A Match? Or Everything You Ever Wanted to Know About HLA Typing but was Afraid to Ask!

I spoke with my MUD (Matched Unrelated Donor) Transplant Coordinator this morning, and she had good news and not so good news.  Because the not so good news was difficult to comprehend, I am going to provide some details to HLA typing that might help those who are wanting to more fully understand what all is going on.

The good news was that the person who went in for their blood test last week was not only a 10 out of 10 match but was even better at 13 out of 14.   Some facilities require 6 of 6, 8 of 8, others 10 of 10.  The more markers that match the better the results.  MD Anderson looks for 10 of 10 or better.   So 13 of 14 is really good.

What are these “markers?”  Human Leukocyte Antigen (HLA) typing is used to match patients and donors for bone marrow or cord blood transplants (also called BMT).  HLA are proteins — or markers — found on most cells in your body.  Your immune system uses these markers to recognize which cells belong in your body and which do not.

Several of you have also asked the difference between a bone marrow transplant and a stem cell transplant.  Basically not much except for how they retrieve the stem cells.  Bone Marrow Transplants (BMT) or Stem Cell Transplants are done to restore the body's ability to produce the different cells that make up the blood.  Bone marrow is the spongy tissue inside large bones.  It contains immature stem cells.   Stem cells mature to become red blood cells that carry oxygen, white blood cells that help fight infection, and platelets that help stop bleeding.  In a bone marrow transplant, the donated stem cells are taken from bone marrow.  In a stem cell transplant, the donated stem cells are taken from circulating blood.  Bone marrow donation is a surgical procedure done in a hospital.  The donor is given anesthesia; then a needle is used to remove marrow from the hip bone (similar to a bone marrow biopsy).  Peripheral blood stem cell donation is done in an outpatient setting.  The donor is given medication over several days to increase the number of stem cells in the bloodstream.  Then a needle is inserted into an arm vein to draw out the blood.  The blood passes through a cell separator machine that removes the stem cells.  The rest of the blood is returned immediately to the donor.   This is the now the more common procedure.

The not so good news is where it starts getting confusing.  When mine was tested, they discovered that I have HLA antibodies in the DP (more on this shortly).  The antibodies are similar to the resistance we develop to Chicken Pox after we’ve had it.  That’s a good thing with Chicken Pox.  But if I have a resistance to a part of my donor’s cell makeup, it could inhibit engrafting.  Engraftment is when the donated cells start to grow and make new blood cells.   A close HLA match reduces the risk of a post-transplant complication called graft-versus-host disease (GVHD).  GVHD occurs when the immune cells from the donated marrow (the graft) attack your body (the host).

There are several groups of HLA markers.  MD Anderson primarily looks at A, B, C, DR, and DQ.  My antibodies are on DP, which most facilities don’t even test.  But because MD Anderson looks for the best match at a detailed level, my antibody situation will be a factor to consider.  If this 22 year old female with 13 of 14 matches ends up being the best match available, then there are extra steps that can be taken at time of transplant to help overcome the antibody issue.  For now, they will continue to search for the best match and keep this one on the back burner. 

For more information on HLA typing, here are a couple helpful sites.

 

http://en.wikipedia.org/wiki/Human_leukocyte_antigen     

http://marrow.org/Patient/Transplant_Process/The_Donor_Selection___Transplant_Process.aspx

The lack of a fully matched donor (8/8 matched, i.e., matched at HLA-A, -B, -C, -DRB1) does not preclude transplantation as a possible treatment option, because transplant outcomes are generally better when patients are transplanted earlier in their disease rather than later.

The NMDP (National Marrow Donor Program) therefore recommends not delaying transplant in the hopes of finding a better matched donor later. The NMDP bases this recommendation on a 2007 study of 3,857 transplants demonstrating that 6/8 patients transplanted in an early disease stage do better than fully matched 8/8 patients transplanted in advanced disease stage. [5] Because disease stage at the time of transplant is the only factor under direct control of a physician, an early referral is perhaps the single most important step that can affect survival. (See the NMDP Clinical Fact Sheet on Outcomes in Unrelated Hematopoietic Cell Transplantation for additional data.)

 (Taken from BeTheMatch.org.) 

With that in mind, I am going back to my local oncologist tomorrow, and then we will meet with my transplant doctor on January 2.  The MUD Coordinator will keep the transplant doctor and the head of the CLL department in the loop with regard to possible donors.  The doctors at MD Anderson were very pleased with our proactive approach.  While it is scary to say the least, the potential for long-term survival is greater with this plan. 

