Biological and targeted therapy

● The fourth treatment modality

● It is a type of cancer treatment that uses the body immune system to kill
cancer cells
● Consist of agent that modify the relationship between host and tumor by
altering the biological response of the host of the tumor cells
● It can be effective in combination with surgery radiation therapy and
chemotherapy
These agent affect host /tumor response in three ways
● Direct antitumor effect
● Restore augment or modulate host immune system
● Interfere with the cells ability to metastasis or differentiation

Targeted Therapy
● It interfere with cancer growth by target line specific cells receptor and
pathway that are important in tumor growth.
Drugs
● interferone- substance that has ability to Interfere with viral replication
Types-alpha beto gamma
Route of administration
● s/cim/intranasal /intro lesion intrathecal intro cavity
2 Interleukin 2 protein produced by leukocytes and act on leukocytes
Route: IVF subcutaneous twice daily
3. BCG vaccine the agent stimulate immune response
4. Monoclonal antibody (route iv) it react ogainst specific antigen on cancer
cells and may enhance patient immune system
5. Haematopietic growth factor colony
stimulating agents hormone like substance produce cells with in immune
system it Regulate the production of all cells in the blood
6 Epidermal growth factor receptors
7.Angiogenic inhibitors
8.Protease inhibitors and other targeted therapies
Side effects
● Fue like symptoms Mgt Acetaminophen Q4Hlarge amount of fluids
● Capillory leak syndrome-lead to pulmoriory edema
● Skin rashes anaphylactic reaction
● Neuro, cardiac and hepatic toxicity

WHAT ARE STEM CELLS

Stem cell are immature cell in the bone marrow that give rise to all your blood
cells

Stem cell sources

Transplant can come from three sources
● Perpheral blood
 ● Marrow
● Umbilical cord

INDICATION FOR BONE MARROW TRANSPLANT SURGERY

It is done to treat a number of cancerous and non cancerous condition such

as
Cancerous condition
● Leukemia
● Lymphoma
● Multiple myeloma
● Myelodysplasia
Non cancerous condition
● Aplastic anemia
● Hemoglobinopathies
● Immunodeficiency disorders and conditions affecting blood present from
birth

TYPES OF BONE MARROW STEM CELLS

There are 2 main types of bone marrow transplantation
● Autologous
● Allogeneic
AUTOLOGOUS
● Before patient receive Chemotherapy or radiation therapy,stem cell are
removed from patient body either by bone marrow harvest or
leukapheresis and stored in freezer (cryopreservation)after completing
Chemotherapy and radiation stem cells are put back in to patient body
to make normal
ALLOGENEIC
● Stem cell are removed from another person (donor).these donor should
be genetically match with patient.donor may be
parents/children/relatives are good match

UMBILICAL CORD BlOOD TRANSPLANT

This is a type of allogeneic transplant.stem cells are removed from a
newborn baby's umbilical cord right after birth. the stem cells are frozen and
stored until they are needed for a transplant.umbilical cord blood cells are very
immature so there is less of a need for matching.but blood counts takes longer
to recover

PRE BONE MARROW TRANSPLANTATION PROCEDURE

● Bone marrow transplantation regimens vary from one patient to
another,and depend upon the type of cancer
● The treatment program used by the medical center
 ● The clinical trial protocol (if patient is enrolled in a clinical trial),as well
as other factors
MATCHING STUDIES
● Matching involves typing human leukocyte antigen (HLA) tissue the
antigens on the surface of these special white blood cells determine the
genetic makeup of a person's immune system.these are at least
100HLA antigens

PREPARATION FOR THE RECIPIENT

● Prior to the transplant, an extensive evaluation is completed by the

bone marrow transplant team. All other treatment options are discussed
and evaluated for risk versus benefit.
● A complete medical history and physical examination are performed,
including multiple tests to evaluate the patient's blood and organ
functions (for example, heart, kidney, liver, and lungs).
● A patient will often come into the transplant center up to 10 days prior to
transplant for hydration, evaluation, placement of the central venous
line, and other preparations
● For an allogeneic transplant, a suitable (tissue tyne matched) donor
must be available. Finding donor can be a challenging and specially if a
sibling match is

PREPARATION FOR THE DONOR:

● ► Donor sources available include: self, sibling, parent or relative,

nonrelated person, or umbilical cord from a related or nonrelated
person. There are national and international registries for nonrelated
persons and cord blood.

● If the potential donor is notified that he or she may be a match for a

patient needing a transplant, he or she will undergo additional tests.
Tests related to his or her health, exposure to viruses, and genetic
analysis will be done to determine the extent of the match

● Once a match for a patient needing a bone marrow transplant is found,

then stem cells will be collected either by a bone marrow harvest
(collection of stem cells with a needle placed into the soft center of the
marrow) or peripheral blood stem cell cells are collected from the
circulation

TWO WAYS OF TREATING BONEMARROW

● Before the transplant, chemotherapy, radiation, or may both

● be given.
Ablative (myeloablative) treatment. High-dose chemotherapy, radiation, or
both are given to kill any cancer cells. This also kills all healthy bone marrow
that remains, and allows new stem cells to grow in the bone marrow.

Reduced intensity treatment, also called a mini transplant: Patients receive

lower doses of chemotherapy and radiation before a transplant. This allows
older patients, and those with other health problems to have a transplant.

Bone marrow harvest.

