Irradiation to prevent TA-GvHD by Dr. Abrar Kabir Shishir.pptx

DR. ABRAR KABIR SHISHIR
ROLE OF IRRADIATION TO PREVENT
TRANSFUSION ASSOCIATED GRAFT
VERSUS HOST DISEASE
Dr. Abrar Kabir Shishir
MBBS, MD (Transfusion Medicine)

INTRODUCTION
 TA-GvHD is a clinical syndrome developing from 2
days to 6 weeks after transfusion characterized by
typical skin rash, diarrhea, fever, enlarged liver,
elevated liver enzyme, marrow aplasia, pancytopenia.
 TA-GvHD occurs in < 1 per million transfusions.
 Mortality rate > 90%.
 Rate of TA-GvHD is increasing due to
• Increasing surgical procedures
• Immuno-suppressive therapies
Picture: A case of TAGvHD

 First, there must be difference in HLA antigen expressed between donor
and recipient.
 Second, immunocompetent cells must be present in the component.
 Finally, the host must be incapable of rejecting immunocompetent cells.
REQUIREMENTS TO DEVELOP TAGVHD

Donor’s viable T lymphocyte enters into recipient’s body
T lymphocyte escape from recipient’s immune system due to
immunocompromised recipient or HLA homozygosity of donor
Donor’s T cell engraft, proliferate and attack various tissue and bone
marrow of recipient
Leads to multiple sign symptoms like
-Maculopapular rash (trunk to limbs)
-Diarrhea, fever, elevated liver enzyme
-Marrow aplasia, pancytopenia
PATHOGENESIS

INVESTIGATIONS
CBC: Pancytopenia
Liver enzymes: Elevated
Serum bilirubin: Increased
Bone marrow: Marrow aplasia

INVESTIGATIONS
 Skin biopsy:
• Superficial chronic inflammation at the junction
between the epidermis and dermis.
• Vacuolar change at the junction.
• Single cell necrosis (apoptosis) of keratinocytes in
the epidermis.
• Clusters of lymphocytes around
individual keratinocytes (lymphocyte satellitosis).

 Leukocyte chimerism (when biopsy findings are doubtful):
• Presence of donor lymphocytes in recipient’s tissue.
 Analysis of microsatellite DNA polymorphisms:
• Demonstrate replacement of recipient WBCs by donor WBCs in
peripheral blood.
INVESTIGATIONS

1. Immature immunological system:
• Fetus
• Neonates and infants
2. Impaired immunological system:
• Thymic alymphoplasia,
• Severe combined immunodeficiency disease
• Wiskott–Aldrich syndrome
• Aplastic anaemia
RISK FACTORS FOR TAGVHD

3. Immunosuppressive medications:
• Purine analogs (fludarabine, cladribine, deoxycoformicin)
• Anti CD52 (alemtuzumab)
4. Malignant conditions:
• Leukaemia (Acute lymphocytic leukaemia)
• lymphoma (Hodgkin, Non Hodgkin)
• Solid tumours (neuroblastoma)
5. Patient undergoing:
• Cardiac surgery.
• Trauma resuscitation
• Male sex
• Age 70 years

6. Immunocompetent patient:
• Donor who is homozygous for an HLA haplotype to a heterozygous recipient

7. Blood Products:
o Whole blood
o RBCs
o Platelets
o Granulocytes
o Cellular components used for intrauterine transfusions
o Fresh (< 72 hours from collection) cellular blood component

TREATMENTS
 Immunosuppressive therapy
 Stem cell transplantation

PREVENTION
 Irradiation
 Pathogen inactivation
 Donor deferral system
Picture: Irradiated blood component

 Irradiation damages the nucleic acid of the donor T lymphocytes and therefore
makes them unable to proliferate and cause disease.
T Lymphocytes activate,
multiply and proliferate
Proliferated T lymphocytes of
donor attack host tissues
Viable
T Lymphocyte
Figure: Irradiation preventing TAGvHD
HOW IRRADIATION WORKS

SOURCES OF IRRADIATION
 Gamma ray:
• Cesium-137
• Cobalt-60
 X ray

GAMMA IRRADIATOR: CESIUM

GAMMA IRRADIATOR: COBALT

ELECTROMAGNETIC SPECTRUM

Picture: Irradiation machine in Treansfusion
Medicine Department of Dhaka Medical College
X RAY

DOSE OF IRRADIATION
 Minimum dose of 25 Gy delivered to the central
portion of container
 Minimum of 15 Gy elsewhere
 No more than 50 Gy delivered to any portion of
the bag

IRRADIATION INDICATOR
• A radiochromic film label is affixed to the
component before irradiation.
• To confirm a product was irradiated
• Darkening of the film confirms irradiation
requirements.

 RBC: 28 days from irradiation or original outdate,
whichever is sooner.
 Platelet and granulocyte: Not impacted by
irradiation
EXPIRY DATE AFTER IRRADIATIION

1. The patient is identified as being at risk of TA-GvHD
2. The donor is a blood relative of the recipient
3. The donor is selected for HLA compatibility by typing or crossmatching
REQUIREMENTS FOR IRRADIATION

INDICATIONS
 Intrauterine transfusions
 Prematurity, low birthweight (<1200 g), erythroblastosis fetalis in newborns
 Hematologic malignancies or solid tumors (neuroblastoma, sarcoma, Hodgkin
disease)
 Peripheral blood stem cell/ marrow transplantation
 Components that are crossmatched or HLA matched, or donation from family
members (blood relatives)
 Fludarabine therapy
 Granulocyte components

COMPLICATIONS
 Hemolysis
 Potassium loss into plasma
• Large volume of irradiated stored blood
 Exchange transfusion
 Extracorporeal circulation
• Preexisting hyperkalaemia
• Pronounced renal failure
• Large volume of blood given by intrauterine transfusion

RADIATION MONITORING
 Dosimeters (Film/ thermoluminescent /rings):
• Change quarterly, some instances monthly
• Protect from high temperature, humidity,
• Stored at work & away from source of irradiation
 Bioassay (Thyroid, whole body counting, urine analysis):
• Whether there is radioactivity inside the body and if so,
how much.
• Quarterly or after an incident whether accidental intake
may have occurred
Picture: Whole body counting
Picture: Film batch dosimeter

 Survey meter:
• Quantitative assessment of radiation hazard.
• Storage areas for radioactive materials or wastes,
• Testing areas during or after completion of procedure,
• Packages/containers of radioactive materials.
• Annually by authorized NRC licensee
 Wipe test
• Area where radioactive materials are handles
o All work surface
o Equipment
o Floor
• Contaminated areas should be checked regularly
Picture: Survey meter
Picture: Wipe test

 Irradiation devices:
• Semiannual or annual dose delivery verification.
• A detection device is sent through an irradiation
cycle, then minimum and maximum radiation dose
is determined.
• If more time required for minimum radiation
exposure, it indicates radioactive source decays

SUMMERY
• TAGvHD is uniformly fatal disease.
• Symptoms within 6 weeks after transfusion should raise suspicion of TAGvHD
and should be excluded.
• Risk group should be identified before any component transfusion.
• Prevention of TAGvHD should be confirmed by irradiation.
• Irradiation machine should be handled with caution

THANK YOU

Irradiation to prevent TA-GvHD by Dr. Abrar Kabir Shishir.pptx

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