What is the early death rate for hematopoietic stem cell transplantation (HSCT)?

Early Death Rate for Hematopoietic Stem Cell Transplantation

The early death rate (treatment-related mortality within 100 days) for HSCT varies substantially by transplant type and underlying disease, ranging from 0% for autologous HSCT in certain conditions to approximately 17-32% for allogeneic HSCT in high-risk hematologic malignancies.

Autologous HSCT Early Mortality

The early treatment-related mortality for autologous HSCT is generally low but varies by indication:

• Overall early TRM (<100 days) is approximately 2.8% in a nationwide survey of 1,482 adult autologous transplant recipients 1
• Disease-specific variation is substantial:
  • AL amyloidosis: 24% early TRM 1
  • Non-Hodgkin's lymphoma: 4.4% early TRM 1
  • Multiple myeloma: 1.9% early TRM 1
  • Breast cancer and chronic lymphocytic leukemia: 0% early TRM 1
• In Ph-positive ALL studies, autologous HSCT showed 0% treatment-related mortality 2

The median time to early death in autologous recipients is 38 days post-transplant 1. Primary causes include infections (fungal, bacterial, viral) and organ toxicity (cardiac and pulmonary complications) 1.

Allogeneic HSCT Early Mortality

Allogeneic HSCT carries significantly higher early mortality risk:

Acute Lymphoblastic Leukemia (ALL)

• Treatment-related mortality ranges from 17% to 32% depending on the study and patient population 2
• The GRAALL study (GRAAPH-2003) reported 32% treatment-related mortality at 4 years in Ph-positive ALL patients undergoing allogeneic HSCT 2
• The Northern Italy Leukemia Group study showed 17% treatment-related mortality at 5 years for allogeneic HSCT in Ph-positive ALL 2
• The Spanish Cooperative Group reported 27% transplant-related mortality in Ph-positive ALL patients 2
• 3-year non-relapse mortality was 21-28% in comparative studies of Ph-positive ALL 2

Other Hematologic Conditions

• For adults with ALL generally, treatment-related mortality can reach up to 30% according to consensus expert recommendations 2
• Acute and chronic graft-versus-host disease rates approach 50% in matched sibling transplants for non-malignant diseases, contributing to overall mortality 2

Sickle Cell Disease

• Overall survival is approximately 95% with matched sibling HSCT in children with sickle cell disease, indicating low early mortality in this population 2

Temporal Trends in Early Mortality

Mortality from all causes has decreased over time in the early post-transplant phases:

• Deaths from infections, GVHD, and toxicity decreased up to 1 year post-transplant when comparing cohorts from 1980-2001 versus 2002-2015 3
• Lethal bacterial and fungal infections decreased between cohorts, though infections of unknown origin remain problematic 3
• However, late mortality (at 5 years) has increased, primarily due to relapse 3

Primary Causes of Early Death

Infections

• Infections of unknown origin are the main cause of infectious deaths across all post-transplant phases 3
• Specific pathogens include fungal (7 cases), bacterial (6 cases), and viral (3 cases) in the autologous setting 1

Organ Toxicity

• Cardiac toxicity is a major concern, particularly with cyclophosphamide-based conditioning regimens 2
• Pulmonary complications contribute significantly to early mortality 1
• In autologous recipients, organ toxicity caused 26 of 42 early deaths (heart: 9, lungs: 7, other: 10) 1

GVHD and Transplant Complications

• Transplant-related complications frequently prevent post-transplant maintenance therapy in allogeneic recipients 2
• Severe chronic GVHD has been described in heavily-transfused end-stage adult patients 2

Risk Factors for Early Mortality

Multiple patient and transplant-related factors influence early death risk:

• Disease type and risk category: Adverse cytogenetic/genetic risk groups show significantly worse outcomes 4
• Patient age: Older age at transplantation is associated with lower progression-free survival 2
• Comorbidity burden: The HCT-CI score independently predicts early death in adult AML patients, particularly those ≥60 years 5
• Donor type and stem cell source: These factors impact infectious death rates across post-transplant phases 3
• Pre-transplant disease burden: Higher skin scores (mRSS >24) in systemic sclerosis predict lower progression-free survival 2
• Cardiac reserve: Low left ventricular ejection fraction is a risk factor for adverse events 2

Clinical Implications

Pre-transplantation cardiac evaluation is recommended and should contribute to reduced transplantation-related mortality when incorporated by transplant centers 2. Attenuation of cyclophosphamide dose should be considered in patients with low cardiac reserve 2.

The substantial variation in early mortality rates underscores the importance of careful patient selection and disease-specific risk stratification when considering HSCT as a treatment option.