Medical lecture on Graft vs Host Disease.pptx

Graft vs Host disease explained

1. Graft vs Host Disease

2. Outline Definition and introduction of GvHD Pathogenesis of GvHD (acute and chronic) Brief outline on clinical features, diagnosis of acute GvHD Brief outline on clinical features, diagnosis of chronic GvHD Treatment, prevention and prognosis of GvHD

3. Definition of GvHD Graft-versus-host disease (GVHD) occurs when immune cells transplanted from a non-identical donor (the graft) recognize the transplant recipient (the host) as foreign, thereby initiating an immune reaction that causes disease in the transplant recipient.

4. Definition and introduction of GvHD Contd … There are two types of GvHD Acute- classically less than 100 days of post-transplant Chronic- occurs more than 100days of post-transplant But the presence of symptoms and signs of acute and chronic GvHD outside of given time period had lead to classify the disease with symptoms rather than given time period. National Institutes of Health (NIH) consensus criteria  is used to classify the disease

5. Definition and introduction of GvHD Contd … Classic acute GVHD  – Cases present within 100 days of HCT and display features of acute GVHD. Persistent, recurrent, late onset acute GVHD  – Cases present greater than 100 days post-HCT with features of acute GVHD. Diagnostic and distinctive features of chronic GVHD are absent. Classic chronic GVHD  – Cases may present at any time post-HCT. Diagnostic and distinctive features of chronic GVHD are present. There are no features of acute GVHD. Overlap syndrome  – Cases may present at any time post-HCT with features of both chronic GVHD and acute GVHD. On occasion, this is colloquially referred to as "acute on chronic" GVHD.

6. Definition and introduction of GvHD Contd … Risk factors for the development of acute graft-versus-host disease (GVHD)  Degree of HLA disparity (HLA mismatch or unrelated donor) Donor and recipient gender disparity (female donor to male recipient) Intensity of the transplant conditioning regimen Acute GVHD prophylactic regimen used Source of graft (peripheral blood or bone marrow greater than umbilical cord blood)

7. Definition and introduction of GvHD Contd … Procedures associated with GvHD Allogenic hematopoietic stem cell transplantation Solid organ transplantation Non-irradiated blood transfusion.

8. Pathogenesis of GvHD -Acute

9. Pathogenesis of GvHD - Chronic

10. Pathogenesis of GvHD - Chronic The pathogenesis of chronic GVHD reactions is less known thymic dysfunction due to conditioning regimen and in some cases also prior acute GVHD decreased negative selection of T cells in thymus. immune deviation to Th2-type cytokine response release of Th2 cytokines and release of fibrogenic cytokines like IL-2, IL-10 and PDGF released by macrophages. decreased numbers of regulatory T cells B cell dysregulation and production of autoantibodies.

11. Brief outline on clinical features, diagnosis of acute GvHD The skin, gastrointestinal tract, and liver are the principal target organs in patients with acute GVHD Further division of organ involvement was reported as: Gastrointestinal tract only – 17 percent Gastrointestinal tract and skin – 24 percent Gastrointestinal tract, skin, and liver – 24 percent Gastrointestinal tract and liver – 9 percent Skin only – 15 percent Skin and liver – 7 percent Liver only – 4 percent

12. Brief outline on clinical features, diagnosis of acute GvHD Skin involvement Acute cutaneous GVHD typically begins with erythematous, blanchable macules on the ears, palms, or soles The lateral neck, cheek, and upper back are additional common sites of early involvement Follicular-based lesions are present in some patients In severe cases, patients develop generalized erythroderma, bullae, or extensive skin sloughing

13. Brief outline on clinical features, diagnosis of acute GvHD Skin biopsy Key histopathologic findings in acute cutaneous GVHD   interface dermatitis (vacuolization of the basal layer of the epidermis and a lymphocytic infiltrate in the superficial dermis) epidermal apoptotic keratinocytes

14. Brief outline on clinical features, diagnosis of acute GvHD Gastrointestinal tract- Acute GVHD frequently involves both the upper and lower gastrointestinal tract. diarrhea and abdominal pain , but may also manifest as nausea , vomiting and anorexia,hematochezia , Diagnosis is confirmed by rectal, colonoscopic or upper GI biopsy On rectal biopsy crypt cell necrosis is observed with the accumulation of degenerative material in the dead crypts  

15. Brief outline on clinical features, diagnosis of acute GvHD Liver - Hepatic involvement is manifested by abnormal LFT, with the earliest and most common finding being elevated conjugated bilirubin and alkaline phosphatase demonstrating damage to bile canaliculi. Elevated serum cholesterol is common but coagulopathy and hyperammonemia are rare. Clinically patients will develop tender hepatomegaly, icterus, pruritus, pale stools.

16. Brief outline on clinical features, diagnosis of acute GvHD Other organs- Hematopoietic- thymic atrophy, cytopenias (especially thrombocytopenia ), and hypogammaglobulinemia (especially IgA deficiency ). Ocular involvement can result in photophobia, hemorrhagic conjunctivitis, and lagophthalmos (inability to shut the eyes completely). Renal involvement can manifest as nephritis or nephrotic syndrome ( eg , membranous nephropathy). Lung involvement can manifest as interstitial pneumonitis

17. Brief outline on clinical features, diagnosis of acute GvHD Diagnosis Clinical grounds- The diagnosis of acute GVHD can be readily made on clinical grounds alone in the patient who presents with a classic rash, abdominal cramps with diarrhea, and a rising serum bilirubin concentration within the first 100 days following transplantation. Histological diagnosis- Needed when clinical manifestations are non-specific

18. Classic acute GVHD  – Cases present within 100 days of HCT and display features of acute GVHD. Persistent, recurrent, late onset acute GVHD  – Cases present greater than 100 days post-HCT with features of acute GVHD. Diagnostic and distinctive features of chronic GVHD are absent. Classic chronic GVHD  – Cases may present at any time post-HCT. Diagnostic and distinctive features of chronic GVHD are present. There are no features of acute GVHD. Overlap syndrome  – Cases may present at any time post-HCT with features of both chronic GVHD and acute GVHD. On occasion, this is colloquially referred to as "acute on chronic" GVHD.

