Hematopoietic Stem Cell Transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord. Depending on where the stem cells originate from the transplantation may be called one of the following: Bone Marrow, Cord Blood, or Peripheral Transplantation. HSCT has been utilized for more than 20 years as a treatment (not a cure) for Krabbe disease. As a result, several published medical journal articles studying HSCT as a therapy to treat Krabbe disease have triggered two effects:
- Early onset (infantile) form progresses rapidly causing children to lose neurologic function quickly consequently, symptomatic patients are often not candidates for transplant. However, with newborn screening or prior family history, transplantation that occur within the first month of life have proven beneficial and provides early onset Krabbe disease patient with a higher quality of life.
- Later onset (diagnosis after the age of 2) are better candidates for HSCT especially, if the patient is pre-symptomatic (not showing signs of disease).
The use of hematopoietic (blood) stem cell transplantation (HSCT) for diseases such as Krabbe disease was centered around a 1968 discovery by Dr. Neufeld’s laboratory. His laboratory observed that the accumulation of material in the lysosomes could be reserved by putting them in culture with normal cells. This scientific phenomenon was termed “cross correction,” and accounts for the cellular groundwork that occurs when a patient undergoes an HSCT.
The rational for the use of HSCT in Krabbe disease is this: the circulation of normal blood cells of patients with Krabbe disease would allow for a continuous source of GALC enzyme throughout the life of the affected patient. In simple terminology, patients not making adequate amounts of GALC (responsible for eliciting neurodegenerative symptoms) undergo an HSCT to prompt “cross correction.” After the transplantation of healthy cells, the body works to accept the new source of GALC enzyme across the blood-brain-barrier.
The Process of Transplantation
Step 1: Perform tissue typing also known as HLA (human leukocyte antigen) typing in the patient being considered for transplant. This step is required to select a donor. Once the DNA information confirmed from tissue typing, a donor match is identified within hours of a search.
Step 2: The patient is admitted to the hospital. Patient will undergo a surgery to have a port placed. A port is a centrally placed device underneath the skin allowing quick access to a major vein. Ports are placed to provide a safe and efficient way to administer medicines and/or treatments over a period of time. The port is often removed once therapy is discontinued or has ended.
Step 3: Patient begins chemotherapy regimen. This step works to eliminate the blood producing cells and the immune system of the patient. A necessary step to help the body accept the new donor cells. It is important you inquire in depth about this process as some facilities utilize a reduced condition chemotherapy regimen.
Step 4: Often referred to as “Transplant Day.” During this step, donor cells are infused intravenously through a vein or port. The infusion of the donor cells takes approximately 30 minutes. Once the donor cells are administered, they immediately begin working their way to the bone marrow cavity and begin to grow a new blood and immune system with the GALC enzyme.
Step 5: Patients are monitored in the hospital for several weeks and then released into an outpatient setting for monitoring. The amount of time in the hospital can vary widely due to several things such as: infections, fevers, graft-versus-host disease, stem cell failure, organ damage, and more. The body’s acceptance of the new stem cells is the first step to preventing further disease progression.
How to Make an Informed Decision on HSCT
Undergoing HSCT is a BIG decision. To assist you in the decision-making process we encourage to:
- Consider printing out KrabbeConnect’s list of questions to help you gather the most information about HSCT.
- Talk and/or meet with at least 1 Krabbe disease expert
- Talk and/or meet with at least 1 family who has undergone HSCT to treat Krabbe disease
- Inquire if any clinical trials are available
- Inquire about the risks and benefits of transplant, chemotherapy, and clinical trials
- Understand the limitations of HSCT as a therapy
- Know your transplant options. Each transplant center has different protocols for chemotherapy conditioning depending on the facility performing the transplant
Rationale for Reduced-Intensity Conditioning (RIC) Transplantation in Krabbe Disease
Tuesday, November 9th at 4:00 pm EST/3:00 pm CST
Bone marrow transplants are utilized in patients diagnosed with Globoid Cell Leukodystrophy (Krabbe) to help treat the debilitating disease. However, some of the chemotherapy medicines utilized to suppress the immune response can leave a patient managing troublesome side effects. Thus, transplant specialists are pioneering a new way to conduct bone marrow transplants in patients with non-malignant disorders such as Krabbe disease. Dr. Paul Szabolcs will present his recent publication discussing the use of RIC in patients with Krabbe disease. Dr. Paul Szabolcs is the Division Director at the Blood and Marrow Transplantation and Cellular Therapies at the University of Pittsburgh.