Cord blood is the blood remaining in the placenta and umbilical cord after birth. This substance is rich in blood-forming stem cells, making it valuable for transplantation. Leukemia is a group of cancers characterized by the abnormal production of blood cells in the bone marrow. Cord blood transplantation replaces the diseased, cancerous blood-forming system with a healthy, new one. This treatment protocol aims to eradicate the cancer and establish a new immune system.
The Cellular Mechanism of Cord Blood Treatment
The therapeutic power of cord blood stems from its high concentration of Hematopoietic Stem Cells (HSCs). These HSCs are foundational cells capable of self-renewal and differentiating into all mature blood cell types, including red cells, platelets, and white cells. The goal of the treatment is to infuse these healthy, donor HSCs into the patient to repopulate the bone marrow and establish a new, functioning blood and immune system.
Cord blood cells possess a unique advantage due to their immunologic immaturity compared to stem cells from adult bone marrow. This means the cells are more tolerant of genetic differences between the donor and the recipient. Consequently, cord blood transplants require a less stringent matching of Human Leukocyte Antigens (HLA). This flexibility makes cord blood a viable option for patients with leukemia who cannot find a perfectly matched adult donor.
The transplanted cells also provide an anti-leukemia effect, often called the graft-versus-leukemia (GVL) reaction. Immune cells within the cord blood unit recognize and attack residual leukemia cells that survived the initial chemotherapy. This reaction is sometimes more pronounced with a slight HLA mismatch, suggesting the immune response is activated to clear the remaining disease.
How Cord Blood Units Are Sourced and Selected
Cord blood units are sourced from two types of banks: public and private. Public banks store altruistic donations for use by any patient who needs a match. Private banks store cord blood only for potential use by the donor’s family. Units used for leukemia treatment are almost exclusively retrieved from public banks, which maintain large, diverse inventories.
The selection of a unit relies on two primary criteria: the degree of HLA matching and the total cell dose. Although cord blood is more forgiving regarding HLA, a closer match still improves outcomes. Physicians aim for at least a four out of six match at the most important HLA loci. The cell dose is calculated based on the recipient’s weight and must meet a minimum threshold, often requiring 20 million total nucleated cells per kilogram of body weight.
Since a single cord blood unit often lacks enough cells for an adult or larger adolescent patient, two separate units from different donors are frequently transplanted. Using two units ensures the patient receives a sufficient number of stem cells for successful engraftment. Once a suitable unit or pair is identified, they are retrieved from cryopreservation for treatment.
The Treatment Process for the Patient
Before the cord blood infusion, the patient undergoes a preparatory phase known as the conditioning regimen. This involves high-dose chemotherapy and sometimes total body irradiation (TBI) administered over several days. This intense treatment serves two purposes: to destroy remaining leukemia cells and to create space in the bone marrow for the new donor cells to settle.
The regimen also suppresses the patient’s existing immune system, which prevents the body from rejecting the cord blood graft. Younger, healthier patients receive a myeloablative regimen to completely destroy the bone marrow. Older or less fit patients may receive a reduced-intensity conditioning regimen to minimize toxicity. After conditioning therapy, a short rest period allows the chemotherapy to clear from the patient’s system.
The cord blood is then administered through a simple intravenous infusion, similar to a standard blood transfusion. The healthy stem cells circulate until they find their way to the bone marrow space, a process known as homing. Once in the marrow, they begin settling in and starting to divide.
Monitoring Engraftment and Recovery
The most anticipated event following infusion is engraftment, when the transplanted Hematopoietic Stem Cells successfully settle in the bone marrow and begin producing new, functional blood cells. This process is monitored by daily blood counts, specifically looking for the recovery of neutrophils, a type of white blood cell. Neutrophil engraftment takes longer with cord blood, often occurring two to four weeks post-infusion, compared to other stem cell sources.
During this period of low blood counts, the patient is susceptible to infections and bleeding. This necessitates protective isolation and supportive care. Once the new blood system is established, recovery focuses on immune system reconstitution. The new immune system, derived from the donor cells, is responsible for fighting off pathogens.
A common complication monitored is Graft-versus-Host Disease (GvHD). This occurs when donor T-cells recognize the patient’s non-cancerous body tissues as foreign and attack them. While cord blood transplants have a lower incidence of chronic GvHD compared to adult donor transplants, acute GvHD can still occur. To manage this risk, the patient receives immunosuppressive medications, such as a calcineurin inhibitor and mycophenolate mofetil, until the new immune system fully matures and tolerance is established.