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.”