Efficacy of Long-Term Decitabine Treatment Combined with Sequential Priming Regimen for Acute Myelocytic Leukemia
Authors: Miao Miao , Depei Wu , Sun Aining , Xu Ting , Jin Song , Yan Lingzhi , Bao Haiyan 
Published: October 2019

Introduction The Sequential priming regimen has been used for newly diagnosed and relapsed/refractory patients with acute myeloid leukemia unfit for intensive chemotherapy. Unfortunately, the rate of CR is not hopeful. Hypomethylating agent, decitabine is active in eldly patients with AML. Long-term decitabine combined with sequential priming regimen treats these patients, its efficacy and side effects and optimal dose are unknown.

Methods A total of 14 inpatients with AML during the period from February 2013 through May 2014 were enrolled in this study, including 8 men and 6 women. The subjects had a median age of 56 years (range, 25–71 years), with 10 cases at ages of over 50 years. Of all participants, transformation of myelodysplastic syndromes (MDS) into AML occurred in 6 cases; 8 cases received treatment for the first time, 5 cases had refractory AML, and 1 case had relapsed AML. Normal chromosome was detected in 9 cases, and chromosomal abnormality +8, t(1;9), -y,t(8;21), t(8;21),mar and complex chromosomal abnormality occurred in one case each; 6 cases (42.9%) had gene mutations, including NPM1/DNMT3, CEBPA, FLT3-ITD/NPM1/DNMT3, FLT3-ITD/NPM1, DEK/CAN and U2AF1, of one case for each mutation. There were 12 cases with concomitant diseases. There were 5 cases with an Eastern Cooperative Oncology Group (ECOG) score of 4 and 7 cases with an ECOG score of 3. The chemotherapy regimen was decitabine at a dose of 20 mg/m2 on days 1 to 6 or 8, and the IAG priming regimen was used in 5 cases, CAG regimen in 5 cases, and HAG regimen in one case. There were 5 cases undergoing a half cycle of the induction therapy (7 days) and 9 cases undergoing a whole cycle of the induction therapy (14 days). A cycle of therapy achieved complete response in 12 cases (85.7%) and no response in 2 cases, including one recurrent case with FLT3-ITD mutation following autologous stem cell transplantation and a refractory case with DEK/CAN mutation.

Results A half cycle ofinduction therapy resulted in completed remission in 4 out of 5 cases, and the whole cycle of therapy resulted in 8 out of 9 cases. All 8 cases receiving therapy for the first time achieved complete remission, and 3 out of 5 refractory cases achieved complete remission. The median time for nonerythroid cell (NEC) count of < 0.5 × 105/L and platelet blood cell (PBC) count of < 20 × 109/L was 12 (range, 0–37) and 18 (range, 0–37) days, respectively. During the half cycle of induction therapy, the median time for NEC count of < 0.5 × 105/L and platelet blood cell (PBC) count of < 20 × 109/L was 17 (range, 6–37) and 18 (range, 7–38) days, respectively, whereas being 11 (range, 0–30) and 12 (range, 0–28) days during the whole cycle of induction therapy, respectively. There were 6 cases with side effects, including 4 cases achieving complete remission. Post-chemotherapy complications included infections, bleeding, and liver function impairment. Of the 10 cases complicated with infections at the first diagnosis, 2 cases developed aggravated pulmonary infection and 4 cases developed new infections at the stage of bone marrow suppression, including one case with infection at the perianal region, one case with infection at pharynx, one case with influenza A, and one case with skin infection. No therapy-induced death was observed.

Conclusions Long-term decitabine treatment in combination with sequential priming regimen is effective for the AML patients undergoing treatment for the first time and recurrent and refractory AML, which is comparable to the standard "7 + 3" remission-induction therapy. In addition, it may improve the prognosis of AML patients with chromosomal abnormality and gene mutations, particularly for patients with DNMT3 and FLT3-ITD mutations. Further multi-center, prospective clinical trials are required to evaluate the efficacy of the new regimen for AML and optimize the treatment regimen.

Disclosures

No relevant conflicts of interest to declare.