Acute Myeloid Leukemia (AML) is a rapidly progressing cancer originating in the bone marrow, where blood cells are produced. In AML, myeloid cells become abnormal, multiply uncontrollably, and fail to mature, interfering with healthy blood cell production. This can result in symptoms like fatigue, easy bruising, bleeding, and frequent infections.
Allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option for AML, offering potential for long-term remission and cure. This procedure replaces the patient’s diseased bone marrow with healthy blood-forming stem cells from a compatible donor, aiming to establish a new, healthy blood-forming system.
Allogeneic Stem Cell Transplantation for AML
Allogeneic hematopoietic stem cell transplantation involves transferring healthy blood-forming stem cells from a donor to a patient. “Allogeneic” means the stem cells are from another individual. These hematopoietic stem cells are multipotent, capable of self-renewal and differentiating into all types of blood cells.
Beyond replacing diseased marrow, a “graft-versus-leukemia” (GVL) effect contributes to the curative potential. In GVL, donor immune cells recognize and attack any remaining leukemia cells in the patient’s body, providing an immune-mediated anti-cancer effect.
The success of an allogeneic transplant relies on compatibility between donor and recipient, particularly Human Leukocyte Antigens (HLA). HLA are proteins on cell surfaces that help the immune system distinguish “self” from “non-self.” A close HLA match reduces the risk of rejection and minimizes graft-versus-host disease (GVHD).
Different donor types are considered based on HLA matching:
A matched related donor, typically a sibling, who has a 25% chance of being a full HLA match.
A matched unrelated donor (MUD) found through national and international registries, whose HLA type closely matches the patient’s.
Haploidentical donors, usually a parent or child, who are a “half-match.”
Umbilical cord blood, which contains hematopoietic stem cells and can be used even with some HLA mismatches.
The Transplantation Process
The transplantation process begins with a pre-transplant evaluation. This involves medical tests and organ function evaluations to ensure treatment tolerance. The evaluation also confirms the leukemia is in remission or at an appropriate stage for transplantation.
The patient then undergoes a conditioning regimen, involving high doses of chemotherapy, and sometimes radiation therapy. This regimen eliminates remaining leukemia cells and suppresses the patient’s immune system to prevent rejection. This intensive treatment, often called myeloablation, also creates space in the bone marrow for new donor cells to engraft.
After conditioning, the patient receives donor stem cells through an intravenous infusion. These stem cells, collected from the donor’s peripheral blood, bone marrow, or umbilical cord blood, travel to the bone marrow. There, they begin engraftment, settling in the marrow and producing new, healthy blood cells.
Engraftment is a gradual process, taking weeks to months, during which blood counts slowly recover. During this period, the patient is susceptible to infections due to their suppressed immune system and low blood cell counts. Patients receive supportive care, including blood transfusions and medications to prevent infections.
Potential Complications and Management
Allogeneic HSCT carries complications.
Graft-versus-host disease (GVHD)
Graft-versus-host disease (GVHD) is a complication where donor immune cells attack the recipient’s healthy tissues. GVHD can be acute (within 100 days, affecting skin, liver, GI tract) or chronic (developing later, affecting almost any organ). Management involves immunosuppressive medications to dampen the donor immune response, balancing GVHD control with preserving the graft-versus-leukemia effect.
Infections
Patients are highly susceptible to infections due to their compromised immune system. Bacterial, viral, and fungal infections are common. Patients often receive prophylactic antibiotics, antivirals, and antifungals. Close monitoring for infection signs and prompt treatment are important.
Organ Toxicity
The intensive conditioning regimen can damage various organs, leading to organ toxicity. The liver, kidneys, and lungs are vulnerable. Complications like veno-occlusive disease (VOD) of the liver can occur, characterized by blockage of small veins leading to liver dysfunction. Monitoring organ function and providing supportive care manage these toxicities.
Leukemia Relapse
Leukemia relapse remains a possibility. Relapse risk varies based on factors like disease status before transplant, AML subtype, and HLA matching. Strategies to reduce relapse include optimizing the conditioning regimen and, in some cases, administering donor lymphocyte infusions (DLIs) to bolster the GVL effect against residual leukemia.
Life After Transplantation
Recovery after an allogeneic stem cell transplant is long and gradual.
Immune Recovery
Immune recovery is a slow process as the new immune system develops and matures. This can take months to years, during which patients remain at increased infection risk. Monitoring immune function guides the duration of prophylactic medications.
Immunosuppression
Immunosuppression is often necessary to prevent or manage GVHD. These medications leave the patient vulnerable to infections and have side effects. Dosage and type are adjusted over time to minimize side effects while controlling GVHD.
Ongoing Follow-up Care
Regular medical appointments, blood tests, and screenings are part of ongoing follow-up care. This monitoring aims to detect and manage late effects like organ dysfunction, secondary cancers, or chronic GVHD. Patients are educated on symptoms to watch for and are encouraged to report new concerns.
Long-term Challenges and Outlook
Patients may experience long-term challenges, including persistent fatigue, emotional impacts, and changes in physical capabilities. Support groups, psychological counseling, and rehabilitation programs can assist. The outlook for long-term remission and survival after allogeneic HSCT for AML has improved with advancements in transplant techniques and supportive care.