Effect of rhG-CSF Combined With Decitabine Prophylaxis on Relapse of Patients With High-Risk MRD-Negative AML After HSCT: An Open-Label, Multicenter, Randomized Controlled Trial

Gao, Lei; Zhang, Yanqi; Wang, Sanbin; Kong, Peiyan; Su, Yi; Hu, Jiong; Jiang, Ming; Bai, Hai; Lang, Tao; Wang, Jishi; Liu, Li; Yang, Tonghua; Huang, Xiaobing; Liu, Fang; Lou, Shifeng; Liu, Yao; Zhang, Cheng; Liu, Hong; Gao, Li; Liu, Jia; Zhu, Lifei; Qin, Wen; Chen, Ting; Wang, Ping; Rao, Jun; Mao, Min; Wang, Cunbang; Duan, Xianlin; Luo, Le; Peng, Xiaoyong; Cassady, Kaniel; Zhong, Jiang; Zhang, Xi

doi:10.1200/jco.19.03277

Cited by 88 publications

(87 citation statements)

References 37 publications

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“…37 The observation that the adverse prognostic impact conferred by the presence of pretransplant MRD was mitigated by the acquisition of FDTCC at 3 months requires further prospective examination and identifies optimization of the GVL effect as an important approach to improve outcome in patients transplanted using an RIC regimen. Such strategies include using a T replete graft, a rapid taper of post-transplant immunosuppression, or early administration of pharmacological agents such as azacitidine, decitabine, [38][39][40] or DLI.…”

Section: Discussionmentioning

confidence: 99%

Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia

Craddock

Jackson

Loke

et al. 2021

JCO

105

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PURPOSE Reduced-intensity conditioning (RIC) regimens have extended the curative potential of allogeneic stem-cell transplantation to older adults with high-risk acute myeloid leukemia (AML) and myelodysplasia (MDS) but are associated with a high risk of disease relapse. Strategies to reduce recurrence are urgently required. Registry data have demonstrated improved outcomes using a sequential transplant regimen, fludarabine/amsacrine/cytarabine-busulphan (FLAMSA-Bu), but the impact of this intensified conditioning regimen has not been studied in randomized trials. PATIENTS AND METHODS Two hundred forty-four patients (median age, 59 years) with high-risk AML (n = 164) or MDS (n = 80) were randomly assigned 1:1 to a fludarabine-based RIC regimen or FLAMSA-Bu. Pretransplant measurable residual disease (MRD) was monitored by flow cytometry (MFC-MRD) and correlated with outcome. RESULTS There was no difference in 2-year overall survival (hazard ratio 1.05 [85% CI, 0.80 to 1.38] P = .81) or cumulative incidence of relapse (CIR) (hazard ratio 0.94 [95%CI, 0.60 to 1.46] P = .81) between the control and FLAMSA-Bu arms. Detectable pretransplant MFC-MRD was associated with an increased CIR (2-year CIR 41.0% v 20.0%, P = .01) in the overall trial cohort with a comparable prognostic impact when measured by an unsupervised analysis approach. There was no evidence of interaction between MRD status and conditioning regimen intensity for relapse or survival. Acquisition of full donor T-cell chimerism at 3 months abrogated the adverse impact of pretransplant MRD on CIR and overall survival. CONCLUSION The intensified RIC conditioning regimen, FLAMSA-Bu, did not improve outcomes in adults transplanted for high-risk AML or MDS regardless of pretransplant MRD status. Our data instead support the exploration of interventions with the ability to accelerate acquisition of full donor T-cell chimerism as a tractable strategy to improve outcomes in patients allografted for AML.

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Section: Discussionmentioning

confidence: 99%

Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia

Craddock

Jackson

Loke

et al. 2021

JCO

105

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“…It was a pity that both studies were single-armed. A phase II randomized controlled trial (RCT) from China has demonstrated that minimal-dose decitabine maintenance combined with recombinant human granulocyte colony-stimulating factor after allo-HSCT could reduce relapse for high-risk AML patients undergoing allo-HSCT, with the 2-year relapse rate of 15.0% and 38.3% in the intervention and non-intervention groups [ 22 ]. Nowadays, there are few reports comparing the effect of preemptive or prophylactic use with hypomethylating agents post-transplantation on the outcomes of AML patients undergoing allo-HSCT.…”

Section: Hypomethylating Agentsmentioning

confidence: 99%

Maintenance therapy in acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

Xuan

Liu

2021

J Hematol Oncol

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Relapse remains the main cause of treatment failure in acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Emerging evidence has demonstrated that AML patients might benefit from maintenance therapy post-transplantation, especially for high-risk AML patients. In this mini-review, we will summarize targeted drugs, such as hypomethylating agents, FLT3 inhibitors and isocitrate dehydrogenase inhibitors, as maintenance therapy post-transplantation in AML patients undergoing allo-HSCT.

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“…Concomitant prophylactic use of decitabine or FLT3 inhibitors followed by DLI could be an option with potentially promising efficacy in reducing relapse in these patients after transplant. In addition, previous studies have shown that using single azacitidine or decitabine as maintenance therapy helped prevent relapse in AML/MDS patients post‐HSCT from matched related donors and matched unrelated donors, 50‐52 and a new study suggested that rhG‐CSF combined with minimal‐dose decitabine maintenance after allo‐HSCT can reduce the incidence of relapse 53 …”

Section: Discussionmentioning

confidence: 99%

Haematologic malignancies with unfavourable gene mutations benefit from donor lymphocyte infusion with/without decitabine for prophylaxis of relapse after allogeneic HSCT: A pilot study

et al. 2021

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Relapse is the main cause of treatment failure for leukaemia patients with unfavourable gene mutations who receive allogeneic haematopoietic stem cell transplantation (allo‐HSCT). There is no consensus on the indication of donor lymphocyte infusion (DLI) for prophylaxis of relapse after allo‐HSCT. To evaluate the tolerance and efficacy of prophylactic DLI in patients with unfavourable gene mutations such as FLT3‐ITD, TP53, ASXL1, DNMT3A or TET2, we performed a prospective, single‐arm study. Prophylactic use of decitabine followed by DLI was planned in patients with TP53 or epigenetic modifier gene mutations. The prophylaxis was planned in 46 recipients: it was administered in 28 patients and it was not administered in 18 patients due to contraindications. No DLI‐associated pancytopenia was observed. The cumulative incidences of grade II–IV and III–IV acute graft‐versus‐host disease (GVHD) at 100 days post‐DLI were 25.8% and 11.0%, respectively. The rates of chronic GVHD, non‐relapse mortality and relapse at 3 years post‐DLI were 21.6%, 25.0% and 26.1%, respectively. The 3‐year relapse‐free survival and overall survival (OS) rates were 48.9% and 48.2%, respectively. Acute GVHD (HR: 2.30, p = 0.016) and relapse (HR: 2.46, p = 0.003) after DLI were independently associated with inferior OS. Data in the current study showed the feasibility of prophylactic DLI with/without decitabine in the early stage after allo‐HSCT in patients with unfavourable gene mutations.

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Effect of rhG-CSF Combined With Decitabine Prophylaxis on Relapse of Patients With High-Risk MRD-Negative AML After HSCT: An Open-Label, Multicenter, Randomized Controlled Trial

Cited by 88 publications

References 37 publications

Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia

Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia

Maintenance therapy in acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

Haematologic malignancies with unfavourable gene mutations benefit from donor lymphocyte infusion with/without decitabine for prophylaxis of relapse after allogeneic HSCT: A pilot study

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