1.
Understanding Cancer and Related Topics
Understanding Blood Stem Cell Transplantation
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Developed by:
Donna Kerrigan, M.S.
Kathryn Hollen
Jeanne Kelly
Brian Hollen
Discusses how bone marrow produces blood-
forming stem cells that include “starter” immune
cells. When diseases like cancer or its treatment
damage these hematopoietic cells, transplanting
healthy stem cells from marrow, peripheral blood,
or other sources can help some patients. Clarifies
how antigens that mark cells as “self” or “non-self”
are critical determinants of transplant success.
Explains autologous, syngeneic, and allogeneic
transplants as well as tissue typing.

2.
Stem Cells
Gastrula
(14 to 16 days)
Fertilized egg
(1 day)
Outer cell mass
Inner cell mass
Blastocyst
(5 to 6 days)
Ectoderm
(external layer)
Skin
Neurons
Pituitary gland
Eyes
Ears
Endoderm
(internal layer)
Pancreas
Liver
Thyroid
Lung
Bladder
Urethra
Mesoderm
(middle layer)
Bone marrow
Skeletal, smooth
and cardiac muscle
Heart and
blood vessels
Kidney tubules

3.
Blood Stem Cells
Bone graft
Multipotential
stem cell
Hematopoietic
stem cell
Platelets
Erythrocytes
Eosinophil
Neutrophil
Megakaryocyte
Basophil
T lymphocyte
Natural killer cell
Dendritic cell
B lymphocyte
Lymphoid progenitor cell
Myeloid
progenitor
cell
Monocyte
Marrow
Bone

4.
From Bone Marrow to the Bloodstream
T lymphocyte
Hematopoietic
stem cell
Erythrocytes
Circulating
blood
Thymus
Lymph
nodes
Spleen
Bone
marrow
To
thymus,
tonsils,
and lymphoid
organs
1 in blood for every
100 in marrow
B lymphocyte
From
thymus

5.
Blood Stem Cell Transplants: When?
No blood stem
cell production
Chemo
Radiation
X

6.
Stem Cells from Self to the Rescue
Patient receives
chemotherapy
or radiation
Self-donated stem
cells are re-infused
into patient
Stem cells are
collected from
patient

7.
Stem Cells from Donor to the Rescue
Stem cells
are collected
from donor
Stem cells are infused
into patient, where they
migrate to bone marrow
Patient receives
chemotherapy or
radiation

8.
Not Just Any Blood Stem Cells Will Do
Self Non-self

9.
Host vs. Graft/Graft vs. Host
Host versus graft reaction Graft versus host reaction

10.
Tissue Typing Matches Donors to Patients
Allogeneic
Patient
= matches to patient
Conflict: only some
marker molecules match
No conflict: all
marker molecules match
Patient
Syngeneic
Autologous
Donor
Identical
twin donor
Unrelated
donor
Related
donor
Allogeneic
Patient
Donor
Patient
Donor
Patient
Donor

11.
Many Names for the “Self” Antigens
Major
histocompatibility
complex (MHC) proteins
(“self” markers)
Blood cell
(leukocyte)
Body cell
Human
leukocyte
antigens (HLAs)
(“self” markers)
=

12.
Haplotypes: Passing on Genes
for “Self” Antigens
DP DR
DQ
No.
of
possible
alleles
at
this
locus
Many Varieties of MHC “Self” Genes
Sample Haplotype: Chromosome 6
DP DQ
A
C
HLA alleles
DR
45
89
19 20
2
323
75
50
25
400
100
0
DP DQ DR
B
93
195
395
B C A

13.
6 Major Genes: 10,000 Antigens
HLA genes
Paternal
chromosome 6
Maternal
chromosome 6
Maternal
leukocyte
Paternal
leukocyte
HLA genes
D B C
D A
D
D B C
D A
D
* are MHC proteins
2 (of 6) major human
leukocyte antigens*
6 major
genes
6 major
genes
2 (of 6) major human
leukocyte antigens*