19. Grading in acute GvHD

20. Grading in acute GvHD Grading is important in terms of assessing the response to prophylaxis or treatment, impact upon survival, and association with graft-versus-leukemia effect . Patients with moderate to severe GVHD have a significantly higher mortality rate compared with those with mild disease

21. Brief outline on clinical features, diagnosis of chronic GvHD The exact incidence of chronic GVHD after allogeneic hematopoietic cell transplant (HCT) is unknown. reported incidence rates range from 6 to 80 percent, depending upon the presence of risk factors and the diagnostic criteria used Additional risk factors includes- previous splenectomy, prior acute GvHD, CMV positivity, Donor EBV positivity. The skin, liver, gastrointestinal tract, and lungs are the principal target organs involved

22. Brief outline on clinical features, diagnosis of chronic GvHD Percentage involvement in cGvHD Skin – 67 percent Mouth – 60 percent Liver – 52 percent Lung – 50 percent Eye – 48 percent Joints and fascia – 48 percent Gastrointestinal tract – 30 percent Genitalia – 12 percent 

23. Eye manifestations of cGvHD Aqueous tear deficiency (Schirmer score ≤5 mm) – 53.4 percent Cataracts – 39.4 percent Corneal epithelial staining – 33.6 percent Conjunctival hyperemia – 10.5 percent Chemosis – 3 percent Brief outline on clinical features, diagnosis of chronic GvHD

24. Brief outline on clinical features, diagnosis of chronic GvHD Skin manifestations Lichen planus-like lesions Sclerotic manifestations- Morpheaform , Lichen sclerosus -like, Deep sclerosis Poikiloderma Nail changes Distinctive features include- dystrophy, longitudinal ridging, splitting, or brittle features; onycholysis

25. Brief outline on clinical features, diagnosis of chronic GvHD Genitalia - Diagnostic features- lichen planus-like features, vaginal scarring, or stenosis Distinctive features- erosions, fissures, and ulcers.

26. Brief outline on clinical features, diagnosis of chronic GvHD Oral lesions Lacy or reticulated white plaques that resemble Wickham's striae of lichen planus may occur on the tongue, buccal mucosa, lips, or palate Hyperkeratotic plaques, mucosal erythema, erosions, and ulceration can also occur. 

27. Brief outline on clinical features, diagnosis of chronic GvHD Liver- cholestasis, with elevations in the serum alkaline phosphatase, ALT or AST, and bilirubin concentrations. There are no signs that are diagnostic or distinctive and the same liver findings occur in patients with acute and chronic GVHD

28. Brief outline on clinical features, diagnosis of chronic GvHD Gastrointestinal tract The presence of an esophageal web and strictures or stenosis in the upper to mid third of the esophagus is diagnostic of chronic GVHD Symptoms similar to acute GvHD also occur

29. Brief outline on clinical features, diagnosis of chronic GvHD Lung involvement  approximately half of patients with chronic GVHD and may manifest as obstructive and/or restrictive changes pathologic evidence of bronchiolitis obliterans is diagnostic

30. Brief outline on clinical features, diagnosis of chronic GvHD Hematopoietic and immune  findings include thrombocytopenia, eosinophilia, lymphopenia, hypo/hypergammaglobulinemia, and autoantibodies Autoantibody profile is similar to connective tissue disorders e.g - ANA, RF, anti-mitochondrial antibody IgA deficiency is a well known entity in both acute and chronic GvHD.

31. Brief outline on clinical features, diagnosis of chronic GvHD Diagnosis- In the presence of history of transplantation occurrence of diagnostic symptoms/signs will establish chronic GvHD and in the presence of distinctive symptoms, relevant biopsy is needed to confirm.

32. Treatment and prevention of acute GvHD Prevention Via mainly avoiding known risk factors for GvHD. Prophylactic treatment with methotrexate and tacrolimus /cyclosporin +/- anti thymocyte globulin will prevent occurrence of GvHD.

33. Treatment and prevention of acute GvHD Treatment of acute GvHD The first-line treatment of acute GVHD is methylprednisolone. Treatment is initiated for acute GVHD of grade II or higher. The initial methylprednisolone dose is 2 mg/kg/day. Methylprednisolone is given in two divided doses per day. The initial dose is continued for seven days. No reduction of the dose is done during the first seven days. Tapering of the dose is done slowly and depending on the response. No marked dose reductions are done in the early phase. Methylprednisolone is not discontinued before all signs of GVHD have disappeared. There is no standard second-line treatment for acute GVHD

34. Treatment and prevention of acute GvHD Treatment of chronic GvHD The first-line treatment of newly diagnosed chronic GVHD is corticosteroids If the patient is already on corticosteroid treatment, cyclosporine is added to the treatment and the dose of corticosteroid is increased.  If the patient is already receiving corticosteroid and cyclosporine at the time of the onset of chronic GVHD, no standard treatment is available.  There is no standard second-line treatment for chronic GVHD.

35. Thank you…