Thalidomide for the treatment of acute myeloid leukemia

• Published in: Leukemia & lymphoma 2003-09, Vol.44 (9), p.1489-1493
• Main Authors: Steins, M B, Bieker, R, Padró, T, Kessler, T, Kienast, J, Berdel, W E, Mesters, R M
• Format: Article
• Language: English
• Subjects: Acute Disease; Aged; Aged, 80 and over; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Bone Marrow - drug effects; Bone Marrow - pathology; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Female; Humans; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - pathology; Male; Middle Aged; Myelodysplastic Syndromes - drug therapy; Neovascularization, Pathologic - drug therapy; Pilot Projects; Prospective Studies; Safety; Thalidomide - adverse effects; Thalidomide - therapeutic use; Treatment Outcome
• ISSN: 1042-8194
• DOI: 10.1080/1042819031000077043

In analogy to solid neoplasms, accumulating data suggest the requirement of angiogenesis also for the development and progression of hematopoietic malignancies including acute myeloid leukemia (AML). Inhibition of increased microvessel density in bone marrow (BM) might be a promising target for pharmacological interventions aimed at reducing disease activity. Among the putative inhibitors of angiogenesis, thalidomide has demonstrated a considerable efficacy in myelodysplastic syndromes (MDS) and AML with overall response rates up to 56% and 25%, respectively. Responders experienced hematologic improvements with increased hemoglobin and platelet counts resulting in temporary transfusion independence. In AML, partial responses--defined as reduction of the leukemic blast cell infiltration of at least 50% in BM--occurred in four of 20 patients after one month of thalidomide administration in a previous phase I/II study. Additionally, we observed a long-term response in one AML patient of more than 20 months, meanwhile fulfilling the criteria of complete remission. The decrease in leukemic blast infiltration in BM of responders was accompanied by a significant reduction of the microvessel density. Overall adverse events caused by the drug consisted mainly of fatigue, constipation, skin rash and polyneuropathy with a tolerable dose of 200-400 mg p.o. per day. In conclusion, thalidomide as a single agent has significant anti-leukemic activity with some evidence for anti-angiogenic effects in BM, although the precise mechanism of action remains to be elucidated.