Immunology · Year 2 · from Immunology
Case 2: Graft-Versus-Host Disease After Stem Cell Transplant
Patient Demographics
- Age: 28 years old
- Sex: Female
- Ethnicity: Caucasian
Chief Complaint
Rash, diarrhea, and jaundice 35 days after bone marrow transplant
History of Present Illness
A 28-year-old woman who underwent allogeneic hematopoietic stem cell transplant (HSCT) 35 days ago for acute myeloid leukemia presents with a progressive rash, profuse watery diarrhea, and yellowing of her skin. The rash began 5 days ago as erythema on her palms and soles, then spread to her trunk and extremities. Over the past 3 days, she has developed watery diarrhea (10-12 episodes daily, approximately 2 liters/day) with crampy abdominal pain. She also notes decreased appetite, nausea, and dark urine.
Transplant Details
- Indication: AML in first complete remission
- Donor: Matched unrelated donor (10/10 HLA match)
- Conditioning: Myeloablative (busulfan/cyclophosphamide)
- GVHD prophylaxis: Tacrolimus and methotrexate
- Engraftment: Day +16 (neutrophils), Day +22 (platelets)
Physical Examination
- General: Ill-appearing woman with obvious jaundice
- Vital Signs: T 38.2C, HR 105, RR 18, BP 100/65
- Skin: Diffuse maculopapular erythematous rash involving >50% BSA; palms and soles affected; no bullae or desquamation
- HEENT: Icteric sclerae; dry mucous membranes; no oral lesions
- Abdomen: Mildly distended; diffuse tenderness; hyperactive bowel sounds
- Extremities: No edema
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| WBC | 4,200/uL | 4,500-11,000/uL |
| ANC | 2,100/uL | 1,500-8,000/uL |
| Hemoglobin | 9.8 g/dL | 12-16 g/dL |
| Platelets | 65,000/uL | 150,000-400,000/uL |
| Total bilirubin | 8.5 mg/dL | 0.1-1.2 mg/dL |
| Direct bilirubin | 6.2 mg/dL | 0-0.3 mg/dL |
| AST | 185 U/L | 10-40 U/L |
| ALT | 210 U/L | 7-56 U/L |
| Alkaline phosphatase | 520 U/L | 44-147 U/L |
| Albumin | 2.8 g/dL | 3.5-5.0 g/dL |
| Stool studies | C. diff negative; cultures negative | Negative |
Skin Biopsy
Interface dermatitis with scattered apoptotic keratinocytes; lymphocytic infiltrate at dermoepidermal junction
Diagnosis
Acute Graft-Versus-Host Disease (Grade III) involving skin, liver, and gastrointestinal tract
Discussion
GVHD occurs when donor T cells attack recipient tissues. Three requirements (Billingham criteria):
- Graft contains immunocompetent cells (donor T cells)
- Recipient expresses antigens foreign to donor (histocompatibility differences)
- Recipient cannot reject donor cells (immunocompromised)
Acute GVHD target organs and staging:
| Stage | Skin | Liver (Bilirubin) | GI (Diarrhea) |
|---|---|---|---|
| 1 | <25% BSA | 2-3 mg/dL | 500-1000 mL/day |
| 2 | 25-50% BSA | 3.1-6 mg/dL | 1000-1500 mL/day |
| 3 | >50% BSA | 6.1-15 mg/dL | >1500 mL/day |
| 4 | Bullae, desquamation | >15 mg/dL | Severe pain, ileus |
Overall grade:
| Grade | Staging |
|---|---|
| I | Skin 1-2, no liver/GI |
| II | Skin 1-3, liver/GI 1 |
| III | Skin 2-3, liver/GI 2-3 |
| IV | Skin/liver/GI 2-4 with severe organ involvement |
This patient's staging:
- Skin: Stage 3 (>50% BSA)
- Liver: Stage 3 (bilirubin 8.5 mg/dL)
- GI: Stage 3 (~2L/day diarrhea)
- Overall: Grade III acute GVHD
Pathology findings:
- Skin: Interface dermatitis, satellite cell necrosis (apoptotic keratinocytes)
- Liver: Bile duct destruction, cholestasis
- GI: Crypt cell apoptosis, mucosal denudation
Treatment
- First-line: High-dose corticosteroids (methylprednisolone 2 mg/kg/day)
- Supportive care:
- IV fluids and electrolyte replacement (for diarrhea)
- Nutritional support (may need TPN)
- Ursodiol for cholestasis
- Infection prophylaxis
- If steroid-refractory (no response by day 7):
- Ruxolitinib (JAK inhibitor) - FDA approved for steroid-refractory acute GVHD
- Other options: ATG, extracorporeal photopheresis
- Continue tacrolimus prophylaxis
- Monitor for infections: Severely immunocompromised
Prognosis: Grade III acute GVHD has significant mortality (50-70%); early treatment improves outcomes
Graft-versus-leukemia effect: Donor T cells also target residual leukemia cells, reducing relapse risk. Complete GVHD suppression may increase leukemia relapse.