Anti-leukemic and anti-angiogenesis efficacy of arsenic trioxide in new cases of acute promyelocytic leukemia.
Arsenic trioxide is now considered the standard agent in treatment of refractory cases of acute promyelocytic leukemia (APL). This drug is also shown to have anti-angiogenesis effect against APL cells in vitro. This study evaluated clinical efficacy and anti-angiogenesis effect of arsenic trioxide in 17 new cases of APL. Arsenic trioxide was given in a dosage of 0.15 mg kg(-1) and remission rate, survival rate, toxicities and effect on vascular density of bone marrow was studied. The bone marrow vascular density was examined using immunohistochemistry for von Willebrand Factor (vWF) and CD31 markers. Bone marrow vascular density was determined by calculating mean vessel number in 3 hot spot, high power microscopic fields. Bone marrow vascular density was reduced as identified by anti-vWF immunohistochemical staining (Mean before treatment = 201.6 mm(-2) +/- 20.4 (SEM), mean after treatment = 109.4 +/- 17.2 (SEM), p < 0.001) and anti-CD31 immunostaining (mean before treatment = 199.17 mm(-2) +/- 21.5 (SEM), mean after treatment = 99.5 mm(-2) +/- 22.1 (SEM), p < 0.05). Treatment efficacy results showed 100% complete remission rate after median of 30 days and 72% survival rate after median 860 days of follow-up. Main toxicities included hyper-leukocytosis, hepatic toxicity and APL differentiation syndrome. The results imply that arsenic trioxide is an effective anti-leukemia and anti-angiogenesis agent in new cases of APL.
Alimoghaddam
Kamran
K
Hematolgy, Oncology and BMT Research Center, Tehran University of Medical Sciences, Tehran, Iran. alimgh@ams.ac.ir
Shariftabrizi
Ahmad
A
Tavangar
S Mohammad
SM
Tavangar
Mohammad
M
Sanaat
Zohreh
Z
Rostami
Shahrbanoo
S
Jahani
Mohammad
M
Ghavamzadeh
Ardeshir
A
D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D007964:Leukocytosis / Q000139:chemically induced / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010087:Oxides / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide