Chronic Lymphocytic Leukemia (CLL) is a cancer originating in the blood and bone marrow—the soft, spongy center of bones. In CLL, the bone marrow produces an excessive number of abnormal white blood cells called lymphocytes. These abnormal cells do not function correctly and survive longer than they should, crowding out healthy blood cells. A bone marrow transplant, also known as a stem cell transplant, is a medical procedure that replaces a person’s unhealthy bone marrow with healthy, blood-forming stem cells.
The Role of Transplants in CLL Treatment
A bone marrow transplant is not a standard initial treatment for Chronic Lymphocytic Leukemia, but a specialized procedure for specific, challenging situations. Doctors consider a transplant for patients whose CLL is categorized as high-risk. This is based on certain genetic changes within the leukemia cells, identified through molecular testing, which can indicate a higher likelihood that the cancer will return.
The procedure is also an option for patients with relapsed CLL, particularly if it returns quickly after initial therapy, or for those with refractory CLL, meaning the cancer did not respond to first-line treatments. A patient’s overall health and age also influence the decision, as it is an intensive procedure.
Types of Transplants Used for CLL
Two primary types of stem cell transplants exist: autologous and allogeneic. An autologous transplant uses the patient’s own stem cells, which are collected and stored, while an allogeneic transplant uses stem cells from a donor. For CLL, the allogeneic transplant is the standard approach.
Since CLL is a cancer of the bone marrow, the patient’s own marrow contains cancerous lymphocytes, creating a high risk of reintroducing malignant cells. An allogeneic transplant avoids this by introducing a completely new, healthy set of stem cells. Furthermore, the donor’s immune cells can recognize and attack any remaining leukemia cells in the patient’s body, a response known as the graft-versus-leukemia effect.
The Transplant Procedure for CLL Patients
The allogeneic transplant process begins with conditioning, a preparatory regimen that readies the body for the transplant. During this period of one to two weeks, the patient receives high doses of chemotherapy and sometimes total body radiation. This intensive therapy destroys the patient’s existing bone marrow, including the cancerous CLL cells, to make space for the incoming donor cells.
Following conditioning, the donor stem cells are infused into the patient’s bloodstream through a central venous catheter, a process similar to a blood transfusion. The patient is awake during the infusion, which takes about an hour.
Once infused, the donor stem cells travel through the bloodstream to the bone marrow, where they begin engraftment. This is the period when the new stem cells settle in and produce new, healthy blood cells. Engraftment takes two to five weeks, and medical teams closely monitor blood counts to track the progress of the new marrow.
Post-Transplant Recovery and Complications
After the transplant, the patient’s recovery begins in the hospital for several weeks. The focus is managing the side effects of conditioning therapy and protecting against infection while the new immune system establishes itself. Low blood cell counts are a concern, making the patient highly susceptible to infections, so the medical team provides supportive care like transfusions and medications.
A complication unique to allogeneic transplants is Graft-versus-Host Disease (GVHD). This condition occurs when the donor’s immune cells recognize the patient’s body tissues as foreign and attack them. GVHD is a common complication, though many cases are mild, and it can manifest in two forms: acute and chronic.
Acute GVHD develops within the first 100 days after the transplant and affects the skin, liver, and gastrointestinal tract, with symptoms like a skin rash or digestive issues. Chronic GVHD appears later, more than 100 days post-transplant, and can affect a wider range of organs. Managing GVHD is a delicate balance, as the same immune response also contributes to the beneficial graft-versus-leukemia effect.
Modern Therapeutic Alternatives to Transplants
The treatment landscape for CLL has been transformed by highly effective targeted therapies, which has reduced the reliance on bone marrow transplants. These modern treatments are better tolerated and have become the preferred option for most patients, including those with high-risk disease.
Two classes of drugs have revolutionized CLL care: BTK inhibitors and BCL-2 inhibitors. BTK inhibitors, such as ibrutinib, acalabrutinib, and zanubrutinib, work by blocking a protein that cancer cells need to survive. BCL-2 inhibitors, most notably venetoclax, target a different protein that helps cancer cells evade natural cell death.
These oral medications can provide long-lasting remissions and are used as first-line treatments or for patients whose disease has relapsed. They can be given as single agents or in combination, offering durable disease control without the intensive risks of a transplant. While transplants remain a curative option for a select group of patients, particularly younger individuals who have exhausted other therapies, these newer drugs mean most people with CLL will never require one.