Azacitidine Alone Or The Combination With Valproic Acid As a Bridge Therapy For Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes Before Transplantation

• Published in: Blood 2013-11, Vol.122 (21), p.2812-2812
• Main Authors: Cabrera, Cristina Calderón, Falantes, Jose F, Gómez, Marina, Parody, Rocío, Márquez Malaver, Francisco J, Martino, María L, González, José, Montero, Isabel, Espigado, Ildefonso, Pérez-Simón, Jose Antonio
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.2812.2812

Intensive chemotherapy (IC) followed by allogeneic stem cell transplantation (AlloSCT) is standard of care for intermediate and high-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). However, morbidity and lack of response are common with IC. Retrospective data have shown similar outcomes with azacitidine (AZA) when compared to IC. Moreover, the combination of AZA with other epigenetic modifiers such as HDAC inhibitors seems to improve quality of responses. Evaluate response, toxicity and feasibility of AlloSCT after AZA alone or the combination with valproic acid (VPA) as a bridge strategy in MDS and AML. Nineteen consecutive patients (pts) receiving azacitidine alone (n=11) or in combination with valproic acid (VPA) (n=8) were analyzed. Median age of the cohort was 57 years (18-67). Diagnosis by WHO classification included: RAEB-2 (n=10/19; 52.6%), RAEB-1 (n=2; 10.5%), RCMD (n=2; 10.5%) and AML (n=5; 26.3%). Four out of 5 AML pts had bone marrow blast count >30% at diagnosis. In MDS patients, according to International Prognostic Scoring System (IPSS): 1 intermediate-1 (7%), 3 intermediate-2 (21.5%) and 10 high-risk (71.5%) and by IPSS-revised (IPSS-R): 1 intermediate (7%), 4 high (29%) and 9 very high (64%). Regarding karyotype, in MDS: 5 good (35.7%), 2 intermediate (14.3%), 6 poor (43%) and 1 insufficient metaphases (7%) whereas in AML Patients 1 intermediate (20%) and 4 adverse (80%). Eleven out of 19 pts (58%) received AZA as frontline therapy. The remaining 8 pts experienced disease relapse after intensive chemotherapy (IC) or had primary refractory AML, and subsequently received AZA plus VPA as salvage therapy. Median courses of previous IC were 2 (1-4). For pts receiving AZA/VPA, median bone marrow blast % and leukocyte were 31% (2-60) and 1.9x10e9/L (0.3-4.2) when therapy started. Most of these pts had refractory or relapsed disease (n=6/8; 75%) with 4 pts displaying poor karyotype. Treatment schema was AZA (75 mg/m2, 7d/4w) and VPA (20-25 mg/kg/d, 10 days). At analysis, 17/19 pts are evaluable for response. Median courses of AZA: 5 (2-53). Overall response (ORR) at 4 courses: 59% (CR=4/17; 23.5%, CRm=5/17; 29.5% and PR=1/17; 6%). For pts receiving AZA/VPA (Table 1, n=8), ORR: 83% (CR=1/6; 17% and CRm=4/6, 66%) in 6 evaluable pts. Median courses to response were 2. Among pts achieving CR/CRm/PR/SD at 4 courses (n=12), 2 pts lost response prior to AlloSCT. Most frequent toxicity was hematological (58% grade 3-4) wit