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

Tibor J. Kovacsovics, Alice Mims, Mohamed Salama, Jeremy Pantin, Narayanam Rao, Ken M. Kosak, Peter Ahorukomeye, Martha J. Glenn, Michael W.N. Deininger, Kenneth M. Boucher, Linda M. Bavisotto, Gerardo Gutierrez-Sanchez, Thomas P. Kennedy, Stephen G. Marcus, Paul J. Shami

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8 Scopus citations

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 is well tolerated when combined with intensive therapy for AML and appears associated with enhanced count recovery and treatment efficacy.

Original languageEnglish (US)
Pages (from-to)381-389
Number of pages9
JournalBlood Advances
Volume2
Issue number4
DOIs
StatePublished - Feb 27 2018
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kovacsovics, T. J., Mims, A., Salama, M., Pantin, J., Rao, N., Kosak, K. M., Ahorukomeye, P., Glenn, M. J., Deininger, M. W. N., Boucher, K. M., Bavisotto, L. M., Gutierrez-Sanchez, G., Kennedy, T. P., Marcus, S. G., & Shami, P. J. (2018). Combination of the low anticoagulant heparin CX-01 with chemotherapy for the treatment of acute myeloid leukemia. Blood Advances, 2(4), 381-389. https://doi.org/10.1182/bloodadvances.2017013391