As the only adult, FACT accredited program in the Washington, D.C. region, we offer multiple treatment options including allogeneic stem cell transplantation. Allogeneic stem cell transplantation involves using stem cells from a healthy donor after receiving chemotherapy to fight your disease.
Many cancers and other blood diseases, including sickle cell disease, are sensitive to the intensity of chemotherapy. While high doses of chemotherapy can destroy the cancer, these same doses can damage the blood-forming stem cells in the bone marrow.
Allogeneic stem cell transplantation allows dose-intensive chemotherapy while the infusion of stem cells from a donor regrows the patient's bone marrow and immune system.
In contrast to autologous stem cell transplantation, which uses the patient’s stem cells, patients undergoing allogeneic transplantation develop the donor's immune system. The donor immune cells can help kill cancer cells – a “graft-versus-disease” effect not seen with autologous transplantation. This immune effect reduces the risk of relapse after transplantation. For this reason, allogeneic transplantation is more effective than autologous transplantation in treating cancers that may be resistant to chemotherapy.
We use allogeneic transplantation to treat diseases involving the hematopoietic stem cell, such as some forms of leukemia, or genetic diseases, like sickle cell anemia. For these diseases, collecting healthy stem cells from the patient for autologous hematopoietic stem cell transplantation is impossible.
Allogeneic stem cell transplantation is commonly used in the treatment of bone marrow diseases that may be sensitive to high doses of chemotherapy or to the graft-versus-disease effect, such as
Acute myeloblastic leukemia (AML)
Acute lymphoblastic leukemia (ALL)
Chronic myelocytic leukemia (CML)
Chronic lymphocytic leukemia (CLL)
Certain genetic blood disorders
Sickle cell disease
However, allogeneic transplantation is a much more complex treatment than autologous stem cell transplantation. Allogeneic transplantation requires that we identify a person who can donate cells. This donor may be related (your blood relative) or unrelated to you (selected from a national database). Also, allogeneic stem cell transplantation carries risks to your health not seen after autologous transplantation.
Your physicians will help you decide if allogeneic stem cell transplantation could effectively treat your disease.
What to expect before allogeneic stem cell transplantation
The first step in performing allogeneic stem cell transplantation is consultation with the transplant physician. This physician will review your disease history and the treatments you have received. This review aims to determine the most effective and least involved treatment for your disease.
During the consultation, the physician will review your overall health and discuss your potential donors, including siblings, relatives, and unrelated donors from one of the donor registries.
A nurse coordinator will assist you in scheduling any pre-transplant testing needed.
The physician may request blood samples at this initial visit to determine the tissue type necessary for identifying a donor, your blood type, and evidence of past viral infections.
The search for a donor frequently requires 8-12 weeks before we can perform the transplant. Therefore, it is important to begin searching for a donor as soon as possible, even if you or your physicians are still considering your treatment options.
When a donor is identified, you will undergo a comprehensive evaluation of your health and disease status. The transplant physician will use this information to decide the type of pre-transplant therapy you will receive.
This testing could include:
Tests of lung function
Bone marrow tests
Your physician and nurse coordinator will review the purpose of these tests and help you in scheduling these tests promptly. The transplant physician will also decide if bone marrow or peripheral blood stem cells will be the better choice for your transplant. The donor has the final choice about what they are willing to donate to you.
Our team will contact your insurance provider to determine if they will cover your allogeneic stem cell transplantation treatment. We understand that medical bills and questions about insurance coverage can be a significant source of concern and stress for patients and their families, so we prioritize keeping you well-informed before you begin your treatment.
We require that allogeneic transplant patients have a primary and a secondary caregiver who can stay with them 24/7 after being discharged from the hospital for at least two months or 100 days after the day of the transplant (discharge dates from the hospital vary).
Your transplant nurse coordinator will work with you and your referring hematologist to develop a treatment calendar that shows the expected dates for collection of stem cells, admission date, chemotherapy dates, radiation dates (if to be given), transplant date, and expected discharge date.
What to expect during allogeneic stem cell transplantation
Transplant involves a chemotherapy and/or radiation therapy regimen followed, one or more days later, by infusion of hematopoietic stem cells from the donor. You will require an intravenous catheter for the chemotherapy and cell infusion. This catheter will be in place for several weeks and will be used for blood draws and intravenous treatments. You will be admitted to the hospital for at least 3 to 4 weeks to receive treatment.
