Reduced-toxicity conditioning for allogeneic hematopoietic cell transplantation in elderly or comorbid patients with AML using fludarabine, BCNU and melphalan: disease stage at transplant determines outcome

Wais, Verena; Kündgen, Lukas; Bohl, Stephan R; Harsdorf, Stephanie von; Schlenk, Richard F.; Döhner, Konstanze; Teleanu, Veronica; Bullinger, Lars; Nguyen, Thanh Mai; Drognitz, Kathrin; Moulin, J-C.; Binnenhei, M.; Döhner, Hartmut; Bunjes, Donald; Kuchenbauer, Florian; Ringhoffer, Mark

doi:10.1038/bmt.2017.211

Cited by 5 publications

(3 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zhu et al reported that HOXA-AS2 was take part in osteogenesis via regulating NF-κB pathway in mesenchymal stem cells [55], and another study found that HOXA-AS2 was involved in inhibiting endothelial inflammation by regulating the NF-κB pathway [37]. Of these three HOXA-AS2-targeted drugs used in AML, carmustine is a broad-spectrum anticancer drug with good curative effect in patients with Hodgkin's disease [56] and AML [57,58], as well as some curative effect in patients with breast cancer [59], lung cancer [60], brain cancer [61,62] and brain metastasis [63,64]. Carmustine can be used to treat elderly or comorbid patients with AML, as well as post-transplant acute leukemia in patients with non-Hodgkin's and Hodgkin's lymphoma [57,58].…”

Section: Discussionmentioning

confidence: 99%

“…Of these three HOXA-AS2-targeted drugs used in AML, carmustine is a broad-spectrum anticancer drug with good curative effect in patients with Hodgkin's disease [56] and AML [57,58], as well as some curative effect in patients with breast cancer [59], lung cancer [60], brain cancer [61,62] and brain metastasis [63,64]. Carmustine can be used to treat elderly or comorbid patients with AML, as well as post-transplant acute leukemia in patients with non-Hodgkin's and Hodgkin's lymphoma [57,58]. As is well-known, no studies have revealed the use of cefoxitin for the treatment of AML, but cefoxitin was used to treat colon tumorigenesis induced by the human commensal enterotoxigenic Bacteroides fragilis in mice [65].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comprehensive investigation of the clinical significance of long non-coding RNA HOXA-AS2 in acute myeloid leukemia using genome-wide RNA sequencing dataset

Huang¹,

Liao²,

Wang³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

Objective: The present study aimed to determine the prognostic value of HOXA cluster antisense RNA2 (HOXA-AS2) in acute myeloid leukemia (AML), and to explore its potential molecular mechanisms. We also screening of potential drugs targeting HOXA-AS2 in AML. Methods: The level 3 raw genome-wide RNA sequencing dataset of AML was download from The Cancer Genome Atlas (TCGA) Data Portal, and the potential molecular mechanisms and drugs prediction of HOXA-AS2 in AML were explored using multiple bioinformatics analysis approaches. Results: TCGA AML cohort dataset indicated that HOXA-AS2 was significantly up-regulated in AML bone marrow tissues, and high HOXA-AS2 expression was related to poor overall survival (log-rank P=0.0284, hazard ratio 1.640, 95% confidence interval 1.046-2.573). Functional enrichment of differentially expressed genes (DEGs) suggested that the difference in prognosis between AML patients with high-and low-HOXA-AS2 expression may be due to differences in biological processes and pathways, including cell adhesion, angiogenesis, mitogen-activated protein kinase, cell differentiation, and other biological processes, and phosphatidylinositol 3 kinase-protein kinase B and Wnt signaling pathways. We also screened out three potential HOXA-AS2-targeted therapeutic drugs for AML, megestrol, carmustine, and cefoxitin, based on these DEGs. Functional enrichment analysis of HOXA-AS2-co-expressed genes revealed that HOXA-AS2 may act a part in AML by regulating nuclear factor-κB transcription factor activity, DNA methylation, angiogenesis, apoptosis, cell migration, Toll-like receptor 4, and Wnt signaling pathways. Conclusion: Our findings suggest that HOXA-AS2 is up-regulated in the bone marrow in patients with AML, and may serve as a novel prognostic biomarker for AML.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comprehensive investigation of the clinical significance of long non-coding RNA HOXA-AS2 in acute myeloid leukemia using genome-wide RNA sequencing dataset

Huang¹,

Liao²,

Wang³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

show abstract

“…Reduced-intensity conditioning (RIC) regimens were initially introduced to reduce the adverse effects associated with myeloablative conditioning (MAC) and to improve the chance of successful hematopoietic stem cell transplantation (HSCT), especially in elderly and frail patients [1]. However, the efficacy of RIC regimens for patients who do not achieve a complete remission (CR) is limited [2]. The combination of fludarabine, amsacrine, and cytarabine (FLAMSA)-polychemotherapy with RIC was initially adopted by Schmid et al for patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) [3,4,5] to combine high anti-leukemic activity with the advantages of RIC.…”