I think that this past month of increased fatigue has helped me begin to accept what the next year or so is going to be like.  I am learning my limits, and while I still push them often, I now know how far is far enough.  As I wrote on an earlier post, we continue to prepare.  It doesn’t feel like much sometimes, but it is all I can do right now.  Prepare and pray.  Pray for the right donor.  Pray for the right timing for the transplant.  Pray that the right pre-transplant treatment is chosen.  Pray that my body accepts the transplant.  Pray for no infections.  Pray for Paul and my mother as they provide care for me before, during, and after.  Pray for continued positive attitude.  Pray for peace.

“And the peace of God, which surpasses all understanding,

will guard your hearts and your minds in Christ Jesus.”  

Philippians 4:7

It’s all in the details….

Many of you have asked for more information as to what exactly the “17p deletion” is and what it means.  Others have asked for details about the bone marrow transplant.  I am going to include both here.  Please forgive the lengthiness and the sterile dialogue.

17p Deletion

To put it as simply as possible, and to quote my oncologist, 17p deletion involves a molecular change in chromosome p53 which creates resistance to chemo.  “Preliminary data indicate that the presence of chromosome 17p deletion (17p-) by fluorescent in-situ hybridization (FISH) in chronic lymphocytic leukemia (CLL) may be uniquely associated with resistance to standard therapy and dismal survival.”   

Bucket A CLL patients can “watch and wait.”  Bucket B patients can be “managed.” But…

“For the last third of patients with the most aggressive form of CLL and all the bad prognostic indicators, accurate diagnosis and risk classification are even more important. These folks are in high risk “Bucket C”. They don't have the luxury of a lot of time to waste.  Dithering is not an option for them.  For this unfortunate subset of CLL patients, making the right first therapy choices is essential.  Under-treating an aggressive form of CLL, waiting too long or wasting time with ineffective and tentative therapies spells trouble of the worst sort.

If you are a younger patient with high risk profile, the game plan becomes a lot more critical. Unlike more elderly patients with a middle of the road prognosis, you are not going to be able to “run out the clock”.  A five to ten year survival prognosis is not good enough, you face too much of a penalty in reduced life span.  Even our best chemotherapy regimens are not going to hold the line for what would otherwise be your normal life span.  I am extremely happy to report that modern advances in stem cell transplants now give us options we did not have just a few years ago. Emerging consensus is that young patients with high risk CLL should be looking at stem cell transplants sooner rather than later.

Think of stem cell transplants as getting rid of your cancerous, no-good-bum of an immune system and replacing it with a healthy immune system from a compatible and willing donor. It helps if you have a well-matched sibling donor, since it saves the hassle of finding a matched unrelated donor, a task that becomes next to impossible for ethnic minorities.  Stem cell transplants are coming up the curve awfully fast.  Survival statistics are improving each year.  But making the decision to go the transplant route is still a tough call and you really need to get your ducks in a row before you can make it.”

There are basically two schools of thought in treatment.  One, wait until I’m more symptomatic before treating.  Or, two, treat now while I’m still young and healthy (yes, my doctor said that 50 is young!) and have a better shot of handling the treatment and transplant.  This is the decision that the MD Anderson specialists and my oncologist will be discussing over the next week or two after they get the results back from all my upcoming tests.

Allogeneic Stem Cell Transplant (via MDA Patient Education)

This section is for patients who may be receiving stem cells from a donor’s peripheral blood or bone marrow. 

General Information

Stem cells are found in a person’s:

· blood,

· bone marrow (spongy tissue found inside the large bones of the body) and a

· newborn baby’s umbilical cord.

During an allogeneic transplant, physicians collect stem cells from a donor and infuse them into a patient.  A special blood test called HLA (human leukocyte antigen) typing checks if a patient and a donor are a match. The donor may be: 

· an identical twin (a syngeneic transplant), 

· a relative, 

· someone who is not a relative (matched unrelated donor, or MUD transplant), or

· a newborn baby (umbilical cord blood transplant)

Before the transplant, the patient receives high doses of chemotherapy and/or radiation to destroy the disease; however, this also damages other parts of the body, including the bone marrow and immune system.  (The immune system is the body’s defense against disease and infection.) Also, the body is not able to make healthy blood cells.  The transplant repairs these effects and creates an environment to accept the donor’s stem cells. 

Graft-Versus-Leukemia Effect

Graft-versus-leukemia or graft-versus-disease effect (GVL/GVD) is a major benefit of an allogeneic transplant. It occurs when the donor’s cells destroy the patient’s cancer cells because it “sees” them as “foreign” and different.

HLA Typing

If you are being considered for an allogeneic transplant, you will need HLA typing.  Antigens are proteins found in white blood cells that make each person’s tissue type unique. HLA typing is a special blood test that finds these antigens and then compares them to the donor’s. Both the patient and all eligible family members should be HLA typed to find a suitable donor.

