From the Guidelines
Cyclosporine is recommended as part of the graft-versus-host disease (GVHD) prophylaxis regimen in leukemia patients undergoing stem cell transplantation, particularly in children and adolescents with chronic myeloid leukemia in blast phase. According to the international pediatric CML expert panel recommendations published in 2023 1, GVHD prophylaxis with anti-thymocyte globulin, methotrexate, and cyclosporine is suggested for patients achieving good remission before transplantation, regardless of the graft source. Some key points to consider when using cyclosporine for GVHD prophylaxis include:
- Starting dose: typically 3-5 mg/kg/day intravenously, then transitioning to oral administration at 5-10 mg/kg/day in divided doses
- Monitoring: regular blood level checks, targeting trough concentrations of 200-400 ng/mL initially, with gradual tapering over 3-6 months if no GVHD occurs
- Side effects: nephrotoxicity, hypertension, tremor, hirsutism, and gingival hyperplasia, which require regular monitoring of kidney function, blood pressure, electrolytes, and drug levels
- Mechanism of action: inhibiting calcineurin to prevent T-cell activation and proliferation, thereby suppressing the immune response that causes GVHD It's essential to note that cyclosporine is part of a comprehensive post-transplant regimen and is often combined with other immunosuppressants like methotrexate or mycophenolate mofetil, as recommended by the expert panel 1.
From the Research
Cyclosporine for Leukemia
- Cyclosporine is used as a graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with leukemia 2, 3, 4, 5, 6.
- The combination of Cyclosporin A (CSA) and Methotrexate (MTX) is considered the standard regimen for GVHD prophylaxis after HSCT from HLA-identical siblings 2.
- Studies have compared CSA/MTX with other regimens, such as CSA/Mycophenolate Mofetil (MMF) 2, Tacrolimus (TAC)/MTX 3, and Post-Transplantation Cyclophosphamide (PTCy) 4, 6, with varying results.
- The use of CSA/MTX has been shown to be effective in preventing GVHD, but may not be superior to other regimens in terms of overall survival, relapse rate, and treatment-related mortality 2, 3, 5.
- PTCy followed by CSA has been shown to be a promising protocol for GVHD prophylaxis in adult patients with acute myeloid leukemia undergoing HSCT from HLA-matched donors, with low cumulative incidences of both acute and chronic GVHD 6.
Types of Leukemia
- Acute myeloid leukemia (AML) is a common type of leukemia treated with HSCT and GVHD prophylaxis 2, 4, 6.
- Other types of leukemia, such as acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML), may also be treated with HSCT and GVHD prophylaxis 2.
- The effectiveness of CSA-based regimens for GVHD prophylaxis may vary depending on the type of leukemia and other patient characteristics 2, 3, 4, 5, 6.
Comparison of Regimens
- CSA/MTX has been compared with TAC/MTX, with TAC/MTX showing a superior effect in preventing acute GVHD and improving overall survival in patients receiving HSCT from unrelated donors 3.
- CSA/MTX has also been compared with PTCy, with PTCy showing a higher incidence of relapse, but similar overall survival and GVHD-free relapse-free survival rates 4.
- The choice of regimen for GVHD prophylaxis may depend on various factors, including the type of leukemia, donor type, and patient characteristics 2, 3, 4, 5, 6.