BONE MARROW
TRANSPLANTATION
Haemopoietic
stem cell transplantation is usually carried out for one of the two
reasons: to replace an abnormal but not malignant marrow that has been
purposefully destroyed with either radiation or chemotherapy, to allow
for the administration of higher than usual doses of myelotoxic
chemotherapy and/or radiation therapy to treat a malignancy. The types
of bone marrow abnormalities treated with this procedure include both
congenital and acquired diseases;the malignancies treated with
hemopoietic support include acute leukemias and lymphomas, as well as
solid tumours that appear to have a dose-response curve to chemotherapy.
SOURCE OF
HEMOPOIETIC STEM CELLS
Stem cells may be obtained from
the bonemarrow, peripheral blood, cord blood, or fetal liver of another
individual, generally one who is immunologically matched at the major
histocompatibility complex. Cord blood is usually available in too small
a volume to reconstitute a adult;thus cord blood transplants are
performed nearly exclusively in children.Fetal liver between 10 and 14
weeks of gestation is a rich source of hemopoietic stem cells, but such
transplants are rarely done because of the scarcity of the material.
TYPES OF
MARROW TRANSPLANTS
When another individual is the
stem cell donor, the transplantation is termed allogenic.Autologous bone
marrow and peripheral blood may also be stored before marrow ablation
for reinfusion after myeloablative therapy.Such transplants are termed
autologous.In the special case where the donor is an identical twin,
i.e., genetically identical to the recipient, the transplantation is
termed syngeneic.In all these types of transplants, hemopoietic stem
cells are infused into a peripheral vein of the recipient and the stem
cells home to the marrow to re-establish hematopoiesis.
DISEASES TREATED WITH
HEMOPOIETIC STEM CELL TRANSPLANTATION
|
MALIGNANCIES |
|
CONDITIONS |
Allogenic |
Autologous |
|
Acute leukemia |
+ |
+ |
|
Chronic myelogenous leukemia |
+ |
+ |
|
Lymphoma |
+ |
+ |
|
Hodgkin's disease |
+ |
+ |
|
Multiple Myeloma |
+ |
+ |
|
Chronic lymphocytic leukemia
|
+ |
+ |
|
Myelofibrosis |
+ |
- |
|
Breast cancer |
- |
+ |
|
Testicular cancer |
- |
+ |
|
Ovarian cancer |
- |
+ |
|
Neuroblastoma |
+ |
+ |
|
Peripheral neuroepithelial tumors |
- |
+ |
|
Wilm's tumour |
- |
+ |
|
Ewing's sarcoma |
-+ |
+ |
|
NON-MALIGNANCIES |
|
CONDITIONS |
Allogenic |
Autologous |
|
Lesch-Nyhan syndrome |
+ |
- |
|
Hemoglobunuria[PNH] |
+ |
- |
|
Aplastic anaemia |
+ |
- |
|
Pure red cell aplasia |
+ |
- |
|
Fanconi's anaemia |
+ |
- |
|
Severe Combined immunodeficiency
|
+ |
- |
|
Sickle cell anaemia |
+ |
- |
|
Thalessemia |
+ |
- |
|
Met.. leukodystrophy |
+ |
- |
|
Adrenoleukodystrophy |
+ |
- |
|
Osteopetrosis |
+ |
- |
|
Type IIa glycogen storage disease
|
+ |
- |
|
Radiation accidents |
+ |
- |
|
Others |
|
|
ALLOGENIC AND SYNGENEIC
BONE MARROW TRANSPLANTATION
Allogenic marrow
transplantation is usually restricted to persons less than 60 yrs of
age.The results tend to be poorer in older patients because of increased
complications associated with graft-versus host disease (GVHD) in this
population.For patients with a twin, an HLA-matched sibling donor is the
best choice for an allogenic bone marrow transplantation.For patients
who may benefit from an allogenic bonemarrow transplanatation but lack
an HLA-matched sibling donor, there are two possibile solutions.One is
to identify an unrelated but closely HLA-matched person willing to
donate marrow or peripheral blood, and the other is to use marrow from a
related donor who is less than perfectly matched.The extremely large
number of HLA phenotypes makes the search for an unrelated donor a
difficult undertaking.Fortunately, in patients with a similar genetic
background certain HLA phenotypes occur more frequently than might be
expected based upon random population genetics.
