Methods for allogenic hematopoietic stem cell transplantation

Abstract

Various embodiments of the present disclosure provide therapeutic compositions comprising Treg and Tcon for improved hematopoietic stem cell transplantation and associated methods, including methods of enhancing protection against graft versus host disease while maintaining an effective immune response, such as a graft anti-tumor immune response.

Claims

1. A multi-component cell therapy product comprising: a) a first single-dose transfer bag, wherein the first single-dose transfer bag contains a first isolated CD45 + The first isolated CD45+ cell population comprises about 1.0×10 per kg body weight of a human subject receiving the product. 5 About 1.0×10 8 CD34 + Hematopoietic stem and progenitor cells (HSPC), about 1.5×10 7 About 1.5×10 10 HSPCs or about 5.0×10 5 to about 5.0×10 8 The first HSPC dose is CD45 + The cell population is formulated with excipients at neutral pH; b) a second single-dose transfer bag, wherein the second single-dose transfer bag contains a second isolated CD45 + cell population, the second isolated CD45+ cell population comprising about 1.0×10 5 About 2.0×10 7 Fresh CD4 + CD25 + CD127 dim Regulatory T cells (Treg), about 1.5×10 7 About 3.0×10 9 Freshly isolated Treg or about 5.0×10 5 About 1.0×10 8 dose of freshly isolated Tregs, wherein the second isolated CD45 + The cell population is formulated with an excipient at a neutral pH, optionally wherein the first single-dose transfer bag and the second single-dose transfer bag are the same transfer bag; and c) a third single-dose transfer bag, the third single-dose transfer bag containing a third isolated CD45 + cell population, the third isolated CD45+ cell population comprising about 1.0×10 5 About 4.0×10 7 Regular CD3 + T cells (Tcon), about 1.5×10 7 About 6.0×10 9 Tcon or about 5.0×10 5 About 2.0×10 8 The dose of Tcon, wherein the third isolated CD45 + The cell population is formulated at neutral pH with an excipient, wherein the excipient comprises one or more cryoprotectants.

