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. In a method of administering a chemotherapeutic agent to a subject with acute myeloid leukemia (AML), wherein the chemotherapeutic agent is a pyrimidine antagonist, an anthracycline agent, or a combination thereof, the improvement comprising:
adjunctively administering to the subject 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 the chemotherapeutic agent.
2. The method of claim 1 , wherein the chemotherapeutic agent is a pyrimidine antagonist.
3. The method of claim 2 , wherein the pyrimidine antagonist is administered intravenously.
4. The method of claim 3 , wherein the pyrimidine antagonist is administered as an intravenous infusion.
5. The method of claim 4 , wherein the pyrimidine antagonist is administered at a dose of 100 mg/m 2 .
6. The method of claim 1 , wherein the chemotherapeutic agent is a pyrimidine antagonist and an anthracycline agent.
7. The method of claim 6 , wherein the pyrimidine antagonist is cytarabine.
8. The method of claim 6 , wherein the anthracycline agent is idarubicin.
9. The method of claim 6 , wherein the anthracycline agent is daunorubicin.
10. The method of claim 6 , wherein the pyrimidine antagonist is cytarabine and the anthracycline agent is idarubicin.
11. The method of claim 6 , wherein the pyrimidine antagonist is cytarabine and the anthracycline agent is daunorubicin.
12. The method of claim 7 , wherein the cytarabine is administered intravenously as a continuous infusion.
13. The method of claim 12 , wherein the cytarabine is administered at a dose of 100 mg/m 2 /day.
14. The method of claim 6 , wherein the anthracycline agent is administered by intravenous injection or intravenous infusion.
15. The method of claim 1 , wherein the heparinoid is ODSH.
16. The method of claim 15 , wherein the ODSH is administered intravenously.
17. The method of claim 16 , wherein the ODSH is administered as one or more bolus injections.
18. The method of claim 16 , wherein the ODSH is administered as a continuous infusion.
19. The method of claim 16 , wherein the ODSH is administered as a bolus injection followed or preceded by a continuous infusion.
20. A method of treating acute myeloid leukemia (AML), comprising:
administering to a subject with AML, a pyrimidine antagonist, an anthracycline agent, and a heparinoid substantially desulfated at the 2-O and 3-O positions, comprising:
administering the pyrimidine antagonist as a continuous intravenous infusion for Days 1 through 7 of at least one 28-day cycle;
administering the anthracycline agent as an intravenous injection or an intravenous infusion once daily for Days 1 through 3 of the at least one 28-day cycle; and
administering the heparinoid as a bolus injection at a dose of 4 mg/kg on Day 1 followed by a continuous intravenous infusion at a dose of 0.25 mg/kg/hr for Days 1 through 7 of the at least one 28-day cycle.