Bonemarrow transplantation
using unrelated donors has become a widely applied therapy.While the
results remain somewhat inferior to those seen when using an HLA-matched
sibling donor, treatment outcomes with this approach have been improving
as the techniques to manage GVHD and graft rejection have been refined.
An alternative approach is to identify a related individual who shares
most, but not all, of the patient's HLA antigens.Successful allogenic
marrow transplantation can be performed using marrow from such donors,
but the risk of graft rejection and GVHD increases with the level of
mismatch.There is a somewhat higher rate of death from GVHD, but there
is a somewhat lower rate of death from tumor relapse because the
mismatched marrow exerts a greater graft-versus-tumour effect. Once a
donor has been identified, the actual transplant procedure begins.It
consists of three phases: preparation for transplant, transplant and
management after transplant.
PREPARATION FOR
TRANSPLANTCOMPLICATIONS OF ALLOGENIC BONE MARROW TRANSPLANTATION
| Approximately one week prior to
transplant, you will enter the hospital as an outpatient to have a
triple-lumen Hickman catheter inserted. The catheter, referred to as
a right atrial catheter (RAC), is used to give you intravenous (IV)
fluids, medications and blood transfusions and to obtain blood
samples. The BMT clinical coordinator will arrange for you and your
caregiver to be shown how to care for the catheter. The coordinator
will also assist in ordering catheter supplies. You and your
caregiver will be responsible for caring for the RAC before and
after the transplant.
Before the transplant
10 days before your allogeneic transplant, you will
be admitted to the Blood and Marrow Transplant Unit at the Hospital
to begin a conditioning phase. Each room in the unit has special air
filtration systems to help protect you from infection. These are
called Laminar Air FLow (LAF) rooms. Everyone who enters your room
must wash his or her hands. To help prevent infection, you will be
allowed out of your room only for special tests.
The conditioning phase consists of several days of
chemotherapy or a combination of chemotherapy and radiation. These
high-dose treatments kill cancer cells, but also kill normal bone
marrow stem cells. Once these stem cells are destroyed, normal blood
cell production will cease. Blood or marrow transplants will restore
normal blood cell production. The RAC will have been inserted before
chemotherapy. Each chemotherapy treatment will take several hours.
A urinary catheter, if indicated, will be inserted
into your bladder. This will be used for continuous bladder
irrigation due to the possible side effects of some chemotherapy
agents. The urinary catheter will be removed after the full course
of treatment is completed. On days you receive chemotherapy and
radiation, you will be given medications to decrease nausea and
vomiting and to help you relax and sleep.
For radiation therapy,if any, you will be
transported by ambulance to your appointment at the Radiation
Oncology Center . The pre-transplant conditioning phase takes
between two and 10 days.
The donor's bone marrow harvest
On the morning of the allogeneic transplant, your
donor will be taken to the operating room and given general
anesthesia. The physician will remove bone marrow from his/her
pelvic bones (the posterior iliac crests). Two or three small
incisions are made over each iliac crest and numerous needle sticks
will be made in the incisions to draw out the bone marrow.
Because the harvest depletes red blood cells, your
donor will receive a transfusion of his/her own blood, which will
have been collected a few days or weeks before the harvest.
The donor's lower back will be sore and stiff after
the harvest. Pain medications are available to ease the discomfort.
He or she may feel lightheaded the first day after the harvest but
should be able to resume normal activities within a week.
Hospitalization for the harvest procedure is usually an overnight
stay.
Allogeneic transplantation
Day 0 is bone marrow transplantation day. Your donor
usually has surgery in the morning. You will receive the bone marrow
infusion (transplant) in the afternoon or evening. Once it has been
processed, the bone marrow is given to you through your RAC over a
few hours, like a blood transfusion. You will be monitored closely
throughout the procedure.
After transplantation
The combined effects of the chemotherapy and
radiation will destroy your bone marrow, which reduces your body's
ability to fight infections. It's common to develop a fever related
to an infection when your white blood count drops. Antibiotics,
anti-viral and anti-fungal medication may be prescribed. Your mouth
may become tender and sore. To soothe your mouth and help keep it
clean, you will be expected to do mouth care four times a day. Your
nurse will provide you with the necessary items. Pain medications
can be used to help control discomfort, so do not hesitate to ask
your nurse for them.
