CYCLOPHOSPHAMIDE CARDIOTOXICITY - AN ANALYSIS OF DOSING AS A RISK FACTOR

  • 1 November 1986
    • journal article
    • research article
    • Vol. 68  (5) , 1114-1118
Abstract
Patients who undergo bone marrow transplantation are generally immunosuppressed with a dose of cyclophosphamide (CYA) which is usually calculated based on the patient''s weight. At these high doses of CYA, serious cardiotoxicity may occur, but definitive risk factors for the development of such cardiotoxicity have not been described. Since chemotherapeutic agent toxicity generally correlates with dose per body surface area, we retrospectively calculated the dose of CYA in patients transplanted at our institution to determine whether the incidence of CYA cardioloxicity correlated with the dose per body surface area. Eighty patients who were to receive CYA 50 mg/kg/d for four days as preparation for marrow grafting underwent a total of 84 transplants for aplastic anemia. Wiskott-Aldrich syndrome, or severe combined immunodeficiency syndrome. Fourteen of 84 (17%) patients had symptoms and signs consistent with CYA cardiotoxicity within ten days of receiving 1 to 4 doses of CYA. Six of the 14 patients died with congestive heart failure. The dose of CYA per body surface area was calculated for all patients and the patients were divided into two groups based on daily CYA dose: Group 1, CYA .ltoreq. 1.55 g/m2/d; Group 2, CYA > 1.55 g/m2/d. Cardiotoxicity that was thought to be related to CYA occurred in 1/32 (3%) of patients in Group 1 and in 13/52 (25%) patients in Group 2 (P < 0.025). Congestive heart failure caused or contributed to death in 0/32 patients in Group 1 v 6/52 (12%) of patients in Group 2 (P < 0.25). There was no difference in the rate of engraftment of evaluable patients in the two groups (P > 0.5). We conclude that the CYA cardiotoxicity correlates with CYA dosage as calculated by body surface area, and that patients with aplastic anemia and immunodeficiencies can be effectively prepared for bone marrow grafting at a CYA dose of 1.55 g/m2/d for four days with a lower incidence of cardiotoxicity than patients whose CYA dosage is calculated based on weight. This study reaffirms the principle that drug toxicity correlates with dose per body surface area.