● This minor surgery is done under general anesthesia. The bone marrow
is removed from the back of both hip bones. The amount of marrow
removed depends on the weight of the person who is receiving it.

Leukapheresis.

● Peripheral blood stem cells (PBSCs) are collected by apheresis, a

process in which the donor is connected to a special cell separation
machine via a needle inserted in arm veins. Blood is taken from one
vein and is circulated though the machine which removes the stem cells
and returns the remaining blood and plasma back to the donor through
another needle inserted into the opposite arm

TRANSPLANT PROCESS (5 STEPS)

(1) Conditioning,
(2) Stem cell infusion,
(3) Neutropenic phase,
(4) Engraftment phase
(5) Post-engraftment period.

CONDITIONING PHASE

The conditioning period typically lasts 7-10 days.

The purposes are (by delivery of chemotherapy and/or radiation)
● to eliminate malignancy
● to provide immune suppression to prevent rejection of new stem cells
● create space for the new cells

Radiation and chemotherapy agents differ in their abilities to achieve these

goals.

STEM CELL PROCESSING AND INFUSION

● Infusion 20 minutes to an hour, varies depending on the volume
infused.
● The stem cells may be processed before infusion, if indicated.
● Depletion of T cells can be performed to decrease GVHD.
 ● Premedication with acetaminophen and diphenhydramine to prevent
reaction
● Infused through a CVL, much like a blood transfusion.

● Anaphylaxis, volume overload, and a (rare) transient GVHD are the

major potential complications involved.
● Stem cell products that have been cryopreserved contain dimethyl
sulfoxide (DMSO) as a preservative and potentially can cause renal
failure, in addition to the unpleasant smell and taste.

NEUTROPENIC PHASE

● During this period (2-4 wk), the patient essentially has no effective
immune system.

● Healing is poor, and the patient is very susceptible to infection

● . Supportive care and empiric antibiotic therapy are the mainstays of
successful passage through this phase.

ENGRAFTMENT PHASE

● During this period (several weeks), the healing process begins with
resolution of mucositis and other lesions acquired.
● In addition, fever begins to subside, and infection often begin to clear.

● The greatest challenges at this time are management of GVHD and

prevention of viral infections (especially CMV).

POST-ENGRAFTMENT PHASE

● This period lasts for months to years. Hallmarks of this phase include
the gradual development of tolerance, weaning off of
immunosuppression, management of chronic GVHD, and
documentation of immune reconstitution.

ADVERSE REACTIONS

Chills Fever
Chest pain
Drop in blood pressure
Flushing mouth
Headache
Nausea
Funny taste in the Hives
Pain
Shortness of breath
GRAFT VERSES HOST DISEASE (GVHD)

● GVHD sometimes occurs with allogeneic transplantation.

● Lymphocytes from the donor graft attack the cells of the host
● GVHD can usually be treated with steroids or other immunosuppressive
agents.
● Acute GVHD occurs before day 100 post-transplant
● Chronic GVHD occurs beyond day 100
● Recent advances have reduced the incidence and severity of this post-
transplant complication, but GVHD, directly or indirectly, still accounts
for approximately 15% of deaths in stem cell transplant patients
● Chronic GVHD can develop months or even years post-transplant

GVHD SYMPTOMS

Skin/Hair Rash
● , scleroderma, lichenoid skin changes, dyspigmentation, alopecia
Eyes
● Dryness, abnormal Schirmer's Test, cornealerosions, conjunctivitis
Mouth Atrophic changes, lichenoid changes, mucositis, ulcers,
xerostomia, dental caries
Lungs
● Bronchiolitis obliterans
GI tract
● Esophageal involvement, chronic nausea/vomiting, chronic
diarrhea,Nmalabsorption, fibrosis, abdominal pain/cramps
Liver
● Abnormal LFTs, biopsy abnormalities
Genitourinary
● Vaginitis, strictures, stenosis, cystitis
Musculoskeletal
● Arthritis, contractures, myositis, myasthenia, fascities
Hematologic
● Thrombocytopenia, eosinophilia, autoantibodies

COMPLICATIONS
● Anemia
● Bleeding in the lungs, intestines, brain, and other areas of the body
● Cataracts
● Clotting in the small veins of the liver
● Damage to the kidneys, liver, lungs, and heart
● Delayed growth in children
● Early menopause
● Graft failure
● Graft-versus-host disease
 ● Infections,
● Mucositis
● Pain
● Diarrhea, nausea, and vomiting

POST-BONE MARROW TRANSPLANTATION CARE

● A two- to four-week waiting period follows the marrow transplant before

its success can begin to be judged.
● The marrow recipient is kept in isolation during this time to minimize
potential infections.
● The recipient also receives intravenous antibiotic, antiviral, and
antifungal medications, as well as blood and platelet transfusions to
help fight off infection and prevent excessive bleeding.
● Blood tests are performed
● daily to monitor the patient's kidney and liver function, as well as
nutritional status.
● Other tests are performed as necessary.
● Further side effects, such as nausea and vomiting, can be treated with
other medications.

THE BONE MARROW TRANSPLANT TEAM

● Doctors.
● Bone marrow transplant nurse coordinator
● Social workers
● Dietitians
● Physical therapists
● Pastoral care
Other team members
● Pharmacists
● Respiratory therapists
● Lab technicians
● Infectious disease specialists
● Dermatologists
● Gastroenterologists
● Psychologists