2. The multi-component cell therapy product according to claim 1, wherein: a) The first isolated CD45 + The cell population comprises the following dosage: about 1.0×10 per kg body weight of the human subject receiving the product 5 or more HSPCs, about 2.0×10 per kg body weight of the human subject receiving the product 5 or more HSPCs, about 3.0×10 per kg body weight of the human subject receiving the product 5 or more HSPCs, about 4.0×10 per kg body weight of the human subject receiving the product 5 or more HSPCs, about 5.0×10 per kg body weight of the human subject receiving the product 5 or more HSPCs, about 6.0×10 per kg body weight of the human subject receiving the product 5 or more HSPCs, about 7.0×10 per kg body weight of the human subject receiving the product 5 or more HSPCs, about 8.0×10 per kg body weight of the human subject receiving the product 5 or more HSPCs, about 9.0×10 per kg body weight of the human subject receiving the product 5 or more HSPCs, about 1.0×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 1.5×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 2.0×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 2.5×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 3.0×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 3.5×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 4.0×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 4.5×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 5.0×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 5.5×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 6.0×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 6.5×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 7.0×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 7.5×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 8.0×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 8.5×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 9.0×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 9.5×10 per kg body weight of the human subject receiving the product 6 or more HSPCs, about 1.0×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 1.5×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 2.0×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 2.5×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 3.0×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 3.5×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 4.0×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 4.5×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 5.0×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 5.5×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 6.0×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 6.5×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 7.0×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 7.5×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 8.0×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 8.5×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 9.0×10 per kg body weight of the human subject receiving the product 7 or more HSPCs, about 9.5×10 per kg body weight of the human subject receiving the product 7 or more HSPCs or about 1.0×10 per kg body weight of the human subject receiving the product 8 or more HSPCs; and / or b) the first isolated CD45 + The cell population contains the following doses: approximately 5.0 × 10 5 or more HSPCs, about 6.0×10 5 or more HSPCs, about 7.0×10 5 or more HSPCs, about 8.0×10 5 or more HSPCs, about 9.0×10 5 or more HSPCs, about 1.0×10 6 or more HSPCs, about 1.5×10 6 or more HSPCs, about 2.0×10 6 or more HSPCs, about 2.5×10 6 or more HSPCs, about 3.0×10 6 or more HSPCs, about 3.5×10 6 or more HSPCs, about 4.0×10 6 or more HSPCs, about 4.5×10 6 or more HSPCs, about 5.0×10 6 or more HSPCs, about 5.5×10 6 or more HSPCs, about 6.0×10 6 or more HSPCs, about 6.5×10 6 or more HSPCs, about 7.0×10 6 or more HSPCs, about 7.5×10 6 or more HSPCs, about 8.0×10 6 or more HSPCs, about 8.5×10 6 or more HSPCs, about 9.0×10 6 or more HSPCs, about 9.5×10 6 or more HSPCs, about 1.0×10 7 or more HSPCs, about 1.5×10 7 or more HSPCs, about 2.0×10 7 or more HSPCs, about 2.5×10 7 or more HSPCs, about 3.0×10 7 or more HSPCs, about 3.5×10 7 or more HSPCs, about 4.0×10 7 or more HSPCs, about 4.5×10 7 or more HSPCs, about 5.0×10 7 or more HSPCs, about 5.5×10 7 or more HSPCs, about 6.0×10 7 or more HSPCs, about 6.5×10 7 or more HSPCs, about 7.0×10 7 or more HSPCs, about 7.5×10 7 or more HSPCs, about 8.0×10 7 or more HSPCs, about 8.5×10 7 or more HSPCs, about 9.0×10 7 or more HSPCs, about 9.5×10 7 or more HSPCs, about 1.0×10 8 or more HSPCs, about 1.5×10 8 or more HSPCs, about 2.0×10 8 or more HSPCs, about 2.5×10 8 or more HSPCs, about 3.0×10 8 or more HSPCs, about 3.5×10 8 or more HSPCs, about 4.0×10 8 or more HSPCs, about 4.5×10 8 or more HSPCs, about 5.0×10 8 or more HSPCs, about 5.5×10 8 or more HSPCs, about 6.0×10 8 or more HSPCs, about 6.5×10 8 or more HSPCs, about 7.0×10 8 or more HSPCs, about 7.5×10 8 or more HSPCs, about 8.0×10 8 or more HSPCs, about 8.5×10 8 or more HSPCs, about 9.0×10 8 or more HSPCs, about 9.5×10 8 or more HSPCs, about 1.0×10 9 or more HSPCs, about 1.5×10 9 or more HSPCs, about 2.0×10 9 or more HSPCs, about 2.5×10 9 or more HSPCs, about 3.0×10 9 or more HSPCs, about 3.5×10 9 or more HSPCs, about 4.0×10 9 or more HSPCs, about 4.5×10 9 or more HSPCs, about 5.0×10 9 or more HSPCs, about 5.5×10 9 or more HSPCs, about 6.0×10 9 or more HSPCs, about 6.5×10 9 or more HSPCs, about 7.0×10 9 or more HSPCs, about 7.5×10 9 or more HSPCs, about 8.0×10 9 or more HSPCs, about 8.5×10 9 or more HSPCs, about 9.0×10 9 or more HSPCs, about 9.5×10 9 or more HSPCs, about 1.0×10 10 or more HSPCs or about 1.5 × 10 10 or more HSPCs; and / or c) The second isolated CD45 + The cell population comprises the following dosage: about 1.0×10 per kg body weight of the human subject receiving the product 5 or more isolated fresh Tregs, about 2.0×10 per kg body weight of the human subject receiving the product 5 or more isolated fresh Tregs, about 3.0×10 per kg body weight of the human subject receiving the product 5 or more isolated fresh Tregs, about 4.0×10 per kg body weight of the human subject receiving the product 5 or more isolated fresh Tregs, about 5.0×10 per kg body weight of the human subject receiving the product 5 or more isolated fresh Tregs, about 6.0×10 per kg body weight of the human subject receiving the product 5 or more isolated fresh Tregs, about 7.0×10 per kg body weight of the human subject receiving the product 5 or more isolated fresh Tregs, about 8.0×10 per kg body weight of the human subject receiving the product 5 or more isolated fresh Tregs, about 9.0×10 per kg body weight of the human subject receiving the product 5 or more isolated fresh Tregs, about 1.0×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 1.5×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 2.0×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 2.5×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 3.0×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 3.5×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 4.0×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 4.5×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 5.0×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 5.5×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 6.0×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 6.5×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 7.0×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 7.5×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 8.0×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 8.5×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 9.0×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh Tregs, about 9.5×10 per kg body weight of the human subject receiving the product 6 or more isolated fresh CD4 + CD25 + CD127 dim Treg, about 1.0×10 per kg body weight of the human subject receiving the product 7 or more isolated fresh Tregs, about 1.5×10 per kg body weight of the human subject