Haematopoietic Stem Cell Transplantation: An Overview

PATHCHAT Edition No. 60
September 2019
Please contact your local Ampath pathologist for more information.

Author: Dr. Pamela Moodley, MBBCh, FCPath (SA) Haematology

What is Haematopoietic Stem Cell Transplantation (HSCT)?

✅ Definition:

• HSCT involves the transplantation of haematopoietic stem cells from any donor and source to repopulate the haematopoietic system.
• Haematopoietic stem cells originate during embryonic development and are found in bone marrow and umbilical cord blood.
• They express the unique CD34 marker, which allows identification via flow cytometry.

✅ Stem Cell Properties:

• Multipotent – Can differentiate into various blood cell types.
• Capable of mobilising from bone marrow into peripheral blood.

📌 HSCT is a potentially curative procedure for malignant and non-malignant disorders affecting blood and the immune system.

Indications for HSCT

🔹 Malignant Haematological Conditions:

• Acute myeloid leukaemia (AML).
• Acute lymphoblastic leukaemia (ALL).
• Non-Hodgkin lymphoma (NHL).
• Hodgkin lymphoma.
• Multiple myeloma.
• Chronic myeloid leukaemia (CML).
• Myelodysplastic syndrome (MDS).

🔹 Malignant Non-Haematological Conditions:

• Neuroblastoma.
• Germ cell tumours.

🔹 Non-Malignant Haematological Conditions:

• Aplastic anaemia.
• Fanconi anaemia.
• Thalassaemia.
• Sickle cell disease.

🔹 Autoimmune Diseases:

• Systemic lupus erythematosus (SLE).
• Systemic sclerosis.

🔹 Immunodeficiency Disorders:

• Severe combined immunodeficiency syndrome (SCID).

🔹 Metabolic Disorders:

• Glycogen storage diseases.
• Gaucher syndrome.

📌 The success of HSCT depends on the underlying condition, donor type, and transplant-related complications.

Types of HSCT Donors

✅ 1. Autologous Transplantation:

• Stem cells are collected from the patient and reinfused after chemotherapy.

✔ Steps in Autologous Transplantation:

1. Mobilisation:
   • Medication is given to release stem cells from bone marrow into the bloodstream.
2. Collection:
   • Peripheral blood stem cells are harvested via apheresis.
3. Cryopreservation:
   • Collected stem cells are frozen until needed.
4. Conditioning:
   • High-dose chemotherapy removes malignant cells.
5. Reinfusion:
   • Thawed stem cells are reintroduced via IV infusion.
6. Supportive Care:
   • Close monitoring while the immune system rebuilds.

✅ 2. Allogeneic Transplantation:

• Stem cells are obtained from a matched donor and transplanted into the recipient.

✔ Donor Types for Allogeneic Transplantation:

• Identical twin (HLA-matched).
• HLA-matched related donor (sibling or relative).
• HLA-matched or mismatched unrelated donor.
• Haploidentical (half-matched) donor.

📌 Allogeneic transplants have a higher risk of graft-versus-host disease (GVHD) but can provide a graft-versus-tumour effect, helping eliminate residual malignant cells.

Stem Cell Sources for HSCT

✅ 1. Bone Marrow:

• Best HLA matching but requires surgical collection.
• Faster engraftment than cord blood.

✅ 2. Peripheral Blood Stem Cells (PBSCs):

• Most common source for adult transplants.
• Faster engraftment than bone marrow.
• Higher risk of chronic GVHD.

✅ 3. Umbilical Cord Blood (UCB):

• Readily available and less restrictive HLA matching.
• Lower risk of GVHD.
• Limited number of cells, leading to slower engraftment.

📌 Each stem cell source has advantages and disadvantages based on the patient's condition and donor availability.

Graft-versus-Host Disease (GVHD)

✅ What is GVHD?

• Occurs when donor T-cells attack recipient tissues.
• Can be acute (within 100 days) or chronic (>100 days).

✅ GVHD Affected Organs:

• Skin: Rash, poikiloderma, sclerosis.
• Gastrointestinal tract: Diarrhoea, nausea.
• Liver: Jaundice, hepatomegaly.
• Lungs & Mucosa: Fibrosis, lichen planus.

✅ Types of GVHD:

✔ 1. Acute GVHD:

• Occurs within 100 days post-transplant.
• Commonly affects skin, GI tract, liver.

✔ 2. Chronic GVHD:

• Occurs after 100 days.
• May present as autoimmune-like disease.

✔ 3. Overlap Syndrome:

• Features of both acute and chronic GVHD.

📌 GVHD can be mitigated with immunosuppressive therapy and HLA matching.

Phases of Allogeneic Transplantation

1️⃣ Conditioning Phase (7–10 days):

• High-dose chemotherapy eliminates malignant cells.

2️⃣ Stem Cell Infusion (20 min – 1 hr):

• Transplanted cells are infused via IV.

3️⃣ Neutropenic Phase (2–4 weeks):

• No immune function; requires supportive therapy.

4️⃣ Engraftment Phase:

• Bone marrow starts producing new blood cells.

5️⃣ Post-Engraftment Period (Months – Years):

• Immune system reconstitution and GVHD monitoring.

📌 Successful engraftment is confirmed through chimerism testing (evaluating donor vs. recipient DNA).

Factors Influencing HSCT Outcomes

✅ 1. Disease Factors:

• Disease type and stage.

✅ 2. Patient-Related Factors:

• Age, comorbidities, performance status.

✅ 3. Donor-Related Factors:

• HLA match, donor viral status (e.g., CMV).

✅ 4. Transplant Factors:

• Conditioning regimen.
• GVHD prevention.
• Stem cell source.

📌 A multidisciplinary approach optimizes HSCT success.

Key Takeaways for Clinicians

✅ HSCT is a curative option for malignant and non-malignant disorders.
✅ Autologous transplants use the patient’s own cells; allogeneic transplants require a donor.
✅ Bone marrow, PBSCs, and cord blood serve as stem cell sources, each with distinct advantages.
✅ GVHD remains a major complication of allogeneic transplants.
✅ Chimerism testing is essential for post-transplant monitoring.

📌 HSCT requires careful donor selection, immunosuppressive management, and long-term follow-up to ensure successful outcomes.