Hematopoietic Stem Cell Transplantation (SCT) is a procedure to replace damaged or diseased bone marrow with healthy blood-forming stem cells. This treatment is often the only hope for curing various blood cancers and other life-threatening disorders. While SCT offers the potential for a cure, the process is highly intensive and carries risks that impact patient survival. These risks are generally categorized by the time frame in which they occur, ranging from immediate organ failure to long-term disease recurrence.
Early Toxicity and Organ Damage
Death in the early period following SCT, typically within the first 30 to 100 days, is often caused by the conditioning regimen. This regimen involves high-dose chemotherapy and sometimes total body irradiation, necessary to destroy existing bone marrow and remaining cancer cells. The intense chemicals and radiation cause direct, non-infectious damage to rapidly dividing cells throughout the body.
The toxicity can lead to acute failure in major organ systems. The liver is particularly susceptible, often developing Sinusoidal Obstruction Syndrome (SOS), formerly Veno-Occlusive Disease (VOD). SOS occurs when toxic metabolites damage the endothelial cells lining the small blood vessels, causing obstruction and liver failure. Severe SOS frequently progresses to multiorgan failure with a mortality rate exceeding 80%.
Beyond the liver, the conditioning can damage the kidneys, resulting in acute kidney injury, or the lungs, leading to pulmonary toxicity or idiopathic pneumonia syndrome. Bleeding is another risk, as the high-dose treatment temporarily destroys the patient’s ability to produce platelets necessary for clotting. Acute organ toxicity from the conditioning regimen is a predictor of mortality within the first 100 days post-transplant.
Life-Threatening Infections
The period immediately following the transplant is marked by profound immunosuppression, making patients vulnerable to infections. The conditioning regimen eliminates white blood cells, causing neutropenia where the body lacks the primary defense against pathogens.
In the first few weeks before engraftment, bacterial infections are the primary concern, often originating from the patient’s gut flora or central venous catheters. Gram-positive and Gram-negative bacteria can lead to overwhelming sepsis in the absence of functioning neutrophils. After engraftment, the immune system remains compromised, shifting the risk toward viral and fungal pathogens.
Viral infections, particularly Cytomegalovirus (CMV), frequently reactivate from a dormant state when the new immune system is weakest (30 to 100 days post-transplant). Other viruses, like Adenovirus, can cause severe, disseminated disease in patients with prolonged T-cell immunodeficiency. Invasive fungal infections, such as Aspergillus or Candida species, are a persistent threat, especially when neutropenia is prolonged or immunosuppression is intensified.
Graft-versus-Host Disease
Graft-versus-Host Disease (GVHD) is a complication unique to allogeneic stem cell transplants. It occurs when the donor’s immune cells recognize the recipient’s body tissues as foreign and mount an attack. This happens because the transplanted T-cells mistakenly target the host’s healthy cells. GVHD is categorized based on when it appears, each type presenting a distinct threat to survival.
Acute GVHD typically manifests within the first 100 days, primarily damaging the skin, gastrointestinal tract, and liver. Severe acute GVHD is often resistant to treatment and can cause organ failure, contributing directly to early mortality. The intensive use of immunosuppressive drugs, such as high-dose corticosteroids, necessary to control the immune attack, further compromises the patient’s defenses and increases the risk of infection.
Chronic GVHD develops later, generally after day 100, and is the leading cause of non-relapse mortality. This condition resembles an autoimmune disorder, potentially affecting nearly every organ system, including the lungs, joints, eyes, and skin. The severe, widespread organ damage and the long-term need for heavy immunosuppression expose patients to recurrent infections and organ failure years after the initial procedure.
Relapse of the Underlying Disease
The failure of the transplant to permanently eradicate the original cancer is a leading cause of long-term mortality. Relapse is the return of malignant cells, such as leukemia or lymphoma. While early deaths relate to procedure toxicities and immune complications, relapse becomes the most frequent cause of death after the first year.
Despite the high-dose conditioning, residual disease can survive the initial treatment and eventually regrow. The timing of this recurrence is a strong indicator of prognosis; patients who relapse within the first six months post-transplant face a poor outlook. The primary goal of the transplant is to eliminate the disease, and when that goal is not met, the return of the aggressive malignancy is often fatal.
The risk of relapse drives the need for continued monitoring and sometimes additional therapies to maintain remission. If the cancer returns, the available salvage options are limited and often associated with high mortality rates.