receiving the product 7 or more isolated fresh Tregs or about 2.0×10 per kg body weight of the human subject receiving the product 7 or more isolated fresh Tregs, optionally wherein the Tregs are FOXP3 + ; and / or d) The second isolated CD45 + The cell population contains the following doses: approximately 5.0 × 10 5 or more isolated fresh Tregs, about 6.0×10 5 or more freshly isolated Tregs, about 7.0×10 5 or more isolated fresh Tregs, about 8.0×10 5 or more freshly isolated Tregs, about 9.0×10 5 or more freshly isolated Tregs, about 1.0×10 6 or more freshly isolated Tregs, about 1.5×10 6 or more freshly isolated Tregs, about 2.0×10 6 or more freshly isolated Tregs, about 2.5×10 6 or more freshly isolated Tregs, about 3.0×10 6 or more freshly isolated Tregs, about 3.5×10 6 or more freshly isolated Tregs, about 4.0×10 6 or more freshly isolated Tregs, about 4.5×10 6 or more isolated fresh Tregs, about 5.0×10 6 or more freshly isolated Tregs, about 5.5×10 6 or more isolated fresh Tregs, about 6.0×10 6 or more freshly isolated Tregs, about 6.5×10 6 or more freshly isolated Tregs, about 7.0×10 6 or more freshly isolated Tregs, about 7.5×10 6 or more isolated fresh Tregs, about 8.0×10 6 or more freshly isolated Tregs, about 8.5×10 6 or more freshly isolated Tregs, about 9.0×10 6 or more freshly isolated Tregs, about 9.5×10 6 or more freshly isolated Tregs, about 1.0×10 7 or more freshly isolated Tregs, about 1.5×10 7 or more freshly isolated Tregs, about 2.0×10 7 or more freshly isolated Tregs, about 2.5×10 7 or more freshly isolated Tregs, about 3.0×10 7 or more freshly isolated Tregs, about 3.5×10 7 or more freshly isolated Tregs, about 4.0×10 7 or more freshly isolated Tregs, about 4.5×10 7 or more isolated fresh Tregs, about 5.0×10 7 or more freshly isolated Tregs, about 5.5×10 7 or more isolated fresh Tregs, about 6.0×10 7 or more freshly isolated Tregs, about 6.5×10 7 or more freshly isolated Tregs, about 7.0×10 7 or more freshly isolated Tregs, about 7.5×10 7 or more isolated fresh Tregs, about 8.0×10 7 or more freshly isolated Tregs, about 8.5×10 7 or more freshly isolated Tregs, about 9.0×10 7 or more freshly isolated Tregs, about 9.5×10 7 or more freshly isolated Tregs, about 1.0×10 8 or more freshly isolated Tregs, about 1.5×10 8 or more freshly isolated Tregs, about 2.0×10 8 or more freshly isolated Tregs, about 2.5×10 8 or more freshly isolated Tregs, about 3.0×10 8 or more freshly isolated Tregs, about 3.5×10 8 or more freshly isolated Tregs, about 4.0×10 8 or more freshly isolated Tregs, about 4.5×10 8 or more isolated fresh Tregs, about 5.0×10 8 or more freshly isolated Tregs, about 5.5×10 8 or more isolated fresh Tregs, about 6.0×10 8 or more freshly isolated Tregs, about 6.5×10 8 or more freshly isolated Tregs, about 7.0×10 8 or more freshly isolated Tregs, about 7.5×10 8 or more isolated fresh Tregs, about 8.0×10 8 or more freshly isolated Tregs, about 8.5×10 8 or more freshly isolated Tregs, about 9.0×10 8 or more freshly isolated Tregs, about 9.5×10 8 or more freshly isolated Tregs, about 1.0×10 9 or more freshly isolated Tregs, about 1.5×10 9 or more freshly isolated Tregs, about 2.0×10 9 or more freshly isolated Tregs, about 2.5×10 9 or more freshly isolated Tregs or about 3.0×10 9 or more isolated fresh Tregs, optionally wherein the Tregs are FOXP3 + ; and / or e) the third isolated CD45 + The cell population comprises the following dosage: about 1.0×10 per kg body weight of the human subject receiving the product 5 or more Tcon, about 2.0×10 per kg body weight of the human subject receiving the product 5 or more Tcon, about 3.0×10 per kg body weight of the human subject receiving the product 5 or more Tcon, about 4.0×10 per kg body weight of the human subject receiving the product 5 or more Tcon, about 5.0×10 per kg body weight of the human subject receiving the product 5 or more Tcon, about 6.0×10 per kg body weight of the human subject receiving the product 5 or more Tcon, about 7.0×10 per kg body weight of the human subject receiving the product 5 or more Tcon, about 8.0×10 per kg body weight of the human subject receiving the product 5 or more Tcon, about 9.0×10 per kg body weight of the human subject receiving the product 5 or more Tcon, about 1.0×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 1.5×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 2.0×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 2.5×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 3.0×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 3.5×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 4.0×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 4.5×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 5.0×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 5.5×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 6.0×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 6.5×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 7.0×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 7.5×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 8.0×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 8.5×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 9.0×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 9.5×10 per kg body weight of the human subject receiving the product 6 or more Tcon, about 1.0×10 per kg body weight of the human subject receiving the product 7 or more Tcon, about 1.5×10 per kg body weight of the human subject receiving the product 7 or more Tcon, about 2.0×10 per kg body weight of the human subject receiving the product 7 or more Tcon, about 2.5×10 per kg body weight of the human subject receiving the product 7 or more Tcon, about 3.0×10 per kg body weight of the human subject receiving the product 7 or more Tcon, about 3.5×10 per kg body weight of the human subject receiving the product 7 or more Tcon or about 4.0×10 per kg body weight of the human subject receiving the product 7 or more Tcon; and / or f) the third isolated CD45 + The cell population contains the following doses: approximately 5.0 × 10 5 or more Tcon, about 6.0×10 5 or more Tcon, about 7.0×10 5 or more Tcon, about 8.0×10 5 or more Tcon, about 9.0×10 5 or more Tcon, about 1.0×10 6 or more Tcon, about 1.5×10 6 or more Tcon, about 2.0×10 6 or more Tcon, about 2.5×10 6 or more Tcon, about 3.0×10 6 or more Tcon, about 3.5×10 6 or more Tcon, about 4.0×10 6 or more Tcon, about 4.5×10 6 or more Tcon, about 5.0×10 6 or more Tcon, about 5.5×10 6 or more Tcon, about 6.0×10 6 or more Tcon, about 6.5×10 6 or more Tcon, about 7.0×10 6 or more Tcon, about 7.5×10 6 or more Tcon, about 8.0×10 6 or more Tcon, about 8.5×10 6 or more Tcon, about 9.0×10 6 or more Tcon, about 9.5×10 6 or more Tcon, about 1.0×10 7 or more Tcon, about 1.5×10 7 or more Tcon, about 2.0×10 7 or more Tcon, about 2.5×10 7 or more Tcon, about 3.0×10 7 or more Tcon, about 3.5×10 7 or more Tcon, about 4.0×10 7 or more Tcon, about 4.5×10 7 or more Tcon, about 5.0×10 7 or more Tcon, about 5.5×10 7 or more Tcon, about 6.0×10 7 or more Tcon, about 6.5×10 7 or more Tcon, about 7.0×10 7 or more Tcon, about 7.5×10 7 or more Tcon, about 8.0×10 7 or more Tcon, about 8.5×10 7 or more Tcon, about 9.0×10 7 or more Tcon, about 9.5×10 7 or more Tcon, about 1.0×10 8 or more Tcon, about 1.5×10 8 or more Tcon, about 2.0×10 8 or more Tcon, about 2.5×10 8 or more Tcon, about 3.0×10 8 or more Tcon, about 3.5×10 8 or more Tcon, about 4.0×10 8 or more Tcon, about 4.5×10 8 or more Tcon, about 5.0×10 8 or more Tcon, about 5.5×10 8 or more Tcon, about 6.0×10 8 or more Tcon, about 6.5×10 8 or more Tcon, about 7.0×10 8 or more Tcon, about 7.5×10 8 or more Tcon, about 8.0×10 8 or more Tcon, about 8.5×10 8 or more Tcon, about 9.0×10 8 or more Tcon, about 9.5×10 8 or more Tcon, about 1.0×10 9 or more Tcon, about 1.5×10 9 or more Tcon, about 2.0×10 9 or more Tcon, about 2.5×10 9 or more Tcon, about 3.0×10 9 or more Tcon, about 3.5×10 9 or more Tcon, about 4.0×10 9 or more Tcon, about 4.5×10 9 or more Tcon, about 5.0×10 9 or more Tcon, about 5.5×10 9 or more Tcon or about 6.0×10 9 or more Tcon.

