Modified cladribine, cytarabine, and G-CSF as a salvage regimen in patients with relapsed/refractory acute myeloid leukemia: a bridge to myeloablative allogeneic hematopoietic stem cell transplantation

Ye, Peipei; Pei, Renzhi; Jin, Jie; Sun, Jie; Li, Kongfei; Cao, Junjie; Zhou, Dandan; Lu, Ying

doi:10.1007/s00277-019-03723-w

Cited by 4 publications

(5 citation statements)

References 26 publications

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“…Additionally, the OS rate of all patients in our study (55.6%) was slightly higher than that of other previous series of relapsed/refractory patients (22.0%, uncensored for the subsequent transplant). 24 These differences may be related to the higher response rates to the Chi-FLAG regimen in patients with intermediate/poor-risk disease and their ability to undergo subsequent transplantation.…”

Section: Discussionmentioning

confidence: 99%

Treating relapsed/refractory acute myeloid leukemia with chidamide, fludarabine, cytarabine and granulocyte-colony stimulating factor with subsequent bridging to myeloablative allogeneic hematopoietic stem cell transplantation

Yao¹,

Fang²,

Jiang³

et al. 2022

Mediterr J Hematol Infect Dis

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To the editor.Despite the significant progress made in treating acute myeloid leukemia (AML) in the last decade, 10%-40% of the patients with standard induction chemotherapy still did not achieve complete remission (CR), 1 and 50%-70% of the patients in the first CR were at risk for relapse. 2 Although few of these patients can be cured with conventional salvage therapy, 2,3 they need to be evaluated regarding eligibility for allogeneic hematopoietic stem cell transplantation (HSCT), the most potent therapeutic strategy for patients who achieve CR after relapse. 2 Before transplantation, salvage chemotherapy regimens need to be employed to reduce the leukemia burden.In relapsed/refractory AML, fludarabine, cytarabine, combination with granulocyte colony-stimulating factor (G-CSF) (FLAG) were used as a reinduction therapy and resulted in only 38.2% CR. 4 Wrzesień-Kuś A et al. utilized the combination of cytarabine, cladribine, and G-CSF as the induction therapy in patients with refractory or early relapsed AML, obtaining a 50% CR rate with 17% early death. 5 Subsequent studies evaluated FLAG plus idarubicin (FLAG-Ida) or FLAG-Ida plus gemtuzumab ozogamicin (FLAGO-Ida) in adult patients with refractory/relapsed AML, showing that the CR/CR with an incomplete blood count recovery (CRi) rate was 51%, with 9% of induction deaths. 6 These data demonstrated the therapy limitation of FLAG in relapsed/refractory AML and the prospects of FLAG combination with other specific drugs.Chidamide is a new histone deacetylase (HDAC) inhibitor of the benzamide class, and it has been approved by China Food and Drug Administration (CFDA) in treating peripheral T-cell lymphoma in China. Additionally, evidence demonstrated that

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Section: Discussionmentioning

confidence: 99%

Treating relapsed/refractory acute myeloid leukemia with chidamide, fludarabine, cytarabine and granulocyte-colony stimulating factor with subsequent bridging to myeloablative allogeneic hematopoietic stem cell transplantation

Yao¹,

Fang²,

Jiang³

et al. 2022

Mediterr J Hematol Infect Dis

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“…Of note, the allo-HSCT rate in patients receiving salvage chemotherapy in this study was 11%, compared with 15% in patients receiving gilteritinib in the phase 3 ADMIRAL trial [6] and 20% in a phase 2 study of the FLT3 inhibitor lestaurtinib [5] in patients with FLT3-ITD AML. In studies of FLT3-unselected populations, allo-HSCT rates with salvage chemotherapy are variable (% 15%-42%) and are often based on small sample sizes with heterogenous populations of patients with differD 3 4 4 X Xing cytogenetic and molecular features and risk factors [35][36][37][38][39][40][41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes in Patients with FLT3-ITD-Mutated Relapsed/Refractory Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation after Quizartinib or Salvage Chemotherapy in the QuANTUM-R Trial

