د.محمد / 2/4/2017
HAEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT)
A process in which abnormal, malignant, or non-functioning marrow cells are replaced with normal marrow stem cells
Two Kinds of Stem Cells :
- Embryonic (also called “pluripotent”) stem cells are capable of developing into all the cell types of the body.
- Adult stem cells are less versatile and more difficult to identify, isolate, and purify.
Source of Stem cells :
Stem cells may be derived from autologus, allogeneic or xenogenic sources. Histocompatability is prerequisite for transplantation of allogeneic stem cells.
Fetal tissue is the best current tissue source for human neural stem cells, however ethical issues are a major concern.
Sources of haemopoetic stem cells
Bone marrow.
Peripheral blood stem cells(PBSC).
Placental (cord blood) blood transplant.
Fetal liver.
Placenta a Source of Stem Cells
Placental stem cells, like umbilical cord blood and bone marrowstem cells, can be used to cure chronic blood-related disorders such as sickle cell disease, thalasemia, and leukaemia.
Umbilical Cord Blood Stem Cell Transplant
Umbilical cord blood stem cell transplants are less prone to rejection than either bone marrow or peripheral blood stem cells.
This is probably because the cells have not yet developed the features that can be recognized and attacked by the recipient's immune system
Types of HSCT
Allogeneic stem cell transplantation:
Normal BM cells are harvested from the donor& infusion into the pts after aggressive marrow ablative therapy.
The success is compromised by the fact that the transplanted lymphocytes may treat with recipients tissues.
Allogeneic – Stem Cells-cont
Sources of stem cells from another donor (allogeneic) are primarily relatives (familial-allogeneic) or completely unrelated donors (unrelated-allogeneic). The stem cells in this situation are extracted from either the donor's body or cord blood
Autologus stem cell transplantation
Is the process of harvesting, purging (treating for residual malignancy) and cryopreserving the patient's own marrow cells for re-infusion after high dose chemotherapy or total body irradiation(TBI).
Autologous Stem Cells –cont.
Sources of the patient's own stem cells (autologous) are either the cells from patient's own body or his or her cord blood. For autologous transplants physicians now usually collect stem cells from the peripheral blood rather than the marrow.
This procedure is easier, unlike a bone marrow harvest, it can take place outside of an operating room and the patient does not have to be under general anaesthesia.
INDICATIONS OF BMT
1-Malignancy
AML (1st remission)
ALL (high risk 1st CR, good risk 2nd CR)
CML
CLL
MDS
Hodgkins disease
NHL
Multiple myeloma.
2-Defective haemopoiesis
Aplasticanaemia.
Sickle cell anaemia.
Thalassemia major.
Granulocyte disease.
3-Immunedeficiency
sever combined immune deficiency(SCID).
Adenosine deaminase(ADA) deficiency
Complications
20-50% of pts will experience one or more of the following :
1-Chemotherapy and radiation toxicity :
- mucositis : GIT, respiratory tract, bladder.
- Intrahepatic vascular occlusive disease (VOD).
- Toxic pneumonitis .
- CNS toxicity.
- Endocrine dysfunction lead to hypothyoidisim.
- Cataract.
2. Graft Versus host disease (GVHD)
Acute 20-100 days
* Due to engrafment of donor T cell, that react against the recipient tissues.
It can affect the skin,causing rashes, the liver, causing jaundice, and the gut, causing diarrhoea, and may vary from mild to lethal. Prevention includes HLA-matching of the donor,
immunosuppressant drugs, including methotrexate,
ciclosporin, alemtuzumab or antithymocyte globulin.
Chronic 6-12 months
It often resembles a connective tissue disorder (scleroderma-like), treated with corticosteroids and prolonged immunosuppression with, for example, ciclosporin.
- Graft versus leukaemia effect?.
3.Infections :
Due to immundeficiency&granulocytopenia :
a-Bacterial infection G+ve, G.-ve .
b-Fungal infection : candidaalbicans.
c-Viral : Herpes zoster, CMV.
d-Parasitic infection : Interstitial pneumonitis caused by Pneumocystisjiroveci
Interstitial pneumonitis :
-chemotherapy & radiation toxicity.
-Mortality 50-90%.