Cladribine with Granulocyte Colony-Stimulating Factor, Cytarabine, and Aclarubicin Regimen in Refractory/Relapsed Acute Myeloid Leukemia: A Phase II Multicenter Study

Abstract

Lessons Learned Studies targeting cladribine in combination with granulocyte colony‐stimulating factor, low‐dose cytarabine, and aclarubicin (C‐CAG) regimen in relapsed and refractory acute myeloid leukemia (R/R AML) are limited. The complete remission rate after two cycles of C‐CAG regimen was 67.6%, and 1‐year overall survival and disease‐free survival rates were 59.7% and 72.9%, respectively. The C‐CAG regimen is significantly effective against R/R AML with a low hematological toxicity and thus serves as an alternative treatment for R/R AML. Background The optimal salvage chemotherapy regimen for relapsed and refractory acute myeloid leukemia (R/R AML) remains uncertain. Therefore, a phase II study was conducted for the prospective evaluation of the efficacy and safety of the purine analog cladribine in combination with granulocyte colony‐stimulating factor (G‐CSF), low‐dose cytarabine, and aclarubicin (C‐CAG) regimen for patients with R/R AML. Methods A total of 34 patients received C‐CAG regimen for salvage treatment as follows: cladribine 5 mg/m2, days 1–5; G‐CSF 300 μg, days 0–9; aclarubicin 10 mg, days 3–6; cytarabine 10 mg/m2 every 12 hours, subcutaneously, days 3–9; 4 weeks per cycle. Patients were allowed to withdraw from the study if complete remission (CR) was not achieved after two courses of chemotherapy. If conditions were right, the patients achieving CR were recommended to receive allogeneic hematopoietic stem cell transplantation. Otherwise, they were treated for a total of six cycles unless disease progression or unacceptable side effects were observed or they withdrew their consent. Results All patients received at least two cycles of C‐CAG regimen chemotherapy. After two cycles of C‐CAG, 23 patients (67.6%) achieved CR, and 5 patients had partial remission (14.7%). At a median follow‐up of 15 months (range, 3–38 months), the 1‐year overall survival (OS) and disease‐free survival (DFS) rates were 59.7% (95% confidence interval [CI], 42.6%–76.8%) and 72.9% (95% CI, 54.3%–91.5%), respectively. The most common adverse effect was myelosuppression. Nonhematological toxicities were mild, and no treatment‐related deaths occurred. Conclusion Preliminary data indicate that the C‐CAG regimen chemotherapy is significantly effective against R/R AML with a high remission rate and a low hematological toxicity. Thus, it may serve as an alternative treatment for R/R AML.

Cladribine, cytarabine, and filgrastim based regimen in relapsed or refractory acute myeloid leukemia: A systematic review and meta-analysis

“…The complete scores are detailed in Table S1, Supplemental Digital Content, http://links.lww.com/MD/ J846. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] 3. Results…”

“…The complete scores are detailed in Table S1, Supplemental Digital Content, http://links.lww.com/MD/J846. [10–24]…”

Cladribine Combined with Low-Dose Cytarabine as Frontline Treatment for Unfit Elderly Acute Myeloid Leukemia Patients: Results from a Prospective Multicenter Study of Polish Adult Leukemia Group (PALG)

“…Recently, a novel combination of cladribine with granulocyte colony-stimulating factor, LD-AC, and aclarubicin has shown significant activity as salvage therapy for relapsed/refractory AML. As hematological toxicity was low, this regimen may be a suitable treatment option for elderly AML patients [35].…”

Efficacy and toxicity of CLAG combined with pegylated liposomal doxorubicin in the treatment of refractory or relapsed acute myeloid leukemia

“…Pharmacological studies have demonstrated that cladribine before treatment promotes cytarabine intracellular absorption and cytarabine triphosphate (Ara‐CTP) buildup in AML blasts both in vitro and ex vivo 4 . A traditional treatment for r/rAML, the CLAG regimen consists of cladribine and cytarabine with G‐CSF priming and has a CR rate of between 50% and 61.7% 5–7 . Numerous investigations have shown that the addition of a different medication with a different mechanism can both increase efficacy and exert an equal amount of harm.…”

“… 4 A traditional treatment for r/rAML, the CLAG regimen consists of cladribine and cytarabine with G‐CSF priming and has a CR rate of between 50% and 61.7%. 5 , 6 , 7 Numerous investigations have shown that the addition of a different medication with a different mechanism can both increase efficacy and exert an equal amount of harm. According to a literature study, CLAG+X was more effective than CLAG alone in a variety of ways for both adults and children, and any side effects are tolerable.…”