The pre-transplant regimen is frequently several days in duration. The stem cell infusion – the actual transplant – occurs after completion of the pre-transplant chemotherapy regimen. You will then remain under the care of the transplant service (typically as an inpatient in the transplant unit) until your bone marrow recovers. During this time, you will also receive supportive medical and nursing care until the immediate side effects of the dose-intensive chemotherapy improve.
The side effects of the pre-transplant chemotherapy and/or radiotherapy regimen will be discussed with you in detail by your physician and nurse coordinator. These will also be listed in the consent form you will be given before the hospital admission. The risk that the donor graft will fail to recover your blood function is small, usually less than a 5% risk.
Unlike types of organ transplantation, there is no surgical component involved in this procedure.
When your bone marrow recovers and the immediate complications of the transplant have improved, you will be discharged home. When discharged, you must go home with your designated caregiver, who has agreed to be with you and has received the required training.
You will be followed very closely after discharge, with frequent visits to the transplant outpatient clinic for several months after transplantation. This close monitoring is essential for a successful transplant. You will have frequent blood testing to monitor your health and the successful recovery of bone marrow function. Your transplant physician and your nurse coordinator will review with you the follow-up care expected during the weeks and months after allogeneic stem cell transplantation.
How do I get matched with a donor?
Allogeneic transplantation depends upon the availability of a healthy donor. There are many considerations in selecting the appropriate donor for a particular patient, including matching for tissue (HLA) type, blood type, sex, and age. Your transplant physician considers all of these factors. Identifying a donor may require 8-12 weeks, so the donor search must begin as soon as possible.
Potential donors include
HLA-matched or mismatched unrelated donors from a donor registry
HLA-mismatched first-, second-, and third-degree relatives, including parents, children, half-siblings, cousins, nieces, or nephews.
The primary considerations are HLA match and donor age (younger, much preferred). Matching blood types and sex matching between donor and patient are much less important. Blood samples will be drawn from you and family members willing to be considered donors for you.
In general, transplantation using a matched related sibling donor has fewer transplant-related complications. However, overall survival does not differ greatly between these sources of donors, and your transplant physician will select the best donor for your treatment.
The donor selected to donate will be evaluated by a different physician at MedStar Georgetown (or by a physician selected by the donor registry) and undergo a physical exam and blood testing. The donor must be healthy enough to donate stem cells for you. Any abnormal results may be reported to your transplant physician, and a decision will be made on whether or not to proceed with this particular donor.
There are no known long-term side effects to the donor from donating hematopoietic stem cells.
It is important to note that your donor must agree to donate blood stem cells or bone marrow for your transplant.
Each of your siblings have a 1 in 4 chance of being an HLA (tissue) match with you, a 1 in 4 chance of not being a match at all, and a 50/50 chance of being a half match. If tissue typing reveals that your family member is a complete match, you will move forward with a family member allogeneic transplant. We call this type of stem cell transplant “matched related.”
Even though you may have a HLA-matched sibling, your transplant physician may recommend a different donor for reasons such as donor age or an underlying health condition.
Please note that an identical twin will not have a different immune system. If an identical twin is selected as your donor, you would not benefit from the graft-versus-disease effect of allogeneic transplantation.
Most patients will require the selection of an unrelated donor or a half-matched (haploidentical) related donor.
We all inherit a set of chromosomes from each parent (and we pass these sets of chromosomes to our children). You can have inherited the same set of chromosomes from one parent but not the other as one of your siblings (including half-siblings). This person is a half-matched or haploidentical match with you. By definition, each of your parents is a half-match with you because you inherited one set of chromosomes from each. It is possible to track these sets of chromosomes through the generations of your family. It is possible that this set of chromosomes may be shared by aunts, uncles, cousins, nieces, and nephews and that any of these relatives could be HLA haploidentical with you.
Haploidentical transplants are a great alternative when a fully matched family member cannot be identified.
ln many cases, haploidentical transplants, which are more common and easily found, can be performed more quickly than waiting for a match from the unrelated donor bone marrow registry. A patient’s half-matched family members can be a readily available resource for patients needing an allogeneic transplant. This is important when treating blood cancers with an increased risk of relapse while waiting for a donor to become available.
