Factors Affecting Clinical Outcomes after CLAG/CLAG-M Chemotherapy in Relapsed/Refractory Acute Myeloid Leukemia
Authors: Park Hyunkyung , Youk Jeonghwan , Koh Youngil , Kim Inho , Park Seonyang , Lee Jeong-Ok , Bang Soo-Mee , Kim Hyo Jung , Yoon Hwi-Joong , Lee Junglim , Yoon Sung-Soo 
Published: October 2019

Abstract
Backgroud:
Substantial number of acute myeloid leukemia(AML) patients does not respond to induction chemotherapy (refractory) or relapse after achieving complete remission (CR) with standard induction chemotherapy. In relapsed/refractory AML, therapeutic options are still undefined and unsatisfactory. By the way, new regimen integrating cladribine yields promising outcomes in recent studies. We intended to reveal the efficacy of CLAG/CLAGM and to find out predictive markers for outcome in relapsed/refractory AML patients.
Methods:
Relapsed/refractory AML patients who were treated with CLAG or CLAGM between 2004.5 - 2014.7 in two institutions (Seoul National University Hospital/Seoul National University Bundang Hospital) were retrospectively reviewed. The regime CLAG consists of cladribine 5mg/m2 on days 1-5, cytarabine 2gm/m2 on days 1-5 and filgrastim 5 mcg/kg on days 0-5. The regimen CLAGM includes addition of mitoxantrone 10mg/m2 to CLAG regimen on days 1-3. We analyzed factors affecting complete remission(CR), relapse free survival(RFS) and overall survival(OS).
Results:
The total of 56 patients (Male:Female = 36:20, median age 51 years) were analyzed. Overall CR rate was 50%, CR rate was 44% for CLAG, 55% for CLAGM respectively, and was not significantly different between the two regimens (p=0.511). Poor predictive markers for CR rates after CLAG/CLAGM included secondary AML (p=0.006), and poor cytogenetic risk group based on MRC criteria (p<0.001). CR rate was higher whether patients achieved CR before CLAG/CLAGM (p = 0.015). In patients who achieved CR after CLAG/CLAGM, the median RFS was 3.4 months (95% CI 2.0 – 4.9 months); 2.0 months (95% CI 0.0 – 4.7 months) for CLAG and 3.4 months (95% CI 1.0 – 5.9 months) for CLAGM.
The median OS who received CLAG/CLAGM was 13.5 months (95% CI; 10.2 – 16.7 months); 13.2 months (95% CI ; 8.9 – 17.5 months) for CLAG and 13.5 months (95% CI ; 10.4 – 16.6 months) for CLAGM, no statistical difference (p=0.899). Poor prognostic factor for OS included secondary AML (p<0.001), poor cytogenetic risk group (p<0.001), presence of FLT3-ITD mutation(p=0.019), whether patients failed to achieve CR before CLAG/CLAGM (p<0.001). Moreover, favorable factor for OS was whether CR period was more than 6 months in 1stinduction chemotherapy (p<0.001) in replased AML patients. The survival period after CLAG/CLAGM chemotherapy was improved when allogeneic stem cell transplantation(ASCT) was given after CLAG/CLAGM as consolidation therapy (p=0.044).
Conclusion:
CLAG/CLAGM is an efficacious regimen for refractory/relapsed AML as previously reported. Especially whether the patients achieved CR before CLAG/CLAGM is favorable prognostic factor. However, only limited benefit is shown in secondary AML patients and poor cytogenetic risk group patients. Allogeneic ASCT as consolidation therapy is definitely necessary to improve outcome.

Disclosures
No relevant conflicts of interest to declare.