Marrow Matters - Bone Marrow Transplant - Aplastic Anemia  
 
 
Aplastic Anemia

 

 
 
Google Scholar

 
 

Aplastic AnemiaHLA Matching

what is HLA matching?

Human leukocyte antigen (HLA) typing is used to match a potential recipient with a donor for a bone marrow or cord blood transplant. Human leukocyte antigen typing is not the same as ABO blood typing. HLA is a protein – or marker – found on most cells in your body. Your immune system uses HLA markers to know which cells belong in your body and which do not.

Essentially, an HLA match indicates that the donor and potential recipient's tissues are immunologically compatible with each other. How well the donor’s and recipient’s HLA tissue types match plays a large part in whether the transplant will work.

Why do some doctors do 6 out 6 matching, while other doctors do 10 out of 10 matching?

The type of matching done by a center depends entirely on their system. HLA typing must be done at a minimum of 6 loci for cord blood units and 8 loci for marrow. Some centers use high-resolution typing for up to 10-12 loci for cord blood or bone marrow. [See PBMT at http://www.pbmtc.org/education/before-your-transplant].

Higher resolution loci matching

Now that transplant centers are more often using high-resolution tests, matching is becoming more complex. Perfect 10 out of 10 matches at that level are much harder to find. But transplant teams are also getting better at figuring out what kinds of mismatches they can get away with in which situations – that is, which mismatched sites are less likely to affect transplant success and survival.

What is matched in an HLA matching test?

Matching a patient to a bone marrow/stem cell donor relies on testing of specific proteins on the surface of white blood cells called human leukocyte antigens (HLA). This is also called histocompatibility testing or tissue typing.

HLA matching is used for several purposes, but not all matching is done at the highest levels. For example, the match for a bone marrow transplant needs to be closer than the match needed for a kidney transplant.

Is GvHD and Graft Failure the same thing? No.

Mismatched Donors & Outcomes

The importance of human leukocyte antigen (HLA) matching in unrelated donor transplantation for nonmalignant diseases (NMD) has yet to be defined. A clinical trial analyzed data from 663 unrelated marrow and peripheral blood stem cell transplants performed from 1995 to 2007 for treatment of NMD. Transplantation from a donor mismatched at the HLA-A, -B, -C, or -DRB1, but not -DQB1 or -DPB1, loci was associated with higher mortality in multivariate analyses (P = .002). The hazard ratio for mortality for single (7/8) and double mismatched (6/8) transplants was 1.29 (0.97-1.72; P = .079) and 1.82 (1.30-2.55; P = .0004), respectively, compared with 8/8 matched transplants.

HLA mismatches were not associated with acute or chronic GVHD, but were strongly associated with graft failure.

After adjustment for other factors, the odds ratio for graft failure for 7/8 and 6/8 (allele and/or antigen) matched pairs compared with 8/8 matched transplants was 2.81 (1.74-4.54; P < .0001) and 2.22 (1.26-3.97; P = .006), respectively. Patients with NMD should receive transplants from allele matched (8/8) donors if possible.

Unlike the case with malignancies, HLA mismatching in NMD is associated with graft failure rather than GVHD.

Doctors keep learning more about better ways to match donors. Today, fewer tests may be needed, for siblings since their cells vary less than an unrelated donor. But more than the basic 6 HLA antigens are often tested on unrelated donors to reduce the risks of mismatched types. Sometimes doctors will want to look at 5 pairs of antigens, for example, to try and get a 10 out of 10 match. Certain transplant centers now require high-resolution matching, which looks more deeply into tissue types. Other centers are doing clinical trials with related half-matched donors and different chemotherapy schedules. This is an active area of research because it’s often hard to find a good HLA match.

hLA antibody testing

In addition to HLA testing to determine if the donor and potential recipient are matched, further tests are conducted to determine if the potential recipient has an HLA antibody.

Positive or Negative antibody Crossmatch

If the patient has antibody to the donor's HLA, a positive crossmatch exists. The donor cells are injured in a positive crossmatch.

A positive crossmatch is a strong indicator against transplant since it indicates a strong potential towards GvHD.

A negative crossmatch indicates that the patient doesn't have HLA antibody against the donor.

Developing Antibody

A patient can also develop antibody to the donor cells post transplant, such as if the patient receives a blood transfusion. HLA Antibody can develop as a result of pregnancy, prior transplant(s) or blood transfusion(s).

