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.
Highlights
Acute myeloid leukemia (AML) is a cancer featured by infiltration of bone marrow, blood, and other tissues resulting from clonal, abnormally differentiated and occasionally poorly differentiated cells of hematopoietic system [1]
The relapsed acute myeloid leukemia (R/R AML) was defined as: Refractory AML—(1) patients do not achieve complete remission rate (CR) after two courses of induction chemotherapy by standard protocol; (2) patients relapse within 6 months after first CR; (3) patients relapse at 6 months or above after first CR and fail by the subsequent induction chemotherapy; (4) patients relapse more than 2 times; (5) extra-medullary infiltration of leukemia
All cases were evaluated according to Eastern Cooperative Oncology Group (ECOG) performance, which showed that 18 (33%), 33 (60%) and 4 (7%) cases in CLAG group were with ECOG performance score 0, 1 and 2; 13 (27%), 30 (63%) and 5 (10%) cases in FLAG group were with ECOG performance score 0, 1 and 2 (p = 0.745)
Summary
Acute myeloid leukemia (AML) is a cancer featured by infiltration of bone marrow, blood, and other tissues resulting from clonal, abnormally differentiated and occasionally poorly differentiated cells of hematopoietic system [1]. It is reported that FLAG achieves CR ranging from 46 to 63% in R/R AML patients and the efficacy of fludarabine is on account of its triphosphate which inhibits RNR and elevates Ara-CTP in leukemic cells [7,8,9] While another cytotoxic agent cladribine, as a new generation of purine analog, has been considered to be a substitute for fludarabine in the combination with Ara-C plus G-CSF (CLAG) as a treatment in R/R AML patients [10], which is due to its same mechanism as fludarabine, and attribute to its additional effects that cladribine induces cells apoptotic process through changing the membrane potential of mitochondria, repressing DNA methyltransferase (DNMT) as well as consuming methyl donors and, we hypothesized that CLAG might be more effective than FLAG [2, 11,12,13]. The difference of outcomes between CLAG and FLAG is still unclear; we conducted this study to investigate the difference of clinical remission and survival between the two treatments as well as predictive factors which may affect the outcomes in R/R AML patients
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