Combined differentiating therapy for myelodysplastic syndromes: A phase II study

• Published in: Leukemia research 1996-10, Vol.20 (10), p.867-876
• Main Authors: Ferrero, Dario, Bruno, Benedetto, Pregno, Patrizia, Stefani, Silvia, Larizza, Elvira, Ciravegna, Giorgio, Luraschi, Annalisa, Vietti-Ramus, Guido, Schinco, Piercarla, Bazzan, Mario, Gallo, Eugenic, Pileri, Alessandro
• Format: Article
• Language: English
• Subjects: 25 α(OH) 2 cholecalciferol; 6-thioguanine; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Blast Crisis; Blood Transfusion; Bone Marrow Transplantation; Chemotherapy; Cholecalciferol - administration & dosage; cis-retinoic acid; Female; Humans; Male; Medical sciences; Middle Aged; Myelodysplastic syndromes; Myelodysplastic Syndromes - blood; Myelodysplastic Syndromes - drug therapy; Pharmacology. Drug treatments; Remission Induction; response; survival; Survival Analysis; Thioguanine - administration & dosage; Tretinoin - administration & dosage
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/0145-2126(95)00156-5

An in vitro synergism between different inducers of AML cell differentiation has been previously observed. Therefore, we treated 53 myelodysplastic (MDS) patients with a low dose combination of cis-retinoic acid (cRA, 20–40 mg/day) and 1,25 α(OH) 2 cholecalciferol [(OH) 2D 3, 1–1.5μg/day] ± intermittent 6-thioguanine (30 mg/m 2/day). The latter was reserved for patients with bone marrow (BM) blast excess (⩾5%). The treatment was well tolerated, without major toxicity. Among 25 patients with BM blasts less than 5%, we observed one complete, eight partial and four minor responses (response rate 52%) with a median response duration of 8 months (2+−24). Median survival, which did not correlate with response, is projected at 76 months. Thirty-one patients with BM blast excess (⩾ 5%), including three of the previous group who progressed to refractory anemia with excess of blasts (RAEB), were treated with the three-drug protocol. One complete, 12 partial and six minor responses were obtained (response rate 61%) with a median response duration of 6 months (2−29+). A significant difference in survival ( P < 0.005) was observed between the 19 responders (median 25 months) and the 12 non-responders (median 9 months). A reduction in the transfusion need was observed in 41% of the transfusion-dependent patients with blast excess and in 53% of those without blast excess. Therefore, combined differentiating therapy seems more effective than previously reported single agent treatments and should be considered for a larger randomized study to assess its actual impact on survival of MDS patients.