Hematopoietic Stem Cell Transplantation (HSCT)
HSCT is the infusion of hematopoietic stem cells from a donor into a patient who has received chemotherapy (usually marrow-ablative) to reestablish normal hematopoietic and immune function for treating various malignant and non-malignant hematologic disorders. 1
Types of HSCT
HSCT is classified based on the source of transplanted cells:
Allogeneic HSCT
- Cells are harvested from a donor other than the transplant recipient
- Most effective treatment for severe aplastic anemia and the only curative therapy for chronic myelogenous leukemia 1
- Donor sources include:
- HLA-identical twin or matched sibling (optimal outcome)
- Unrelated donor from registry organizations
- Mismatched family member
- Umbilical cord blood (UCB)
- Most common indications: Acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndromes (MDS) 1
- Higher risk of graft-versus-host disease (GVHD) - a condition where donated cells recognize recipient's cells as foreign and attack them 1
Autologous HSCT
- Patient's own cells are harvested before high-dose therapy and reinfused afterward
- Used when patients require high-dose chemotherapy but have healthy bone marrow
- Preferred when immunologic antitumor effect of allograft is not beneficial
- Most common indications: Multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma 1
- No risk of chronic GVHD 1
Syngeneic HSCT
- HLA-identical twin serves as donor
- No risk of chronic GVHD 1
Stem Cell Sources
Three primary sources of hematopoietic stem cells:
Peripheral Blood Stem Cells (PBSCs):
- Most common source, especially for autologous transplants 1
- Harvested after mobilization with growth factors (G-CSF or GM-CSF)
- Advantages: Easier collection, no general anesthesia, faster engraftment, reduced graft failure risk, lower transplant-related mortality 1
- Disadvantage: Higher risk of GVHD in allogeneic setting 1, 2
Bone Marrow (BM):
- Traditional source, still used particularly in allogeneic setting
- Harvested through bone marrow aspiration under anesthesia
- Lower risk of GVHD compared to PBSCs in allogeneic transplants 2
Umbilical Cord Blood (UCB):
Clinical Considerations and Complications
Pre-transplant Conditioning
- Chemotherapy, serotherapy, and/or radiation administered before HSCT
- Goals: Eradicate malignant cells and induce immunosuppression for engraftment 1
Major Complications
- Infection - leading cause of death among allogeneic transplants and major cause of morbidity in autologous HSCTs 1
- GVHD - particularly in allogeneic transplants
- Graft failure or rejection
- Relapse of primary malignancy
- Conditioning-related toxicity
- Immunodeficiency 3
GVHD Management
- Prophylaxis typically includes cyclosporine or tacrolimus in combination with other immunosuppressive agents (methotrexate or corticosteroids) 1
- T-lymphocyte depletion techniques can reduce GVHD but increase risks of graft rejection and infections 1
Outcomes and Prognosis
Despite high morbidity and mortality risks, long-term survivors generally enjoy good health:
- 93% of long-term survivors (>5 years) report good health
- 89% return to work or school full-time
- 88% of adult survivors feel benefits outweigh side effects 1
Outcomes vary based on:
- Disease type and stage
- Patient's overall health
- HLA-match degree (for allogeneic HSCT)
- Stem cell source 1
Recent Advances
- Double cord blood transplants
- Haploidentical transplants
- Improved conditioning regimens
- Better GVHD prophylaxis and treatment
- Enhanced supportive care including transfusion medicine support 4
HSCT has evolved from primarily a rescue therapy after high-dose chemotherapy to an adoptive immune therapy for malignancies and autoimmune disorders, offering curative potential for previously lethal diseases 5.