Intensive chemotherapy for acute myeloid leukemia relapse after allogeneic hematopoietic cell transplantation

Krakow, Elizabeth F.; Walter, Roland B.; Nathe, Julia M; Perez, Tess; Ahmed, Ali R.; Polissar, Nayak L.; Miljacic, Ljubomir; Halpern, Anna B.; Flowers, Mary E.D.; Estey, Eli

doi:10.1002/ajh.26540

Cited by 3 publications

(4 citation statements)

References 5 publications

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“…In addition to the heterogeneity of the study population, this difference may also be due to inadequate Ven-HMAs combined with cell therapy (only 25% of patients were treated with DLI at the base of Ven-HMAs). Although IC + DLI has a high remission rate, the 2-year survival rate of the patients is not high, which may be associated with a higher rate of treatment-related death (TRM) caused by IC and an inability to maintain a long-term remission [ 12 , 52 ]. Though TRM was not mentioned explicitly in the studies included in this meta-analysis, previous findings showed that Ven-HMAs did not cause a high rate of TRM in R/R-AML [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

Du,

Li,

Zhao

et al. 2023

BMC Cancer

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Background Currently, there is no standard treatment for managing relapse in patients with acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after allogeneic hematopoietic cell transplantation. Venetoclax-based therapies have been increasingly used for treating post-transplantation relapse of AML. The aim of this systematic review and meta-analysis was to evaluate the efficacy and adverse events of Venetoclax combined with hypomethylating agents (HMAs) for AML/MDS relapse post-transplantation. Methods We searched PubMed, Web of Science, Excerpta Medica Database, Cochrane Library, and Clinical. gov for eligible studies from the inception to February 2022. The Methodological Index for Non-Randomized Studies was used to evaluate the quality of the included literatures. The inverse variance method calculated the pooled proportion and 95% confidence interval (CI). Results This meta-analysis included 10 studies involving a total of 243 patients. The pooled complete response and complete response with incomplete blood count recovery rate of Venetoclax combined with HMAs for post-transplantation relapse in AML/MDS was 32% (95% CI, 26-39%, I2 = 0%), with an overall response rate of 48% (95% CI, 39-56%, I2 = 37%). The 6-month survival rate was 42% (95% CI, 29-55%, I2 = 62%) and the 1-year survival rate was 23% (95% CI, 11-38%, I2 = 78%). Conclusion This study demonstrated a moderate benefit of Venetoclax in combination with HMAs for patients with relapsed AML/MDS post-transplantation (including those who have received prior HMAs therapy), and may become one of treatment options in the future. Large-scale prospective studies are needed to confirm the potential benefit from venetoclax combined with HMAs.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

Du,

Li,

Zhao

et al. 2023

BMC Cancer

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“…Previous researches on IC treatment for post-transplantation AML relapse have demonstrated CR rates from 13% to 71% and 1-year OS from 25% to 34.4% ( 20 ). A recent study including 175 patients showed a remission rate of 36% and median OS of 188 days, while early mortality within 28 days occurred in 12% patients ( 21 ). The promising efficacy of venetoclax-based treatment in newly-diagnosed AML also promoted its use in R/R AML and post-transplantation relapse of myeloid malignancies.…”

Section: Discussionmentioning

confidence: 99%

Venetoclax plus hypomethylating agents versus intensive chemotherapy for hematological relapse of myeloid malignancies after allo-HSCT

Chen

Zhen²,

Zhang³

et al. 2023

Front. Oncol.

