EARLY COMPLICATIONS (0–30 days)
Mucositis (very common) Nausea/vomiting Diarrhea (chemotherapy-related vs infection vs GVHD) Organ injury: Hepatic (transaminase elevation) Renal toxicity (from calcineurin inhibitors, chemo) Pulmonary toxicity (bleomycin, busulfan)
Myelosuppression & Pancytopenia
Peak neutropenia around days 7–14 Infection risk is highest Need prophylaxis (bacterial, fungal, viral)
Infections
Due to prolonged neutropenia and mucosal barrier injury. Bacterial: gram+ line infections, gram– sepsis Fungal: Candida, Aspergillus Viral: HSV reactivation (common), VZV, early CMV risk
Graft Failure (Allogeneic) Primary graft failure: failure to engraft Secondary graft failure: loss of engraftment after initial success
Causes include HLA mismatch, inadequate conditioning, drugs, infections.
Tumor Lysis Syndrome: More common with high tumor burden (leukemias/lymphomas).
Veno-Occlusive Disease (VOD) / Sinusoidal Obstruction Syndrome
Usually occurs days 10–20 Painful hepatomegaly Weight gain, ascites Hyperbilirubinemia Risk factors for VOD: busulfan, cyclophosphamide, prior liver disease
Treatment: Defibrotide
INTERMEDIATE COMPLICATIONS (30–100 days)
Acute Graft-Versus-Host Disease (aGVHD) — Allogeneic only
Typically day 20–100 Skin: maculopapular rash → desquamation GI: diarrhea, abdominal pain, ileus Liver: elevated bilirubin/ALP Treatment: high-dose steroids, Calcineurin inhibitors (tacrolimus), JAK inhibitors.
Infections
Immune reconstitution still incomplete. CMV reactivation (major cause of morbidity) EBV → PTLD (post-transplant lymphoproliferative disorder) Fungal: Aspergillus, Mucor Pneumocystis jirovecii (PJP)
Graft-versus-Tumor (GVT) effect is beneficial effect of allogeneic transplant—but increases GVHD risk.
Organ Complications Liver: drug toxicity vs GVHD Lungs: diffuse alveolar hemorrhage, idiopathic pneumonia syndrome Kidney: calcineurin-inhibitor nephrotoxicity Heart: cardiomyopathy (anthracyclines, cyclophosphamide)
LATE COMPLICATIONS (>100 days)
1. Chronic GVHD (cGVHD) — Allogeneic
Multisystem disorder resembling autoimmune disease.
Affected systems: Skin: sclerosis, hyperpigmentation Eyes: dryness, keratoconjunctivitis sicca Mouth: lichen planus–like lesions Lungs: bronchiolitis obliterans Liver: cholestasis Genital: vaginal/penile scarring
2. Late Infections
Immune reconstitution takes 6–12+ months. Encapsulated bacteria (S. pneumoniae) VZV reactivation CMV late reactivation Fungal infections remain possible
3. Relapse of Original Disease
More common in autologous HSCT because there is no graft-versus-tumor effect.
4. Secondary Malignancies
Risks increase over time: Skin cancers Solid tumors (breast, thyroid, colorectal, esophageal) Therapy-related Myelodysplastic Sx,AML Posttransplant lymphoproliferative disorder -EBV-driven
5. Endocrine / Metabolic Hypothyroidism Infertility / gonadal failure Growth delay (in children) Metabolic syndrome from chronic steroids
6. Pulmonary Complications bronchiolitis obliterans– hallmark of chronic GVHD Restrictive lung disease from fibrosis Cryptogenic organizing pneumonia
7. Cardiovascular Accelerated atherosclerosis Cardiomyopathy from previous chemotherapy Stroke risk elevated
8. Bone/Musculoskeletal • Osteoporosis secondary to steroids • Avascular necrosis (hips/shoulders)
A. Autologous HSCT
No GVHD Major issues: • Infections early on • Mucositis • Relapse of original malignancy • Secondary cancers are less frequent
B. Allogeneic HSCT
All autologous risks plus: • Graft failure • Acute and chronic GVHD • Higher risk of opportunistic infections • GVT effect • Posttransplant lymphoproliferative disorder -EBV-driven