14.
Three Most Important Antigens
3 most important
antigens for tissue
matching
Leukocyte
Human leukocyte antigens (MHC proteins)
DP
DQ
B
C
DR
A
No.
of
possible
alleles
at
this
locus
Many Varieties of MHC “Self” Genes
DP DQ DR
45
89
19 20
2
323
75
50
25
400
100
0
DP DQ DR
93
195
395
B C A

15.
A “Clinical Match”
Child A (patient)
HLA-A
HLA-B
Child E (donor)
a perfect match
Child D
Haplotype 3
Child C
Sperm
Ovum
Child B
Haplotype 1
HLA-A HLA-DR
HLA-B
HLA-DR
HLA-A
HLA-B
Haplotype 4
Haplotype 2
HLA-A HLA-DR
HLA-B
HLA-DR

16.
Some Haplotypes Occur More Often
25–30% chance
>90% chance
50–60% chance
40–50% chance

17.
Sometimes a 3-Antigen Match Is Necessary
3-antigen match

18.
A Delicate Balance:
Graft vs. Tumor/Graft vs. Host
Stem cells plus
haplo-identical
white blood cells
Cancer cell
destroyed
Cancer
cell
Transplant attacks patient
Transplant attacks tumor
in patient
A Delicate Balance
Should I
give the patient
steroids?

19.
Success in Matching
Varies With Population
Japanese
99%
African
American
50%
North
American
Caucasian
93%
Asian
50%

20.
Preparing Patients for
Myeloablative Allogeneic Transplants
High-dose
radiation
and/or
High-dose
chemotherapy
Lymphocytes
destroyed
Cancer
cells
destroyed

21.
Preparing Patients for Reduced-
Intensity Allogeneic Transplants
Before Transplant
Donor’s white
blood cells
Sometimes
After Transplant
Low-dose
or standard
radiation
and/or
Low-dose
or standard
chemotherapy
Immunosuppressant
drugs

22.
Preparing Donors for
Allogeneic Transplants
Growth factor
to amplify and
mobilize stem cells
Allogeneic transplant
Stem cells
ready for
infusion
Stem cells
ready for
infusion

23.
Apheresis: Harvesting Stem Cells
From Peripheral Blood
Whole
blood is
collected
from
donor
Blood,
minus stem
cells, is
returned to
donor
Stem
cells out
Whole
blood in
Blood-forming
stem cells

24.
Preparing Patients for
Autologous/Syngeneic Transplants
Syngeneic:
Peripheral Blood
Growth factor
to amplify
and mobilize
stem cells
Patient
Autologous:
Peripheral Blood
Cells
for
infusion
into my
twin
Identical twin
donor
Cells for
re-infusion
Growth factor
to amplify
and mobilize
stem cells

25.
Cord Blood as a Source of Stem Cells
Placenta
Umbilical cord
Placenta
Primitive
stem cells
Liver
Uterus
Umbilical
cord

26.
Placental and Cord-Blood
Stem Cell Transplants
After the birth of
the baby, blood is
collected into a
special blood bag
Umbilical
cord
Placenta
Virus-free, tissue-typed
stem cells stored in
liquid nitrogen for
future transplant
Cryoprotectant added to minimize
damage during freezing
Stem cells transferred
to a new bag

27.
Using More Than One Cord-Blood Donor
Cells from one unit
dominate the other; both
attack patient’s immune
system
Cord blood
from donor 2
Cord blood
from donor 1
No, I’m
in charge!
I’m in
charge!
2
1

28.
Placental and Cord-Blood Transplants:
Pros and Cons
Cons
 1/10 number of cells vs.
bone marrow transplant
 Longer time for
transplant to “take”
 Slight chance of
maternal cell/genetic
disease contamination
 Adults need more than
one cord-blood donor
Pros
 Lifesaver when there
is no eligible donor
 Available quickly
(about 2 weeks)
 Unlikely to harbor
cytomegalovirus

29.
New Development: Stockpiling

30.
When a Blood Stem Cell Transplant Works
Your biopsy was
negative, and your
immune cells look good!

31.
National Marrow Donor Program Helps Many
Thank you, DONORS!

32.
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