Ganguly

Cortés

Krämer

et al. 2021

Transplantation and Cellular Therapy

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Despite the substantial clinical activity of fms-related tyrosine kinase 3 (FLT3) inhibitors in relapsed or refractory (R/R) FLT3-ITD-positive acute myelogenous leukemia (AML), durable remissions and prolonged survival in this population require allogeneic hematopoietic stem cell transplantation (allo-HSCT). Quizartinib, a once-daily oral, highly potent, and selective FLT3 inhibitor, significantly prolonged overall survival (OS) and improved clinical benefit compared with salvage chemotherapy (median OS, 6.2 months versus 4.7 months; hazard ratio [HR], .76; 95% confidence interval [CI], .58 to .98; P = .018; composite complete remission [CRc] rate, 48% versus 27%; median duration of CRc, 2.8 months versus 1.2 months; mortality rate, .8% versus 14% by day 30, 7% versus 24% by day 60) in patients with R/R FLT3-ITD AML in the phase 3 QuANTUM-R trial. In this post hoc analysis, we described the characteristics of and clinical outcomes in patients who underwent on-study HSCT in QuANTUM-R at the investigator's discretion and institutional practices. Of 367 randomized patients, 78 (32%) in the quizartinib arm and 14 (11%) in the salvage chemotherapy arm underwent on-study allo-HSCT without any intervening therapy for AML after quizartinib or study-specified salvage chemotherapy. Pooled data of patients from both treatment arms showed a longer median overall survival (OS) in transplant recipients versus those treated without HSCT (12.2 months versus 4.4 months; HR, .315; 95% CI, .233 to .427). Pooled data also showed a longer median OS in patients with a last recorded response of CRc before allo-HSCT versus patients without a CRc (20.1 months versus 8.8 months; HR, .506; 95% CI, .296 to .864). By treatment arm, the median OS was 25.1 months with quizartinib and 20.1 months with salvage chemotherapy in patients with a last recorded response of CRc before allo-HSCT. Fortyeight patients in the quizartinib arm continued quizartinib treatment after allo-HSCT. In the 31 patients with a last recorded response of CRc before allo-HSCT who continued quizartinib after allo-HSCT, the median OS was 27.1 months. Continuation of quizartinib after allo-HSCT was tolerable, and no new safety signals were identified. These results suggest that post-transplantation survival following salvage chemotherapy and quizartinib treatment are similar. However, quizartinib response occurs more frequently than with salvage chemotherapy, potentially allowing more patients to undergo transplantation and achieve durable clinical benefit. In addition,

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“…The median OS in the standard CLAG group was 7.3 to 14 months, in the CLAG-combined group 7.8 to 13.3 months. However, the study by Ye et al [ 21 ] is a modified CLAG regimen without any drug combinations, with the median OS of the modified CLAG regimen was 10.8 months with 95% CI of 6.0–15.7.…”

Section: Resultsmentioning

confidence: 99%

“…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…”

Section: Discussionmentioning

confidence: 99%

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

Cao,

Tao,

Wang

et al. 2023

Medicine

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Background: To ascertain the efficacy and safety of cladribine, cytarabine, and filgrastim-based regimen in relapsed or refractory (R/R) AML patients. Methods: Clinical studies were searched in PubMed, Cochrane Library, Embase data. We selected available factors including complete remission (CR), overall response rate (ORR), overall survival (OS) to evaluate the efficacy, and early death (ED), and adverse events to evaluate safety. Results: 15 records with 812 R/R AML patients were finally included and analyzed using the R software. Subgroups analysis was also conducted. The pooled CR rate for CLAG regimen, CLAG-M regimen, and CLAG combined with any other drugs regimen is 56% (95% CI: 46–66), 46% (95% CI: 34–56), 44% (95% CI: 26–64), respectively. The relapsed and refractory groups showed a CR rate of 68% (95% CI: 53–80), and 51% (95% CI: 45–58) with CLAG related regimens. As risk grade decreases, the pooled CR rate increases. Regarding the safety for CLAG-related protocols, systematic review was conducted. Conclusion: The CLAG-related regimen is an effective and safe therapy for R/R AML patients, CLAG seems to have more superiority than CLAG combined therapy, though further studies including cladribine combination treatment protocols, are still needed to confirm our results further.

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Modified cladribine, cytarabine, and G-CSF as a salvage regimen in patients with relapsed/refractory acute myeloid leukemia: a bridge to myeloablative allogeneic hematopoietic stem cell transplantation

Cited by 4 publications

References 26 publications

Treating relapsed/refractory acute myeloid leukemia with chidamide, fludarabine, cytarabine and granulocyte-colony stimulating factor with subsequent bridging to myeloablative allogeneic hematopoietic stem cell transplantation

Treating relapsed/refractory acute myeloid leukemia with chidamide, fludarabine, cytarabine and granulocyte-colony stimulating factor with subsequent bridging to myeloablative allogeneic hematopoietic stem cell transplantation

Clinical Outcomes in Patients with FLT3-ITD-Mutated Relapsed/Refractory Acute Myelogenous Leukemia Undergoing Hematopoietic Stem Cell Transplantation after Quizartinib or Salvage Chemotherapy in the QuANTUM-R Trial

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

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