Method of treating a hematopoietic associated disease or disorder with plasma-depleted, but not erythrocyte-depleted cord blood compositions

• US 8,048,619 B2
• Filed: 06/29/2007
• Issued: 11/01/2011
• Est. Priority Date: 06/02/2005
• Status: Active Grant

• Current Assignee: Stemcyte Inc
• Original Assignee: Stemcyte Inc
• Inventors: Chow, Robert
• Primary Examiner(s): SAUCIER, SANDRA E
• Application Number:
  US11/771,942
• Publication Number:
  US 20080008693A1
• Time in Patent Office: 1,586 Days
• Field of Search: None
• US Class Current: 435/2
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C12N 5/0641 Erythrocytes
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

The umbilical cord blood (UCB) compositions of the present invention possess the unique features of having plasma that is substantially depleted from the UCB unit and red blood cells (RBC) that are not depleted from the UCB unit. Such UCB units can be prepared by a process that combines plasma depletion with cryopreservation, selection, thawing, and/or transplantation of hematopoietic stem cells to provide superior clinical outcome by maximizing post-processing cell recovery and post-thaw infusion cell dose. Methods for treating a wide variety of malignant diseases and benign diseases associated with the hematopoietic system by administering the UCB compositions of the present invention are also provided.

Claims

1. A method for treating a malignant disease or benign disorder associated with the hematopoietic system, said method comprising:

administering to a mammalian subject an effective amount of a composition comprising anticoagulated, plasma-depleted umbilical cord blood and a cryoprotectant,

wherein the anticoagulated plasma-depleted umbilical cord blood is not depleted in red blood cells when compared to whole blood umbilical cord blood,

wherein the anticoagulated plasma-depleted umbilical cord blood is at least 50% red blood cells by volume, and

wherein the anticoagulant is about 5% to about 40% by volume of the plasma-depleted umbilical cord blood.

2. The method of claim 1, wherein said anticoagulated plasma-depleted umbilical cord blood comprises at least 65% red blood cells by volume.

3. The method of claim 1, wherein said anticoagulated plasma-depleted umbilical cord blood comprises from 0% to about 30% plasma by volume.

4. The method of claim 1, wherein said anticoagulated plasma-depleted umbilical cord blood comprises stem cells.

5. The method of claim 4, wherein said stem cells are hematopoietic stem cells.

6. The method of claim 1, wherein said anticoagulated plasma-depleted umbilical cord blood comprises from about 5% to about 20% by volume of the anticoagulant.

7. The method of claim 1, wherein the anticoagulant is selected from the group consisting of citric acid, sodium citrate and mixtures thereof.

8. The method of claim 1, wherein the cryoprotectant is dimethyl sulfoxide (DMSO).

9. The method of claim 1, wherein the cryoprotectant is a mixture of DMSO and Gentran®

40.

10. The method of claim 1, wherein the cryoprotectant is a mixture of DMSO and hydroxyethyl starch (HES).

11. The method of claim 1, wherein the cryoprotectant is glycerol.

12. The method of claim 1, wherein the composition comprises a red blood cell concentration of from about 3.2×

10⁶ to about 8×

10⁶ red blood cells/μ

l.

13. The method of claim 1, wherein the composition comprises a white blood cell concentration of greater than 10×

10⁶ white blood cells/ml.

14. The method of claim 1, wherein the composition comprises a CD34+cell number of from 2.1 to 8.0×

10⁵/kg of the mammalian subject'"'"'s body weight.

15. The method of claim 1, wherein the composition comprises a total nucleated cell number of from 4.8×

10⁷ to 15×

10⁷/kg of the mammalian subject'"'"'s body weight.

16. The method of claim 1, wherein the malignant disease is a hematologic malignancy.

17. The method of claim 16, wherein said hematologic malignancy is selected from the group consisting of acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic disorders, juvenile chronic myelogenous leukemia, and non-Hodgkin'"'"'s lymphoma.

18. The method of claim 1, wherein the benign disorder associated with the hematopoietic system is selected from the group consisting of a hemoglobinopathy, a bone marrow failure syndrome, an immune deficiency, a metabolic/storage disease, a neutrophil disorder, a platelet disease, and an autoimmune disorder.

