Abstract

We conducted a study exploring the clinical safety and efficacy of decitabine in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), combined with a complex karyotype. From April 2009 to September 2013, a total of 35 patients with AML/MDS combined with a complex karyotype diagnosed in the First Affiliated Hospital of Soochow University were included for retrospective analysis. All patients were treated with decitabine alone (20 mg/m2 daily for 5 days) or combination AAG chemotherapy (Acla 20 mg qod*4d, Ara-C 10 mg/m2 q12h*7d, G-CSF 300 μg qd, the dose of G-CSF adjusted to the amount in blood routinely). In 35 patients, 15 exhibited a complete response (CR), and 6 a partial response (PR), the overall response rate (CR+PR) being 60% (21 of 35). Median disease-free survival was 18 months and overall survival was 14 months. In the 15 MDS patients with a complex karyotype, the CR rate was 53.3% (8 of 15); in 20 AML patients with complex karyotype, the overall response rate was 65% (13 of 20). The response rate of decitabine alone (22 cases) was 56.5% (13 of 22), while in the combination chemotherapy group (13 cases), the effective rate was 61.5% (8 of 13)(P>0.05). There are 15 patients with chromosome 7 aberration, after treatment with decitabine, 7 CR, 3 PR, overall response rate was 66.7% (10 of 15). Of 18 patients with 3 to 5 kinds of chromosomal abnormalities, 66.7% demonstrated a response; of 17 with more than 5 chromosomal abnormalities, 52.9% had a response. In the total of 35 patients, with one course (23 patients) and ≥two courses (12 patients), the overall response rate was 40.9% and 92.3% (P<0.05). Grade III to IV hematological toxicity was observed in 27 cases (75%). Grade III to IV infections were clinically documented in 7 (20%). Grades I to II non-hematological toxicity were infections (18 patients), haematuria (2 patients), and bleeding (3 patients). With follow-up until September 2013, 7 patients were surviving, 18 had died and 10 were lost to follow-up. In the 6 cases who underwent allogeneic hematopoietic stem cell transplantation (HSCT) all were still relapse-free survivors. Decitabine alone or combination with AAG can improve outcome of AML/MDS with a complex karyotype, there being no significant difference decitabine in inducing remission rates in patients with different karyotype. Increasing the number of courses can improve efficiency. This approach with fewer treatment side effects in patients with a better tolerance should be employed in order to create an improved subsequent chance for HSCT.

Highlights

  • Complex karyotype defined as more than or equal to 3 independent chromosomal abnormalities

  • Analysis of 15 myelodysplastic syndromes (MDS) patients with complex karyotype received the treatment of decitabine, 8 patients achieved complete response (CR), 7 no response (NR), the CR rate was 53.3%(8 of 15); 20 acute myeloid leukemia (AML) patients with complex karyotype treated with decitabine were analysed

  • Decitabine has been approved by the USA Food and Drug Administration (FDA) for the treatment of the MDS in 2006

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Summary

Introduction

Complex karyotype defined as more than or equal to 3 independent chromosomal abnormalities. Complex karyotype AML belongs to unfavorable category, this category of patients characterized by a low overall response rate and easy to relapse after clinical treatment (Yang et al, 2012;Wawrzyniak et al, 2013). We conducted a study exploring the clinical safety and efficacy of decitabine in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), combined with a complex karyotype. There are 15 patients with chromosome 7 aberration, after treatment with decitabine, 7 CR, 3 PR, overall response rate was 66.7% (10 of 15). Conclusions: Decitabine alone or combination with AAG can improve outcome of AML/MDS with a complex karyotype, there being no significant difference decitabine in inducing remission rates in patients with different karyotype.

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