11.4 Solid Organ and HPC Transplantation

11.4 Solid Organ and HPC Transplantation

Quick Answer: Kidney and heart require ABO-compatible grafts; liver is more tolerant of ABO mismatch in emergencies. Passenger-lymphocyte syndrome is delayed hemolysis from donor B cells making antibody against remaining recipient red cells. HPC major ABO mismatch (recipient antibody vs donor RBC) → RBC-reduce the graft; watch for delayed erythroid engraftment and PRCA. Minor mismatch → plasma-reduce; watch for passenger-lymphocyte hemolysis. Support with irradiated, CMV-safe components and switch ABO types only when forward/reverse typing and isoagglutinin titers say so.

Outline III.B.5. Chapter 4.4 covered HPC as an HCT/P (DMSO, CD34, 21 CFR 1271). Chapter 9.4 covered HLA as a platelet/TRALI antigen. This section is transplant compatibility, hemolysis, and the transfusion timeline.

ABO in solid-organ transplant

Graft endothelium expresses ABO antigens. Preformed recipient isoagglutinins can bind that endothelium and cause hyperacute rejection. That is why routine kidney and heart allocation is ABO identical or compatible — the same direction as red-cell transfusion (O to all; A to A/AB; B to B/AB; AB only to AB). HLA matching and a negative DSA/crossmatch matter enormously for kidney survival; they do not replace ABO compatibility. Heart and liver are allocated more by urgency and size than by HLA, but heart still needs ABO compatibility in the usual adult.

Liver is the exception the exam wants. The liver is more resistant to ABO-mediated hyperacute rejection and is sometimes transplanted ABO-incompatible in a true emergency (fulminant failure, no compatible organ). That choice raises later rejection and biliary-complication risk; it is not “ABO does not matter in liver.” It is “liver is less strict than kidney or heart.”

Infants (typically under about 12–14 months, still isoagglutinin-poor) can receive ABO-incompatible hearts under protocols that monitor titers. Do not apply the infant-heart exception to an adult kidney.

Special adult ABO-incompatible kidney protocols exist (A2 into selected O/B recipients, titer reduction, rituximab). Those are program exceptions, not the default BB answer. If the stem does not describe a desensitization protocol, kidney = ABO compatible.

Passenger-lymphocyte syndrome

A solid organ or HPC graft carries donor B lymphocytes. In a minor ABO mismatch (group O graft into an A, B, or AB recipient — or a group A graft into AB), those passenger lymphocytes can produce donor-type isoagglutinins against remaining recipient red cells. Hemolysis appears about 1–3 weeks post-transplant, with a newly positive DAT, falling hemoglobin, and donor-origin anti-A or anti-B in the eluate. Liver (more lymphoid tissue) is the classic solid organ; it also follows minor-mismatch HPC.

Management is supportive: transfuse graft-compatible (donor-type or group O) red cells, avoid plasma that contains antibody against remaining recipient cells, and wait for the passenger clone to fade. This is not a mislabeled unit and not routine issue of group O red cells to a group A floor patient.

Non-ABO passenger antibodies (anti-D, Kidd, others) occur; the mechanism is the same — donor lymphocytes, recipient antigen.

HPC: major versus minor ABO incompatibility

HPC grafts are HLA-matched first. ABO mismatch is expected and managed, not used as the primary matching rule.

• Major mismatch — recipient has antibody against donor red cells (group A, B, or AB graft into group O; A into B; B into A). Residual donor RBCs in the product can hemolyze at infusion → RBC-reduce (especially marrow, which is red-cell rich). Later, persistent recipient isoagglutinins attack the new donor erythroid lineage → delayed red-cell engraftment and, in a subset, pure red-cell aplasia (PRCA). PRCA is most famous after O recipient / A donor. Plasma and platelets should be donor-compatible (safe for donor-type red cells). Red cells stay recipient-type or group O until anti-donor isoagglutinin is gone, the DAT is negative, and the forward type is donor.
• Minor mismatch — donor has antibody against recipient red cells (group O graft into A, B, or AB). Extra plasma in the product can hemolyze recipient cells at infusion → plasma-reduce. Later risk is passenger-lymphocyte hemolysis. Red cells can be donor-type or group O immediately. Plasma/platelets stay recipient-type or AB until recipient red cells are gone.
• Bidirectional (A ↔ B) combines both. Default support is group O red cells and AB plasma/platelets until both directions convert.

Delayed erythroid engraftment is not the same as graft failure of neutrophils and platelets. In major-mismatch PRCA the myeloid graft has taken; only the red-cell line is suppressed by leftover isoagglutinin. Treatment is time, immunosuppression adjustment, rituximab, plasma exchange, or EPO — not “the CD34 dose was wrong” as the first explanation.

Transfusion support, ABO switch, TA-GVHD

HPC recipients — and many solid-organ recipients on heavy immunosuppression — need modified components:

• Irradiation (25 Gy to the center of the bag) prevents TA-GVHD. Viable donor lymphocytes can engraft in an immunocompromised or HLA-haploidentical recipient and destroy marrow, gut, and skin. Leukoreduction is not sufficient for TA-GVHD prevention. Pathogen reduction also inactivates lymphocytes. Irradiate all cellular components for HPC patients from conditioning onward (and for directed blood-relative or HLA-matched products in anyone). TA-GVHD presents with fever, rash, diarrhea, and pancytopenia; mortality is high; prevention is the only reliable strategy.
• CMV-safe means leukoreduced or CMV-seronegative. For a CMV-negative HPC recipient (especially a CMV-negative donor/recipient pair), programs require CMV-safe cellular components. Leukoreduction is accepted as CMV-safe for most patients; some intrauterine/perinatal protocols still specify seronegative and leukoreduced.

ABO switch is laboratory-documented, not calendar-based. Typical adult scheme:

Do not switch a major-mismatch patient to donor-type red cells while anti-donor isoagglutinin is still detectable. Do not give minor-mismatch patients donor-type plasma that contains isoagglutinin against remaining recipient red cells.

Worked scenario. Group O patient, group A HPC graft, RBC-depleted. Day 0 through early engraftment: issue group O (or remaining recipient-type) irradiated CMV-safe red cells and group A or AB plasma/platelets. Neutrophils recover; hemoglobin stays transfusion-dependent at day +80 with persistent anti-A and a hypoplastic erythroid marrow. That is major-mismatch PRCA, not a forgotten irradiation order and not passenger-lymphocyte syndrome (the antibody is the recipient’s anti-A, not a new donor anti-H).

Exam traps. Kidney/heart are stricter ABO organs than liver. Major = recipient vs donor RBC = RBC reduce + PRCA risk. Minor = donor vs recipient RBC = plasma reduce + passenger lymphocytes. Irradiation prevents TA-GVHD; leukoreduction does not. CMV-safe is leukoreduced or seronegative. Switch ABO when the type and titer change, not on day +14 by habit.