METHODS FOR ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

1 - 214 . (canceled)

215 . A multi-component pharmaceutical treatment to be administered to a human subject in need thereof, the multi-component treatment comprising:

(a) a solution comprising a first population of CD45+ cells comprising hematopoietic stem and progenitor cells (HSPCs) and granulocytes, wherein at most about 10% of the first population of CD45+ cells comprises granulocytes;

(b) a solution comprising a population of cells enriched for regulatory T cells (Tregs);

(c) a solution comprising a second population of CD45+ cells, wherein the second population of CD45+ cells comprises at least about 20% CD3+ conventional T cells (Tcons), at least about 10% monocytes, and at least about 10% granulocytes; and

(d) a solution comprising one or more doses of a graft vs host disease (GVHD) prophylactic agent.

216 . The multi-component pharmaceutical treatment of claim 215 , wherein the GVHD prophylactic agent is tacrolimus.

217 . The multi-component pharmaceutical treatment of claim 216 , wherein the tacrolimus is formulated for administration in an amount to maintain or that maintains a target blood level of at least about 3 ng/ml for at least about 20 days after administering the second population of CD45+ cells.

218 . The multi-component pharmaceutical treatment of claim 215 , wherein the first population of CD45+ cells comprises at most about 3% monocytes.

219 . The multi-component pharmaceutical treatment of claim 215 , wherein the first population of CD45+ cells comprises at most about 2% lymphocytes.

220 . The multi-component pharmaceutical treatment of claim 215 , wherein the second population of CD45+ cells comprises at least about 0.5% NK cells.

221 . The multi-component pharmaceutical treatment of claim 215 , wherein the second population of CD45+ cells comprises at least about 0.1% CD34+ cells or from about 0.2% to about 20% CD34+ cells.

222 . The multi-component pharmaceutical treatment of claim 215 , wherein the treatment further comprises a conditioning regimen.

223 . The multi-component pharmaceutical treatment of claim 222 , wherein the conditioning regimen is a myeloablative conditioning regimen.

224 . The multi-component pharmaceutical treatment of claim 223 , wherein the conditioning regimen comprises at least three conditioning reagents, wherein at least one conditioning reagent comprises thiotepa.

225 . The multi-component pharmaceutical treatment of claim 224 , wherein the conditioning regimen comprises one or more doses of busulfan, fludarabine and thiotepa.

226 . The multi-component pharmaceutical treatment of claim 225 , wherein the one or more doses of busulfan, fludarabine and thiotepa comprises from about 5 to about 12 mg of thiotepa per kg human subject's actual or ideal body weight, from about 7 to about 11 mg of busulfan per kg human subject actual or ideal body weight, and from about 100 to about 200 mg of fludarabine per meter 2 body surface area respectively.

227 . The multi-component pharmaceutical treatment of claim 215 , wherein the first population of CD45+ cells comprises less than about 5 EU of endotoxins per ml of the solution, the population of cells enriched for Tregs comprises less than about 5 EU of endotoxins per ml of the solution, and/or the second population of CD45+ cells comprises less than about 5 EU of endotoxins per ml of the solution.

228 . The multi-component pharmaceutical treatment of claim 215 , wherein said HSPCs are CD34+, and said Tregs are CD4+CD25+CD127dim or CD4+CD25+CD127dim or CD4+FOXP3+.

229 . The multi-component pharmaceutical treatment of claim 215 , wherein:

a) said first population of CD45+ cells comprising HSPCs comprises from about 5×10 5 to about 2×10 7 HSPCs per kilogram of ideal body of said human subject;

b) said population of cells enriched for Tregs comprises from about 1×10 5 to about 1×10 7 Tregs per kilogram of actual or ideal body weight of said human subject, or from about 5×10 5 to about 4×10 6 Tregs per kilogram of actual or ideal body weight of said human subject; and

c) said second population of CD45+ cells comprises from about 1×10 5 to about 1×10 7 Tcons per kilogram of actual or ideal body weight of said human subject, or from about 5×10 5 to about 5×10 6 Tcons per kilogram of actual or ideal body weight of said human subject.

230 . The multi-component pharmaceutical treatment of claim 215 , wherein a first dose of the one or more doses of the GVHD prophylactic agent is formulated for administration after administration of the second population of CD45+ cells.

231 . A method of treating a human subject having a hematologic malignancy, the method comprising administering to the human subject the multi-component pharmaceutical treatment of claim 215 .

232 . The method of claim 231 , wherein risk and/or severity of an adverse event associated with administration of the multi-component pharmaceutical treatment is reduced as compared to administration of a similar pharmaceutical treatment wherein a human subject receives Tcons but does not receive Tregs.

233 . A method of transplanting a conventional T cell (Tcon) population into a human subject without eliciting a stage 2 or higher graft versus host disease (GVHD) response up to about 100 days after transplanting, the method comprising:

i. administering a heterogenous cell population comprising lymphocytes, granulocytes and monocytes, wherein at least about 30% of said lymphocytes comprises conventional T cells (Tcons); and

ii. administering a population of regulatory T cells (Tregs);

wherein the heterogenous cell component and/or the population of Tregs comprise less than about 5 EU/ml endotoxins.

234 . A method of treating a human subject comprising:

a) administering a plurality of populations of cells, wherein the plurality of populations of cells comprises:

iii. a population of hematopoietic stem and progenitor cells (HSPCs);

iv. a population of cells comprising regulatory T cells (Tregs); and

v. a population of conventional T cells (Tcons); and

b) administering no more than one graft versus host disease (GVHD) prophylactic agent for less than about 120 days,

wherein the population of HSPCs comprises less than about 2% CD3+ cells.