Cyclosporine Dose Adjustment According to Calcineurin Activity After Allogeneic Hematopoietic Stem-cell Transplantation

Reduction of Acute and Chronic Graft-versus-host Disease After Allogeneic Hematopoietic Stem-cell Transplantation by Adapting Cyclosporine Doses According to Calcineurin Activity : a Proof-of-concept Trial

The purpose of this trial is to assess whether an adaptation of cyclosporine (CsA) dose according to a longitudinal calcineurin (CN) activity monitoring would prevent the onset of graft-versus-host disease (GVHD).

Our previous studies established a correlation between increased calcineurin (CN) activity and the risk of developing severe acute GVHD in allogeneic stem cell transplant recipients receiving immunosuppressive therapy with calcineurin inhibitors.

This proof-of-concept trial is aiming at evaluating CALCIneurin activity as a monitoring biomarker of efficacy of cyCLOsporine - (CALCICLO) - for the prophylaxis of acute GVHD. Our aim is to assess whether a longitudinal monitoring of CN activity would permit to adapt and optimize the dose of CsA that would prevent the onset of severe acute GVHD, yet still maintaining an acceptable tolerability profile.

Inclusion Criteria:

• Patients were between the age of 12 and 60 years
• Patients planned to receive an allogeneic HSCT following a myeloablative conditioning regimen

Exclusion Criteria:

• Transplant from a syngeneic donor
• Evidence of refractory disease
• Nonmyeloablative conditioning
• Any participation to a study with a new investigational drug within the previous 3 months