Efficacy of common salvage chemotherapy regimens in patients with refractory or relapsed acute myeloid leukemia: A retrospective cohort study

Abstract

To assess treatment response and overall survival (OS) in refractory or relapsed acute myeloid leukemia (R/R AML) patients treated by different common salvage chemotherapy regimens.Medical records data from 142 R/R AML patients were reviewed in this retrospective study. Patients were treated with regimens based on the following drugs: cytarabine, granulocyte colony-stimulating factor (G-CSF), and fludarabine (FLAG) (n = 46); cytarabine and G-CSF in addition to aclarubicin or daunorubicin (CAG/DAG) (n = 30); cytarabine, G-CSF, and cladribine (CLAG) (n = 27); cytarabine, etoposide, and mitoxantrone (MEA) (n = 17); cytarabine plus idarubicin, daunorubicin, or mitoxantrone (IA/DA/MA) (n = 12); and homoharringtonine, cytarabine, and aclarubicin or daunorubicin (HAA/HAD) (n = 10).A total of 43 (35.2%) patients achieved complete remission (CR), 60 (49.2%) patients achieved overall remission rate (ORR), and 18 (14.8%) patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR. Median OS was 8.0 (95% CI 6.6-9.4) months with a 1-year OS rate of (29.9 ± 3.9)% and 3-year OS rate of (11.1 ± 3.6)%. No difference of CR (P = .621), ORR (P = .385), and allo-HSCT (P = .537) achievement was observed among different chemotherapy regimens. Interestingly, we observed that the CLAG-based regimen did not affect CR (P = .165), while it achieved a numerically higher ORR (P = .093) and was an independent factor for prolonged OS (P = .016). No other regimens were determined to be correlated with CR, ORR, or OS.FLAG-, CAG/DAG-, CLAG-, MEA-, IA/DA/MA- and HAA/HAD-based regimens were found to achieve similar CR rates, while the CLAG-based regimen achieved numerically higher ORR rates and significant favorable OS. Therefore, CLAG-based regimens should be a prioritized treatment option for R/R AML patients.

Figure 1

Accumulating OS by different treatments. (A) K-M curve analysis of OS in total R/R AML patients. Salvage chemotherapy regimens achieved a median OS of 8.0 (95% CI 6.6–9.4) months with 1-year OS rate of 29.9% ± 3.9% and 3-year OS of 11.1% ± 3.6%. (B) K-M analysis of OS by different treatments. The CLAG-based regimen achieved median OS of 10.0 (95% CI 3.4–16.6) months, and the FLAG-, CAG/DAG-, MEA-, IA/DA/MA-, and HAA/HAD-based regimens achieved 9.0 (95% CI 6.6–11.4) months, 7.0 (95% CI 2.8–11.2) months, 5.0 (95% CI 2.3–7.7) months, 5.0 (95% CI 0.0–11.8) months, and 8.0 (95% CI 6.6–9.4) months, respectively. No difference of OS among salvage chemotherapy regimens was found (P = .230). Comparison among groups was performed with log-rank test. P < .05 was considered significant. AML = acute myeloid leukemia, CAG/DAG = cytarabine and G-CSF in addition to aclarubicin or daunorubicin, CI = confidence interval, CLAG = cytarabine, G-CSF, and cladribine, FLAG = fludarabine, G-CSF = granulocyte colony-stimulating factor, HAA/HAD = homoharringtonine, cytarabine, and aclarubicin or daunorubicin, IA/DA/MA = cytarabine, idarubicin, daunorubicin, or mitoxantrone, K-M = Kaplan–Meier, MEA = cytarabine, etoposide, and mitoxantrone, OS = overall survival, R/R AML = relapsed or refractory acute myeloid leukemia.