stem cell transplantation

1. STEM CELL
TRANSPLANTATION

2. STEM CELLS
All blood cells are derived from
pluripotent haematopoietic stem cells.
These comprise only 0.01% of the total marrow cells, but they can self-
renew (i.e. make more stem cells) or differentiate to produce a hierarchy
of lineage-committed progenitor cells.
The resulting primitive progenitor cells cannot be identified
morphologically, so they are named according to the types of cell (or
colony) they form during cell culture experiments.

4. Bone marrow transplantation, was the original term used to describe
the collection and transplantation of hematopoietic stem cells.
Hematopoietic stem cell transplantation, is preferred term, because
the peripheral blood and umbilical cord blood are also used as source
of stem cells.
Transplantation of haematopoietic stem cells (HSCT) has
offered the only hope of ‘cure’ in a variety of haematological
and non-haematological disorders.

5. • Definition.: Hematopoietic stem cell transplantation is defined as the
process of collecting and infusing hematopoietic stem cells obtained
from bone marrow (bone marrow transplantation) and peripheral
blood (peripheral stem cell transplantation).

6. Stem cell transplantation is a procedure that can restore marrow
function for patients who have had severe marrow injury or
abnormalities of the immune system.
Marrow injury can occur because of primary marrow failure,
destruction or replacement of marrow by disease, or intensive
chemical or radiation exposure.

7. TYPE OF HSCT
Allogeneic (from different genes) HSCT, the stem cells come from a donor –
either a related donor (usually an HLA-identical sibling) or a closely HLA-
matched volunteer unrelated donor (VUD).
Autologous (from self) transplant, the stem cells are harvested from the
patient and stored in the vapour phase of liquid nitrogen until required.
Stem cells can be harvested from the bone marrow or from the blood.
Syngeneic ( from same genes)-HSC are obtained from an identical twin.

8. Types of Stem Cell Transplants
Autologous Allogeneic
stem cells obtained from the patient Stem cells from a donor
• Stem cells frozen in lab before
conditioning chemotherapy
• Donor must ‘match’ (what do we mean
by a match
• Rejection is never a problem
• Rejection can occur in both directions
• Fast recovery
• Takes longer for immune system to
recover
• For Myeloma and Lymphoma • For other blood cancers like AML, ALL,
MDS, etc

9. Indications for allogeneic Haematopoietic stem
cell transplantation
Red blood disorders
Severe aplastic anaemia
Thalassemia major
Fanconi anemia
Sickle cell disease
Pure red cell aplasia
WBC disorders
Leukemia –ALL.,CML.,AML.
Myelodysplastic syndrome
,myelofibrosis
Lymphomas: Hodgkin & non-Hodgkin
Multiple myeloma

10. Immunological disorders
• Severe autoimmune disorders:- scleroderma ,lupus erythematosus
• Immune deficiency syndromes
Solid tumors
• Germ cell tumors
• Neuroblastoma

11. • Purpose of HSC transplantation:
To repopulate or replace totally or partly recipient's hematopoietic
system. HSC are self renewing cells which can repopulate all the cell
lineages in the blood.

12. Major sources of hematopoietic stem cells:
 Bone marrow- obtained directly from bone marrow by multiple
aspirations from the pelvic bones.
 Peripheral blood (peripheral blood stem cells).
 Umbilical cord blood.

14. Origin of hematopoietic stem cell used for transplantation.
Origin of hematopoietic stem cell
• -Autologous
• -Syngeneic
• -Allogeneic
• -Genotypically HLA-identical siblings
• -Phenotypically HLA-identical or HLA-mismatched family members
• -Unrelated volunteer donors

15. Bone marrow: marrow is the original source of stem cell. They are
removed by bone marrow puncture.
Peripheral blood : this has become a preferred alternative to marrow
to obtain stem cells. Stem cells have to mobilized into peripheral
blood by injecting granulocyte-macrophage colony -stimulating factor
(GM-CSF) .
Placental blood : T lymphocytes in placental blood appear to be less
alloreactive than T cells from adults and hence less likely to produce
GVHD. Placental blood is obtained from the umbilical cord after birth.

16. Characteristic Bone marrow Peripheral blood Cord blood
Stem cell content Adequate Good Low
Risk of tumor cell
contamination
High N/A N/A
HLA matching Close matching Close matching Less restrictive
Engraftment Medium Fastest Slowest
Risk of aute graft-
versus-host disease
High High Lowest
Risk of chornic GVHD Medium Highest Lowest

17. Transplantation
Stem cell transplantation is a procedure that can restore marrow
function for patients who have had severe marrow injury or
abnormalities of the immune system.
Marrow injury can occur because of primary marrow failure,
destruction or replacement of marrow by disease, or intensive
chemical or radiation exposure.

