Treatment of myelosuppression
Methods are presented for attenuating myelosuppressive side effects of treatment regimens, promoting thrombopoiesis and neutrophil production, and increasing efficacy of treatment regimens, by administering PF4-interacting heparinoids.
1. A method of attenuating a myelosuppressive side effect of an antineoplastic treatment regimen, comprising:
adjunctively administering to a patient receiving an antineoplastic treatment regimen a heparinoid that is substantially desulfated at the 2-O and 3-O positions, in an amount effective to attenuate a myelosuppressive side effect of the antineoplastic treatment regimen.
2. The method of claim 1 , wherein the heparinoid is at least 90% desulfated at each of the 2-O and 3-O positions.
3. The method of claim 2 , wherein the heparinoid is at least 95% desulfated at each of the 2-O and 3-O positions.
4. The method of claim 2 , wherein the heparinoid has an average molecular weight of about 8 kDa to about 15 kDa.
5. The method of claim 4 , wherein the heparinoid has an average molecular weight of about 11 kDa to about 13 kDa.
6. The method of claim 1 , wherein the heparinoid is administered intravenously.
7. The method of claim 6 , wherein the heparinoid is administered as one or more bolus injections.
8. The method of claim 6 , wherein the heparinoid is administered as a continuous infusion.
9. The method of claim 6 , wherein the heparinoid is administered as an intravenous bolus followed by a continuous intravenous infusion.
10. The method of claim 1 , wherein the heparinoid is administered subcutaneously.
11. The method of claim 1 , wherein the myelosuppressive side effect is thrombocytopenia.
12. The method of claim 11 , wherein the amount of heparinoid is sufficient to maintain platelet levels above levels that indicate grade 3 thrombocytopenia.
13. The method of claim 1 , wherein the antineoplastic treatment regimen comprises administering one or more chemotherapeutic agents.
14. The method of claim 1 , wherein the antineoplastic treatment regimen comprises radiation therapy.
15. In a method of treating cancer by administering to a patient with cancer one or more antineoplastic treatment regimens having a myelosuppressive side effect, the improvement comprising:
adjunctively administering to the patient a heparinoid that is substantially desulfated at the 2-O and 3-O positions, in an amount that is effective to attenuate a myelosuppressive side effect of said antineoplastic treatment regimen.
16. The method of claim 15 , wherein the patient has a cancer selected from the group consisting of: pancreatic cancer, ovarian cancer, uterine cancer, breast cancer, metastatic breast cancer, recurrent breast cancer, head and neck cancer, bladder cancer, urothelial cancer, lung cancer, colorectal cancer, gastric cancer, esophageal cancer, lymphoma, liver cancer, melanoma, prostate cancer, osteosarcoma, leukemia, acute myelogenous leukemia (AML) and pediatric acute lymphoblastic leukemia.
17. The method of claim 16 , wherein the cancer is pancreatic cancer.
18. The method of claim 17 , wherein the pancreatic cancer is metastatic.
19. The method of claim 17 , wherein the antineoplastic treatment regimen comprises administration of gemcitabine and nab-paclitaxel.
20. The method of claim 16 , wherein the cancer is acute myelogenous leukemia (AML).
21. The method of claim 16 , wherein the cancer is a lymphoma.
22. The method of claim 15 , wherein the cancer is a pediatric cancer.
23. The method of claim 15 , wherein the heparinoid has less anticoagulant activity than unfractionated heparin.
24. The method of claim 23 , wherein the heparinoid has reduced affinity for anti-thrombin III as compared to unfractionated heparin.
25. The method of claim 23 , wherein the heparinoid has reduced anti-Xa activity as compared to unfractionated heparin.
26. The method of claim 23 , wherein the heparinoid is substantially non-anticoagulating.
27. The method of claim 15 , wherein the heparinoid is produced by alkaline hydrolysis of unfractionated heparin.
28. A method of treating or preventing radiation-induced thrombocytopenia, comprising:
administering to a subject exposed to ionizing radiation a heparinoid that is substantially desulfated at the 2-O and 3-O positions, in an amount effective to attenuate radiation-induced thrombocytopenia.
29. The method according to claim 28 , wherein the radiation is part of a treatment regimen.
30. The method of claim 28 , wherein the radiation is not part of a treatment regimen.