Uses of IL-12 in hematopoiesis
View Patent ↗Methods for enhancing or stimulating hematopoiesis including the step of administering Interleukin-12 (IL-12) to yield hematopoietic recovery in a mammal in need. Preferred methods include the step of administering IL-12 as an adjuvant therapy to alleviate the hematopoietic toxicities associated with one or more treatment regimens used to combat a disease state. Other methods include administering IL-12 to ameliorate various hematopoietic deficiencies. Still other methods are directed to uses of IL-12 for in-vivo proliferation of hematopoietic repopulating cells, hematopoietic progenitor cells and hematopoietic stem cells. Other disclosed methods are directed to uses of IL-12 for bone marrow preservation or recovery.
1. A method for protecting or restoring hematopoiesis or enhancing peripheral blood cell counts in a mammal having a hematopoietic malignancy, said method comprising:
(a) administering a treatment which comprises chemotherapy to the mammal, wherein the treatment targets the hematopoietic malignancy and has an associated hematopoietic toxicity; and
(b) administering one therapeutically effective dose of IL-12 near the time of administration of the treatment, wherein the administration of IL-12 to the mammal reduces the hematopoietic toxicity of the treatment;
wherein IL-12 is administered without the addition of other cytokines;
wherein the dose of IL-12 is between 1 ng/kg and 2000 ng/kg;
wherein the mammal does not have a solid tumor; and
wherein the therapeutically effective dose of IL-12 is administered (1) at 48 hours before the treatment, (2) less than 48 hours before the treatment, (3) less than 48 hours after the treatment, or (4) at 48 hours after the treatment.
2. The method of claim 1 , wherein the mammal is a human.
3. The method of claim 1 , wherein the hematopoietic malignancy is selected from the group consisting of acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, acute malignant myelosclerosis, multiple myeloma, polycythemia vera, and agnogenic myelometaplasia.
4. The method of claim 1 , wherein:
(a) the treatment comprises one or more high dose treatment modalities;
(b) the treatment is administered in a dose dense treatment regimen; or
(c) a combination thereof.
5. The method of claim 1 , wherein the chemotherapy treatment comprises administration of more than one chemotherapy.
6. The method of claim 1 , wherein the treatment leads to a deficiency in one or more hematopoietic cell types or lineages and the administration of IL-12 ameliorates the deficiency.
7. The method of claim 1 , wherein:
(a) the administration of IL-12 results in protection of bone marrow cells from the associated hematopoietic toxicity of the treatment; or
(b) the administration of IL-12 results in chemoprotection of bone marrow cells.
8. The method of claim 7 , wherein the bone marrow cells comprise hematopoietic repopulating cells, hematopoietic stem cells, hematopoeitic progenitor cells, or any combination thereof.
9. The method of claim 1 , wherein:
(a) the white blood cell count of the mammal is increased; or
(b) the T-cell count of the mammal is increased.
10. The method of claim 1 , wherein the dose of IL-12 is between 10 ng/kg and 2000 ng/kg.
11. The method of claim 1 , wherein the dose of IL-12 is 400 ng/kg.
12. The method of claim 1 , wherein the dose of IL-12 is less than 500 ng/kg.
13. The method of claim 1 , wherein the dose of IL-12 is less than 100 ng/kg.
14. The method of claim 1 , wherein the IL-12 is administered before the treatment.
15. The method of claim 1 , wherein the IL-12 is administered after the treatment.
16. The method of claim 1 , wherein IL-12 is administered at 48 hours or less before the treatment.
17. The method of claim 1 , wherein IL-12 is administered at 36 hours or less before the treatment.
18. The method of claim 1 , wherein IL-12 is administered at 20 hours or less before the treatment.
19. The method of claim 1 , wherein IL-12 is administered at 12 hours or less before the treatment.
20. The method of claim 1 , wherein IL-12 is administered at 1 hour or less before the treatment.
21. The method of claim 1 , wherein IL-12 is administered at 1 hour or less after the treatment.
22. The method of claim 1 , wherein IL-12 is administered at 12 hours or less after the treatment.
23. The method of claim 1 , wherein IL-12 is administered at 20 hours or less after the treatment.
24. The method of claim 1 , wherein IL-12 is administered at 24 hours or less after the treatment.
25. The method of claim 1 , wherein IL-12 is administered at 36 hours or less after the treatment.
26. The method of claim 1 , wherein IL-12 is administered at 48 hours or less after the treatment.