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Blood Adv. 2018 Feb 27;2(4):381-389. doi: 10.1182/bloodadvances.2017013391.

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

Author information

1
Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
2
Hollings Cancer Center, Medical University of South Carolina, Charleston, SC.
3
Department of Pathology and Associated Regional and University Pathologists Laboratories, University of Utah, Salt Lake City, UT.
4
Division of Hematology/Oncology, Augusta University, Augusta, GA.
5
Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
6
Porta Clinica PLLC, Seattle, WA.
7
Complex Carbohydrate Research Center, University of Georgia, Athens, GA.
8
Division of Pulmonary Medicine, Wake Forest University, Winston-Salem, NC; and.
9
Cantex Pharmaceuticals, Weston, FL.

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.

PMID:
29467192
PMCID:
PMC5858478
DOI:
10.1182/bloodadvances.2017013391
[Indexed for MEDLINE]
Free PMC Article

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