Page 15 - Heart Transplant Protocol

Heart Function Service: Heart Transplant Protocols

HLA-Incompatible Heart Transplantation

When patient produces alloantibody to human leukocyte antigen (HLA), it is called an HLA antibody. HLA
antibodies develop when a patient is exposed to extraneous human tissues – eg homograft, blood
transfusions, pregnancy or organ transplant. Sensitization can occur when no known sensitizing events
have occurred and it is postulated that this is due to cross reactive antibodies with pathogens eg viral
coats. Sensitized patients are at risk of severe rejection and poor graft outcomes. Their options are to
wait for a heart which doesn’t have the HLA they have antibodies to. This may be almost impossible if
the patient is highly sensitized and leads to high waitlist mortality. An alternative is desensitize the
patient prior to transplant by removing the antibodies and preventing new ones from being produced or
to transplant across the antibodies and deal with the rejections etc afterwards. The last two options are
discussed further below.

The presence and strength of the HLA antibody is detected by the HLA single antigen test and reported
as mean fluorescence intensity (MFI). When an HLA antibody measures above 7000 MFI, it is correlated
with a positive crossmatch by flow cytometry or the complement dependent cytotoxicity (CDC) test. At
Children’s Medical Center, Dallas, an HLA antibody measurement of >3000 MFI is correlated with a
positive crossmatch. Patients that are sensitized pre transplant have a reduced likelihood of a “matched
organ”. The actual likelihood depends upon the number of different antibodies formed (often called the
panel reactive antibody or PRA). To increase the chances of a “matched” transplant (and thus less
rejection) desensitization can be undertaken to reduce the antibody strength and breadth.
Desensitization can thus be undertaken prior to transplant if the patients is highly sensitized to potential
donors. Scientific validation of these strategies has yet to be achieved. If desensitization is
contemplated then the plan should be discussed with the heart transplant team including the
immunologist and parents should be informed about the risks and outcomes based on current literature
and the discussion documented in the medical record.

Desensitization Protocol
Send blood for Heart Recipient HLA antibody profile (with C1q) and CD19 B cell count. C1q has to be
ordered in paper form (see next page): Send form to the HLA lab along with the sample for the HLA
antibody profile. Both tests will be processed from the same sample.

Desensitization is usually accomplished by a combination of removal of existing antibodies with
plasmapheresis and preventing new antibodies being formed.

a. Existing antibodies are removed by plasmapheresis (usually 4 -10 cycles) and
replacement IVIG (0.1 G/kg) given after each procedure.
2
b. The production of new antibodies is reduced by giving Rituximab (375 mg/m for 4
doses) until the B cell population is eliminated and Bortezomib (1.3 mg/m ) twice a
2
week for two weeks and then a week off to reduce the plasma cell population. Two or
more Bortezomib cycles may be required. Bortezomib is given after the plasmapheresis
when the plasma cells are maximally stimulated.
c. Then high dose immunoglobulin (2G/kg) is given weekly to continue antibody
suppression to transplant

Updated November 9, 2017 15