Reduced Relapse Incidence with FLAMSA–RIC Compared with Busulfan/Fludarabine for Acute Myelogenous Leukemia Patients in First or Second Complete Remission: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Heinicke, Thomas; Labopin, Myriam; Schmid, Christoph; Polge, Emmanuelle; Socié, Gérard; Blaise, Didier; Mufti, Ghulam J.; Huynh, Anne; Brecht, Arne; Ledoux, Marie‐Pierre; Cahn, Jean Yves; Milpied, Noël; Scheid, Christof; Hicheri, Yosr; Mohty, Mohamad; Savani, Bipin N.; Nagler, Arnon

doi:10.1016/j.bbmt.2018.07.007

Cited by 16 publications

(15 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, new combinations including these drugs are still being tested in clinical trials. For example, a recent trial found that mAMSA could reduce relapse incidence in AML-patients [ 66 ].…”

Section: Top2b As An Anti-cancer Drug Targetmentioning

confidence: 99%

TOP2B: The First Thirty Years

Austin

Lee

Swan

et al. 2018

IJMS

View full text Add to dashboard Cite

Type II DNA topoisomerases (EC 5.99.1.3) are enzymes that catalyse topological changes in DNA in an ATP dependent manner. Strand passage reactions involve passing one double stranded DNA duplex (transported helix) through a transient enzyme-bridged break in another (gated helix). This activity is required for a range of cellular processes including transcription. Vertebrates have two isoforms: topoisomerase IIα and β. Topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the 30 years since its discovery.

show abstract

Section: Top2b As An Anti-cancer Drug Targetmentioning

confidence: 99%

TOP2B: The First Thirty Years

Austin

Lee

Swan

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…A total of eighteen articles underwent full-text review and 9 of them were excluded because they did not report the primary outcomes of interest. Finally, 12 studies fulfilled the eligibility criteria and were included in the meta-analysis [3,6,7,8,9,10,11,12,13,14,15,16]. A manual review of the bibliography of the included studies, and some selected review articles, did not yield any additional eligible studies.…”

Section: Resultsmentioning

confidence: 99%

“…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. Although several variations have been published [6,7,8,9,10,11,12,13,14,15,16], the ‘classic’ FLAMSA-RIC regimen consists of fludarabine, amsacrine, and cytarabine, followed by RIC with 4-Gy total body irradiation (TBI), high-dose cyclophosphamide (Cy), antithymocyte globulin (ATG), and prophylactic donor lymphocyte infusions (DLI) if indicated. Because of initially promising data, especially in poor prognosis AML patients, FLAMSA-RIC was adopted by many transplantation centers, and variations that included busulfan (Bu) or treosulfan were established.…”

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

“…De novo non-M3 AML patients have a high overall mortality rate, ranging from 60% to 76% at 5-year. [7][8][9][10] Accurate prognostic models for individuals are needed, not only to select appropriate treatment regimens but also to inform patients regarding their long-term outcomes (which may aid them in their goals of care decisions). Mohamed et al developed an AML composite model, to estimate the risk of death within 1 year after initial chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6] Furthermore, 5-year overall survival (OS) for patients with non-M3 AML range from 24% to 40%. [7][8][9][10] Currently, several factors which can aid with prognostication and prediction of clinical outcomes [e.g., risk strati cation, age, white blood cell (WBC) count, coexisting comorbidities and a history of an antecedent hematologic disorder]. [2,3,[11][12][13][14][15][16][17] The European Leukemia Net(ELN) [3] and National Comprehensive Cancer Network(NCCN) [2] risk strati cations are the most widely used criteria to stratify patients with AML.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Cytogenetical Characteristics-Related Nomograms for Assessing Outcome of Acute Myeloid Leukemia Patients Post IA Induction

Wang

Dai

Desai³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Acute myeloid leukemia(AML) is a highly heterogeneous hematological malignancy. Despite, increase in treatment options for AML over the past decade, prognosis for AML remain dismal. Numerous prognostic models have been developed for this disease, however nomograms predicting long-term survival in AML patients after induction chemotherapy(IA regimen) have not been described.Method: We constructed nomograms to predict disease-free survival(DFS) and overall survival(OS) by analyzing the cohort of patients with de novo non-M3 AML patients who underwent induction chemotherapy between June 2008 to August 2019. We utilized univariable and multivariable Cox proportional hazards regression analyses to obtain the selected variables for the nomograms. The discriminative ability and calibration were tested using C statistics, calibration plots, and Kaplan-Meier curves.Results: A total of 360 patients who underwent induction chemotherapy with IA regimen were included in the study. Of these 55% were male with a median age was 48 years. Using the univariate and multivariate analyses, the following variables were identified in the prediction of DFS: age(HR, 1.770; 95%CI, 1.160-2.702; P = 0.008), Hb(HR, 0.634; 95%CI, 0.462-0.870; P = 0.005), albumin(HR, 0.473; 95%CI, 0.363-0.615; P < 0.001) and cyto/molecular risk group(intermediate vs. favorable: HR, 1.614; 95%CI, 1.128-2.309; P = 0.001; poor vs. favorable: HR, 2.459; 95%CI, 1.645-3.676; P < 0.001) at the time of diagnosis, and allo-HSCT treatment(HR, 0.341; 95%CI, 0.234-0.497; P < 0.001). Factors which predicted OS were Hb (HR, 0.616; 95%CI, 0.438-0.866; P = 0.005), albumin (HR, 0.448; 95%CI, 0.340-0.591; P < 0.001), cyto/molecular risk group (intermediate vs. favorable: HR, 1.558; 95%CI, 1.068-2.275; P = 0.021; poor vs. favorable: HR, 2.348; 95%CI, 1.523-3.620; P < 0.001), allo-HSCT treatment (HR, 0.256; 95%CI, 0.166-0.396; P < 0.001), and age (HR, 1.528; 95%CI 0.980-2.382; P = 0.061). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.715 for DFS and 0.731 for OS). Conclusion: Independent predictors of survival and relapse risk after IA regimen for AML can be utilized to obtain survival nomograms. These nomograms were able to predict DFS and OS while having good calibration accuracy and discriminative ability on internal validation.

show abstract

Reduced Relapse Incidence with FLAMSA–RIC Compared with Busulfan/Fludarabine for Acute Myelogenous Leukemia Patients in First or Second Complete Remission: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Cited by 16 publications

References 26 publications

TOP2B: The First Thirty Years

TOP2B: The First Thirty Years

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

Clinical and Cytogenetical Characteristics-Related Nomograms for Assessing Outcome of Acute Myeloid Leukemia Patients Post IA Induction

Contact Info

Product

Resources

About