10.4 Hematopoietic Progenitor Cell Transplantation

HPC Product Types

Hematopoietic progenitor cell (HPC) transplantation replaces or restores marrow function using stem cells collected from one of three recognized sources, and SBB/AABB nomenclature labels each explicitly:

• HPC-A (apheresis): peripheral blood stem cells collected by apheresis after mobilization, most often with G-CSF and, when mobilization is poor, the CXCR4 antagonist plerixafor. HPC-A is now the dominant product type for both autologous and allogeneic transplant because collection avoids general anesthesia and yields faster neutrophil and platelet engraftment than marrow.
• HPC-M (marrow): collected by direct bone marrow harvest, typically from the posterior iliac crest under anesthesia. Marrow is still preferred in some pediatric and severe aplastic anemia protocols and carries a lower risk of chronic graft-versus-host disease (GVHD) than peripheral blood in some allogeneic settings.
• HPC-C (cord blood): collected from the umbilical cord and placenta after delivery, cryopreserved, and banked. Cord blood tolerates a greater degree of HLA mismatch than adult donor sources, expanding donor availability, but its fixed, comparatively low total nucleated and CD34+ cell dose limits its use mostly to smaller recipients or requires a double cord-unit transplant in larger patients.

Transplants are further classified by donor relationship: autologous (the patient is their own donor, common in multiple myeloma and some lymphomas), allogeneic (a related or unrelated donor, needed when the marrow itself harbors disease or a healthy immune graft-versus-tumor effect is desired), and syngeneic (an identical twin donor, genetically identical but still classified separately from autologous).

Cell Dose, Conditioning, and Cryopreservation

A widely referenced minimum CD34+ cell dose for reliable engraftment is around 2 x 10^6 cells/kg recipient body weight for autologous HPC-A products; higher doses generally give faster, more reliable engraftment, and institutional or product-specific thresholds vary, so the exam expects recognition of the concept and rough magnitude rather than a single rigid legal number. Before infusion, patients receive a conditioning regimen - myeloablative (high-dose chemotherapy or radiation that destroys the recipient's own marrow, requiring the graft to rescue hematopoiesis) or reduced-intensity/nonmyeloablative (lower-intensity regimens that rely more on a graft-versus-tumor immune effect, used for older or more comorbid patients who cannot tolerate full myeloablation).

Collected HPC products that are not infused immediately are cryopreserved, typically with 10% DMSO (dimethyl sulfoxide) as the cryoprotectant, and stored in the vapor or liquid phase of nitrogen. Post-thaw viability testing, commonly by a dye-exclusion method, confirms the product meets a minimum viability threshold before infusion. DMSO itself causes transient infusion reactions - nausea, a garlic-like odor, and occasionally cardiac or renal effects at high infused volumes - which is why premedication and a controlled infusion rate are standard practice.

ABO Mismatch in Hematopoietic Cell Transplant

Unlike solid organ transplant, where ABO antigens matter because of vascular endothelium, HPC transplant ABO mismatch is entirely about red cells carried within or produced by the graft, and the SBB exam expects the three mismatch categories memorized cold:

For major mismatch, the concern is analogous to giving an incompatible red cell transfusion directly from the product's residual red cells, so laboratories reduce the red cell content of the graft before infusion, and may recommend red cell exchange or plasma exchange of the recipient pretransplant to lower isohemagglutinin titers when the mismatch is severe. For minor mismatch, the risk is delayed and mirrors passenger lymphocyte syndrome from solid organ transplant: newly engrafted donor lymphocytes produce antibody against the recipient's remaining native red cells, so the product's plasma is reduced, and the recipient is monitored for hemolysis as donor engraftment proceeds.

Transfusion support strategy during and after an ABO-mismatched HCT follows the changing chimeric state: give red cells compatible with both recipient and donor ABO type while engraftment is incomplete, often the recipient's original type or group O when uncertain, and transition toward the donor's ABO type once serologic and chimerism evidence confirms the marrow has fully converted to donor origin.

Supportive Transfusion, GVHD Prevention, and Chimerism

Every HPC transplant recipient, before and after transplant, must receive irradiated cellular blood components - red cells, platelets, and granulocytes - to inactivate residual donor lymphocytes in the transfused product and prevent transfusion-associated graft-versus-host disease (TA-GVHD), a nearly always fatal complication in this immunosuppressed population; this requirement is independent of, and in addition to, any leukoreduction already performed. Chimerism testing, typically short tandem repeat (STR)-based molecular analysis comparing pre- and post-transplant DNA, tracks the percentage of donor- versus recipient-derived cells in blood or marrow after allogeneic transplant, confirming successful engraftment, detecting graft failure, or flagging early relapse through falling donor chimerism well before it would be apparent on a CBC.

Exam Traps

Keep major versus minor straight by anchoring on whose antibody is doing the attacking: major mismatch means the recipient's antibody threatens donor red cells in the product, so red cells are reduced; minor mismatch means the donor's (graft) antibody threatens the recipient's red cells, so plasma is reduced. Do not confuse HPC-A, HPC-M, and HPC-C source labels with the ABO mismatch categories - they answer two completely different questions, where the cells came from versus whose antibody attacks whom.