The document provides a comprehensive overview of bone marrow transplantation, detailing its history, types, indications, suitable disorders, stem cell sources, donation process, and the significance of HLA matching. It discusses the procedure for transplantation, life post-transplant, potential complications, and outcomes for different patient demographics. Ultimately, it concludes that bone marrow transplantation can effectively restore immune function and serves as a viable alternative to thymic transplantation when a suitable donor is available.

1. BONE MARROW TRANSPLANTATION

2. HAFIZ M WASEEM UNIVERSITY
OF EDUCATION LAHORE

3. CONTENTS:
1. Introduction
2. Types
3. Indications
4. Disorders suitable for Bone Marrow Transplantation
5. Sources of Bone Marrow Stem Cells
6. Donating Bone Marrow
7. Why is HLA Matching Important
8. Procedure for Transplantation
9. Life after Transplant
10. Complications after Transplant
11. Outcome
12. Results
13. References

4. INTRODUCTION:
• Introduced in early 1960s by Mathe, McFarland and Donnal Thomas.
• Rapidly developed from experimental procedure to established treatment.
• The number of patients with this disease increased 10 fold during 1980s.
• Medical knowledge of Bone Marrow Transplantation is often limited.

5. • TYPES:
There are differen types of transplantation which are as follow:
• Modality:
1. Allogenic
Stem cells from HLA matched donor
2. Syngeneic
Stem cells from an HLA identical donor
• Stem Cell Source:
1. Peripheral Blood Stem Cells
Collected using a peripheral blood pheresis after chemotherapy-based regimen.

6. 2. Bone Marrow
Collected directly from Bone marrow generally no pre-procedure mobilization but require general anesthesia.
3. Umbilical Cord Blood:
Removed from umbilical cord and placenta after normal delivery of infant.

7. INDICATIONS:
• Bone Marrow Transplantation is a method of providing patient with normal haematopeitic and immune system
when these have been rendered defective.
• This may be due to effect of high dose of chemotherapy or radiotherapy.
• Bone marrow transplantation allows doctor to overcome problem of marrow suppression.
• Allogenic bone marrow transplantation also help to eliminate residual disease by system recognizing tumour as
non-self with subsequent tumour destruction.

8. DISORDERS SUITABLE FOR BONE MARROW TRANSPLANTATTION:
• Acquired Disorders
1. Malignanant Diseases
Acute lymphoblastic leukaemia- high risk patients
Acute myeloid leukaemia- consider for all patients
Chronic myeloid leukaemia- all patients, if there is young and suitable donor
Hodgkin’s and non-Hodgkin’s lymphoma- selected patients at high risk of relapse
Solid tumours- selected patients with breast cancer, small cell lung cancer, testicular tumours, ovarian cancer,
neuroblastoma, severe aplastic anaemia.
2. Inherited Diseases
Haemoglobinopathies- thalassaemia major , sickle cell disease
Inborn errors of metabolism- Gaucher’s disease, Osteopetrosis
Immunodeficiency Syndromes- severe combined immunodeficiency, Wiskott Aldrich Syndrome
Congenital Severe aplastic Anaemia- Fanconi’s anaemia

9. SOURCES OF BONE MARROW STEM CELLS:
• Basis of bone marrow transplantation is provision of haematopoeitic stem cells to repopulate bone marrow.
• Initially bone marrow was the only source but recently alternative sources of stem cells have been recognized.
• Most transplants are of matched allogenic bone marrow.
DONATING BONE MARROW:
• Before Donation full history is taken and donor is examinef and investigated.
• The harvest is performed under general anaesthesia and lasts 30-45 minutes.
• In an adult 800-1000ml of bone marrow is removed and subsequently processed by cell separator.
• The separated red cells can be returned to donor transfusion of homologous blood is generally not required.
• Donors can be expect to be in hospital for 48 hours.
• Generally only mild analgesics such as paracetamol are required after donation.

11. WHY is HLA MATCHING IMPORTANT:
• HLA our Genetic Finger Print
Human leukocyte antigens (HLA) are proteins found on surface of most cells of body.The immune system uses HLA
to verify that given cell is part of body and not foreign.There are many different HLA protein (HLA-A,B,C etc) and
there are many varieties of each one.
• HLA Matching
If the donor stem cell are not the same HLA type as the recipient, they will recognize the recipient as being different
and attack.If recipient cells win you get graft rejection.If donor cells win you get graft-versus-host disease (GVHD).
PROCEDURE FOR TRANSPLANTATION:
• Firstly the patient undergoes conditioning
• The purpose of conditioning is to remove the patient’s own bone marrow and immune system thereby creating
suitable microenviroment for marrow engrafment.
• A second purpose it to eliminate any residual malignant disease.
• The conditioning generally involves a high dose of chemotherapy frequently combined with body total irradiation.
• Then stem cells infuse into central vein and migrate to bone marrow space .
• Before these stem cells engraft and produce cellular elements of blood there is period when patient is anaemic
(require regular blood transfusion).
• The patient also experience other side effects of conditioning like nausea and diarrhoea etc.

12. • Patients can expect to be in hospital for 4-6 weeks, although this is highly variable.
• Peripheral stem cells have lead to more rapid engraftment and shorter duration of hospitalisation.
• Most patients will not return to work for at least nine months after transplantation.

13. LIFE AFTER TRANSPLANT:
• Recovery_Early Days after Transplant
1. 14-21 days of extreme immune suppression.
2. Very low white blood cell , red blood cell and platelet counts.
3. Risk for serious infection and organ damage.
4. Antibiotics , Blood and platelet transfusion given as needed.
• Engraftment
1. Term used for establishment of new stem cells
within bone marrow.
2. Occurs 10-28 days after transplant.
3. Risk for infection and bleeding decreases
following engraftment.
• Getting Discharged
You will be discharged from hospital when:
1. No active infection
2. No active graft-versus-host disease
3. Able to take foods and medicine by mouth.

14. COMPLICATIONS AFTER TRANSPLANT:
• Low Cell Counts
1. Results in fatigue , bleeding and infectious risk
2. Dependent on transfusion of RBCs and platelets during chemotherapy.
• Toxicity From Chemotherapy
1. Organ toxicity…..heart , liver , lung , kidney
2. Nausea , vomiting , rash , mouth sores eyc.
• Graft Failure
1. Donor stem cells not engrafted within host marrow fail to produce necessary hematopoeitic stem cells.
2. Certain disease states.
• Late Effects
1. Late infection
2. Cardiovascular diseases
3. Ishemic heart disease
4. Pulmonary toxiciry
5. Treatment related malignancies
6. Increased risk for secondary solid tumours.

15. OUTCOME:
• Autologous transplant overcome the problem of GVHD as patients are their own donor
• Allogenic transplant seems to be superior to autologous transplant in reducing risk of disease relapse
• About 30% of patients fail to survive allogenic bone marrow transplantation but less than 10% do not survive
autologous transplantation.
• Increased safety of autologous transplantation means it is more suitable for patients.
• Upper age range for autologous transplantation is about 50 years but only 30-40 years for allogenic
transplantation.
• Allogenic transplantation with unrelated matched donor is more hazardous.It is generally reserved for very
young patients with no other hope of cure.

16. Autologous Transplantation Allogenic Transplantation

17. CONCLUSION:
We concluded that Bone marrow transplantation achieves long-lived reconstitution of immune function in complete
DGS and is a good alternative to thymic transplantation in patients with suitable donor.
REFERENCES:
https://www.researchgate.net/publication