Haematopoietic Stem Cell Transplant

Indications

Contraindications

There are no absolute contraindications; however, we must balance the risk of transplant with the likelihood of cure. For example, patients with ALL are advised to achieve an MRD (minimal-residual disease) negative to be eligible for transplant as there is a high chance of relapse if MRD is not achieved, and the risk outweighs the benefits.

Key Definitions2

• MHC – Major Histocompatibility Complex: genes on the short arm of chromosome 6 that encode human leukocyte antigens (HLA), leading to different proteins.

• HLA – Human Leukocyte Antigen: proteins on the cell surface which express alloimmunity. There are varying types. They are encoded by MHC class 1. They are expressed on all cell types and recognised by CD8+ T cells. Other HLA types are coded by MHC II, which are on antigen-presenting cells recognised by CD4+ T cells.

• Engraftment – the process of the transplanted stem cells producing mature cells in the circulation.

• Preparative regimen/conditioning – high dose chemotherapy and/or total body irradiation (TBI) causing immunosuppression for engraftment.

Types of HSCT

Peripheral vs Bone Marrow HSCT3

This is a debate amongst transplant specialists.

It is logistically easier to harvest cells peripherally compared to multiple bone marrow aspirations associated with the general anaesthetic risk. However, there have been reported complications from the leukapheresis procedure, including the question of long-term effects of rhG-CSF administration. Meanwhile, bone marrow harvesting is a trialled and tried method known for 30 years, though associated with discomfort and a longer recovery time for the donor.

There is some research that suggests that peripheral transplants lead to better outcomes, as it leads to faster haematological recovery (better platelet and neutrophil reconstitution), lower risk of acquiring GVHD and less chance of disease relapse.

Complications

Acute (within the first 90 days)

• Myelosuppression with neutropenia
• Anaemia
• Thrombocytopenia
• Veno-occlusive disease due to conditioning regimen (oral busulfan & cyclophosphamide)
  • Presentation
    • Hepatomegaly
    • Jaundice (hyperbilirubinaemia)
    • Ascites
    • Weight gain (fluid retention)
  • Pathophysiology
    • Endothelial damage to hepatic sinusoids causing obstruction and necrosis of the liver
  • Treatment – ursodeoxycholic acid
• Mucositis
• Infections (bacterial, viral, opportunistic, fungal)
  • Patients are put on prophylactic antibiotics, PCP, antifungals, antivirals (depending on the situation)
• Graft Rejection
  • Chimerism (presence of cell population donor v. patient) is important to check the engraftment
• Acute Graft-Versus-Host Diseae (GVHD) (within 100 days)
  • Donor T cells reacting to histoincompatible antigens on the host tissues
  • Usually in Allogeneic transplant
  • Risk factors
    • HLA disparity
    • Recipient/ donor in older age group
    • Type & status of underlying disease
    • Transplant conditioning regimen
    • ABO compatibility
  • GVHD can be important in a mild form to achieve graft vs leukaemia; however severe GVHD can be equally problematic
  • Prophylaxis can be used including:
    • Calcineurin-based inhibitor (Ciclosporin/ Tacrolimus)
    • Low-dose methotrexate
    • Mycophenolate
  • Treatment
    • Systemic corticosteroid
    • Additional immunosuppressants

By TeachMeSeries Ltd (2026)

GVHD Target Organ Staging4

Chronic (after the first 90 days)

• Chronic GVHD (>100 days post-transplant)
  • Aetiology less understood, more an autoimmune process
  • More organ involvements
• Infections (bacterial, viral, opportunistic, fungal)
• Relapse of disease
• Infertility (due to conditioning regimen)

References