Section: Introductionmentioning

confidence: 99%

FLAMSA-RIC for Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis

Owattanapanich

Ungprasert

Wais

et al. 2019

JCM

View full text Add to dashboard Cite

Reduced-intensity conditioning (RIC) regimens are established options for hematopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the efficacy of RIC regimens for patients with high-risk disease is limited. The addition of a fludarabine, amsacrine, and cytarabine (FLAMSA)-sequential conditioning regimen was introduced for patients with high-risk MDS and AML to combine a high anti-leukemic activity with the advantages of RIC. The current systematic literature review and meta-analysis was conducted with the aim of identifying all cohort studies of patients with AML and/or MDS who received FLAMSA-RIC to determine its efficacy and toxicity. Out of 3044 retrieved articles, 12 published studies with 2395 overall patients (18.1–76.0 years; 96.8% AML and 3.2% MDS; follow-up duration of 0.7–145 months; 50.3% had active AML disease before HSCT) met the eligibility criteria and were included in the meta-analysis. In the pooled analysis, the 1- and 3-year overall survival (OS) rates were 59.6% (95% confidence interval (CI), 47.9–70.2%) and 40.2% (95% CI, 28.0–53.7%), respectively. The pooled 3-year OS rate of the patients who achieved CR1 or CR2 prior to HSCT was 60.1% (95% CI, 55.1–64.8%) and the percentage of those with relapse or refractory disease was 27.8% (95% CI, 23.3–32.8%). The pooled 3-year leukemia-free survival (LFS) rate was 39.3% (95% CI, 26.4–53.9%). Approximately 29% of the patients suffered from grades 2–4 acute graft-versus-host disease (GVHD), while 35.6% had chronic GVHD. The pooled 1- and 3-year non-relapse mortality (NRM) rates were 17.9% (95% CI, 16.1–19.8%) and 21.1% (95% CI, 18.8–23.7%), respectively. Our data indicates that the FLAMSA-RIC regimen is an effective and well-tolerated regimen for HSCT in patients with high-risk AML and MDS.

show abstract

Comparison of fludarabine/melphalan (FM140) with fludarabine/melphalan/BCNU (FBM110) in patients with relapsed/refractory AML undergoing allogeneic hematopoietic cell transplantation – a registry study on behalf of the EBMT Acute Leukemia Working Party

Duque-Afonso,

Finke,

Ngoya

et al. 2024

Bone Marrow Transplant

View full text Add to dashboard Cite

The treatment of relapsed/refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The allogeneic hematopoietic cell transplantation (allo-HCT) is frequently performed as salvage therapy. Reduced intensity conditioning protocols have been developed with the aim of reducing the leukemia burden without increasing their toxicity. We compared the reduced intensity conditioning FM140 (fludarabine, 150 mg/m2; melphalan 140 mg/m2) with FBM110 (fludarabine 150 mg/m2; BCNU, also known as carmustine, 300–400 mg/m2; and melphalan 110 mg/m2). From the European Bone Marrow Transplantation (EBMT) Acute Leukemia Working Party registry, we identified 293 adult patients (FM140, n = 118 and FBM110, n = 175) with AML with relapsed/refractory disease prior to allo-HCT. There were some differences such as age (FM140 = 59.5 years vs. FBM110 = 65.1 years, p < 0.001) and graft-versus-host disease (GvHD) prophylaxis based on in vivo T-cell depletion (TCD, FM140 = 39% vs. FBM110 = 75%, p < 0.001). No differences were observed between FM140- and FBM110-treated patients regarding overall survival (OS) (2-year OS: 39.3% vs. 45.7%, p = 0.58), progression-free survival (PFS) (2-year PFS: 36.1% vs. 37.3%, p = 0.69), non-relapse mortality (NRM) (2-year NRM: 15.3% vs. 25.7%, p = 0.10) and relapse incidence (RI) (2-year RI: 48.6% vs. 37.0%, p = 0.7). In conclusion, despite differences in age and GvHD prophylaxis, AML patients with active disease undergoing allo-HCT after FBM110 conditioning showed similar outcomes compared to FM140.

show abstract

Reduced-toxicity conditioning for allogeneic hematopoietic cell transplantation in elderly or comorbid patients with AML using fludarabine, BCNU and melphalan: disease stage at transplant determines outcome

Cited by 5 publications

References 15 publications

Comprehensive investigation of the clinical significance of long non-coding RNA HOXA-AS2 in acute myeloid leukemia using genome-wide RNA sequencing dataset

Comprehensive investigation of the clinical significance of long non-coding RNA HOXA-AS2 in acute myeloid leukemia using genome-wide RNA sequencing dataset

FLAMSA-RIC for Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis

Comparison of fludarabine/melphalan (FM140) with fludarabine/melphalan/BCNU (FBM110) in patients with relapsed/refractory AML undergoing allogeneic hematopoietic cell transplantation – a registry study on behalf of the EBMT Acute Leukemia Working Party

Contact Info

Product

Resources

About