3. The multicomponent cell therapy product of claim 1 or claim 2, wherein the product further comprises a pharmaceutical composition comprising a dose of the graft-versus-host disease (GVHD) preventive agent tacrolimus sufficient to maintain a trough blood level of about 5 ng / mL to about 10 ng / mL in the human subject receiving the product, optionally wherein the pharmaceutical composition comprises a dose of tacrolimus ranging from about 0.01 mg per kg body weight of the human subject receiving the product to about 0.50 mg per kg body weight of the human subject receiving the product twice daily, optionally wherein the administration of the third CD45 + After administering the product to the human subject, the tacrolimus is administered in an amount to maintain or sustain a target blood level of about 1 ng / mL to about 10 ng / mL in the human subject receiving the product for about 20 days or more, about 25 days or more, about 30 days or more, about 35 days or more, about 40 days or more, about 45 days or more, about 50 days or more, about 55 days or more, about 60 days or more, about 65 days or more, about 70 days or more, about 75 days or more, about 80 days or more, about 85 days or more, about 90 days or more, about 95 days or more, about 100 days or more, about 110 days or more, about 120 days or more, about 130 days or more, about 140 days or more, or about 150 days.

4. The multicomponent cell therapy product according to any one of claims 1 to 3, wherein: a) The first isolated CD45 + cell population, the second isolated CD45 + cell population and / or the third isolated CD45 + The cell population is formulated in a volume ranging from about 5 mL to about 1 L; and / or b) the neutral pH is in the range of about 6.8 to about 7.6; and / or c) the excipient comprises a transfer buffer, optionally wherein the transfer buffer comprises about 120 to about 160 mEq sodium and / or the transfer buffer comprises about 270 to about 320 mOsmol / L total, optionally wherein the transfer buffer is selected from the group consisting of: phosphate buffered saline (PBS), human serum, PlasmaLyte, and any combination thereof, optionally wherein the transfer buffer further comprises about 0.1 wt% by volume to about 10 wt% by volume of a human carrier protein, optionally wherein the human carrier protein is selected from the group consisting of: human serum albumin (HSA), intravenous immunoglobulin (IVIG), AB serum, and any combination thereof; and / or d) any one of the first single-dose bag, the second single-dose bag, and the third single-dose bag is a polyvinyl chloride (PVC) transfer bag or an ethylene vinyl acetate (EVA) transfer bag; and / or e) the one or more cryoprotectants are selected from the group consisting of sorbitol, dimethyl sulfoxide (DMSO), propylene glycol, glycerol, polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG), serum, HSA, hydroxyethyl starch, CRYOSTOR CS2, CRYOSTOR CS5 and CRYOSTOR CS10.

5. The multicomponent cell therapy product according to any one of claims 1 to 4, wherein the first separated CD45 + cell population, the second isolated CD45 + The cell population and the third isolated CD45+ cell population are from an allogeneic donor having at least one HLA mismatch relative to the human subject receiving the product, optionally wherein the HLA-mismatched donor is unrelated to the human subject receiving the product, or the HLA-mismatched donor is related to the human subject receiving the product, optionally wherein the at least one HLA mismatch is at an allele selected from the group consisting of: HLA-A, HLA-B, HLA-C, HLA-DRB1, and any combination thereof, optionally wherein the cells having at least one HLA mismatch are from a donor that is 6 / 8 HLA mismatched relative to the human subject receiving the product or 7 / 8 HLA mismatched relative to the human subject receiving the product, optionally wherein the human subject receiving the product is homozygous for the HLA allele. or because the donor is heterozygous for the HLA allele and the human subject receiving the product has a mismatched HLA allele relative to the donor having the at least one HLA mismatch, or because the donor is heterozygous for the HLA allele and the human subject receiving the product is homozygous for the HLA allele and therefore has a mismatched HLA allele relative to the donor having at least one HLA mismatch relative to the human subject receiving the product, or because both the donor and the human subject receiving the product are heterozygous for the HLA allele and therefore has a mismatched HLA allele relative to the donor having at least one HLA mismatch relative to the human subject receiving the product, optionally wherein after administration, the first isolated CD45 + cell population, the second isolated CD45 + The cell population and the third isolated CD45+ cell population reduce the incidence of non-relapse mortality and / or increase the overall survival of the human subjects receiving the product, wherein the corresponding human subjects have been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT) that is 7 / 8 HLA mismatched relative to the corresponding human subjects.

6. A method of treating a human subject having or suspected of having a hematological malignancy, the method comprising administering to the human subject a multi-component cell therapy product according to any one of claims 1 to 5, or a multi-component drug treatment comprising: a) comprising a first isolated CD45 + a solution of cell populations, wherein the first separated CD45+ cell population comprises hematopoietic stem and progenitor cells (HSPCs); b) comprising a second isolated CD45 + a solution of cell populations, wherein the second separated CD45+ cell population comprises regulatory T cells (Treg); c) contains a third isolated CD45 + A solution of a cell population, wherein the third separated CD45 + The cell population contains CD3 + Conventional T cells (Tcon); and d) a solution comprising one or more doses of a graft-versus-host disease (GVHD) preventive agent, The first isolated CD45 + cell population, the second isolated CD45 + Cell population and the third isolated CD45 + The cell population is obtained from a single allogeneic donor having at least one HLA mismatch relative to the human subject, and wherein the incidence of non-relapse mortality in the human subject is reduced after administration and / or the overall survival of the human subject is increased after administration relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT) from a donor who has at least one HLA mismatch relative to the corresponding human subject, optionally wherein the hematological malignancy is selected from the group consisting of acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome, myelofibrosis and blastic plasmacytoid dendritic cell neoplasm (BPDCN), optionally wherein the administering comprises administering the first isolated CD45 + cell population, the second isolated CD45 + Cell population and the third isolated CD45 + The cell population is infused into the human subject, optionally wherein the third isolated CD45 + The cell population was first isolated with CD45 + cell population about 24 hours to about 120 hours after administration, optionally the third isolated CD45 + The cell population was isolated in the second CD45 + about 24 hours to about 120 hours after the cell population, optionally wherein the human subject is administered the third isolated CD45 + wherein the human subject has not developed higher than stage 2 GVHD within about 100 days, about 180 days, about 200 days, or about 1 year of the human subject's isolated CD45 T cells, optionally wherein the human subject has been previously or is being concurrently treated for the hematological malignancy, optionally wherein the GVHD preventive agent is tacrolimus and is initially administered to the human subject at about 0.03 mg / kg of the human subject's actual or ideal body weight / day, optionally wherein the GVHD preventive agent is administered prior to administration of the third isolated CD45 T cells, optionally ... GVHD preventive agent is administered prior to administration of the third isolated CD45 T cells, optionally wherein the GVHD preventive agent is administered prior to administration of the third isolated CD45 T cells, optionally wherein the GVHD preventive agent is administered prior to administration of the third isolated CD45 T cells, optionally wherein the GVHD preventive agent is administered prior to administration of the third isolated CD45 T cells, optionally wherein the GVHD preventive agent is administered prior to administration of the third isolated CD45 T cells, optionally wherein the GVHD preventive agent is administered prior to administration of the third isolated CD45 T cells, optionally wherein the GVHD preventive agent is administered prior to administration of the third isolated CD45 T cells, optionally wherein the GVHD preventive agent is administered prior to administration of the third isolated CD45 T cells, optionally wherein the GVHD preventive agent is administered prior to administration of the third isolated CD4 + The administration begins about 12 hours to about 24 hours after the cell population, optionally wherein the tacrolimus is administered prior to administration of the third isolated CD45 + The cell population is then administered in an amount to maintain a target blood level of at least about 3 ng / ml for at least about 20 days or about 40 days, optionally wherein the tacrolimus is administered prior to administration of the third isolated CD45 + wherein the administration of the GVHD preventive agent is tapered beginning about 90 days after the initial administration of the GVHD preventive agent, wherein the method further comprises administering about 1000 mg of mycophenolate mofetil (MMF), wherein the MMF is administered prior to administering the third isolated CD45 + wherein the administration of MMF is tapered off beginning about 30 days, about 35 days, about 40 days, about 41 days, about 42 days, about 43 days, about 44 days, about 45 days, about 46 days, about 47 days, about 48 days, about 49 days, or about 50 days after the initial administration of MMF, optionally wherein the at least one HLA mismatch is at an allele selected from the group consisting of: HLA-A, HLA-B, HLA-C, HLA-DRB1, and any combination thereof, optionally wherein there is at least The allogeneic donor with one HLA mismatch is 6 / 8 HLA mismatched relative to the human subject or is 7 / 8 HLA mismatched relative to the human subject, optionally wherein the allogeneic donor with at least one HLA mismatch relative to the human subject has a mismatched HLA allele because the allogeneic donor is homozygous for the HLA allele and the human subject is heterozygous for the HLA allele, or wherein the allogeneic donor with at least one HLA mismatch has a mismatched HLA allele because the allogeneic donor is heterozygous for the HLA allele and the human subject is heterozygous for the HLA allele (a) to (d) wherein the allogeneic donor is homozygous for the HLA allele, and thus the allogeneic donor having at least one HLA mismatch relative to the human subject has a mismatched HLA allele, or the allogeneic donor and the human subject are both heterozygous for the HLA allele, and thus the allogeneic donor having at least one HLA mismatch relative to the human subject has a mismatched HLA allele, optionally wherein the method further comprises a conditioning regimen, wherein the conditioning regimen is administered prior to any one of (a) to (d), optionally wherein the conditioning regimen is a myeloablative conditioning regimen The myeloablative conditioning regimen comprises at least three conditioning agents, wherein at least one conditioning agent comprises thiotepa, optionally wherein the myeloablative conditioning regimen comprises one or more doses of busulfan, fludarabine, and thiotepa, optionally wherein the one or more doses of busulfan, fludarabine, and thiotepa comprise about 5 mg to about 12 mg of thiotepa / kg actual or ideal body weight of the human subject, about 7 mg to about 11 mg of busulfan / kg actual or ideal body weight of the human subject, and about 100 mg to about 200 mg of fludarabine / kg, respectively. 2 body surface area, optionally wherein the human subject's GVHD-free and relapse-free survival (GFRS) is increased by at least about 3.5-fold after administration, the overall survival is increased by at least about 1.25-fold after administration, and / or the incidence of non-relapse mortality is reduced by at least about 60% after administration relative to a corresponding human subject who has been administered standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT).