18. TRANSPLANT PROCESS
• Donor evaluation
• Stem cell collection
• Processing and cryopreservation
• Conditioning of patient
• Chemotherapy
• Stem cell transfusion
• Recovery

20. Transplant Eligibility
Before receiving an SCT, patients must have a checkup to make sure
that they are healthy enough for the procedure.
In order to find out if a patient is a good candidate for SCT, the
patient’s doctor will consider.

21. The patient’s general health
Results of the physical checkup and medical tests
The type and stage of cancer or disease
Previous medical treatments
The likelihood that the disease will respond to the transplant
The ability to use the patient’s own stem cells, or the availability of a
suitable donor
Some patients may not be eligible for standard SCT due to
advanced age or other major health problems such as heart, lung
or kidney disease

22. • Side Effects of Conditioning Treatment for Stem Cell Transplantation
The conditioning treatment given prior to allogeneic or autologous
transplantation can affect any body system that depends on
replacement by stem cells or that may be directly affected by
chemotherapy or radiation.
Some of these effects manifest quickly; others may not appear for
years

23. Side Effects
• Cataracts
• Loss of blood cell formation
• Congestive heart failure
• Mucositis
• Diarrhea
• Nausea and vomiting
• Growth retardation
• Occlusion (blockage) of veins in
liver
• Hair loss
• Pneumonitis (pneumonia)
• Infertility
• Premature menopause

24. POST TRANSPLANTATION
Post transplantation Autologous or allogeneic stem cell
transplantation, or a portion of an either type, may be done in an
outpatient or inpatient setting.
The patients who are treated on an inpatient basis recover
sufficiently to leave the hospital in three to five weeks post
transplant.
The recovery rate of blood cell counts and the severity of other
associated complications, especially graft-versus-host disease (GVHD),
vary from patient to patient.

25. A patient is ready for discharge when.,
The patient’s marrow is producing a sufficient number of healthy red
cells, white cells and platelets
There are no severe treatment complications
The patient has a sense of well-being (as a result of restored blood
cell counts)
Mouth sores and diarrhea lessen or disappear
Appetite improves; it is important that patients be able to eat and
drink to get sufficient fluid and nourishment before they are
discharged from the hospital
The patient does not have fever and is not vomiting.

26. Complications of hematopoietic cell transplantation
• Vascular access complications:
Graft failure
• Blood group
incompatibilities&hemolytic
complications:
Acute GVHD
Chronic GVHD
Infectious complications
Bacterial infections,
Fungal infection,
Cytomegalovirus infection,
Herpes simplex virus,
Varicella-zoster virus ,
Epstein barr virus,
Adenovirus.

27. Gastrointestinal complications
Mucosal ulceration/bleeding
Nutritional support
Hepatic complications
Sinusoidal obstructive syndrome
Hepatitis
Cardiac toxicity
 Structural (valvular abnormalities
or CAD)
 Functional (cardiomyopathies)
Lung injury
 Interstitial pneumonitis,
 Diffuse alveolar hemorrhage,
 Bronchiolitis.
Renal –Nephrotoxicity.
Bladder –Hemorrhagic cystitis.
Endocrine – Drug-drug
interactions , Thyroid
dysfunction

28. • Osteoporosis/osteopenia
• Avascular necrosis
• Dental problems
• Cataracts
• Chronic fatigue
• Psychosocial effects & rehabilitation
Late onset non malignant complications
• Lymphoma
• Solid tumors of the tongue, salivary gland, brain ,thyroid
• Malignant melanoma
• Squamous cell carcinoma
• Basal cell carcinoma
Secondary malignancies

29. Infections during recovery from haematopoietic stem cell transplantation (HSCT)
Infection Time after HSCT Management
Herpes simplex 0–4 weeks (aplastic phase) Acyclovir prophylaxis and therapy
Bacterial, fungal 0–4 weeks (aplastic phase)
As for acute leukaemia – antibiotic
and antifungal prophylaxis and
therapy
Cytomegalovirus
5–21 weeks (cell-mediated
immune deficiency)
Antigen screening in blood (PCR)
and pre-emptive therapy (e.g.
ganciclovir)
Varicella zoster After 13 weeks
Acyclovir prophylaxis
and therapy
Pneumocystis jirovecii 8–26 weeks Co-trimoxazole
Encapsulated
bacteria
8 weeks to years (immunoglobulin
deficiency, prolonged with GVHD
Prophylaxis and
revaccination

31. THANK YOU