Treatment of Relapsed ACUTE Leukemia after ALLO-HSCT By Salvage Chemotherapy with Low-Dose Cytarabine and Aclarubicin Combined with G-CSF Priming: More Effective and LESS Toxic?

Background: Recurrence is a major cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia, and subsequential treatment options are very limited.

Aims: We evaluate the efficacy and toxicity of cytarabine and aclarubicin combined with granulocyte colony-stimulating factor priming (CAG regimen), consisting of concurrent use of granulocyte colony-stimulating factor (G-CSF) with low-dose cytarabine and aclarubicin, as a salvage therapy for acute leukemia patients who relapsed after allo-HSCT.

Methods: Fifty-nine patients (32 male and 27 female) with acute leukemia, with a median age of 27 years, relapsed post allo-HSCT and received salvage chemotherapy. Twenty-seven patients received CAG regimen while 32 patients received non-CAG regimen such as intensive chemotherapy.

Results: 1.The overall response rate (ORR) of CAG was significantly superior than that of non-CAG groups (55.6% vs 28.1%, P= 0.033). Especially for AML patients (64.3% vs 20%, P= 0.025). However, ORR of ALL in CAG group was similar with that in non-CAG group (50% and 35.2% respectively; P = 0.471).

2. Median overall survival (OS) from the starting of CAG chemotherapy and the estimated 2-year OS of CAG group were 9 (1-27) months and 16.1%. Meanwhile, median OS and the estimated 2-year survival of non-CAG group were 4 (1-49) months and 8.8% (Figure1). For the patients who received donor lymphocyte infusion (DLI) as a subsequential therapy, two-year OS of CAG and non-CAG group were 17.2% and 12.5% respectively (P=0.577).

3. The median duration of neutropenia and thrombocytopenia of CAG group were significantly shorter than that of non CAG group, 6 (1-12) vs 11 (5-28) days (P=0.000) and 8 (1-14) vs 14 (7-35) days (P=0.000). Treatment related mortality (TRM) was found in 2 cases in CAG group compared with 10 cases in non-CAG group.

4. For CAG group, univariate analysis results showed that lower leukocyte level and lower medullar blast percentage at relapse post-transplant were significantly associated with a higher overall response rate (P=0.005 and P=0.000).Furthermore, multivariate analysis results showed that the response to chemotherapy was the only factor that correlated with better survival (HR 0.426, P=0.016)

Conclusion: CAG regimen as a salvage chemotherapy for relapsed acute leukemia post allo-HSCT could effectively reduce tumor burden with mild toxicity, especially for hypoplastic acute leukemia patients. For certain type of relapsed acute leukemia patients post allo-HSCT, CAG regimen may be an optimal choice as the bridge therapy followed by DLI or second allo-HSCT.