Cyclosporin monitoring at 2 hours from oral intake leads to less toxicity and better compliance in patients undergoing haematopoietic stem cell transplantation and immunosuppressive treatment for severe aplastic anaemia

Background: Nephrotoxicity derived from Cyclosporin treatment is a well known complication and for this reason drug level baseline is usually monitored (before morning oral intake). Recently, data in the literature demonstrated a higher reliability of drug serum level after 2 hours from oral intake as regards to absorption and needed doses in the specific patient. These reports are obtained among Solid Organ Transplant settings. Aim: To assess if cyclosporin blood level at 2 h from oral intake is a more reliable tool than the pre-intake level to prevent or reduce nephrotoxicity in Hematopoietic Stem Cells Transplantation (HSCT)and Severe Aplastic Anemia (SAA) patients, and to tailor the required dose in each patient. Materials and methods: Patients. From February to November 2008 we prospectively enrolled 11 patients post HSCT and 4 under Immunosuppressive treatment (IS) for SAA. We monitored serum level of cyclosporin at time 0 and after 2 hours from oral intake, creatinine and urea serum levels, drug toxicity, and Graft versus host disease (GvHD) in HSCT group. Oral dose was then modified according to the 2 hours post cyclosporin results. Results: The incidence of hypercreatininemia, renal failure, hypomagnesiemia, headache and tremors was trivial and drug withdrawal was very seldom required. Creatinine serum level was ≥ 1.5 in 3 patients (20%). Only 2 out of 15 patients (13%) needed cyclosporine withdrawal: one for renal toxicity, the other one for trombotic trombocitopenic purpura; both of them were in HSCT group. Other side effects (headache and tremors) were evident only in 2 (13%) patients, one with SAA, the other one in HSCT group. Cyclosporin level after 2 hours seemed to be independent from the dosage/Kg of body weight, especially in children. In 7 out of 11 HSCT patients (63%) acute GvHD (grade I-II) was evident whereas limited chronic GvHD in 4 out of 11 patients (36%) was found. Both SAA and HSCT patients tolerated cyclosporin with 2 hour level monitoring very well, with apparent less toxicity. The two patients requiring cyclosporin withdrawal were both in the HSCT group. Conclusions: Our data suggest that dose adjustment of cyclosporin according to 2-hour level is more accurate than the basal one and more effective to prevent toxicity and side effects. Furthermore, it also provides a better compliance. The scarce number of patients doesn't allow to draw definite and firm conclusions, prompting the need to further prospective studies.