Hematopoietic Stem Cell Transplantation (HSCT)

Background:

• Allogeneic HSCT is generally reserved for high-risk or relapsed hematologic malignancies, while autologous HSCT is used for chemosensitive diseases such as multiple myeloma and certain lymphomas.

  • Allo-HSCT: Infusion of hematopoietic cells from a HLA-compatible donor after cytotoxic conditioning to eradicate disease and enable engraftment.

• Common indications of HSCT in classic hematology:

  • Severe aplastic anemia

  • Hemoglobinopathies (sickle cell disease, β-thalassemia major)

  • Inherited BM failure syndromes

  • Congenital immunodeficiencies

Pre-Transplant Evaluation:

• Confirmation of diagnosis and disease status

  • Cytogenetics/molecular testing, MRD, etc.

• Performance status (ECOG/KPS)

• Comorbidity index:

  • HCT-CI: Hematopoietic Cell Transplantation- Comorbidity Index

• Organ function (PFTs, cardiac, renal, hepatic)

• Infectious disease screening (CMV, HBV, HCV, HIV)

• Psychosocial evaluation/ support systems

• HLA typing for allogeneic candidates

Donor Selection:

• The preferred donor is an HLA-matched sibling.

• If unavailable, matched unrelated donors, haploidentical family members, or umbilical cord blood may be considered.

  • Graft source (peripheral blood, bone marrow, umbilical cord blood) is chosen based on disease, patient comorbidities, and urgency.

  • Peripheral blood is most common but increases chronic GVHD risk.

• HLA matching is critical to minimize graft failure and GVHD.

• Donor age and health are important predictors of outcome.

  
  

Conditioning Regimens:

• Conditioning intensity is tailored to patient age, comorbidities, disease type, and remission status.

  • Myeloablative regimens (cyclophosphamide + TBI, busulfan-based):

    • Preferred for younger, fit patients with aggressive disease.

  • Non-myeloablative regimens/ Reduced-intensity:

    • For older or comorbid patients, or those with indolent disease.

Transplant Procedure:

• After conditioning, donor hematopoietic cells (from peripheral blood, bone marrow, or UCB) are infused.

• Peripheral blood is most common due to ease of collection and rapid engraftment, but is associated with higher chronic GVHD risk.

• UCB is reserved for patients lacking other donors and requires specialized expertise.

• Engraftment is monitored by blood counts and chimerism analysis (for allo-HSCT).

Post-Transplant Care:

• Intensive supportive care is required until engraftment.

• Monitoring includes surveillance for GVHD (unique to allo-HSCT), infections, organ toxicities, and disease relapse.

  • Veno-Occlusive Disease/ Sinusoidal Obstruction Syndrome (VOD/SOS):

    • Life-threatening complication of HSCT and certain chemotherapy regimens

    • Characterized by toxic injury to the sinusoidal endothelial cells of the liver → their necrosis and detachment → obstruction of small hepatic venules and sinusoids → post-sinusoidal portal HTN and impaired hepatic blood flow

  • GVHD is a major cause of non-relapse mortality.

• Long-term follow-up addresses late effects, chronic GVHD, and survivorship issues.