Combination of the low anticoagulant heparin CX-01 with chemotherapy for the treatment of acute myeloid leukemia

Blood Advances
Tibor J KovacsovicsPaul J Shami

Abstract

Relapses in acute myelogenous leukemia (AML) are a result of quiescent leukemic stem cells (LSCs) in marrow stromal niches, where they resist chemotherapy. LSCs employ CXCL12/CXCR4 to home toward protective marrow niches. Heparin disrupts CXCL12-mediated sequestration of cells in the marrow. CX-01 is a low-anticoagulant heparin derivative. In this pilot study, we combined CX-01 with chemotherapy for the treatment of AML. Induction consisted of cytarabine and idarubicin (7 + 3) with CX-01. Twelve patients were enrolled (median age, 56 years; 3 women). Three, 5, and 4 patients had good-, intermediate-, and poor-risk disease, respectively. Day 14 bone marrows were available on 11 patients and were aplastic in all without detectable leukemia. Eleven patients (92%) had morphologic complete remission after 1 induction (CR1). Eight patients were alive at a median follow-up of 24 months (4 patients in CR1). Three patients received an allogeneic stem cell transplant in CR1. Median disease-free survival was 14.8 months. Median overall survival was not attained at the maximum follow-up time of 29.4 months. No CX-01-associated serious adverse events occurred. Median day to an untransfused platelet count of at least 20 × 109/L was 21. CX-01...Continue Reading

References

Jul 1, 1992·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·W R VoglerP L Banks
Aug 14, 1999·The Journal of Biological Chemistry·A AmaraF Arenzana-Seisdedos
Nov 23, 2000·The Journal of Biological Chemistry·R SadirH Lortat-Jacob
Sep 20, 2002·Blood·James W VardimanRichard D Brunning
Nov 9, 2002·Analytical Biochemistry·Ronald I W OsmondDeirdre R Coombe
Jun 20, 2003·Nature Reviews. Drug Discovery·Erik De Clercq
Dec 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bruce D ChesonUNKNOWN International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards
Aug 5, 2006·Blood·Anke C SpooJan A Burger
Jan 12, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Marina Y Konopleva, Craig T Jordan
Feb 10, 2012·Thrombosis and Haemostasis·M V JoglekarG M Arepally
Jun 1, 2012·Cell Adhesion & Migration·Aysegul Ocal Sahin, Miranda Buitenhuis
May 17, 2013·The Journal of Clinical Investigation·Ye ChenMichael Andreeff
Jan 7, 2014·Frontiers in Bioscience (Landmark Edition)·Olga Blau
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Oct 17, 2014·American Journal of Hematology·Elihu H Estey
Oct 20, 2014·Nature Medicine·Ingmar BrunsPaul S Frenette

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Citations

Feb 5, 2019·Current Oncology Reports·Marco Cerrano, Raphael Itzykson
Feb 27, 2020·Nature Reviews. Neurology·Susan L LindsaySusan C Barnett
Nov 7, 2019·Frontiers in Immunology·Zuzanna Urban-WojciukDavid R Goodlett
Aug 6, 2020·Frontiers in Cell and Developmental Biology·Alicia VillatoroLorena Arranz
Oct 6, 2020·Frontiers in Oncology·Daniel CancillaJohn F DiPersio
Feb 17, 2019·AAPS PharmSciTech·Tori CzechMoses O Oyewumi
Jul 3, 2019·Biology·George A McCanneySusan C Barnett
Jun 17, 2020·Cell Adhesion & Migration·Sai-Nan MaJin-Hai Tang
Nov 11, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cinzia Lanzi, Giuliana Cassinelli
Nov 25, 2020·Journal of Cellular Physiology·Bahareh KashaniSeyed H Ghaffari
Apr 7, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Angel Y F KamPhuong L Doan
Dec 17, 2020·International Journal of Molecular Sciences·Antonino Di LorenzoLaura Conti
Jul 3, 2021·International Journal of Molecular Sciences·Vincent KuekLaurence C Cheung
Jul 12, 2021·Experimental Hematology & Oncology·Yiyi YaoHuafeng Wang
Jul 9, 2021·Current Research in Translational Medicine·Daohong Chen

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