Post transplant antibody development is referred to as Percent Reactive Antibody (PRA).

Percent Reactive Antibody

Percent Reactive Antibody, or PRA, is the amount of HLA antibody present in the patient's blood serum. The PRA can be determined by comparing the patient's serum to 60 different types of HLA. If the patient's serum reacts with 30 out of 60 types of HLA, the patient's PRA is 50%.

PRA is often calculated on a montly basis.

PRA Specifity

In addition to determining a patient's PRA level, these tests can also help us understand the degree to which the antibody is specific to the donor HLA. Antibody is often developed post transfusion.

Some patients have one or two antibody specificities, and some have numerous specifities.

Specifity can be determined at the time PRA is determined.

How is bone marrow taken for an HLA match test?

Surprisingly enough, even though an HLA matching test is performed to match a donor's match to a recipient for a bone marrow transplant, the bone marrow isn't taken to conduct the match. Rather, the blood that flows through a person's bloodstream is used to perform a preliminary match to determine whether a full-scale match should be conducted.

The preliminary match analyzes four proteins of each person's blood cells, namely the white blood cells. If the initial test produces a match, the second and much more indepth matching process is conducted seeking to match up to 12 possible markers. Most hospitals run a 10 marker matching test, some run an eight marker test, and a few still run a six marker test. The greater the match of proteins, the greater the success anticipated from a transplant.

how is bone marrow taken for a donation?

Bone marrow can be extracted from a donor in several manners; the two most common methods of acquiring bone marrow from a donor are from the blood stream, and from the bone marrow.

A bone marrow transplant usually consists of a transplant of blood stem cells while some transplants include actual marrow. Blood stem cells produce blood cells. The body is full of blood stem cells; they are in the tissues, the blood stream, and throughout a person's body. A major number of blood stem cells exist in the bone marrow where blood cells are created. The bone marrow is the center portion of all bones. The largest bone marrow depositories in a person's body are in the femur - the longest bone in the body positioned between the hip and the knee - bone, in the breast bone and in the large hip bones.

The numbers of blood stem cells that exist in the blood stream are insufficient for an effective bone marrow transplant. In cases in which doctors seek to extract blood stem cells from the blood stream, a drug is given to the donor that causes a proliferation of blood stem cells into the blood stream. Once there is a sufficient quantity of blood stem cells in the bloodstream, the donation of the stem cells is a simple matter of a giving blood.

Blood stem cell donations from the bloodstream are not the preferred method. Blood stem cells taken directly from the bone marrow are more plentiful, and research has indicated that in some situations, bone marrow donations are much more successful.

Blood stem cell donations from the marrow are usually extrapolated from the hips in a place called the dimple. The donor is taken into outpatient surgery because they are put under anesthesia so that they cannot feel the aspiration of bone marrow. The process takes about 2-3 hours.

aplastic anemia Information:

For more information about Aplastic Anemia, please consider these sites:

Donor Selection

Aplastic Anemia Association

One Life Matters BLOG

Marrow.Org

Bone Marrow Donation

Bone Marrow Testing

Here is an excellent white paper from NIH on the subject of HLA matching: http://www.ncbi.nlm.nih.gov/pubmed/16790851

The abstract: Human leukocyte antigen (HLA) molecules are expressed on almost all nucleated cells, and they are the major molecules that initiate graft rejection. There are three classical loci at HLA class I: HLA-A, -B, and -Cw, and five loci at class II: HLA-DR, -DQ, -DP, -DM, and -DO. The system is highly polymorphic, there being many alleles at each individual locus. Three methods for HLA typing are described in this chapter, including serological methods and the molecular techniques of sequence-specific priming (SSP) and sequence-specific oligonucleotide probing (SSOP). The influence of HLA matching on solid organ and bone marrow transplantation is also described. HLA matching has had the greatest clinical impact in kidney and bone marrow transplantation, where efforts are made to match at the HLA-A, -B, and -DR loci. In heart and lung transplantation, although studies have shown it would be an advantage to match especially at the DR locus, practical considerations (ischemic times, availability of donors, clinical need of recipients) make this less of a consideration. Corneal grafts are not usually influenced by HLA matching, unless being transplanted into a vascularized (or inflamed) bed.