7. A method for preparing a multi-component cell therapy product, comprising: a) obtaining a peripheral blood apheresis sample for HSPC mobilization from a donor who is allogeneic with respect to the human subject receiving the product; and b) selecting a first sample, a second sample, and a third sample from the apheresis sample, wherein the first sample comprises about 1.0×10 5 About 1.0×10 8 CD34 + Hematopoietic stem and progenitor cells (HSPC), about 1.5×10 7 About 1.5×10 10 HSPCs or about 5.0×10 5 to about 5.0×10 8 HSPCs, the second sample comprising approximately 1.0×10 HSPCs per kg body weight of the human subject receiving the product 5 About 2.0×10 7 CD4 + CD25 + CD127 dim Regulatory T cells (Treg), about 1.5×10 7 About 3.0×10 9 Treg or about 5.0×10 5 About 1.0×10 8 Tregs, and the third sample contains about 1.0×10 Tregs per kg body weight of the human subject receiving the product. 5 About 4.0×10 7 Regular CD3 + T cells (Tcon), about 1.5×10 7 About 6.0×10 9 Tcon or about 5.0×10 5 About 2.0×10 8 wherein the multicomponent cell therapy product comprises the Tcon, the HSPC and the Treg, optionally wherein the first sample is sorted with one or more ISPs specific for CD34 and a population enriched in CD34 is selected to select the HSPC, optionally wherein the second sample is sorted with one or more ISPs specific for CD25, with one or more ISPs specific for CD4 and / or with one or more ISPs specific for CD127 and CD4 is selected + and CD127 dim said Tregs are selected from a cell population, optionally wherein said third sample is sorted using one or more ISPs specific for CD3 to select said Tcons, optionally wherein said third sample is cryopreserved.

8. A multicomponent cell therapy product produced by the method according to claim 7, optionally wherein the multicomponent cell therapy product is a multicomponent cell therapy product according to any one of claims 1 to 5.

9. A method for treating a human subject having or suspected of having an acute leukemia in complete remission, active leukemia, primary refractory acute leukemia, or acute leukemia with minimal residual disease, wherein the method comprises administering to the human subject a multicomponent cell therapy product according to any one of claims 1 to 5, optionally wherein the acute leukemia is in complete remission with incomplete hematological recovery, optionally wherein minimal residual disease is present in the human subject or minimal residual disease is absent in the human subject, optionally wherein the acute leukemia is classified as an intermediate risk to very high risk acute leukemia, optionally wherein the acute leukemia is acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and / or mixed phenotype acute leukemia (MPAL).

10. A method for treating a human subject having or suspected of having low-risk acute myeloid leukemia (AML), high-risk AML in complete remission, or chronic myeloid leukemia (CML), wherein the method comprises administering to the human subject a multicomponent cell therapy product according to any one of claims 1 to 5, optionally wherein the high-risk AML comprises a complex karyotype with three or more clonal chromosomal abnormalities, wherein the three or more clonal chromosomal abnormalities are each selected from the group consisting of: monosomal karyotype -5, 5q-, -7 or 7q-, t(11q23, t(9;11), inv(3), t(3,3)t(6;9)t(9;22), a normal karyotype with an fms-like tyrosine kinase 3 (FLT3)-ITD mutation, and any combination thereof, optionally wherein the CML is in blast crisis, in second chronic phase, in chronic phase, is accelerated, has a history of blast crisis, and / or is intolerant to one or more first or second generation tyrosine kinase inhibitors (TKIs).

11. A method for treating a human subject having or suspected of having high-risk myelodysplastic syndrome, therapy-related myelodysplastic syndrome, and / or secondary myelodysplastic syndrome, wherein the method comprises administering to the human subject a multicomponent cell therapy product according to any one of claims 1 to 5, optionally wherein the human subject has active disease at the time of treatment with the multicomponent cell therapy, optionally wherein the human subject has about 10% or less blast burden in his or her bone marrow, optionally wherein the therapy-related myelodysplastic syndrome and / or secondary myelodysplastic syndrome is in complete remission and is classified as intermediate risk to high risk.

