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Haematologica 2003 - Supplements

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143<br />

Evaluation of Bone Marrow Angiogenesis in newly<br />

diagnosed myeloma patients before and after treatment<br />

with the combination VAD containing liposomal<br />

doxorubicin plus Thalidomide.<br />

E. Hatjiharissi1, M. Papaioannou1, V. Kaloutsi2, C.<br />

Hatjileontis2, N.Eleftheriadis1, C. Tsimirika1, M.A.<br />

Dimopoulos,3 J. Christakis1, K. Zervas1<br />

1Department of Hematology-Oncology, Theagenion Cancer<br />

Center, Thessaloniki, Greece; 2Department of Pathology, Aristotle<br />

University of Thessaloniki, Thessaloniki, Greece; 3Department of<br />

Clinical Therapeutics and Internal Medicine, University of Athens,<br />

School of Medicine, Athens<br />

Background Bone marrow angiogenesis (BMA) is increased in<br />

Multiple Myeloma (MM) and its extent is considered as an<br />

important prognostic factor. However, the impact of treatment in<br />

BMA is still controversial. Aim of study. The purpose of this<br />

study was to evaluate in newly diagnosed myeloma patients the<br />

changes in BMA after treatment with combination VAD<br />

containing liposomal doxorubicin plus Thalidomide. Patients<br />

Nineteen consecutive myeloma patients, (12 females, 7 males)<br />

with median age 67 years (range 47-76) were included into the<br />

study. The patients were treated with liposomal doxorubicin<br />

(40mg/m2) day 1, vincristine (2mg) day 1, dexamethasone (40<br />

mg d 1-4) orally, every 4 weeks. Thalidomide was given daily at<br />

the dose of 200mg. Patients were reevaluated for response after<br />

four cycles of treatment. Methods. We studied BMA in bone<br />

marrow biopsy specimens at diagnosis and after the fourth cycle<br />

of treatment. Angiogenesis was estimated by microvessel density<br />

(MVD) using standard immunohistochemical staining for CD 34<br />

MoAb. Microvessels were counted in the whole cellular bone<br />

marrow at 400x magnification. MVD was expressed as number of<br />

vessels per mm2. Angiogenesis was also estimated in a control<br />

group of 10 normal bone marrow biopsies. MVD values in<br />

patients were compared using paired t-test. Cox regression<br />

analysis was used to evaluate the prognostic significance of<br />

pretreatment MVD, and known prognostic factors such as serum<br />

beta-2 microglobulin, C-reactive protein, albumin and LDH.<br />

Results: Sixteen out of nineteen patients (84%) achieved<br />

objective response and three had progressive disease. Median<br />

MVD in controls was 3.06 (range 2.3-3.8) and the mean value<br />

was 3.1 ± 0,6. The pretreatment median MVD in patients was<br />

19.02 (range13.5-28.9), mean 19,85 ± 4,96. After four cycles of<br />

treatment the median and mean MVD were 12,9 (range7,9-21,6)<br />

and 13,5 ± 4,7 respectively. There was significant difference in<br />

MVD between controls and patients at diagnosis (p

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