Bone Marrow Transplantation

Blood
 Blood is a body fluid in humans and
other animals that delivers
necessary substances such as
nutrients and oxygen to the cells and
transports metabolic waste products
away from those same cells.
 Vertebrate blood is bright red when

its hemoglobin is oxygenated and

dark red when it is deoxygenated.
 Blood is circulated around the body through
blood vessels by the pumping action of the
heart.
 In animals with lungs, arterial blood carries

oxygen from inhaled air to the tissues of the

body, and venous blood carries carbon
dioxide, a waste product of metabolism
produced by cells, from the tissues to the
lungs to be exhaled.
 In vertebrates, it is composed of blood cells
suspended in blood plasma. Plasma, which
constitutes 55% of blood fluid, is mostly water
(92% by volume), and contains proteins,
glucose, mineral ions, hormones, carbon
dioxide.
 The blood cells are mainly red blood cells (also

called RBCs or erythrocytes), white blood cells

(also called WBCs or leukocytes) and platelets
(also called thrombocytes).
 Blood accounts for 7% of the human body
weight with an average density very close to
water.
 One microliter of blood contains:
 4.7 to 6.1 million (male), 4.2 to 5.4 million (female) red
blood cells
 4,000–11,000 white blood cells
 200,000–500,000 platelets
 These cells are all developed in bone marrow of
our body.
Bone Marrow
 It is a spongy matrix
located in the center of
many bones.
 It contains stem cells.
 It is the factory where
all the cellular
components of blood
are made.
 Video: Operation ouch-
Bone marrow
University Healthcare
[Link]
[Link]
Bone marrow, red and yellow
Bone Marrow
From stem cells to blood cells
Red blood Cells
 Red blood cells (RBCs, erythrocytes, left) are
the most common type of blood cell and the
vertebrate's principal means of delivering
oxygen (O2) to the body tissues—via blood
flow through the circulatory system.
 RBCs take up oxygen in the lungs, or gills of

fish, and release it into tissues while

squeezing through the body's capillaries.
 The cytoplasm of RBCs is rich in hemoglobin, an
iron-containing biomolecule that can bind oxygen
and is responsible for the red color of the cells
and the blood.
 In humans, mature RBCs are flexible and oval

biconcave disks. They lack a cell nucleus and

most organelles, in order to accommodate
maximum space for hemoglobin; they can be
viewed as sacks of hemoglobin, with a plasma
membrane as the sack.
 Approximately 2.4 million new RBCs are
produced per second in human adults. The
cells develop in the bone marrow and circulate
for about 100–120 days in the body before
their components are recycled by
macrophages. Each circulation takes about 60
seconds (one minute).
 Approximately 84% of the cells in the human

body are red blood cells. Nearly half of the

blood's volume (40% to 45%) is red blood cells.
White blood cells
 White blood cells (WBCs, leukocytes, right)
are the cells of the immune system that are
involved in protecting the body against both
infectious disease and foreign invaders.
 All white blood cells are produced and

derived from multipotent cells in the bone

marrow known as hematopoietic stem cells.
Leukocytes are found throughout the body,
including the blood and lymphatic system.
 Allwhite blood cells have nuclei, which
distinguishes them from the other blood cells,
the anucleated red blood cells (RBCs) and
platelets.
 WBCs can be divided into the five main

types: neutrophils, eosinophils (acidophiles),

basophils, lymphocytes, and monocytes.
Monocytes and neutrophils are phagocytic.
Platelets
 Platelets,also called thrombocytes, are a
component of blood whose function (along
with the coagulation factors) is to react to
bleeding from blood vessel injury by
clumping, thereby initiating a blood clot.
 Platelets have no cell nucleus: they are

fragments of cytoplasm that are derived from

the megakaryocytes of the bone marrow, and
then enter the circulation.
Bone Marrow Disease
Problems with Bone Marrow
 Thereare many diseases that affect the bone
marrow such as:
 Cancers (i.e. Leukemia & Lymphomas)
 Genetic Disorders ( i.e. SCID, Fanconi anemia…)
 Many of these diseases are often fatal!
 BM transplant may be the last line of

defense.
Bone Marrow Transplantation
 Hematopoietic stem cell transplantation
(HSCT) is the transplantation of multipotent
hematopoietic stem cells, usually derived
from bone marrow, peripheral blood, or
umbilical cord blood.
 It may be autologous (the patient's own stem

cells are used), allogeneic (the stem cells

come from a donor) or syngeneic (from an
identical twin).
BM Transplantation
A bone marrow transplant replaces a
patient's unhealthy stem cells in the bone
marrow with healthy stem cells from a
volunteer donor.
 The recipient's immune system is usually

destroyed with radiation or chemotherapy

before the transplantation.
 Infection and graft-versus-host disease are

major complications of allogeneic HSCT.

Is Blood Transfusion the
Same??
2 completely different things!
 Blood is a finished product that is constantly

replenished every 3 months.

 Only offers a temporary symptomatic fix.