12. A method of treating a human subject having or suspected of having a myeloproliferative syndrome, the method comprising administering to the human subject the multicomponent cell therapy product of any one of claims 1 to 5.

13. A method for treating a human subject having or suspected of having non-Hodgkin's lymphoma having an adverse risk profile that is not suitable for autologous hematopoietic cell transplantation (HCT), the method comprising administering to the human subject a multicomponent cell therapy product according to any one of claims 1 to 5.

14. A method according to any one of claims 9 to 13, wherein: a) the third isolated CD45 + The cell population was first isolated with CD45 + The cell population is administered about 24 hours to about 120 hours after administration; and / or b) the third isolated CD45 + The cell population was isolated in the second CD45 + The cell population is administered about 24 hours to about 120 hours after administration; and / or c) the multicomponent cell therapy further comprises a solution comprising one or more doses of a graft versus host disease (GVHD) preventive agent, optionally wherein the GVHD preventive agent is tacrolimus, optionally wherein the tacrolimus is provided in an amount sufficient to maintain a trough blood level of about 5 ng / mL to about 10 ng / mL in the human subject, optionally wherein the tacrolimus is provided in a dose ranging from about 0.01 mg per kg body weight of the human subject to about 0.50 mg per kg body weight of the human subject twice daily, optionally wherein the tacrolimus is provided prior to administration of the third isolated CD45 + Cell population, optionally wherein administration of tacrolimus is tapered beginning about 90 days after the initial administration of tacrolimus; and / or d) the first isolated CD45 + The cell population contains approximately 1.0×10 cells per kg body weight of the human subject. 5 About 1.0×10 8 HSPCs, about 5.0×10 5 to about 5.0×10 8 HSPCs or about 1.5 × 10 7 About 1.5×10 10 HSPCs; and / or e) the second isolated CD45 + The cell population contains approximately 1.0×10 cells per kg body weight of the human subject. 5 About 2.0×10 7 Treg, about 1.5×10 7 About 3.0×10 9 Treg or about 5.0×10 5 About 1.0×10 8 Tregs, optionally wherein the Tregs are FOXP3 + ; and / or f) the third isolated CD45 + The cell population contains approximately 1.0×10 cells per kg body weight of the human subject. 5 About 4.0×10 7 Tcon, about 5.0×10 5 About 2.0×10 8 Tcon or about 1.5×10 7 About 6.0×10 9 Tcon; and / or g) administering the third isolated CD45 + The cell population does not develop higher than stage 2 GVHD within about 100 days, about 180 days, about 200 days, or about 1 year; and / or h) the first isolated CD45 + cell population, the second isolated CD45 + The cell population and the third isolated CD45+ cell population are from an allogeneic donor having at least one HLA mismatch relative to the human subject, optionally wherein the HLA-mismatched donor is unrelated to the human subject or the HLA-mismatched donor is related to the human subject, optionally wherein the at least one HLA mismatch is at an allele selected from the group consisting of: HLA-A, HLA-B, HLA-C, HLA-DRB1, and any combination thereof, optionally wherein the donor having at least one HLA mismatch is 6 / 8 HLA mismatched relative to the human subject or 7 / 8 HLA mismatched relative to the human subject, optionally wherein due to the donor being related to the human subject the donor having at least one HLA mismatch relative to the human subject has a mismatched HLA allele because the donor is homozygous for the HLA allele and the human subject is heterozygous for the HLA allele, or the donor having at least one HLA mismatch relative to the human subject has a mismatched HLA allele because the donor is heterozygous for the HLA allele and the human subject is homozygous for the HLA allele, or the donor having at least one HLA mismatch relative to the human subject has a mismatched HLA allele because both the donor and the human subject are heterozygous for the HLA allele; and / or i) wherein the incidence of non-relapse mortality in the human subject is reduced following administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT) from a donor who has at least one HLA mismatch relative to the corresponding human subject; and / or j) wherein the overall survival rate of the human subject is increased following administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT) from a donor who has at least one HLA mismatch relative to the corresponding human subject; and / or k) the method further comprises collecting one or more or two or more mobilized peripheral blood donations from the donor, optionally wherein the peripheral blood donations are mobilized by granulocyte colony stimulating factor (GCSF), granulocyte macrophage colony stimulating factor (GM-CSF), plerixafor or any combination thereof, optionally wherein at least one of the mobilized peripheral blood donations is processed and sorted using one or more immunoseparation particles (ISPs) to enrich for CD34 + cells and Tregs; and / or l) The method further comprises a conditioning regimen, wherein the conditioning regimen is administered prior to administering the multicomponent cell therapy, optionally wherein the conditioning regimen is administered about two days to about ten days prior to administering the multicomponent cell therapy, optionally wherein the conditioning regimen is a total body irradiation (TBI-based) regimen, optionally wherein the TBI-based regimen further comprises one or more conditioning agents, optionally wherein the one or more conditioning agents are selected from the group consisting of cyclophosphamide, etoposide, thiotepa, and any combination thereof, optionally wherein the conditioning regimen is a myeloablative conditioning regimen, optionally wherein the myeloablative conditioning The method comprises one or more conditioning agents, optionally wherein the one or more conditioning agents are selected from the group consisting of thiotepa, busulfan, melphalan, fludarabine, cyclophosphamide, anti-thymocyte globulin (ATG), and any combination thereof, or wherein the myeloablative conditioning regimen comprises one or more doses of busulfan, fludarabine, and thiotepa, optionally wherein the one or more doses of busulfan, fludarabine, and thiotepa comprise about 5 mg to about 12 mg of thiotepa / kg body weight of the human subject, about 7 mg to about 11 mg of busulfan / kg body weight of the human subject, and about 100 mg to about 200 mg of fludarabine / kg body weight of the human subject, respectively. 2 Body surface area; and / or m) the human subject's GVHD-free and relapse-free survival (GFRs) is increased by at least about 3.5-fold following administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT); and / or n) the overall survival rate of the human subject after administration of the multicomponent cell therapy is increased by at least about 1.25-fold relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT); and / or o) the incidence of non-relapse mortality in the human subject is reduced by at least about 60% following administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT); and / or p) an increase in chronic GVHD-free survival rate after administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject experiences chronic GVHD lasting about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more, about 1.50 years after administration of the multicomponent cellular therapy or longer, about 1.75 years or longer, about 2 years or longer, about 2.25 years or longer, about 2.50 years or longer, about 2.75 years or longer, about 3 years or longer, about 3.25 years or longer, about 3.50 years or longer, about 3.75 years or longer, about 4 years or longer, about 4.25 years or longer, about 4.50 years or longer, about 4.75 years or longer, or about 5 years or longer of chronic GVHD-free survival; and / or q) the incidence of primary graft failure or secondary graft failure is reduced after administration of the multi-component cell therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject persists for about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more, about 1.50 years after administration of the multi-component cell therapy or more, about 1.75 years or more, about 2 years or more, about 2.25 years or more, about 2.50 years or more, about 2.75 years or more, about 3 years or more, about 3.25 years or more, about 3.50 years or more, about 3.75 years or more, about 4 years or more, about 4.25 years or more, about 4.50 years or more, about 4.75 years or more, or about 5 years or more without primary graft failure or secondary graft failure; and / or r) the incidence, severity, timing, or any combination thereof of grade I to IV acute GVHD is reduced following administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject persists for about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more following administration of the multicomponent cellular therapy , about 1.50 years or more, about 1.75 years or more, about 2 years or more, about 2.25 years or more, about 2.50 years or more, about 2.75 years or more, about 3 years or more, about 3.25 years or more, about 3.50 years or more, about 3.75 years or more, about 4 years or more, about 4.25 years or more, about 4.50 years or more, about 4.75 years or more, or about 5 years or more without Grade I to IV acute GVHD; and / or s) the incidence of steroid-refractory acute GVHD is reduced after administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject persists for about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more, about 1.50 years after administration of the multicomponent cellular therapy or more, about 1.75 years or more, about 2 years or more, about 2.25 years or more, about 2.50 years or more, about 2.75 years or more, about 3 years or more, about 3.25 years or more, about 3.50 years or more, about 3.75 years or more, about 4 years or more, about 4.25 years or more, about 4.50 years or more, about 4.75 years or more, or about 5 years or more without developing steroid-refractory acute GVHD; and / or t) GVHD-free and relapse-free survival (GFRs) are increased after administration of the multicomponent cell therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject experiences a relapse-free survival (GFRs) lasting about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more after administration of the multicomponent cell therapy , a GFRS of about 1.50 years or more, about 1.75 years or more, about 2 years or more, about 2.25 years or more, about 2.50 years or more, about 2.75 years or more, about 3 years or more, about 3.25 years or more, about 3.50 years