Decitabine for Older AML Patients: An Effective Therapy Associated with Short Hospitalization and No Invasive Fungal Infection.

The treatment of older patients (pts) with acute myeloid leukemia (AML) continues to be controversial because of the lack of effectiveness and the toxicity of available therapies. We investigated the efficacy, toxicity, and factors predictive of response to decitabine as initial therapy in older pts with AML.

This is the largest single institution, retrospective study for pts older than 60 years with either De novo AML or MDS related AML who were treated initially with IV decitabine 20 mg/m² for 5 consecutive days of a 4-week cycle from 01/01/2005- 01/01/2010. Pts continued to receive decitabine until disease progression or an unacceptable adverse event occurred. Pts with secondary AML were excluded.

45 pts were treated. Median age 71 (range, 61–83). Males-27 (60%). Females-18 (40%). Caucasians-40 (89%). African-Americans- 4 (9%). Asian-1 (2%). De novo AML-24 (53%). MDS related AML-21 (47%). Karyotypes: poor-27 (60%), intermediate -10(22%), unknown-8(18%). Median presenting WBC's 2.8 k (range, 0.6–122.2) with 26.6% of WBC's > 10k. The best response to therapy was CR/CRi-13 (29%), Stable disease/ partial remission (SD/PR) - 22 (49%), progressive disease (PD) -10 (22%). Pts who achieved CR/CRi: De novo AML-8, MDS related AML-5, poor cytogenetics-6, unknown cytogenetics-4, intermediate cytogenetics-3, presenting WBC's <10k-9, presenting WBC's >10k-4. Median number of cycles for CR/CRi was 4 (range, 1 to 5 cycles). Median number of cycles for CR/CRi was 4 in pts with presenting WBC's <10k and 4.5 in pts with presenting WBC's> 10k. 2 pts in CR/CRi group underwent consolidative BMT while on decitabine. The median duration of CR/CRi was 393 days (range, 184–748). The median time from first cycle till plt count recovery was 49 days (range, 0–294). Plt count recovery was the first hematological sign for CR preceding bone marrow biopsy confirmation in 10 out13 pts (77%). Plt count recovery on day 90 of therapy was achieved in 18 pts (40%) of whom 9 out of 18 achieved CR. The median overall survival (OS) from the time of diagnosis was 8.75 months (mo) (range, 0.5–59.8), CR/CRi-18.9 mo (range, 7.8–37.9), SD/PR-7.3 mo (range, 1.9–59.8), PD-1.9 mo (range, 0.5–12.1). Median OS for pts presented with WBC's< 10k was 11.0 mo (range, 0.5–59.8) and WBC's >10k was 7.1 mo (range, 1.9–32.7). In CR/ Cri group, the median OS for pts presented with low and high WBC's was 19.2 mo (range, 10–37.9) and 11.2 mo (range, 10.5–32.7) respectively. The 30, 60, and 100 day mortality rates after first cycle of therapy were (6/45)13.3%, (9/45) 20%, and (10/45) 22.2% respectively. The mean number of days for hospitalization while on decitabine was 19.2 days (range, 0–59), CR/CRi 14.3 days (range, 0–59), SD/PR 19.4 days (range, 0–54), PD 25.3 days (range, 5–52). 28 culture documented infection events noted in all groups: CR /CRi-5, SD/PR-22, PD-1. Staph species 14 events, Pseudomonas Aeruginosa 4 events, E-coli 3 events, C. difficile 2 events, candida species 2 events, and 1 event for each of: bacillius species, achromobacter, and enterobacter cloacae. No documented invasive fungal infections were seen. Bleeding events were observed in 3 pts (2 gastrointestinal and 1 fatal SDH due to fall). Salvage therapy was offered to 10 pts after decitabine failure (5 in CR/CRi group, 4 in SD/PR group and 1 in PD group). Different salvage regimens used including idarubicine + cytarabine (5), FLAG (1), SAHA (3), PXD 101 (1), and Gemtuzumab (1). CR was achieved in 3 out of 4 pts who received 7+3 all in CR/CRI group. Univariate analysis of factors predictive of CR and Survivals are shown in table 1.

Multivariate analysis for factors predictive of survival was significant for intermediate risk cytogenetics with P value of 0.0410.

Decitabine resulted in CR/CRi in 29% of pts after a median of 4 cycles of therapy. Median duration of CR was 393 days. The mean duration for hospital stay was 19.2 days. No documented invasive fungal infections seen and 1 fatal bleed reported.

No relevant conflicts of interest to declare.