Adjusted-dose continuous-infusion cyclosporin A to prevent graft-versus-host disease following allogeneic bone marrow transplantation

Abstract

Graft-versus-host disease (GVHD) remains a major obstacle to allogeneic bone marrow transplantation. We administered cyclosporin A (CsA) by continuous intravenous infusion for prophylaxis against GVHD and adjusted the dose to maintain a constant whole blood level. Forty-five patients, ranging in age from 16 to 56, mean 39.5 years, undergoing allogeneic transplantation for various hematological malignancies received CsA as a continuous intravenous infusion. CsA was started on day -1 and continued until day +22 when oral CsA was initiated. The whole blood level of CsA was determined and the dose adjusted to maintain a fixed level. Methotrexate 15 mg/m2 i.v. was given on day +1, followed by 10 mg/m2 on days +3 and +6. CsA administered as a continuous infusion was well tolerated. All patients required multiple adjustments of the infused dose of CsA to maintain the targeted whole blood level. The mean rise in creatinine was 0.89 mg/dl. There was an association between the concomitant administration of amphotericin B and CsA and the development of nephrotoxicity. Hypertension developed in 30/45 patients, and all responded to oral nifedipine. Tremors were noted in 16/45 patients. None of the patients developed serious neurological side effects. Greater than grade-I acute GVHD developed in only 13% of the patients. We conclude that administering CsA as an adjusted dose by continuous intravenous infusion is well tolerated and effective in preventing acute GVHD in patients undergoing allogeneic bone marrow transplantation.

Assessment of converting from intravenous to oral administration of cyclosporin A in pediatric allogeneic hematopoietic stem cell transplant recipients

“…infusion may be more effective, and it is associated with less serious side effects than bolus CsA, for the prevention of GVHD in allogeneic SCT recipients. 13,[29][30][31] As a consequence, in some centers CsA is administered as a continuous infusion in the early period after stem cell transplantation. Thereafter, when patients were able to eat normally, usually around 25 days after HSCT, they were converted from i.v.…”

“…infusion of CsA has been effective in preventing acute GVHD in HSCT recipients. 29,30 Moreover, a continuous infusion is associated with a decrease in the incidence of serious CsA-related toxicities compared with a short i.v. infusion.…”

“…infusion. 29,31 Based on these data, we administered CsA for a continuous i.v. infusion in the early period after stem cell transplantation; it was continued until the patient could tolerate oral dosing after recovery from treatment-related GI complications.…”

A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease

“…CSA was administered by CI through an indwelling catheter starting on day À1 and continuing to þ 50 as described previously. 30 Briefly, CSA was started at a dose of 2.5 mg/kg/ day and subsequently adjusted to maintain a whole blood level between 475 and 525 ng/ml, as determined by fluorescence polarization immunoassay (Abbott TDX, Abbott Park, IL, USA). 30 MTX was administered as an intravenous bolus infusion on day þ 1 (15 mg/m 2 ) and day þ 3 (10 mg/m 2 ).…”

Reduced respiratory and skeletal muscle strength in survivors of sibling or unrelated donor hematopoietic stem cell transplantation

“…[3][4][5] PFTs Spirometry, lung volumes and diffusing capacity were all measured using a Sensormedic Vmax 229 system according to the guidelines of the American Thoracic Society (ATS) 6 as previously described. 1 Skeletal muscle (grip) strength Grip strength (GS) was used as a measure of skeletal muscle strength and was measured using a hand dynamometer in the dominant hand with the elbow at 901 flexion and with the arm and wrist in neutral position (JAMAR, JA Preston Corporation, Clifton, NJ, USA), 7 as previously described.…”