or more, about 3.75 years or more, about 4 years or more, about 4.25 years or more, about 4.50 years or more, about 4.75 years or more, or about 5 years or more; and / or u) an increase in relapse-free survival rate following administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject experiences relapse lasting about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more, about 1.50 years following administration of the multicomponent cellular therapy or longer, about 1.75 years or longer, about 2 years or longer, about 2.25 years or longer, about 2.50 years or longer, about 2.75 years or longer, about 3 years or longer, about 3.25 years or longer, about 3.50 years or longer, about 3.75 years or longer, about 4 years or longer, about 4.25 years or longer, about 4.50 years or longer, about 4.75 years or longer, or about 5 years or longer of recurrence-free survival; and / or v) the incidence, severity, timing, or any combination thereof of moderate to severe chronic GVHD is reduced after administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject persists for about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more after administration of the multicomponent cellular therapy or more, about 1.50 years or more, about 1.75 years or more, about 2 years or more, about 2.25 years or more, about 2.50 years or more, about 2.75 years or more, about 3 years or more, about 3.25 years or more, about 3.50 years or more, about 3.75 years or more, about 4 years or more, about 4.25 years or more, about 4.50 years or more, about 4.75 years or more, or about 5 years or more; and / or w) the incidence, severity, timing, or any combination thereof of non-relapse mortality is reduced following administration of the multi-component cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject persists for about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more following administration of the multi-component cellular therapy , about 1.50 years or more, about 1.75 years or more, about 2 years or more, about 2.25 years or more, about 2.50 years or more, about 2.75 years or more, about 3 years or more, about 3.25 years or more, about 3.50 years or more, about 3.75 years or more, about 4 years or more, about 4.25 years or more, about 4.50 years or more, about 4.75 years or more, or about 5 years or more without experiencing non-relapse mortality; and / or x) a reduction in grade 3 or higher infection following administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject is about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more, about 1.50 years or more following administration of the multicomponent cellular therapy time, about 1.75 years or more, about 2 years or more, about 2.25 years or more, about 2.50 years or more, about 2.75 years or more, about 3 years or more, about 3.25 years or more, about 3.50 years or more, about 3.75 years or more, about 4 years or more, about 4.25 years or more, about 4.50 years or more, about 4.75 years or more, or about 5 years or more without a Grade 3 or higher infection; and / or y) the incidence, timing, or incidence and timing of neutrophil engraftment is increased following administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein neutrophil engraftment is increased at about 5 days or more, about 6 days or more, about 7 days or more, about 8 days or more, about 9 days or more, about 10 days or more, about 11 days or more, about 12 days or more, about 13 days or more, about 14 days or more, about 15 days or more, about 16 days or more, about 17 days or more, about 18 days or more following administration of the multicomponent cellular therapy about 19 days or more, about 20 days or more, about 22 days or more, about 22 days or more, about 23 days or more, about 24 days or more, about 25 days or more, about 26 days or more, about 27 days or more, about 28 days or more, about 29 days or more, about 30 days or more, about 33 days or more, about 33 days or more, about 33 days or more, about 34 days or more, about 35 days or more, about 36 days or more, about 37 days or more, about 38 days or more, about 39 days or more, about 40 days or more, about 44 days or more, about 45 days or more, about 44 days or more, about 44 days or more, about 45 days or more, about 46 days or more, about 47 days or more, about 48 days or more, about 49 days or more, about 50 days or more, about 55 days or more, about 55 days or more, about 55 days or more, about 55 days or more, about 55 days or more, about 56 days or more, about 57 days or more, about 58 days or more, about 59 days or more, about 60 days or more, about 6 ... 7 days or more, about 68 days or more, about 69 days or more, about 70 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 78 days or more, about 79 days or more, about 80 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 89 days or more or about 90 days or more; and / or z) the incidence, timing, or incidence and timing of platelet engraftment is increased following administration of the multicomponent cell therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein platelet engraftment is increased at about 5 days or more, about 6 days or more, about 7 days or more, about 8 days or more, about 9 days or more, about 10 days or more, about 11 days or more, about 12 days or more, about 13 days or more, about 14 days or more, about 15 days or more, about 16 days or more, about 17 days or more, about 18 days or more, about 19 days or more, about 20 days or more, about 21 days or more, about 22 days or more, about 23 days or more, about 24 days or more, about 25 days or more, about 26 days or more, about 27 days or more, about 28 days or more, about 29 days or more, about 30 days or more, about 31 days or more, about 32 days or more, about 33 days or more, about 34 days or more, about 35 days or more, about 36 days or more, about 37 days or more, about 38 days or more, about 39 days or more, about 40 days or more, about 41 days or more, about 42 days or more, about 43 days or more, about 44 days or more, about 45 days or more, about 46 days or more, about 47 days or more, about 48 days or more, about 49 days or more, about 50 days or more, about 51 days or more, about 52 days or more, about 53 days or more, about 54 days or more, about 55 days or more, about 56 days or more, about 57 days or more, about 58 days or more, about 59 days or more, 9 days or more, about 20 days or more, about 22 days or more, about 22 days or more, about 23 days or more, about 24 days or more, about 25 days or more, about 26 days or more, about 27 days or more, about 28 days or more, about 29 days or more, about 30 days or more, about 33 days or more, about 33 days or more, about 33 days or more, about 34 days or more, about 35 days or more, about 36 days or more, about 37 days or more, about 38 days or more, about 39 days or more, about 40 days or more, about 44 days or more, about 45 days or more, about 46 days or more, about 47 days or more, about 48 days or more, about 49 days or more, about 50 days or more, about 51 days or more, about 52 days or more, about 53 days or more, about 54 days or more, about 55 days or more, about 56 days or more, about 57 days or more, about 58 days or more, about 59 days or more, about 60 days or more, about 61 days or more, about 62 days or more, about 63 days or more, about 64 days or more, about 65 days or more, about 66 days or more, about 67 days or more, about 68 days or more, about 69 days or more, about 70 days or more, about 71 days or more, about 72 days or more, about 73 days or more, about 74 days or more, about 75 days or more, about 76 days or more, about 77 days or more days or more, about 44 days or more, about 45 days or more, about 46 days or more, about 47 days or more, about 48 days or more, about 49 days or more, about 50 days or more, about 55 days or more, about 55 days or more, about 55 days or more, about 55 days or more, about 55 days or more, about 56 days or more, about 57 days or more, about 58 days or more, about 59 days or more, about 60 days or more, about 66 days or more, about 66 days or more, about 66 days or more, about 66 days or more, about 67 days or more, about 68 days or more, about 69 days or more, about 70 days or more, about 71 days or more or more, about 68 days or more, about 69 days or more, about 70 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 77 days or more, about 78 days or more, about 79 days or more, about 80 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 88 days or more, about 89 days or more or about 90 days or more; and / or aa) the overall survival rate is increased after administration of the multicomponent cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject experiences a period of about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more, about 1.50 years or more, after administration of the multicomponent cellular therapy an overall survival rate of about 1.75 years or more, about 2 years or more, about 2.25 years or more, about 2.50 years or more, about 2.75 years or more, about 3 years or more, about 3.25 years or more, about 3.50 years or more, about 3.75 years or more, about 4 years or more, about 4.25 years or more, about 4.50 years or more, about 4.75 years or more, or about 5 years or more; and / or bb) wherein the incidence of hospital readmission is reduced following administration of the multi-component cellular therapy relative to a corresponding human subject who has been administered a standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), optionally wherein the human subject continues to have a reduced incidence of hospital readmission for about 1 month or more, about 2 months or more, about 3 months or more, about 6 months or more, about 9 months or more, about 1 year or more, about 1.25 years or more, about 1.5 0 years or more, about 1.75 years or more, about 2 years or more, about 2.25 years or more, about 2.50 years or more, about 2.75 years or more, about 3 years or more, about 3.25 years or more, about 3.50 years or more, about 3.75 years or more, about 4 years or more, about 4.25 years or more, about 4.50 years or more, about 4.75 years or more, or about 5 years or more without requiring a readmission; and / or cc) the human subject is about 3 months or older, or the human subject is between about 3 months and about 18 years of age, or the human subject is about 18 years of age or older, or the human subject is between about 18 years of age and about 65 years of age, or the human subject is between about 18 years of age and about 75 years of age, or the human subject is about 66 years of age to about 75 years of age, or the human subject is between about 3 months and about 75 years of age; and / or dd) the human subject has received one to five prior lines of therapy.

