Comparison of clinical remission and survival between CLAG and FLAG induction chemotherapy in patients with refractory or relapsed acute myeloid leukemia: a prospective cohort study

Abstract

PurposeTo compare the clinical remission and survival between CLAG and FLAG induction chemotherapy in treating patients with refractory or relapsed acute myeloid leukemia (R/R AML).Methods103 R/R AML patients were consecutively enrolled in this prospective cohort study. 55 patients were treated by CLAG induction chemotherapy as follows: 5 mg/m2/day cladribine (days 1–5); 2 g/m2/day cytarabine (days 1–5) and 300 μg/day filgrastim (days 0–5). While 48 patients were treated by FLAG: 30 mg/m2/day fludarabine (days 1–5), 2 g/m2/day cytarabine (days 1–5), and 300 μg/day filgrastim (days 0–5).ResultsCLAG induction chemotherapy achieved 61.7% complete remission rate (CR) and 78.7% overall remission rate (ORR), which was similar with FLAG chemotherapy which realized 48.7% CR and 69.2% ORR. No difference of overall survival (OS) was discovered between two groups either. Age cytarabine 60 years, secondary disease, poor risk stratification and BM blast ≥ 42.7% and second or higher salvage therapy were independent factors for worse prognosis. Subgroups analysis revealed that in patients with second or higher salvage therapy, CLAG seemed to achieve a higher CR than FLAG. And in patients with relapsed disease, poor risk stratification or CR at first induction, CLAG seemed to realize a prolonged OS compared to FLAG.ConclusionCLAG was equally effective to FLAG induction chemotherapy in total R/R AML patients, while CLAG seemed to be a better option than FLAG in patients with relapsed disease, poor risk stratification, CR at first induction or second or higher salvage therapies.Electronic supplementary materialThe online version of this article (doi:10.1007/s12094-017-1798-8) contains supplementary material, which is available to authorized users.

The use of venetoclax‐based salvage therapy for post‐hematopoietic cell transplantation relapse of acute myeloid leukemia

“…The management of post‐HCT relapsed disease is challenging. Overall response rates (ORR) with cytotoxic salvage therapy are variable, but far poorer after HCT 12‐18 . In a large registry analysis, only 15% of post‐HCT relapsed AML patients achieved a subsequent complete remission (CR); less than 5% of patients who relapsed within 6 months, and 12% of patients who relapsed 6‐24 months after HCT were alive at 3 years 18 …”

<p>Efficacy and toxicity of cladribine for the treatment of refractory acute myeloid leukemia: a meta-analysis</p>

“…Three of the 10 trials use the cladribine or cladribine-base treatment protocol 11,17,21. The remaining seven trials used CLAG or CLAG-based treatment protocol, of which three trials were standard CLAG chemotherapy (2-CdA 5 mg/m 2 iv d1–5, Ara-C 2 g/m 2 iv d1–5, G-CSF 300 µg sc d0–5) 12–14. And the other four trials were CLAG in a combination of another chemotherapy drug like MIT, imatinib mesylate, and topotecan 15,16,22,23…”

“…Data for CR rate were available for analysis from a total of 10 trials including 422 patients. The CR rate ranged from 0% to 61.7%, with the lowest one in the cladribine-based schedule,11,17 and the highest one in the standard CLAG chemotherapy 12. The overall rate of CR was 42.2% (95% CI: 31.0–54.3%) as determined by the random-effects model since the CR rates of 10 trials were highly heterogeneous (Q=38.846, I 2 =76.82, P <0.001, Figure 2).…”

“…As a single drug, cladribine has antileukemic activity in patients with AML 9–11. It is also suggested that cladribine (CdA), cytarabine (Ara-C), and granulocyte-colony stimulating factor (G-CSF) (CLAG) regimen may also improve the prognosis of refractory AML 12–14. In addition, adding mitoxantrone (MIT) to the CLAG regimen may create synergies in the activity of antileukemic 15,16…”

Prediction of FLAG ± Ida Regimen Efficacy in Patients with Relapsed/ Refractory Acute Myeloid Leukemia

“…В различных исследованиях уровень достижения ремиссии после режимов FLAG и FLAG-Ida составил 56-80 % [25][26][27][28]. Кроме того, данные режимы продемонстрировали приемлемый уровень гематологической и негематологической токсичности [29][30][31].…”