Finding an HLA-Matched Donor

It is important to find the most highly matched donor available. If the donor and patient are HLA-matched, there is less risk of complications.   The best donor for an allogeneic transplant is an HLA-matched sibling. This is because parents pass on one-half of their HLA typing to their children. Therefore, each brother or sister has a 25 percent chance of being a match with the patient. There is about a 1 percent chance of being matched with a parent, child or distant relative.

Collection of Peripheral Blood Stem Cells or Bone Marrow

Stem cell collection is a procedure that involves separating and collecting stem cells from the blood or bone marrow, then the stem cells are stored for transplant use. 

There are two main ways of collecting stem cells: 

· Apheresis is the process of collecting peripheral blood stem cells (PBSC) from the

bloodstream. 

· Bone marrow collection (harvest) is the process of collecting the cells directly from the bone marrow.

Admission for Stem Cell Transplant

Pre-admission Testing

Before you are admitted for your stem cell transplant, you will need a series of tests. All of the tests evaluate your disease or personal health. Unfortunately, some of the tests are repeats of tests you have already had, but they need to be done within 30 to 45 days of your transplant.  (NOTE:  My tests begin October 10.)

Conditioning Phase

During the conditioning phase, patients receive high doses of chemotherapy and/or total body irradiation before the transplant. This:

· Eliminates the existing bone marrow cells to make room for the donor’s new, healthy cells

· Destroys any existing tumor cells if there is cancer or a tumor

(NOTE:  my doctor has already decided on the FCR regimen.)

Stem Cell Infusion

The collected cells are infused after the completion of the high dose chemotherapy and/or radiation. Using your CVC, the cells are infused into the bloodstream, similar to a blood transfusion. The infusion lasts from 30 minutes to several hours.

Initial Recovery Period

After the stem cells are infused: 

· You will stay in the hospital for about three to four weeks while your counts recover. 

· Your treatment team will monitor your blood counts daily and help manage any side effects. 

· You may take many IV medicines and fluids. 

· Once you have “engrafted,” meaning that your white blood cells have recovered, and you are eating and drinking well, you will be discharged from the hospital.

· Each patient will be evaluated on an individual basis and circumstances will vary. For example, you may need to stay in the hospital if you have a fever or other condition requiring care.

Follow-up/Post-Discharge Recovery

After being discharged from the hospital:

· During this time, you must have a caregiver with you 24 hours a day.  

· You will be monitored in the Ambulatory Treatment Center (ATC) for up to 100 days after the transplant.  Some patients may need to stay longer in the ATC. Follow-up is generally every day and will adjust to every other day or twice a week depending on your health and needs.  

· Each patient will be evaluated on an individual basis and circumstances will vary

· Our goal is that you will be able to return home after the first 100 days, but this may vary depending on individual needs. Once you are told that you may leave the Houston area, you will continue to have follow-up appointments with your cancer or primary care physician in your home community. Some patients may require continued monitoring and symptom management. If this is the case, you will need to stay within 30 minutes of MD Anderson until your physician tells you it is okay to stay further away.  

· Before you are discharged from the Houston area, you will attend a survivorship class.

Once you are discharged home, you will be asked to have regular lab tests done and the results will be sent to MD Anderson for review. You will need to return for tests and exams every three to six months for at least the first year and then every six to twelve months thereafter. This will vary for each patient, depending on your condition. Your physician will make the follow-up plan for you.

Potential Complications of an Allogeneic Transplant

Complications could occur when having an allogeneic transplant. These are: 

Graft Failure

The immune system may reject the transplant. This is uncommon because the chemotherapy and/or radiation given before the transplant suppresses (damages) the patient’s immune system.

Graft-Versus-Host Disease 

Graft-versus-host disease develops in patients who receive any type of allogeneic transplant.   GVHD occurs when the new bone marrow (the graft) reacts against the tissues of the body (the host). There are two forms of GVHD: acute GVHD (short-term) and chronic GVHD (long-term).

Acute GVHD

Acute GVHD happens in the first 100 days after a transplant. You will receive medicines before, during and after the transplant to help prevent and/or treat acute GVHD. The seriousness of GVHD varies from mild and temporary to serious and chronic. It can be life-threatening.

Chronic GVHD

Chronic GVHD develops from three months to several years after the transplant, and it affects multiple tissues in the body.

Weakened Immune System

The immune system is very weak for several months after an allogeneic transplant. It takes over a year for the immune system to recover completely. The first three months after a transplant are critical. Physicians normally prescribe antibiotics during this period, and they monitor patients closely for infections.

Just as an FYI, this is just a nibble of all the information that we have been ingesting over the last couple months.  Please pray for my doctors (and us) as we decide which course of action to take and when.  I hope these excerpts provided some answers to the many questions that have been asked. 

Walking with Him…

Psalms 119:105 “Your word is a lamp to my feet and a light for my path.”