Haploidentical donor transplantation has similar success rates to conventional matched sibling donor allogeneic transplant.
Unrelated registry donors
If blood testing reveals that you do not have a suitable sibling or family member match, finding an unrelated donor from the bone marrow registry may be the best choice. We will conduct a thorough search to ensure that we find a donor that closely matches your DNA. We prefer a complete HLA match, but mismatched unrelated donors may also be used for allogeneic transplantation. The donor is evaluated through the registry to ensure that he or she is in good health and can donate blood stem cells or bone marrow for your transplant. The process is completely anonymous, and you and your donor will not be given any personal information about the other. You may be given the option to meet them later after your transplant if that is something you and the donor would like to do. It is important to note that the donor must agree to donate stem cells for you.
The probability of finding an unrelated donor depends upon your ethnic background. The sets of chromosomes you inherited from your parents are much more likely to be shared with other people of the same ethnic background.
Unrelated donor transplantation has similar success rates to conventional matched-sibling donor allogeneic transplant.
You will be receiving many medications and antibiotics that are new to you. Most of these medications are intended to prevent complications of transplantation, including serious infections and rejection of the graft.
You may be weaned from many of these prophylactic medications beginning about 12 weeks after transplantation.
The donor immune system is very immature immediately after transplantation. Viral infections, including outbreaks of viruses that people normally carry in their bodies, may occur. Your transplant team will provide you with instructions about water and food safety and proper personal hygiene and isolation techniques to help you prevent developing new infections. The immune system will mature over several months after transplantation.
Revaccination with vaccines that you probably received as a child will be recommended beginning about six months after transplantation. It is important that you receive the influenza vaccine each year.
What is graft-versus-host disease?
The donor immune system provides a powerful graft-versus-disease benefit after allogeneic transplantation, but the same donor immune system can attack normal cells in your body, a reaction called graft-versus-host disease (GvHD). This can be a serious complication of allogeneic stem cell transplantation, with side effects lasting years or indefinitely after transplantation. You must work closely with your transplant team in the early identification and proper management of this complication.
GvHD is defined as “acute” or “chronic” but with overlap both in terms of when GvHD occurs after transplantation and the manifestations of this complication.
Acute GvHD affects about 50% of people undergoing transplantation and usually becomes obvious about five weeks after transplantation. “Late” acute GvHD may occur even several months after transplantation. The first sign is often a skin rash similar to a sunburn. GvHD can affect the stomach and intestines, causing nausea and diarrhea, or, least commonly, the liver. Treatment for acute GvHD takes about 6-8 weeks.
Chronic GvHD can affect many different organs including skin, joints, mouth, eyes, vagina, intestines, and lungs. The risk of developing chronic GvHD is about 30% to 50% and is higher if you receive peripheral blood stem cells for transplantation or if you first have acute GvHD. Treatment for chronic GvHD can take months or longer.
Prednisone or other corticosteroids are commonly used to control both acute and chronic GvHD. Prednisone use has many complications including muscle weakness, loss of bone strength, and blood sugar control. Your transplant physician will wean you from steroids as rapidly as possible to minimize these side effects. There are many other medications that may be used in combination with steroids to allow more rapid weaning of the steroid medication.
GvHD can lead to chronic health issues. You must work closely with your transplant physician to prevent these complications.
Relapse of disease:
Relapse of disease is the primary reason allogeneic (or autologous) transplantation fails. You will be monitored closely by blood and marrow testing for any evidence of relapse. Maintenance therapy with low doses of chemotherapy drugs or infusion of additional immune cells from the donor may be recommended by your transplant physician to reduce the risk of relapse.
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MedStar Health: Stem Cell Transplant and Cellular Immunotherapy Program at MedStar Georgetown University Hospital
3800 Reservoir Rd., NW 2 East Main Building Washington, DC 20007
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Anne Renteria, MD
Hematologic Malignancy & Hematology Oncology
Alaa Ali, MD,MSC
Cellular Therapy, Hematology & Medical Oncology
Pashna N. Munshi, MD