Effect of Low-Dose Cytarabine and Aclarubicin in Combination with Decitabine and Granulocyte Colony-Stimulating Factor Priming on the Outcome of Patients with Myeloid neoplasms

Patients older than 60 years with acute myeloid leukemia (AML) or with chronic myeloid leukemia in blast phase (CML-BC) or myelodysplastic syndrome (MDS) have non-intensive treatment options because of the lack of effectiveness and the toxicity of available therapies. We investigated the efficacy and toxicity of the low-dose cytarabine and aclarubicin in combination with hypomethylating agent decitabine and granulocyte colony-stimulating factor priming as induction therapy in MDS, CML-BC and older patients with AML.

We described 28 consecutive patients (median age 65.5 years, range 49–78 years with MDS (n= 7) or AML (n= 17), or CML-BC (n=4). Among them, Seventeen were cases of AML (10 previously untreated AML, 3 bone marrow relapse, 2 extramedullary relapse and 1 MDS-AML); 4 were cases of CML-BC who were resistant to imatinib or nilotinib therapy and 7 were cases of MDS. Cytogenetic analysis was performed in all the patients, showing 7 patients had cytogenetic aberrations. All patients were treated with decitabine 15 mg/m2 intravenously for 5 consecutive days (d1-5) in combination with cytarabine 10 mg/m2 q12h for 7 days (d3-9) and aclarubicin 10mg every day for 4 days (d3-6) and granulocyte colony-stimulating factor (G-CSF) 300μg every day (d 0–9) priming (D-CAG). G-CSF was withdrawn when the white blood cell count (WBC) >20×109/L. Hydroxyurea or in combination with homoharringtonine 1mg/d intravenously was treated until WBC was <10×109/L before decitabine was given. CML-BC patients continued to be treated with imatinib or nitotinib during the D-CAG. Response was assessed by weekly complete blood count and bone marrow biopsy was taken at the time of recovery of peripheral hemogram or 3–4 weeks later after each course. Patients with MDS and AML continued to receive the second cycle. All of patients underwent baseline and efficacy evaluations.

Fifteen older patients with AML (median 68 years, range 60–78 years) were enrolled. Among those patients, 10 were in previously untreated AML, 3 bone marrow relapse, 1 extramedullary relapse and 1 secondary AML. The overall response rate (ORR) was 86.7% (13/15) in all older patients, 80.0% (8/10) in patients with previously untreated AML, and the complete rate (CR) was 73.3% after one cycle. 3 older patients with bone marrow relapse achieved. Two patients with extramedullary relapse achieved partial remission (PR) after one cycle. Two fourth of patients with high WBC more than 100×109/L at the time of diagnosis achieved CR. 7 patients with MDS (6 high-risk MDS, 1 RCMD) achieved the therapy. 3/5 patients achieved the CR or 2/5 PR. Other 2 high-risk MDS patients with refractory to convenient regimens such as CAG and HA had non-response to D-CAG regimen. All of the CML-BC patients received the one cycle of D-CAG regimen. Three fourth CML-BC patients achieved the CR and one stopped disease progression. All patients completed the treatment and there was no induction mortality. Grade 4 neutropenia and thrombocytopenia was universal. Median duration of granulocyte recovery (0.5×109/L) was 13 days(4–20), and that of platelet recovery (×109/L) was 10 days(2–16).The platelets rose above 600×109/L in 5 patients and all counts returned to the normal range with a week and there were no thrombotic complications including one patient with atrial fibrillation. The most common toxicities were myelosuppression, febrile neutropenia.

D-CAG regimen as the induction therapy seemed to be a safe and effective regimen for patients with untreated/relapsed AML, MDS and CML-BC, including older patients, and it has well tolerance.

No relevant conflicts of interest to declare.