09/22/2017

STEM CELL TRANSPLANTATION

By Dr.Narumalar MBBS., DGO, MS - General Surgery - Sun Nov 06, 8:07 am

STEM CELL TRANSPLANTATION
Dr. A. Narumalar

Introduction:
Stem Cells are master cells of the body , from which all other cells with specialized function are created.
They retain the ability to renew themselves through mitotic cell divisions and can differentiate into a diverse range of specialized cell types. Research by Candaian scientists Emest A Mcculloh and
James E Till in 1960.

Two broad types of mammalian stems are embryonic stem cells found in blastocysts and adult stem cells found in adult tissues.

Properites of Stem Cells:
Self Renewal
They go through cycles of cell division while maintaining the undifferentiated state.
Potency
The capacity to differentiate into specialized cell types. They are either totipotent or pluripotent – to be able to give rise to any mature cell types.
Embryonic stem cell lies are culture of cells divide from the epiblast tissue of the inner cell mask of a blastocyst or earlier morula stage embryo.
Human ES Cells are grown on a feeder layer of mouse embryonic fibroblasts and require the presence of basic fibro blast growth factor without optimal culture conditions or genetic manipulation, embryonic stem cells will rapidly differentiate.
To generate cultures of specific types of differentiated cells Scientists controlled the differentiation of embryonic stem cells – directed differentiation of stem cells.
Adult tissues reported to contain stem cells include brain, bone marrow, peripheral blood, blood vessels, skeletal muscules, skin and liver.

TYPES OF STEM CELL TRANSPLANTATION:
Auto Logus SCT – stem cells collected from an individual is given back to the same individual after high dose of myelo ablative therapy. The collected stem cells are treated with anti-cancer drugs to decrease the number of cancerous cells. This is called purging. The bone marrow or peripheral blood stem cells are harvested while the disease is in remission. The graft is cryo preserved at – 80 degree centrigrade (Freezer) or at -180 degree centrigrade (Liquid Nitrogen N2). The harvested graft is stored in a cryo protectant bag after mixing with DMSO. The marrow is myelo ablated with high dose of chemotherapy / radio therapy (Conditioning) followed by reinfusion of the cryo preserved BM or PMSC.

Allogenic SCT – Stem cells are taken from HLA matched related or unrelated donor. Used for a variety of malignant and non-malignant disorders to reconstruct the defective host marrow or immune system with normal donor marrow and immune system. Best matches are where HLA antigens are same.
Syngenic SCT – Stem cells are taken from an indentical twin of the receipent. Graft rejection is less.
Tandem Auto Logus Transplant – Double auto logus transplant requires the patient to undergo two Auto Logus SCT within 6 months.
Mini (Non-myelo ablative) – Allogenic SCT – The use of donor lymphocyte infusion for graft verses tumor effect has led to less intensive conditioning regimens. Older patients get good results.

INDICATIONS OF ALLOGENIC SCT
Malignancy –
Accute Myeloid Leukemia
Accute Lympha Blastic Leukemia
Chronic Myeloid Leukemia
Chronic Lympho Blastic Leukemia
Myelo Dysplasia
Hodgkins diseases
Non-Hodgkins disease
Multiple Myeloma

Immuno Deficiency
Severe combined immune deficiency
Wiskott Aldrich Syndrome
Adenocine Deaminase deficiency
Xlinked Lympho Proliferative Syndrome
Cartialage Hair Hypoplasia

Defective Haemopoiesis
Aplastic Aneamia
Sickle cell disease
Fanconi`s aneamia
Thalassemea major
Platellete Disorder
Bernard Soulire Syndrome
Osteo Petrosis
Glanzeman Thrombos thenia

SCT Process:
1. Establishing a venous access – a double or triple lumen central silastic flexible catheter is used.
2. Conditioning – Aim is to ablate the abnormal clone of cells and create space in the bone marrow for engraftment of the new graft. It also suppresses the host immune system to prevent rejection of the new graft. Agents used for conditioning are : (a) Immuno supression – irradiation to Lymphoid system, cyclo phosphamaid, anti lymphocyte globulin.. (b) Myelo ablation – Busul pham, melphalan. (c) for both immune suppression and meylo ablation – whole body irradiation.

Harvest of BM or PBSC – To acquire a cell dose of total nucleated cells 1 to 3 x10 cells or CD – 34 of 3 x 10 (six) cells. Bone Marrow is harvested under GA and PBSC is harvested using a cell separator after priming with G-CSF for 5 days. This graft is then infused into the patient using central line
For GVHD – various protocols using combination of immune suprresive drugs like cyclo sporin A and methotrexate are used.

Engraftment – Once a peripheral neutrofil count of 500 / cubic mm is achieved on 3 successive days.
Failure to engraft – Graft Failure is due to defective stem cells or host resistance to implantation.
Supportive Care
Good Supportive care is mandatory .
Protective Isolation of the patient by housing in rooms with laminar air flow or using high efficiency particulate air filters.
Anti microbial support to manage fibrile neutron penia.
Blood Component Support.
Nutritional Support

COMPLICATIONS :
Early – within 100 days of post SCT
Accute graft versus host disease
GIT – Nausea, vomiting
Mucositis
Oesophagitis
Gastro Duodenitis
Diarrahoea
Pancreatitis and Cholecystitis

Hepitic Veno Occulsive Disease
Interstitial Pneumonia
Renal and Urinary tract complications
Cardio vascular complications
Metabolic complications – Fluid and Electrolye imbalance
Neurological complications – Seizures, CNS Haemorrhage, Encephalopathy

LATE COMPLCATIONS OF SCT – It occurs 100 days post SCT
Chronic GVHD
Malignant relapse
Secondary malignancy
Growth retardation
Hypo thyroidism
Hypo Gonadism
Catarract
Oesteoprosis

Appropriate cost for each transplant is 4 to 8 lakhs.
SCT program is available in India –
TMH – Mumbai
CMCH – Vellore
AIIMS – New Delhi
Apollo Hospital – Chennai
Army Hospital – Delhi
Adyar Cancer Institute – Chennai.

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