For Education

1. Transfusion-Associated Graft
Versus Host Disease (TA-GVHD)
Dr. RAFIQ AHMAD
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2. Outline
Introduction
Incidence and Outcome
Background and Mechanism
Blood Products associated with TA-GVHD
Pathophysiology
Risk factors
Clinical presentation
Diagnosis
Treatment and Prevention
Summary
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3. Incidence and Outcome
 Rare
UK 1996 to present: 13 cases (SHOT)
China: 12 cases
Probably under-reported
Majority of the cases in Japan
Total 66 cases reported only worldwide
0.1-1% of transfusions in susceptible recipients
 High mortality
90-100%
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4. Serious Hazards of Transfusion (SHOT
Year Number of Cases Diagnosis
1996-1997 4 Congenital Immunodeficiency
No Patient risk factor
B Cell NHL (2 cases)
1997-1998 4 Waldenstrom’s macroglobulinemia
B cell NHL
Cardiac surgery
Autoimmune thrombocytopenia
1998-1999 4 Myeloma
Uncharacterized immunodeficiency
Cardiac surgery (2 cases)
1999-2000 -
2000-2001 1 ALL (1 case)
2001-2010 -
2010-2019 -
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5. TA-GVHD: Background
 Donor
 donor anti-recipient immune response
 Viable immunocompetent lymphocytes
 Recipient
 Recipient anti-donor immune response)
 Differs antigenically
 Normal: Immune system destroys donor lymphocytes
 TA-GVHD: Unable to adequately respond
• Leukopenia
• Immunosuppression (congenital or acquired)
• HLA one-way compatibility
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6. TA-GVHD: Mechanism
 Donor T lymphocytes
 Proliferate in recipient
 Recognize HLA as “non-self”
 Release cytokines with activate NK cells,
macrophages, and other T cells
 tissue destruction
 Recipient
 Overcome
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7. Blood Products
Any non-frozen component containing viable
lymphocytes
Whole blood
Packed red cells
Platelets
Granulocytes
Fresh plasma
Can occur with as few as 8 x 104 lymphocytes
Leukocyte reduction filters
 US: < 5 x106 lymphocytes
 Europe: < 1 x106 lymphocytes
Higher Risk
Fresh blood (<3 days)
Granulocyte transfusions
Directed donations: Any component from relatives
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8. Counting Lymphocytes
Product Lymphocytes
Whole blood 1-2 x 109
Packed red blood cells 1-2 x 109
Platelet concentrates 4 x 107
Apheresis platelets 3 x 108
Washed or microaggregate-filtered red
blood cells
2.5 x 108
Granulocytes by apheresis 5-10 x 109
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9. Pathophysiology
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10. Who’s At Risk
Lymphopenia
Immunodeficiency
 Acquired
Autologous and allogeneic SCT
Hodgkin’s and non-Hodgkin’s lymphoma
Acute leukemias
Chemotherapy  fludarabine and cladribine
Not HIV/AIDS
 Congenital
SCID and DiGeorge
 Premature infants
 Newborns
 Intrauterine transfusions
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11. Who’s At Risk
 Partial/Shared HLA Matching
Donor is homozygous for HLA haplotype
Recipient is heterozygous for HLA haplotype
Depends on the heterogeneity of the population
 Problem in Japan (10-20 x increased risk)
HLA-matched platelets
Directed donations from relatives
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12. Who’s At Risk
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13. Clinical Presentation
Delayed  2-30 days
Dermatitis  erythematous, maculopapular rash
Enterocolitis  watery diarrhea
Hepatitis  elevated LFTs
Bone marrow suppression
 pancytopenia (16 days)
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14. 14

15. Diagnosis
 Clinical Presentation
 Skin/GI/Liver Biopsy
 Bone Marrow Biopsy
 HLA Testing  genetic chimerism
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16. Treatment
 Poor response
 Corticosteroids, Azathioprine,
Antithymocyte globulin, Methotrexate,
Cyclosporine
 Experimental
 UV irradiation, Succinylacetone,
Pentoxifylline, Interleukin-1 receptor
antagonists, Thalidomide, Stem cell
transplant
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17. Prevention
Inactivation of lymphocytes
Gamma irradiation
 Inhibits replication
Cesium-137 or cobalt-60
Linear Accelerator
X-ray radiation
Dose
 25 Gy  center
 At least 15 Gy  any other point
Shelf life -28 days post-irradiation
Potassium load  wash
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18. Irradiators
X-ray radiation
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Cobalt-60
Cesium-137
Gamma Irradiators

19. Other Modalities
 Universal Leukoreduction
Filters  3-5 log reduction in white cell number
UK surveillance study  SHOT
Immunocompetent recipients
Shown to lower the incidence of TA-GVHD
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20. Other Modalities
 Pathogen-Inactivation Technologies
Photoactivation Compound + Ultraviolet Light
 Riboflavin or psoralen-based compound
PEN 110 and S-303
 Reduce lymphocyte proliferation
Added benefit of reducing cytokines
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21. Pathogen Inactivation Methods
Current
Use
Products
Treated
CompanyMethod
EuropePlasmaOctapharmaSolvent/detergent
Europe
UD
Plasma
Platelets
MacoPharmaMethylene Blue
+ UVC Light
Europe
Europe
UD
Plasma
Platelets
Whole Blood
Terumo BCTMirosal
(Riboflavin + UV-Light)
Europe
USA
Plasma
Platelets
CerusPsoralen (Amotosalen)
Intercept (S-59 + UV Light)
UDRBCCerusFRALE (S-303)
HaltedRBCVI TechnologiesINACTINE (PEN 110)
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22. Summary
 TA-GVHD is rare complication of
transfusion of blood products
 Immunodeficient recipients
 HLA similarities
 Not many cases universally reported, but it
a very fetal associated with more than 90% of
mortality
 Early detection
 Effective treatment?
 Prevention is the key
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23. The end!!!
Thank you
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