Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The treatment of elderly, nonfit acute myeloid leukemia (AML)/MDS patients with relapsed/refractory (R/R) disease remains challenging. As histone demethylase LSD1 (KDM1A) is a rational therapeutic target in AML, we conducted a phase I trial ("rolling-six design") with the LSD1 inhibitor tranylcypromine (TCP, dose levels [DL] 20, 40, 60, 80 mg p.o. d1-28) combined with fixed-dose ATRA (45 mg/m p.o. d10-28) and low-dose cytarabine (LDAC, 40 mg s.c. d1-10). The primary endpoint was dose-limiting toxicity (DLT) in the first 28 days of treatment. The aim was the determination of the maximum tolerated TCP dose (MTD). Twenty-three patients with AML and 2 with MDS were accrued. TCP was administered for a median of 39.5 days (range: 11-228). No DLTs were observed at any DL; MTD could not be established. No differentiation syndrome occurred. Two patients attained a PR; SD was achieved in 10 of 22 evaluable patients. Median OS was 62 days (range: 14-325). Accompanying studies included pharmacokinetics, serial determinations of fetal hemoglobin (HbF), detection of CD38 upregulation with treatment, as well as transcriptome changes in purified blood blasts over time. In conclusion, the combination of TCP with ATRA and LDAC was well feasible, even at the highest DL. Hence, studies with more potent LSD1 inhibitors appear warranted. Trial Registration: German Clinical Trials Register (DRKS): DRKS00006055. For further Information see https://drks.de/search/en/trial/DRKS00006055.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12319880 | PMC |
| http://dx.doi.org/10.1111/ejh.14426 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Longitudinal single-cell analysis reveals treatment-resistant stem and mast cells with potential treatments for pediatric AML.
Leukemia
September 2025
Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.
Pediatric acute myeloid leukemia (pAML) is a heterogeneous malignancy driven by diverse cytogenetic mutations. While identification of cytogenetic lesions improved risk stratification, prognostication remains inadequate with 30% of standard-risk patients experiencing relapse within 5 years. To deeply characterize pAML heterogeneity and identify poor outcome-associated blast cell profiles, we performed an analysis on 708,285 cells from 164 bone marrow biopsies of 95 patients and 11 healthy controls.
View Article and Find Full Text PDFPML::RARα+ myeloid cells display metabolic alterations that can be targeted to treat resistant/relapse acute promyelocytic leukemias.
Leukemia
September 2025
I.R.C.C.S Santa Lucia Foundation, Via del Fosso di Fiorano, Rome, Italy.
At present there is no metabolic characterization of acute promyelocytic leukemia (APL). Pathognomonic of APL, PML::RARα fusion protein rewires metabolic pathways to feed anabolic tumor cell's growth. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based therapies render APL the most curable subtype of AML, yet approximately 1% of cases are resistant and 5% relapse.
View Article and Find Full Text PDFImpact of Measurable Residual Disease Status on Outcomes After HLA-Matched Donor Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia.
Clin Lymphoma Myeloma Leuk
August 2025
The Mikael Rayaan Foundation Global Transplantation and Cellular Therapy Consortium, Kansas City, KS; Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS; U.S Myeloma Innovations Research Collaborative, Kansas City, KS. Electronic addres
Background: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a key treatment for acute myeloid leukemia (AML). Measurable residual disease (MRD) predicts post-transplant outcomes. This study evaluates the impact of pretransplant MRD status on outcomes in AML patients undergoing allo-HCT.
View Article and Find Full Text PDFEfficacy and safety of haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood infusion in hematologic malignancies: a prospective phase II clinical trial.
Transplant Cell Ther
September 2025
Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Hematological disorders, Hangzhou, China; Zhejiang Key Laboratory for Precision Diagnosis and Treatment of Hematological Maligancies, Han
Background: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) offers curative potential for hematologic malignancies but is often limited by high incidences of graft-versus-host disease (GVHD), delayed engraftment, and transplant-related mortality-especially when donors are aged ≥40 years. Umbilical cord blood (UCB) infusion may mitigate these risks by promoting immune tolerance and hematopoietic recovery. However, the efficacy of this strategy in the context of older donors remains insufficiently studied.
View Article and Find Full Text PDFOptimizing MMF Dosing for GVHD Prophylaxis in Umbilical Cord Blood Transplantation: A Retrospective Study in Non-Remission Myeloid Malignancies.
Transplant Cell Ther
September 2025
Department of Hematology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
Background: Umbilical cord blood transplantation (UCBT) is a valuable treatment option with the potential for curative outcomes in patients with myeloid malignancies in non-remission status, but relapse and early non-relapse mortality (NRM) remain significant barriers. Tacrolimus and mycophenolate mofetil (MMF) are widely used as graft-versus-host disease (GVHD) prophylaxis in UCBT, but there is no consensus on the appropriate MMF dose for GVHD prophylaxis.
Objectives: We conducted a retrospective analysis to investigate the impact of MMF dose on outcomes in patients undergoing UCBT at our institution.