Grafalon: Appropriate Use in Transplantation and Hematology
Grafalon (ATG-Fresenius) is a rabbit anti-T-lymphocyte globulin used primarily as induction immunosuppression in solid organ transplantation and as part of conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Primary Indications
Solid Organ Transplantation (Kidney and Liver)
For kidney transplantation, Grafalon should be administered at 6 mg/kg total dose as induction therapy to prevent acute rejection and delayed graft function 1, 2. This dosing is based on real-world evidence from Indian cohorts showing:
- Death-censored graft survival of 99-100% at 12-18 months 1, 2
- Overall patient survival of 96-97% 1, 2
- Biopsy-proven acute rejection (BPAR) rates of 6.7-12.5% 1, 2
For liver transplantation, Grafalon demonstrates safety and efficacy with BPAR rates of 12.5% in the first year and one-year survival of 90% 3.
Hematopoietic Stem Cell Transplantation
In allo-HSCT for leukemia/MDS, Grafalon (ATG-F) is used in alternative donor transplantations at a dose range of 20-40 mg/kg as part of myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens 4. The specific dose depends on:
- Standard-intensity conditioning: 20-40 mg/kg for alternative donor transplants 4
- Patient age: MAC regimens for patients <55 years; RIC regimens for patients ≥55 years or those with poor organ function 4
- Disease status: Intensified regimens for refractory/relapsed disease 4
Dosing Protocols
Kidney Transplantation Dosing
The standard Grafalon dose is 6 mg/kg total body weight, typically divided over 3-5 days perioperatively 1, 5, 2. Real-world data shows average doses of 5.81-6.2 mg/kg are effective 1, 2.
Combine Grafalon with standard triple immunosuppression: tacrolimus, mycophenolate mofetil (MMF), and prednisolone 6.
HSCT Conditioning Dosing
For MAC regimens in leukemia/MDS: use 20-40 mg/kg total dose of ATG-F (Grafalon) in combination with cyclophosphamide, busulfan, or TBI-based protocols 4.
For RIC regimens: incorporate Grafalon into fludarabine-containing regimens for patients >55 years or with HSCT-CI ≥3 4.
Expected Adverse Effects and Monitoring
Hematologic Effects
Peak thrombocytopenia (64% incidence) and leukocytopenia (31% incidence) occur on postoperative day 4 in liver transplant recipients 3. However, severe leukocytopenia resolves after the first postoperative week 3.
In kidney transplantation, hematologic parameters normalize by 7 days to 1 month, though absolute lymphocyte counts may remain lower at 12 months 5.
Infectious Complications
Expect infectious complications in 13.6-22.5% of patients, with urinary tract infections being most common (18%) 1, 2. Specific infection rates include:
- Localized bacterial infections: 28% 3
- Bacteremia: 21% 3
- Fungal pneumonia: rare but potentially fatal 1
Monitor closely for infections during the first postoperative week and maintain vigilance throughout the first year 1, 3.
Comparative Efficacy: Grafalon vs. Thymoglobulin
At standard doses (Grafalon 6 mg/kg vs. Thymoglobulin 3 mg/kg), both agents show equivalent short-term outcomes for patient survival, graft survival, and infection rates 5. However, one retrospective study found significantly higher BPAR rates with Grafalon (12.8% vs. 5.1%, P=0.04) 6, though this finding was not replicated in prospective studies 5.
Thymoglobulin produces more sustained lymphocyte depletion at 12 months compared to Grafalon 5.
Critical Clinical Pitfalls to Avoid
Do not use Grafalon doses below 6 mg/kg in kidney transplantation, as lower doses may increase rejection risk 6. The single study showing higher rejection rates used the same 6 mg/kg dose as successful studies, suggesting other factors (ABO incompatibility, patient selection) may have contributed 6.
Do not confuse Grafalon (ATG-Fresenius) with Thymoglobulin dosing—they are not interchangeable and require different mg/kg doses 4, 5.
In HSCT, do not use intensified conditioning regimens in elderly patients or those with poor organ function, as this increases treatment-related mortality without improving overall survival 4.
Ensure adequate monitoring for cytopenia during the first postoperative week, particularly on day 4 when hematologic nadirs occur 3.