Blood will be drawn daily or as needed from your RAC
to evaluate your blood counts. During these first weeks, you will
receive red blood cells and platelet transfusions as your blood
count indicates the need for them. Because therapy suppresses their
immune system, all BMT patients must receive blood products that
have been irradiated before they are transfused.
A rising white blood count usually means that the
donated bone marrow or stem cells have taken hold, or engrafted. If
the new bone marrow or stem cells react against your body, you can
develop what is called graft-versus-host disease (GVHD). The
symptoms of GVHD can be short term (acute) or long-term (chronic).
You will be observed closely for three forms of GVHD:
- Skin GVHD. Your skin is assessed daily for a rash
or other changes.
- Liver GVHD. Your skin and eyes are checked for
any yellowing discoloration that would indicate liver involvement.
Blood tests are used to monitor your liver funtions.
- Intestinal GVHD. Your stool will be monitored for
diarrhea. The amount of stool passed can indicate intestinal GVHD.
Other symptoms include abdominal pain, bloating, tenderness,
nausea and vomiting.
Medications are available to manage and treat GVHD
symptoms. These medications are started before the transplant to
prevent GVHD. |
EARLY COMPLICATIONS
REGIMEN RELATED-
-TOXICITY
-
Cystitis
-
Mucositis
-
Pulmonary complications
- Renal
toxicity
-
Neurologic toxicity
|
OTHERS
-
Venoocclusive disease of the liver
-
Idiopathic pneumonia syndrome
- Graft
failure
-
Immunodeficiency
- Acute
graft Vs host disease
|
LATE COMPLICATIONS
REGIMEN RELATED-
- TOXICITY
-
Cataracts
-
Neurologic toxicity
-
Gonadal toxicity
-
Endocrine toxicity
-
Abnormal growth &
development
|
OTHERS
-
Immunodeficiency
-
Infection
-
Chronic graft Vs host disease
-
Relapse of primary tumor
- Second
malignancy
|
AUTOLOGOUS BONE MARROW
TRANSPLANTATION
Autologous
bone marrow transplantation involves the use of patient's own
hemopoietic progenitor cells to reestablish hemopoietic cell function
after the administration of high-dose chemotherapy and/or radiation
therapy.The reinfused hematopoietic progenitors may come from the
patients marrow or peripheral blood.Generally, before peripheral stem
cell harvest, the stem cell content of the blood is augmented by
treating the patient with chemotherapy and CSFs, especially granulocyte
CSF, a manipulation that results in marrow stem cells being released in
to the peripheral blood.
Autologous bone marrow
transplantation differs from allogenic transplantation in several
ways.Although many of the complications are similar to those encountered
in allogenic transplants, usually the incidence is lower and there are
no complications related to GVHD.The early clinical problems arise
mainly from regimen-related toxicity.CSFs are essentially always used in
autologous transplants.Because of this more favourable toxicity profile,
autologous transplantation may safely be employed in older patients.
A concern related specifically
to autologous transplantation is the possible presence of contaminating
tumor cells in the graft.A number of approaches have been employed to
rid the graft of tumor cells, including purging tumor cells with
antibody plus complement, an immunotoxin, and incubating the marrow with
chemotherapeutic agents.It has also been observed that the act of
freezing the marrow and thawing it for delivery to the patient may
preferentially kill the tumor cells.Despite all this concern, there is
little evidence that purging-techniques influence disease free
survival.Nevertheless, three pieces of information support the concept
that the graft may be a source of tumour.
CONCLUSIONS
Allogenic
marrow transplantations is likely to remain an important treatment
modality for leukemia, aplastic anaemia, and certain genetic disorders
for many years to come.Autologous marrow transplantation as a treatment
for malingant disease might be avoided in some patients as effective new
chemotherapeutic agents are developed and/or new generations of
hematopoietic growth factors become available.IF genetic manipulation of
hemopoietic progenitor cells becomes practical, autologous bone marrow
transplantation might become a common treatment for a variety of
non-malignant disorder |
bravenet.com
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