Treatment of chronic myelogenous leukmia, resistant or intolerant to ST1571, involving homoharringtonine alone or combined with other agents
The present invention concerns a method of treating chronic myelogenous leukemia, a related myeloproliferative disorder or a Ph-positive acute lymphocytic leukemia in a subject animal, comprising: (a) selecting or identifying an animal suffering from chronic myelogenous leukemia or a related myeloproliferative disorder and showing resistance or intolerance to treatment with STI571; and (b) administering to the animal homoharringtonine. In a preferred embodiment, the animal is a human being.
1. A method of treating chronic myelogenous leukemia, a related myeloproliferative disorder or a Ph-positive acute lymphocytic leukemia in a subject animal, comprising:
(a) selecting or identifying an animal suffering from chronic myelogenous leukemia or a related myeloproliferative disorder and showing resistance or intolerance to treatment with STI571; and
(b) administering to the animal homoharringtonine.
2. The method of claim 1 , wherein homoharringtonine is combined with one or more other antileukemic agents.
3. The method of claim 1 , wherein homoharringtonine is combined simultaneously with one or more other antileukemic agents.
4. The method of claim 1 , wherein homoharringtonine is combined sequentially with one or more other antileukemic agents.
5. The method of treatment of claim 1 , wherein homoharringtonine is combined sequentially by addition to existing STI571 therapy, comprising the following steps (a) to (d), and optionally (e):
(a) administering to patients with chronic myelogenous leukemia, optionally further resistant to standard interferon alpha therapy, STI571 until a complete cytogenetic response or at least a complete hematologic response is obtained;
(b) in patients partially STI571-resistant, reducing to 300 to 400 mg daily but not removing STI571 treatment, in those patients who failed to have or lost their complete cytogenetic or hematologic response;
(c) administering homoharringtonine subcutaneously and/or intravenously or/and orally, at a dose of 0.25 to 5 mg/m 2 ;
(d) adjusting the homoharringtonine dose and/or STI571 dose according to cytopenia and/or side effects; and
(e) optionally, subcutaneously or intravenously administering an oral nucleoside synergistic with homoharringtonine, wherein said oral nucleoside may be added simultaneously or sequentially to homoharringtonine.
6. The method of claim 5 , wherein said oral nucleoside in step (e) is cytarabine, wherein cytarabine may be added simultaneously or sequentially to homoharringtonine.
7. A method for inhibiting proliferation of a hyperproliferative myeloid cell resistant to STI5171, comprising:
a) contacting the cell with STI571; and
b) contacting the cell with homoharringtonine,
wherein STI571 and homoharringtonine are provided in an amount effective to inhibit proliferation of said myeloid cell.
8. A method of treating chronic myelogenous leukemia, a related myeloproliferative disorder or a Ph-positive acute lymphocytic leukemia in a subject animal, comprising:
a) administering to the animal in a first course of treatment STI571, wherein said CML or disorder displays resistance and/or intolerance to STI571; and
b) administering to the animal in a second course of treatment a combination of homoharringtonine and STI571 in an amount effective to inhibit proliferation of myeloid cells.
9. The method of treatment of claim 2 , wherein the other antileukemic agents are interferon alpha and/or one or more nucleosides and/or a farnesyl transferase inhibitor (FTI).
10. The method of treatment of claim 4 , wherein the other antileukemic agent is interferon alpha or PEG-interferon.
11. The method of treatment of claim 4 , wherein the other antileukemic agent is one or more nucleosides.
12. The method of treatment of claim 9 , wherein the other antileukemic agents is a farnesyl transferase inhibitor (FTI).
13. The method of treatment of claim 11 , wherein the nucleosides are cytarabine (Ara-C) and/or decitabine and/or troxacytabine.
14. The method of treatment of claim 13 , wherein a nucleoside is cytarabine (Ara-C).
15. The method of treatment of claim 9 , wherein the other agents are a combination of interferon alpha and cytarabine.
16. The method of treatment of claim 1 , wherein the animal is a human being.
17. The method of claim 2 , wherein homoharringtonine is combined with STI571.
18. The method of claim 3 , wherein homoharringtonine is combined simultaneously with STI571.
19. The method of claim 3 , wherein homoharringtonine is combined simultaneously with STI571 which is continued from previous treatment.
20. The method of claim 4 , wherein homoharringtonine is combined sequentially with STI571.
21. The method of treatment of claim 20 , wherein administration of the ST1571 is continued.
22. The method of treatment of claim 5 , wherein the STI571 is administered in a dosage of 400 to 800 mg daily.
23. The method of treatment of claim 5 , wherein the homoharringtonine is administered at a dose of 2.5 mg 2 .
24. The method of treatment of claim 5 , wherein the homoharringtonine is administered for 2 to 14 days per 28-day cycle.
25. The method of treatment of claim 8 , wherein the animal is a human being.