This is an introductory lecture about stem cell transplantation

1. MUNEER H. AL BAGSHI, MD
Consultant Pediatric Hematologist Oncologist
Almana General Hospital-Hofuf

2. introduction
Definition
Source
Type
Indications
Preparations
Complications
Outcome

3. 1950s till 1967 ; 200 BMT
Chemotherapy use for BMT
trials
1968 first BMT for WAS, X-ID
successful
HLA system (1990s), and
beore
1988 cord blood
transplantation
1990 PSCT

4.  Bone marrow consists of blood forming cells + other cellular
contents + cytokines and other substances necessary for
growth

5. Intravenous transferring stem cells to the
recipient to replace an (abnormal) stem cells
or to reconstitute treated marrow.

6. Autologous : self
Allogeneic : non self
- Syngeneic (identical twin)
- Related
- Unrelated

7. Bone marrow
Peripheral blood
stem cell
Cord blood

8. Solid organs:
-Life long immune suppression
-No need conditioning before
the transplant.
-Rejection a problem.

9. 
1. Purpose – High doses of chemotherapy and/or
radiation; overcome resistance to chemotherapy
with high doses.
 Autologous stem cells collected from bone
marrow or peripheral blood before transplant and
frozen (cryopreserved).
e.g. Breast cancer, Rhabdomyosarcoma, Ewing’s
sarcoma, neuroblastoma, lymphoma, brain tumurs,
etc.

10. - Purpose: replacing defective bone marrow with
normal bone marrow immune system.
- Requires total destruction of patient’s bone
marrow and severe immune suppression
of
patient.
- Rejection = host versus graft (residual host
cells attack donor cells;
-GVHD = graft versus host (T-cells from donor
attack patient).

11. - Refractory or high risk leukemia
* ALL in second or higher remission
* AML is first or higher remission
* Refractory AML
* CML is chronic or accelerated
phase
* Juvenile myelomonocytic
leukemia(JMML)
* Infant leukemia
* Certain chromosomal
abnormalities (cytogenetics)

12. Bone marrow failure disorders
- Severe aplastic anemia, Fanconi anemia, Blackfan Diamond
anemia
Immunodeficiencies
- Severe combined immunodeficiency (SCID)
-Wiskott Aldrich-Syndrome (WAS)
-Adhesion molecule deficiencies

13. Hemoglobinopathies
 Beta thalassemia major
 Sickle cell disease
Platelets disorders
•Glanzmann disease
•CAT
•TAR
White cells disorders: Kostman, LAD

14.  Genetic Diseases
-Storage diseases (lack a specific enzyme to
metabolize carbohydates, etc)
*Hurler Syndrome, Gaucher’s disease
-Bone disorders
* Osteoporosis :Too much bone, not
enough blood
* Osteogenesis Imperfecta: Too little bone,
too many fractures, not enough
growth.

15. Donor selection

16.  Not enough to match red
blood cell type (ABO, Rh)
for successful BMT
 HLA system: human
leukocyte antigen = genes
on chromosome 6
determine polymorphic
proteins on surface of most
body tissues.

17. HLA-Antigens
- Class I: A,B,C; found on all nucleated
cells in the body.
* Present antigens and activate CD8 +
cells.
-Class II: DR, DQ, DP; found on surface
of antigen-presenting cells such as
dendrite cells, monocytes, B-cells,
activated T-cells
* Present antigens and activate CD4 + T-
cells.

18. Half HLA antigens from each parent
Many other minor antigens that may have a
role in BMT
In the West 25% chance to have HLA match
donor
In KSA up to 50% chance to have HLA
match donor

20.  Full match: all 6 antigens identical
 Mismatch: one or more Ag different
 Haploidintical: only 3 are match
 Sex mismatch: donor and recipient are different sex
 Sex match: both donor and recipient have the same sex
 Match related donor
 Match unrelated donor :(MUD)

22. Healthy from disease
Cardiac
Blood profile status
Infectious diseases screening

23. It require BM harvest at first
Count nucleated cells or CD 34 positive
cells for marrow dose
Repeat the harvest if dose not
adequate
Freeze if autologous

25. Conventional: High dose chemotherapy and/or
radiation therapy (total body irradiation)
Mini-transplants/non-myeloablative/etc.: Lower
doses of chemotherapy radiation therapy; more
immune suppression.

26. Hematopoietic stem cells circulate in blood
and can be identified and quantified using
flow cytometry (cells express the CD34
antigen).
 Colony-stimulating factors (G-CSF,GM-
CSF) to patients or donors releases marrow
stem cells into the peripheral blood, which
can be collected from the veins of the patient
or donor

27.  Apheresis of the nucleated
cells and calculation of the
dose which is max for SAA
 Usually 1 log more than
BM harvest is collected,
early BM recovery

29. 1988 successful for a boy with Fanconi
Anemia
High numbers of hematopoietic stem cells
with superior proliferative capacity
compared with hematopoietic stem cells
from marrow and blood in adults are present
in umbilical cord blood collected at the time
of delivery

30. Low immunogenic status allow degree of
HLA disparity
CMV low titers
Small volume: limitations
Bacterial contamination
Cryopreserved
Loss of the graft
 Banking

31.  (1) Conditioning
 (2) Stem cell infusion
 (3) Neutropenic phase
 (4) Engraftment phase
 (5) Postengraftment period

32.  7-10 days before stem cell infusion
 Chemotherapy and for selected cases total body radiation
(TBI) to kill all hematopoietic cells and immune system
 GVHD prophylaxis
 Anti rejection: ATG,ALG
 Patient in reversed isolation

33.  Volume and stem cell count
 T cell depletion if needed
 Red cell depletion
 Tumor purging
 Central line insertion
 Hydration and premedication
 Infusion of graft

34. Neutropenic phase: 2-4 weeks
Engraftment usually after 2-3 weeks
( ANC > 500)
Acute GVHD it mean pt engrafted.

35. Tolerance of the graft
Gradual weaning of immune
suppression
Immunization
infections

36. Outcome

37. Conditioning mortality is up to 15%
Disease factors: type, staging etc..
Patient factors: age, performance status.
Donor selection: HLA, virus (CMV), sex.
Peritransplant: conditioning, GVHD
prophylaxis, stem cell dose.
Post-transplant : GVHD, Rejection, infection

39. THANK YOU