The Clinical Outcome of FLAG Chemotherapy without Idarubicin in Patients with Relapsed or Refractory Acute Myeloid Leukemia

Lee, Se Ryeon; Yang, Deok Hwan; Ahn, Jae Sook; Kim, Yeo Kyeoung; Lee, Je Jung; Choi, Young Jin; Shin, Ho Jin; Chung, Joo Seop; Cho, Yoon Young; Chae, Yee Soo; Kim, Jong Gwang; Sohn, Sang Kyun; Kim, Hyeoung Joon

doi:10.3346/jkms.2009.24.3.498

Cited by 25 publications

(16 citation statements)

References 25 publications

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“…However, the authors noted a high risk of toxicity (48% of infectious death), and therefore recommended reduced doses of continuous infusion cytarabine. Our CR rates with FLAG‐Ida/FLAGO‐Ida compares favourably to other first salvage regimens, such as high‐dose cytarabine alone (32%) or with mitoxantrone (44%) (Karanes et al , ), or mitoxantrone plus etoposide (32–43%) (Ho et al , ; Daenen et al , ), similar to cladribine, cytarabine, G‐CSF and mitoxantrone (44–58%) (Martin et al , ), or FLAG (46–55%) (Montillo et al , ; Jackson et al , ; Lee et al , ), but unfavourably to mitoxantrone plus intermediate‐dose cytarabine combined with etoposide (66%) (Amadori et al , ) or GO (63%) (Chevallier et al , ). Nevertheless, the vast majority of these studies were performed in relatively small cohorts of patients with different characteristics, preventing us from making any conclusions regarding the superiority of any of the aforementioned regimens.…”

Section: Discussionsupporting

confidence: 57%

A prognostic model for survival after salvage treatment with FLAG‐Ida +/− gemtuzumab‐ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia

et al. 2016

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The combination of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-Ida) is widely used in relapsed/refractory acute myeloid leukaemia (AML). We retrospectively analysed the results of 259 adult AML patients treated as first salvage with FLAG-Ida or FLAG-Ida plus Gentuzumab-Ozogamicin (FLAGO-Ida) of the Programa Español de Tratamientos en Hematología (PETHEMA) database, developing a prognostic score system of survival in this setting (SALFLAGE score). Overall, 221 patients received FLAG-Ida and 38 FLAGO-Ida; 92 were older than 60 years. The complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 51%, with 9% of induction deaths. Three covariates were associated with lower CR/CRi: high-risk cytogenetics and t(8;21) at diagnosis, no previous allogeneic stem cell transplantation (allo-SCT) and relapse-free interval <1 year. Allo-SCT was performed in second CR in 60 patients (23%). The median overall survival (OS) of the entire cohort was 0·7 years, with 22% OS at 5-years. Four independent variables were used to construct the score: cytogenetics, FLT3-internal tandem duplication, length of relapse-free interval and previous allo-SCT. Using this stratification system, three groups were defined: favourable (26% of patients), intermediate (29%) and poor-risk (45%), with an expected 5-year OS of 52%, 26% and 7%, respectively. The SALFLAGE score discriminated a subset of patients with an acceptable long-term outcome using FLAG-Ida/FLAGO-Ida regimen. The results of this retrospective analysis should be validated in independent external cohorts.

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Section: Discussionsupporting

confidence: 57%

A prognostic model for survival after salvage treatment with FLAG‐Ida +/− gemtuzumab‐ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia

et al. 2016

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“…Based on data collected from 15 blood disease research centers in North China, we found a similar trend in the present study: the CR rate of t(8;21) AML patients in China was similar to the results reported from other countries, but the OS and RFS were far lower than the results reported by others [13,14,15,16,17]. Previously, this discrepancy was attributed to factors such as the race of the patients [18,19]. However, through years of clinical practice, we have found that Chinese physicians often empirically reduce the dose of Ara-c for considerations of poor ward conditions, limited complication management, and fear of the possible toxicity associated with high-dose Ara-c, etc.…”

Section: Discussionsupporting

confidence: 57%

Comparison of Clinical Efficacy of Cytarabine with Different Regimens in Postremission Consolidation Therapy for Adult t(8;21) AML Patients: A Multicenter Retrospective Study in China

