HEMATOPOIETIC STEM-CELL TRANSPLANTATION
The term hematopoietic stem-cell transplantation (HSCT) denotes replacement of abnormal or deficient pluripotent stem cells or progenitor hematopoietic cells with normal cells from same or different donor.
As bone marrow is the commonest source of normal stem cells for this purpose, the term Bone-marrow transplantation (BMT) is frequently used interchangeably with HSCT. However, stem cells may also be obtained from: (a) peripheral blood, (b) umbilical cord, (c) fetal liver. Types: According to the source, HSCT/BMT may be classified as:
• Autologous, i.e. use of patient's own bone-marrow or stem cells, which is aspirated, treated with ablative chemotherapy, preserved, and at a later date, retransfused into him.
• Allogenic, i.e. use of bone-marrow or stem cells from a HLA-matched donor, who may be either a non-identical but histocompatible related sibling or unrelated donor from donor registry.
Indications: HSCT is one of the most effective and potentially curative interventions in many hemato- oncological disorders. Currently it is the treatment of choice in:
• Aplastic anemia: Congenital or acquired
• Hemoglobinopathies, e.g. thalassemia
• Refractory/relapsed leukemia: ALL, AML
• Lymphomas: Hodgkin and NHL
• Refractory/high-risk solid tumors: Wilms tumor, neuroblastoma
• Inherited immunodeficiency disorders
• Inborn errors of metabolism: Gaucher disease, MPS, osteopetrosis
Principle: Although specific details of HSCT are beyond the scope of this book, general principles involves following steps:
a. Identification of donor and HLA cross-matching with recipient;
b. Pre-transplant conditioning of recipient to eradicate residual malignant cells and provide sufficient immunosuppression to facilitate engraftment of donor stem cells. Chemotherapy and total body irradiation is used for this purpose.
c. Harvesting, cryopreservation and storage of donor stem cells from bone marrow or peripheral blood;
d. Infusion of donor stem cells into recipient;
e. Post-HSCT immunosuppressive therapy to prevent graft rejection. Prophylaxis of opportunistic infections, nutritional supplementation and infection prevention is equally important.
Immunization of HSCT donors and recipients before the procedure and of recipient immunization after transplant is an important issue, discussed in Ch 9.4.
Complications of HSCT are conventionally divided into early and late complications with first 100 postprocedure days as dividing period.
• Early complications (lt;100 days):
± Opportunistic infection due to disease/therapy- related immunosuppression
± Acute graft versus host disease
± Iatrogenic, e.g. GIT upsets, hemorrhagic cystitis, mucositis, interstitial pneumonitis, etc.
• Late complications include:
± Iatrogenic: growth failure, hypothyroidism, etc.
± Chronic graft versus host disease
± Second malignancies, e.g. lymphoma.
Graft versus host disease (GVHD) denotes activation of donor T-cells after engraftment in an immunologically compromised host, clinically presenting as:
• Acuteform (within 100 days of BMT) characterized by local erythroderma, cholestatic jaundice and enteritis.
• Chronicform (after 100 days), manifesting as Sjogren's syndrome, SLE and scleroderma, lichen planus and biliary cirrhosis.
Immunosuppressive therapy for variable period is used for the prevention and treatment of GVHD.
19.15.3