Methods to enhance chemotherapy

1 . A method to enhance the effectiveness of a chemotherapeutic method in a subject afflicted with a hematopoietic or myeloid malignancy, which method comprises administering a chemotherapeutic method to said subject along with

administering to said subject an amount at least one CXCR4 antagonist

which is effective to enhance the effectiveness of said chemotherapeutic method.

2 . The method of claim 1 wherein the CXCR4 antagonist is of the formula

Z-linker-Z′  (1)

or pharmaceutically acceptable salt or prodrug forms thereof

wherein Z is a cyclic polyamine containing 9-32 ring members of which 2-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system;

or Z is of the formula

wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms,

Z′ may be embodied in a form as defined by Z above, or alternatively may be of the formula

—N(R)—(CR 2 ) n —X

wherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan,

or Z′ is absent;

“linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.

3 . The method of claim 2 wherein Z and Z′ are both cyclic polyamines.

4 . The method of claim 3 wherein the compound of formula (1) is 1,1′-[1,4-phenylene-bis-(methylene)-bis-1,4,8,11-tetraazacyclotetradecane (AMD3100).

5 . The method of claim 2 wherein Z is a cyclic polyamine and Z′ is N(R)—(CR 2 ) n —X.

6 . The method of claim 5 wherein each R is H, n is 2 and X is substituted or unsubstituted pyridyl.

7 . The method of claim 6 wherein the compound of formula 1 is N-[1,4,8,11-tetraazacyclotetradecanyl-(1,4-phenylene-bis-(methylene)]-2-aminoethyl-2-pyridine (AMD3465).

8 . The method of claim 2 wherein

Z is of the formula

wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms.

9 . The method of claim 8 wherein A is 5,6,7,8-tetrahydroquinolin-8-yl and B is 1H-benzimidazol-2-yl methyl.

10 . The method of claim 9 wherein Z′ is absent and the linker is an omega aminoalkyl substituent.

11 . The method of claim 10 wherein the compound of formula 1 is N 1 -(1H-benzimidazol-2-yl methyl)-N 1 -(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine (AMD11070).

12 . The method of claim 2 wherein the compound of formula (1) is administered to said subject in the dosage range of about 0.1 μg/kg-5 mg/kg of body weight.

13 . A pharmaceutical composition comprising an effective amount of a CXCR4 antagonist in unit dosage form for enhancing the effectiveness of a chemotherapeutic method in a subject.