signaling Peptides and Proteins - blood; Karyotyping; Leukemia, Lymphocytic, Chronic, B-Cell - blood; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Life Tables; Lymphokines - blood; Male; Medical sciences; Middle Aged; Neoplasm Proteins - blood; Neoplasm Staging; Neovascularization, Pathologic; Prognosis; Risk; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-01-0084

Because 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 (BCLL) and correlated to upstaging and progression-free survival during a 40-month follow-up period. Their microvessel areas and counts were significantly higher than those of patients with anemia due to iron or vitamin B12deficiencies. A cutoff value of 0.90 mm2 × 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 BCLL is suggested. A risk stratification inside Rai is proposed. The prognostic usefulness of BM angiogenesis in patients with BCLL is envisaged.