 By providing stem cells, a BM transplant

gives one the ability to constantly renew

blood cells.
History of BMT
 Georges Mathé, a French
oncologist, performed the first
European bone marrow transplant in
November 1958 on five Yugoslavian
nuclear workers whose own marrow
had been damaged by irradiation
caused by a criticality accident at the
Vinča Nuclear Institute, but all of
these transplants were rejected.
 Fortunately, the five treated were able to
ultimately recover, perhaps in part due to the
transplants. Mathé later pioneered the use of
bone marrow transplants in the treatment of
leukemia.
 Stem cell transplantation was pioneered
using bone-marrow-derived stem cells by a
team at the Fred Hutchinson Cancer
Research Center from the 1950s through the
1970s led by E. Donnall Thomas, whose
work was later recognized with a Nobel Prize
in Physiology or Medicine (1990).
 Thomas' work showed that bone marrow cells
infused intravenously could repopulate the
bone marrow and produce new blood cells. His
work also reduced the likelihood of developing
a life-threatening complication called graft-
versus-host disease.
 Collaborating with University of Washington

Professor Eloise Giblett, he discovered genetic

markers that could confirm donor matches.
 The first physician to perform a successful
human bone marrow transplant on a disease
other than cancer was Robert A. Good at the
University of Minnesota in 1968.
 In 1975, John Kersey, M.D., also of the

University of Minnesota, performed the first

successful bone marrow transplant to cure
lymphoma. His patient, a 16-year-old-boy, is
today the longest-living lymphoma transplant
survivor.
 In 2006, a total of 50,417 first hematopoietic
stem cell transplants were recorded
worldwide, according to a global survey of
1,327 centers in 71 countries conducted by
the Worldwide Network for Blood and Marrow
Transplantation. Of these, 28,901 (57
percent) were autologous and 21,516 (43
percent) were allogeneic (11,928 from family
donors and 9,588 from unrelated donors).
 The main indications for transplant were
lymphoproliferative disorders (55 percent)
and leukemias (34 percent), and the majority
took place in either Europe (48 percent) or
the Americas (36 percent).
 The Worldwide Network for Blood and

Marrow Transplantation reported the millionth

transplant to have been undertaken in
December 2012.
Bone Marrow Registry Database
 Ages 18-60
 A small sample of blood is obtained

 HLA cell type determined

 Donors must have similar cell types as recipient in
order to prevent bad reactions.
 Video : What is HLA matching
 Information is confidentially put into the
national registry.
HLA determining self from
non-self and eliminating it
Necessity of the Registry
 There remains a low number of participants
in the registry.
 It is difficult for a recipient to find a complete

match(1/20,000); the more people in the

registry the higher the likelihood of matching.
 Compounded Problem
 Patients are more likely to match with someone in
their ethnic group; however, there are even fewer
underrepresented people in the registry.
 Worldwide, there are 36,431,750 donors
registered in 2019(0.47%).
 The highest total number of bone marrow

donors registered were those from the U.S.

(8.0 million, 2.4%), and the highest number
per capita were those from Cyprus (15.4
percent of the population).
 In Taiwan, there are 438,233 donors

registered (1.84%).
 Africans are more genetically diverse than
people of European descent, which means
that more registrations are needed to find a
match.
 Many people belonging to different races are

requested to donate as there is a shortage of

donors in African, mixed race, Latino,
aboriginal, and many other communities.
Recipients in the world,
BTCSCC
 Recipients in the world

Others 4.4% Taiwan

S. Korea 3.9% 45.7%
Singapore 2.5%

HK 2%

USA 2%
Thailand 1.11%
China
38.5%
The Process
 Donor will be contacted if he/she matches the
patient’s cell type and the process is
explained.
 Donor may still back out.

 If committed, the donor will meet the medical

team and the method of stem cell extraction

is determined.
 Bone Marrow Stem Cell or Peripheral Blood Stem Cell
Marrow Collection
 Surgical day procedure
 Marrow extracted from
pelvis (hip) using a
hollow needle
 Anesthesia is used to
minimize pain.

Copyright © 2005 Nucleus Communications, Inc.

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Marrow Collection
 Most patients will go home the same day.

 Many experience lower back pain and

stiffness for several days.

 Themarrow stem cells will completely

regenerate in 4-6 weeks.
Peripheral Blood Stem Cell
(PBSC)
 Allows collection of
stem cells through the
blood rather than bone
 A drug (G-CSF) must
be taken a week prior
to extraction to induce
the stem cells
 An apheresis process
is used in extraction.
[Link]
bone_marrow_donor_5_nmdp_steps.htm
G-CSF:Granulocyte Colony-Stimulating Factor
PSBC Collection
 The whole process may take several hours.

 Side
effects include headache and muscle
aches during a week prior to collection.
Summary
 The whole donation process will not cost the
donor anything; it will be covered by the
recipient’s insurance.
 BM transplant is a life-saving procedure that

offers hope to many afflicted with certain

diseases.
Questions?