Low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming regimen versus idarubicin plus cytarabine regimen as induction therapy for older patients with acute myeloid leukemia

The prognosis of elderly patients with acute myeloid leukemia (AML) is poor, and the recommendation of standard-dose or low-intensity induction regimen for these patients remains controversial. We retrospectively analyzed treatment outcome and prognostic factors of elderly AML patients who had received either standard-dose or low-intensity induction regimens.Two hundred forty-eight elderly AML patients with good Eastern Cooperative Oncology Group performance status (ECOG PS ≤ 2) received one of three regimens for induction in this study: standard-dose cytarabine plus idarubicin (IA; n = 144) or daunorubicin (DA; n = 42); low-intensity cytarabine, aclarubicin, and granulocyte colony-stimulating factor (G-CSF) (CAG; n = 62).After first induction treatment cycle, the overall complete remission (CR) rate was 42.7%. Patients in IA group had a higher CR rate than in DA or CAG group (49.3%, 35.7%, and 32.3%, respectively; P = 0.046). The 1-year, 3-year, and 5-year overall survival (OS) rates were 42.2%, 18.9%, and 13.5% for these 248 patients, with median survival of 9.2 months. Long-term survival of IA group was better than DA or CAG group. The 1-year, 3-year, and 5-year OS rates of IA group were 45.9%, 23.5%, and 19.4%, respectively, as compared to 39.8%, 8.3%, and estimated 2.4% in DA group, and 34.9%, 15.9%, and 6.3% in CAG group, respectively. Early induction mortality and 2-year relapse rates showed no difference among 3 groups. Univariate analysis and multivariate analysis identified lactic dehydrogenase (LDH) more than two times of upper normal limit at diagnosis and nonremission after first induction cycle as adverse prognostic factors for OS. A simple and valid scoring model was constructed for risk stratification and prediction of long-term survival of elderly AML patients.Standard-dose IA regimen could improve the prognosis of elderly AML patients with good performance status compared with standard-dose DA or low-intensity CAG regimen. All prognostic factors and risk assessment should be considered to ensure that each patient receives the suitable individualized treatment.

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“…The safety and efficacy of the CAG regimen has been previously confirmed in some studies at several medical centers. [9,10] …”

Section: Introductionmentioning

confidence: 99%

The outcome and prognostic factors of 248 elderly patients with acute myeloid leukemia treated with standard-dose or low-intensity induction therapy

Chen

Yang²,

Zheng³

et al. 2016

Medicine

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“…A previous study reported that a GHA priming regimen containing G-CSF, HHT, and low-dose AraC was effective for relapsed/refractory AML and middle-and-high-risk MDS with excess blasts. 33 Pre-chemotherapy administration of G-CSF is thought to drive G0-phase cells into the proliferative phase and thus promotes chemosensitivity. Intracellular ATP level is elevated, enhancing the cytotoxic effect of AraC on leukemic cells.…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular ATP level is elevated, enhancing the cytotoxic effect of AraC on leukemic cells. 33 Low-concentration decitabine has been reported to demethylate a key transcription factor of myeloid differentiation in vitro, and to induce cell maturity and remission of leukemia; however, the clinical efficacy of decitabine alone remains low. A priming regimen combining decitabine with low-dose AraC was thus hypothesized to improve efficacy, though the optimal administration sequence and required dosage remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

Dose-enhanced combined priming regimens for refractory acute myeloid leukemia and middle-and-high-risk myelodysplastic syndrome: a single-center, retrospective cohort study

Wang

Yang

et al. 2016

OTT

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ObjectiveTo assess chemotherapeutic regimens for refractory acute myeloid leukemia (AML) and middle-and-high-risk myelodysplastic syndrome (MDS).MethodsBetween 2004 and 2014, 44 patients with refractory AML and 36 patients with MDS were treated with new priming regimens (CHAG, CHTG, CHMG, or CTMG), and 77 patients with refractory AML and 52 patients with MDS were treated with conventional priming regimens (CHG or CAG). This was a single-center retrospective analysis of remission, adverse event, mortality, and survival. The capacity of clinical features (including the expression of co-stimulatory molecule B7.1 on tumor cells) to influence survival was assessed by multivariate Cox regression.ResultsComplete and partial remission rates (RRs) were significantly higher in AML patients treated with new regimens compared to conventional ones (68.2% vs 13.6%, P<0.05). Complete and partial remission were also significantly higher in patients with MDS treated with new regimens (55.6% vs 19.4%, P<0.05). However, although survival advantages were observed in the first year, the new regimens did not significantly improve 3-year overall survival (P>0.05). Patients administered the new regimens experienced more severe and sustained myelosuppression (P<0.05), but no severe adverse events or treatment-related deaths were observed. The rate of non-hematological side effects did not differ significantly between treatment regimens (P>0.05). Both RR and B7.1 expression were significantly higher in patients with AML-M2 and M5 (P<0.05).ConclusionThe new priming regimens improved the RR, lowered the recurrence rate, and improved survival in AML and middle-and-high-risk MDS, without significantly increasing adverse events.

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“…Chemotherapy with a cytarabine plus anthracycline (doxorubicin or daunorubicin) combination (7+3 regimen) has resulted in a CR rate of between 50%-70% in AML patients younger than 60 years, although rates are variable for elderly patients. [4][5][6][7] CR is commonly defned as bone marrow blast count of ≤5% with recovery of all the 3 cell lines in the peripheral blood. CR with incomplete count recovery, defned as no evidence of persistent disease but an incomplete recovery of blood counts, occurs frequently and is associated with a worse prognosis compared with patients with normal count recovery.…”

Section: Original Reportmentioning

confidence: 99%

Prognostic value of complete remission with superior platelet counts in acute myeloid leukemia

Mangaonkar

Jamal

et al. 2016

J Community Support Oncol

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Low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming regimen versus idarubicin plus cytarabine regimen as induction therapy for older patients with acute myeloid leukemia

Cited by 16 publications

References 29 publications

The outcome and prognostic factors of 248 elderly patients with acute myeloid leukemia treated with standard-dose or low-intensity induction therapy

The outcome and prognostic factors of 248 elderly patients with acute myeloid leukemia treated with standard-dose or low-intensity induction therapy

Dose-enhanced combined priming regimens for refractory acute myeloid leukemia and middle-and-high-risk myelodysplastic syndrome: a single-center, retrospective cohort study

Prognostic value of complete remission with superior platelet counts in acute myeloid leukemia

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