Gong

Li²,

Hu³

et al. 2016

Acta Haematol

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Background: The survival of patients with acute myeloid leukemia (AML) with t(8;21) was reported to be shorter in China than in other countries. Patients: We analyzed the correlation between different cytarabine (Ara-c) regimens and outcome in 255 t(8;21) AML patients in China who received postremission consolidation chemotherapy only. Results: The 5-year overall survival (OS) of the high-dose Ara-c group (HDAC; 2≤ Ara-c ≤3 g/m²), intermediate-dose Ara-c group (MDAC; 1.0≤ Ara-c <2.0 g/m²), low-dose Ara-c group (LDAC; 0.2< Ara-c <1.0 g/m²) and standard-dose Ara-c group (SDAC; 0.1≤ Ara-c ≤0.2 g/m²) were 65.3, 39.4, 25.2 and 27.9%, respectively (p = 0.003). In the HDAC group, but not in the MDAC group, the 5-year OS of patients who achieved 3-4 cycles of chemotherapy was superior to those who underwent 1-2 cycles (84.4 vs. 43.6%, p < 0.05), and the 3-year OS of patients who achieved an accumulated 36 g/m² of Ara-c was significantly higher compared to those who did not (85.3 vs. 39.2%, p < 0.05). Multivariate analysis indicated that factors such as WBC >3.5 × 10⁹/l, PLT ≤30 × 10⁹/l, and extramedullary infiltration were associated with a poor prognosis. Conclusion: The survival of t(8;21) AML patients treated with high-dose Ara-c (≥2 g/m²) was superior to other dose levels in postremission consolidation chemotherapy. Patient survival was improved by 3-4 cycles of chemotherapy with an accumulated concentration of 36 g/m² of Ara-c. WBC >3.5 × 10⁹/l, PLT ≤30 × 10⁹/l and extramedullary infiltration could be indicative of a poor clinical prognosis.

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“…The FLAG regimen is composed of fludarabine, Ara-C and G-CSF, which has achieved satisfactory CR rate in treating refractory or relapsed AML. The FLAG regimen is repeatedly described as a well-tolerated salvage regimen in AML with CR rates between 47.5 and 68% (5,18,19). …”

Section: Discussionmentioning

confidence: 99%

“…Fludarabine, a purine analog, markedly increases the intracellular accumulation of Ara-C triphosphate (Ara-CTP), the active metabolite of Ara-C (4). The combination of a middle dose of Ara-C along with fludarabine has also achieved a satisfactory CR rate in refractory or relapsed AML, from 47.5 to 64% (5,6). Adding another chemotherapeutic agent to the FLAG regimen has become one of the hot issues of study.…”

Section: Introductionmentioning

confidence: 99%

Clinical study of Mito-FLAG regimen in treatment of relapsed acute myeloid leukemia

Luo

Cai

Jiang

et al. 2013

Experimental and Therapeutic Medicine

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Patients with relapsed acute myeloid leukemia (AML) have unfavorable prognosis and require innovative therapeutic approaches. In this study we used fludarabine combined with a middle dose of cytosine arabinoside (Ara-C), mitoxantrone and granulocyte-colony stimulating factor (G-CSF) as a salvage therapy for patients with relapsed AML in China. Forty-five patients with relapsed AML were treated with the Mito-FLAG regimen consisting of mitoxantrone (7 mg/m2, day 1, 3 and 5), fludarabine (30 mg/m2, days 1–5), Ara-C (1 g/m2, over 3 h every 12 h, days 1–5) and G-CSF [5 μg/kg/day subcutaneously from day 0 until the white blood count (WBC) was >20×109/l]. Patients with a partial response (PR) received another course of the same regimen. Patients with a suitable donor and aged <50 years received allogeneic stem cell transplantation (allo-SCT). Twenty-three patients (51%) and 3 patients (7%) achieved complete remission (CR) and PR, respectively, following one or two courses of Mito-FLAG, and the overall response (OR) rate was 58%. Nine patients (20%) received allo-SCT and 4 patients (9%) succumbed early. Hematological toxicity and infections were the most prominent toxicities of this regimen. Other toxicities included nausea, vomiting, bleeding, hyperbilirubinemia, renal toxicity and arrhythmia. The probability of overall survival (OS) at 4 years was 19% (95% CI, 11–26%) and the probability of 4-year disease-free survival (DFS) was 29% for all 23 patients in CR (95% CI, 18–41%). Our data suggest that Mito-FLAG is a highly effective and well-tolerated salvage regimen for relapsed AML.

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The Clinical Outcome of FLAG Chemotherapy without Idarubicin in Patients with Relapsed or Refractory Acute Myeloid Leukemia

Cited by 25 publications

References 25 publications

A prognostic model for survival after salvage treatment with FLAG‐Ida +/− gemtuzumab‐ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia

A prognostic model for survival after salvage treatment with FLAG‐Ida +/− gemtuzumab‐ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia

Comparison of Clinical Efficacy of Cytarabine with Different Regimens in Postremission Consolidation Therapy for Adult t(8;21) AML Patients: A Multicenter Retrospective Study in China

Clinical study of Mito-FLAG regimen in treatment of relapsed acute myeloid leukemia

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