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

Tibor J. Kovacsovics, Alice Mims, Mohamed E. 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 and Paul J. Shami

Key Points

  • In a pilot study, the nonanticoagulant heparin derivative CX-01 was well tolerated when combined with chemotherapy for the treatment of AML.

  • Preliminary results show encouraging complete remission rates and rapid platelet recovery.

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.

  • Submitted October 16, 2017.
  • Accepted January 21, 2018.
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