What is Graft-Versus-Host Disease (GVHD) in the context of a bone marrow or stem cell transplant?

What is Graft-Versus-Host Disease (GVHD)?

GVHD is a condition where donated stem cells or bone marrow recognize the transplant recipient's body as foreign and attack it, occurring primarily after allogeneic (donor-based) transplants and representing a major cause of death and disability after stem cell transplantation. 1

Basic Mechanism

• GVHD occurs when donor immune cells (particularly T-lymphocytes) identify the recipient's tissues as "nonself" and mount an immune attack against them. 1
• This complication occurs primarily in allogeneic transplant recipients, especially those receiving matched unrelated donor transplants, while autologous (using your own cells) or syngeneic (identical twin) transplants carry minimal to no risk of chronic GVHD. 1

Two Distinct Forms

Acute GVHD

• Acute GVHD typically occurs within the first 2 months after transplant and manifests as injury to three main organ systems: skin, gastrointestinal tract, and liver. 1
• It is graded on a scale of I-IV based on severity. 1
• Incidence rates after matched sibling donor transplants with standard conditioning: 12.6% (grade 2-4) in patients ≤16 years and 16% in those >16 years. 1

Chronic GVHD

• Chronic GVHD resembles autoimmune connective-tissue disorders like scleroderma or lupus and can occur as early as 40 days post-transplant, though classically described as occurring after 100 days. 1
• It is graded as either limited or extensive chronic GVHD. 1
• Incidence after matched sibling donor transplants: 14.6% in patients ≤16 years and 23% in those >16 years. 1
• Risk factors include increasing age, unrelated or non-HLA identical donors, and a history of acute GVHD. 1

Clinical Impact on the Body

Immune System Dysfunction

• GVHD causes profound and prolonged immunodeficiency, making patients extremely vulnerable to life-threatening infections. 1
• Chronic GVHD patients develop multiple immune defects including:
  • Macrophage deficiency and impaired neutrophil chemotaxis 1
  • Long-lasting IgA, IgG, and IgG subclass deficiencies despite normal or high total immunoglobulin levels 1
  • Poor response to vaccinations 1
  • Impaired ability to fight encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis) 1

Organ-Specific Manifestations

• Skin involvement is the most common and usually the first presenting sign of GVHD. 2
• Gastrointestinal GVHD causes severe mucositis, intractable vomiting, malabsorption, and protracted diarrhea. 3
• Liver involvement manifests as hepatic injury. 1
• Chronic GVHD can affect virtually any organ system, leading to heterogeneous clinical presentations. 4

Why GVHD Matters for Survival

• GVHD is the leading cause of non-relapse mortality in stem cell transplant survivors. 3
• Infection remains the most common cause of death among allogeneic transplant recipients, with GVHD being a substantial risk factor because it delays immune recovery and the immunosuppressive drugs used to treat it increase vulnerability to opportunistic viral and fungal infections. 1
• Patients with chronic GVHD face particularly high risk for life-threatening bacterial infections from encapsulated organisms. 1

Treatment Implications

• The immunosuppressive medications used to prevent and treat GVHD (such as cyclosporine, tacrolimus, methotrexate, and corticosteroids) further increase infection risk and can cause additional complications like fluid retention. 1, 5
• Corticosteroids remain the mainstay frontline treatment for acute GVHD despite decades of use. 6
• Treatment of steroid-refractory GVHD remains challenging with no consensus on second-line therapy. 2

Recovery Timeline

• After chronic GVHD resolves—which can take years—cell-mediated and humoral immunity functions are gradually restored. 1
• Immune system recovery follows three phases: preengraftment (<30 days), postengraftment (30-100 days), and late phase (>100 days), with GVHD significantly prolonging immunodeficiency. 1

Quality of Life Impact

• GVHD significantly impacts quality of life through restricted activities, troubling multi-organ symptoms, confusion about which symptoms are GVHD-related, unpredictable disease course, and weight loss. 3, 4
• Despite these challenges, long-term survivors (>5 years) who overcome GVHD report 93% are in good health and 89% return to work or school full-time. 1