Analysis of Efficacy and Prognostic Factors of CLAG Treatment in Chinese Patients with Refractory or Relapsed Acute Myeloid Leukemia

Abstract

Background/Aims: The aim of this work was to investigate the efficacy and predictive factors of CLAG treatment in refractory or relapsed (R/R) acute myeloid leukemia (AML) patients. Methods: Sixty-seven R/R AML patients were enrolled in this prospective cohort study and treated by a CLAG regimen: 5 mg/m²/day cladribine (days 1–5), 2 g/m²/day cytarabine (days 1–5), and 300 μg/day filgrastim (days 0–5). The median follow-up duration was 10 months. Results: A total of 57 out of 67 patients were evaluable for remission after CLAG therapy, of whom 57.9% achieved a complete remission (CR) and the overall remission rate was 77.2%. The median overall survival (OS) was 10.0 months, with a 1-year OS of 40.3 ± 6.0% and 3-year OS of 16.7 ± 5.7%. CR at first induction after the initial diagnosis was associated with a favorable CR. Age above 60 years, high risk stratification, second or higher salvage therapy, and bone marrow (BM) blasts ≥42.1% were correlated with an unfavorable CR. Secondary disease, age ≥60 years, high risk stratification, and second or higher salvage therapy were associated with worse OS. Patients developed thrombocytopenia (41, 61%), febrile neutropenia (37, 55%), leukopenia (33, 49%), neutropenia (18, 27%), and anemia (9, 13%). Conclusion: CLAG was effective and well tolerated for R/R AML. BM blasts ≥42.1%, age ≥60 years, high risk stratification, and second or higher salvage therapy were independent factors for a poor prognosis.

The use of venetoclax‐based salvage therapy for post‐hematopoietic cell transplantation relapse of acute myeloid leukemia

“…The management of post‐HCT relapsed disease is challenging. Overall response rates (ORR) with cytotoxic salvage therapy are variable, but far poorer after HCT 12‐18 . In a large registry analysis, only 15% of post‐HCT relapsed AML patients achieved a subsequent complete remission (CR); less than 5% of patients who relapsed within 6 months, and 12% of patients who relapsed 6‐24 months after HCT were alive at 3 years 18 …”

MicroRNA‑144 targets APP to regulate AML1/ETO+ leukemia cell migration via the p‑ERK/c‑Myc/MMP‑2 pathway

“…Due to the continued improvement of chemotherapeutic agents, the remission rate of leukemia has significantly improved (1)(2)(3). However, the recurrence rate remains as high as 30-40% (4).…”

Successful treatment of two relapsed patients with t(11;19)(q23;p13) acute myeloid leukemia by CLAE chemotherapy sequential with allogeneic hematopoietic stem cell transplantation: Case reports

“…This regimen has been demonstrated to improve the long-term survival rate from 20 to 50%; however, reinduction chemotherapy-related side effects must be acceptable to patients (27). Previous studies have reported that FLAG-IDA (granulocyte colony-stimulating factor, fludarabine, cytarabine, and idarubicin), CLAG (cladribine, cytarabine, granulocyte colony-stimulating factor), CLAM (cladribine, cytarabine, mitoxantrone) and MEC (mitoxantrone, etoposide, and cytarabine) chemotherapy regimens achieve high CR rates in patients with R/R AML (28)(29)(30)(31). However, CR rates in response to common salvage regimens decrease (10-15%) in refractory or early relapsed patients with AML (26).…”

“…Another study reported the feasibility and efficacy of FLAG-IDA chemotherapy sequential with Flu-Bu3 conditioning regimen in patients with refractory AML (34). Based on previous studies (28)(29)(30)(31) and patient characteristics, the present study selected the CLAE regimen sequential with Flu-Bu conditioning regimen for allo-HSCT in the assessed patients. Patient 1 received CLAE regimen sequential with haploid transplantation, and exhibited granulocyte deficiency at 21 after chemotherapy, the neutrophil and platelet engraftments were achieved on days 14 and 12.…”