Graft Versus Host Disease by kk4RGwmf

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									Graft Versus Host Disease
 Criteria for Development of GVHD

 Graft contains immunologically
  competent cells
 Host appears foreign to the
  graft; it has alloantigens that are
  capable of antigenically
  stimulating the graft
 Host is unable to mount an
  effective immunological reaction
  against the graft
Patients at High Risk for GVHD

Allogeneic & autologous hematopoietic
 cell transplantation (age, HLA disparity,
 gender disparity, allosensitized donor)
Solid organ transplantation (liver, small
 bowel)
Transfusion of unirradiated blood products
 (fetuses, neonates, immunodeficiency
 syndromes, chemoradiotherapy)
Pathophysiology of GVHD – 3 stages

Damaged host tissue cytokines (TNFα,
 IL1) stimulate APCs recognition of
 host Ag by donor T cell
Donor T cell activated cytokines (IFNγ,
 IL2) induce CTL, NKC, phagocytes
Phagocytes release more cytokines cell
 lysis/apoptosis tissue destruction
Pathophysiology of GVHD
2 Types of GVHD

 Acute (10-30 days posttransplant)
  - triad of derm, hepatic, and GI manifestations
    (barriers to infection thus APCs)
  - 40-80% incidence (depends on HLA match)
 Chronic ( >100 days posttransplant)
  - diverse range of affected organ systems
  - 70-90% evolve from acute GVHD
  - 20% occur de novo
  - 10% occur after acute GVHD resolves
Acute GVHD – Dermatological

Painful or pruritic erythematous macules of
 palms, soles, trunk, limbs
Confluent erythema, erythroderma and/or
 papule formation
Subepidermal bullae and vesicle formation
Stages 1-4 based on % BSA involved and
 presence of bullae/vesicles
Acute GVHD – Dermatological
 Boy who developed stage
  3 skin involvement with
  acute graft versus host
  disease despite receiving
  prophylaxis with
  cyclosporin A. The donor
  was a sister matched for
  human leukocyte antigen.
  The gender disparity
  increased the risk for
  acute graft versus host
  disease.
Acute GVHD – Hepatic

Asymptomatic elevations in bilirubin, ALT,
 AST, alkaline phosphatase similar to
 cholestatic jaundice
Acute GVHD – GI

Anorexia
Dyspepsia
Cramping abdominal pain
Diarrhea (secretory diarrhea may persist
 despite NPO)
Intestinal bleeding
Ileus
Chronic GVHD - Dermatological
 Same as acute GVHD
 Atrophy and erythema
  of oral mucosa
 Lichenoid lesions of
  skin, buccal and labial
  mucosa
 Sclerodermatous skin
  thickening
 Joint contractures
Chronic GVHD – Ocular
 Keratoconjunctivitis
  sicca may lead to
  corneal erosions
 Hemorrhagic
  conjunctivitis
 Pseudomembrane
  formation
 Lagophthalmos
Chronic GVHD – Pulmonary

Obstructive lung disease
Dyspnea, wheezing, chronic cough
Nonresponsive to bronchodilators
Bronchiolitis obliterans
Chronic GVHD – GI

Same as acute GVHD
Sensitivity to acidic or spicy foods
Odyno/Dysphagia
Esophageal strictures or dysmotility
Weight loss
Chronic GVHD – Hepatic

Same as acute GVHD
Hyperbilirubinemia – jaundice, pruritis and
 excoriations
Portal HTN, cirrhosis, and hepatic failure
 are rare
Chronic GVHD – Neuromuscular

Weakness
Neuropathic pain
Muscle cramps
Symptoms may resemble myasthenia
 gravis or polymyositis
Chronic GVHD – Misc.

Many similarities to autoimmune disorders
SLE
Sjogren syndrome
Rheumatoid arthritis
Primary biliary cirrhosis
Lichen planus
Prevention

Depletion of T cells from donor has
 reduced the incidence of GVHD, however,
 this results in increased incidence of graft
 failure and malignancy occurrence
Leukemic cells may have specific antigen
 profiles that make them susceptible to the
 GVL effect.
Graft vs. Leukemia Effect


 Mortality of GVHD
  with no leukemic
  relapse vs. mortality
  of leukemic relapse
  and no GVHD is
  under investigation
Prophylactic Treatment

Cyclosporine (CSP) + Methotrexate (MTX)
 +/- Prednisone 180 days
Tacrolimus (Prograf) + MTX 180 days
IVIG for antibody prophylaxis Qweek x12
 (good for acute , not chronic)
Primary Treatment for Acute GVHD

CSP or Prograf + methylprednisolone
 (MP)
Antihymocyte globulin (ATG)
Mycophenolate mofetil (CellCept)
Anti-CD5 immunotoxin
XomaZyme – pan T cell immunotoxin
Secondary Treatment for Acute GVHD

ATG
Increased MP doses
Muromonab-CD3
IL-1 receptor antagonist
Conversion from CSP to Prograf
Psoralen +UVA light (PUVA) for
 cutaneous GVHD
Primary Treatment for Chronic GVHD
 Prednisone 1 mg/kg QOD +/- CSP
 Thalidomide
Secondary Treatment for Chronic GVHD

Azathioprine (Imuran)
Alternating CSP & Prednisone
Thalidomide
Clofazimine (antileprosy agent) and PUVA
 for cutaneous GVHD
Prognosis
 Acute GVHD: response to tx 25% mortality vs.
  75% mortality with no response or progression.
 Chronic GVHD: 6 yr. mortality is 58% overall and
  90% for progressive disease.
 Mortality for both acute and chronic GVHD is
  mostly due to sepsis.
 Higher mortality in patients with HLA
  mismatched donor, bilirubin > 2 mg/dL,
  thrombocytopenia, lichenoid skin histology, high
  dose prednisone.
References
Fleming DR, Graft-vs-host disease: what
 is the evidence? Evidence-based
 Oncology 2002; 3.
Mandanas RA, et al. Graft versus host
 disease. Emedicine.com/med/topic926.
Hoffman: Hematology: Basic Principles
 and Practice, 3rd ed., 2000.
Kuechle MK, et al. Graft versus host
 disease. Emedicine.com/derm/topic478.

								
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