Chapter 39: Principles of Hematopoietic Cell Transplantation

TYPES OF TRANSPLANTS

Autologous Transplantation

• Infusion of autologous hematopoietic stem cells (HSCs) permits the administration of very-high-dose therapy to induce remission and potentially cure the underlying disease. The autologous HSC infusion restores hematopoiesis and makes mortality from cytotoxic therapy–induced marrow aplasia unlikely.

• The use of chemotherapy and immunotherapy just prior to mobilization of blood-derived HSCs reduces tumor cell contamination (“in vivo purging”) of the collected product and simultaneously provides a reduction in total tumor burden in the patient prior to the high-dose regimen.

• Autologous hematopoietic cell transplantation (autoHCT) is associated with the lowest rate of nonrelapse morbidity and mortality of any transplant strategy but with the highest risk of relapse.

Allogeneic Transplantation

• Compared with autoHCT, allogeneic (allo) HCT involves more pretransplantation preparation, poses a greater risk of complications to the patient, is associated with a significantly higher nonrelapse morbidity and mortality, and has a considerably longer period of intensive posttransplantation follow-up. However, unlike autologous HSC products, there is no risk of tumor contamination with allogeneic products.

• In addition, because tumor cells are host derived and allogeneic immune cells recognize them as foreign, the potential exists for the graft to attack the residual tumor cells (termed a graft-versus-tumor effect) in the patient following transplantation. The evidence that alloHCT outcomes are greatly affected by this graft-versus-tumor effect includes the following: tumor relapse is lower after allogeneic than after syngeneic (identical twin) HCT, tumor relapse is higher in recipients of T-cell–depleted grafts, and donor lymphocyte infusions can induce remissions.

SOURCES OF HEMATOPOIETIC STEM CELLS

Marrow

• Marrow is aspirated by repeated placement of large-bore needles into the posterior iliac crest, generally 50 to 100 aspirations simultaneously on both sides, while the patient is under general (or, less commonly, regional) anesthesia. A volume of up to 20 mL/kg donor body weight is considered safe to remove during the collection procedure.

• The lowest cell dose to ensure stable long-term engraftment has not been defined with certainty. Typical collections contain more than 2 × 10⁸ total nucleated marrow cells/kg recipient body weight.

• The risk of serious complications is about 2%.

Blood

• Mobilization of autologous peripheral blood progenitor cells (PBPCs), also known as peripheral blood stem cells (PBSCs), is with granulocyte colony-stimulating factor (G-CSF) with or without chemotherapy or G-CSF plus plerixafor (a CXCR4 antagonist).

• Mobilization of PBSCs for alloHCT is typically with G-CSF alone. The procedure is safe, and in a review of nearly 7000 healthy unrelated donors, serious side effects were uncommon (<1%) with the most common side effect being bone pain. Trials of G-CSF and plerixafor and of plerixafor plus novel agents in allogeneic donors are ongoing.

• Once mobilized, PBPCs are collected by apheresis.

• A minimum of 2 × 10⁶ CD34+ cells per kg recipient body weight is usually recommended for ...