19. The method of claim 18, wherein the hemoglobinopathy is thalassemia.

20. The method of claim 18, wherein the hemoglobinopathy is sickle cell disease.

21. The method of claim 1, wherein said composition increases the cumulative incidence of neutrophil engraftment in said mammalian subject relative to red blood cell-depleted cord blood.

22. The method of claim 1, wherein said composition increases the cumulative incidence of platelet engraftment in said mammalian subject relative to red blood cell-depleted cord blood.

23. The method of claim 1, wherein said composition increases the speed to neutrophil engraftment in said mammalian subject relative to red blood cell-depleted cord blood.

24. The method of claim 1, wherein said composition increases the speed to platelet engraftment in said mammalian subject relative to red blood cell-depleted cord blood.

25. The method of claim 1, wherein said composition increases the disease free survival rate in said mammalian subject relative to red blood cell-depleted cord blood.

26. The method of claim 1, wherein said composition decreases the transplant related mortality rate in said mammalian subject relative to red blood cell-depleted cord blood.

27. The method of claim 1, wherein said composition increases the overall survival rate in said mammalian subject relative to red blood cell-depleted cord blood.

28. The method of claim 1, wherein said composition is administered as a multiple dose to said mammalian subject.

29. The method of claim 28, wherein said multiple dose decreases the relapse rate in said mammalian subject relative to a single dose.

30. The method of claim 1, wherein said composition is administered in combination with bone marrow or peripheral blood stem cells.

31. The method of claim 1, further comprising freezing the composition and washing the cryoprotectant from the composition prior to administering the composition.

32. The method of claim 1, wherein said composition is diluted between thawing and administering to said mammalian subject.

33. The method of claim 1, wherein said composition is administered by infusion.

34. The method of claim 1, wherein said mammalian subject is a human.

35. The method of claim 34, wherein said human has a weight of greater than about 50 kg.

36. The method of claim 34, wherein said human has a weight of less than about 50 kg.

37. The method of claim 1 further comprising:

removing a volume of plasma from an anticoagulated umbilical cord blood sample to form the anticoagulated, plasma-depleted umbilical cord blood sample and then

adding a cryoprotectant to the anticoagulated, plasma-depleted umbilical cord blood sample to form a mixture.

38. The method of claim 37, further comprising:

lowering the temperature of the anticoagulated, plasma-depleted umbilical cord blood sample and cryoprotectant mixture at a rate of about −

1°

C. per minute from about 4°

C. to about −

50°

C.

39. The method of claim 38, further comprising:

lowering the temperature of the anticoagulated, plasma-depleted umbilical cord blood sample and cryoprotectant mixture at a rate of about −

10°

C. per minute from about −

50°

C. to about −

90°

C.

40. The method of claim 39, further comprising:

storing the anticoagulated, plasma-depleted umbilical cord blood sample and cryoprotectant mixture below about −

135°

C.

41. The method of claim 40, further comprising:

thawing the stored anticoagulated, plasma-depleted umbilical cord blood sample and cryoprotectant mixture.

42. The method of claim 41, wherein the thawing comprises incubating the stored anticoagulated, plasma-depleted umbilical cord blood sample and cryoprotectant mixture in a water bath maintained at between about 37°

C. and about 41°

C.

43. The method of claim 41, wherein said composition is not washed between thawing and administering to said mammalian subject.

44. The method of claim 43, wherein said post-thaw unwashed composition increases the cumulative incidence of platelet engraftment in said mammalian subject relative to post-thaw washed cord blood.

45. The method of claim 43, wherein said post-thaw unwashed composition increases the speed to neutrophil engraftment in said mammalian subject relative to post-thaw washed cord blood.

46. The method of claim 43, wherein said post-thaw unwashed composition increases the speed to platelet engraftment in said mammalian subject relative to post-thaw washed cord blood.

47. The method of claim 43, wherein said post-thaw unwashed composition decreases the incidence of Grade III-IV acute GVHD and extensive chronic GVHD in said mammalian subject relative to post-thaw washed cord blood.

48. The method of claim 1, wherein said anticoagulant is a mixture of citric acid, sodium citrate, sodium phosphate and dextrose.

49. The method of claim 1, wherein said cryoprotectant comprises from about 5% to about 15% by volume of DMSO.

50. The method of claim 49, wherein said cryoprotectant further comprises Gentran®

40.

51. The method of claim 1, wherein said anticoagulant is a mixture of citric acid, sodium citrate, sodium phosphate, dextrose and adenosine.