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IntroductionSince allogeneic stem cell transplantation (allo-HSCT) is considered one of the curative treatments for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), hematological relapse following allo-HSCT remained a crucial concern for patients’ survival. MethodsWe retrospectively compared patients who received venetoclax plus hypomethylating agents (VEN+HMA, n=23) or intensive chemotherapy (IC, n=42) for hematological relapse of myeloid malignancies after allo-HSCT. HMA selection included decitabine (n=2) and azacitidine (n=21), and combined donor lymphocyte infusion was administered to 21 and 42 patients in VEN+HMA and IC groups, respectively. ResultsMedian age of all patients was 39 (16-64) years old. Overall response rates, including complete response (CR), CR with incomplete recovery of normal neutrophil or platelet counts (CRi) and partial response (PR), were not significantly different between VEN+HMA and IC groups (60.1% versus 64.3%, P=0.785). CR/CRi rate was 52.2% in VEN+HMA and 59.5% in IC group (P=0.567). The rate of relapse after response was 66.7% in VEN+HMA group and 40.7% in IC group (P=0.176). Median overall survival was 209.0 (95%CI 130.9-287.1) days for VEN+HMA group versus 211.0 (95%CI 28.7-393.3) days for IC group (P=0.491). The incidence of lung infection (17.4% versus 50.0%, P=0.010), thrombocytopenia (73.9% versus 95.2%, P=0.035) and acute graft-versus-host disease (aGvHD) (50.0% versus 13.0%, P=0.003) was significantly higher in IC group. DiscussionIn conclusion, VEN+HMA is not inferior to IC regimen in terms of improving response and survival, and is associated with a lower incidence of adverse events and aGvHD. However, further research is required to enhance long-term survival.

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“…Also, only 29.2% of the Ven + HMAs regimens in this study were combined with DLI therapy and were not su ciently combined with cell therapy. Although IC + DLI has a high remission rate, the 2year survival rate of the patients is not high, which may be associated with a higher rate of treatment-related death (TRM) caused by IC and an inability to maintain long-term remission [12,44]. Though TRM was not mentioned explicitly in the studies included in this meta-analysis, previous ndings showed that Ven + HMAs did not cause a high rate of TRM in R/R-AML [45][46].…”

Section: Discussionmentioning

confidence: 99%

“…There is no standard regimen for the treatment of post-transplant relapse due to the disease heterogeneity, tness of a patient, ways of transplantation, time to post-transplant relapse, etc. At present, post-transplant relapse treatment options primarily include supportive care, withdrawal of immunosuppression, donor lymphocyte infusion (DLI), intense chemotherapy (IC) ± DLI, hypomethylating agents (HMAs) therapy, and secondary allo-HCT (allo-HCT2) [10][11][12][13] Three investigators (YFD, CHL, and ZJZ) independently read the title, abstract, and full text to decide whether to include a study. Any discrepancy in the included literature was resolved by consensus or by consulting another senior investigator.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post-transplantation: a systematic review and meta-analysis

Zhang

et al. 2023

Preprint

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Background Currently, there is no standard treatment for managing relapse after allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome (AML/MDS). Venetoclax (Ven)-based therapies have been increasingly used for treating post-transplant relapse. The aim of this systematic review and meta-analysis was to evaluate the efficacy and adverse events of Ven combined with hypomethylating agents (HMAs) for AML/MDS relapse post-transplantation. Methods We searched PubMed, Web of Science, Excerpta Medica Database, Cochrane Library, and Clinical. gov for eligible studies from the inception to February 2022. The Methodological Index for Non-Randomized Studies was used to evaluate the quality of the included literature. The inverse variance method calculated the pooled proportion and 95% confidence interval (CI). Results This meta-analysis included 9 studies involving a total of 202 patients. The pooled complete response and complete response with incomplete blood count recovery rate of Ven combined with HMAs for post-transplant relapse in AML/MDS was 32% (95% CI, 25%-40%, I2 = 0%), with an overall response rate of 50% (95% CI, 40%-59%, I2 = 38%). The 6-month survival rate was 43% (95% CI, 28%-59%, I2 = 68%) and the 1-year survival rate was 27% (95% CI, 13%-42%, I2 = 72%). Conclusion This study demonstrated a moderate benefit of Ven in combination with HMAs for AML/MDS patients with relapsed post-transplantation (including those who have received prior HMAs therapy), and may become one of the treatment options in the future. Large-scale prospective studies are needed to confirm this study in future.

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Intensive chemotherapy for acute myeloid leukemia relapse after allogeneic hematopoietic cell transplantation

Cited by 3 publications

References 5 publications

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

Venetoclax plus hypomethylating agents versus intensive chemotherapy for hematological relapse of myeloid malignancies after allo-HSCT

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post-transplantation: a systematic review and meta-analysis

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