15. A cell therapy kit comprising a multicomponent cell therapy product according to any one of claims 1 to 5, optionally wherein the kit further comprises written instructions for using the cell therapy to treat a hematological malignancy in a human subject, optionally wherein the hematological malignancy is selected from the group consisting of leukemia, acute leukemia, chronic myeloid leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome, myeloproliferative syndrome, myelofibrosis and blastic plasmacytoid dendritic cell wherein the acute leukemia is in complete remission or in complete remission with incomplete hematologic recovery, wherein minimal residual disease is present in the human subject or minimal residual disease is absent in the human subject, wherein the acute leukemia is classified as an intermediate-risk to very-high-risk acute leukemia, wherein the acute leukemia is primary refractory acute leukemia or acute leukemia with minimal residual disease, wherein the acute leukemia is acute myeloid leukemia (AML) ML), acute lymphoid leukemia (ALL) and / or mixed phenotype acute leukemia (MPAL), optionally wherein the AML is low-risk AML to high-risk AML, optionally wherein the high-risk AML comprises a complex karyotype with 3 or more clonal chromosomal abnormalities selected from the group consisting of monosomal -5, 5q-, -7 or 7q, t(11q23, t(9;11), inv(3), t(3,3)t(6;9)t(9;22), a normal karyotype with an fms-like tyrosine kinase 3 (FLT3)-ITD mutation, and any thereof any combination, optionally wherein the CML is in blast crisis, in second chronic phase, in chronic phase, is accelerated, has a history of blast crisis and / or is intolerant to one or more first or second generation tyrosine kinase inhibitors (TKIs), optionally wherein the myelodysplastic syndrome is classified as high risk, optionally wherein the myelodysplastic syndrome is therapy-related myelodysplastic syndrome and / or secondary myelodysplastic syndrome, optionally wherein the non-Hodgkin's lymphoma is a non-Hodgkin's lymphoma with an adverse risk profile that is not suitable for autologous hematopoietic cell transplantation (HCT).

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