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Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor
MA Goldberg, JH Antin, EC Guinan and JM Rappeport
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
cardiotoxicity 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 less than or
equal to 1.55 g/m2/d; Group 2, CYA greater than 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 less than 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 less than 0.25). There was
no difference in the rate of engraftment of evaluable patients in the two
groups (P greater than 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.
Volume 68,
Issue 5,
pp. 1114-1118,
11/01/1986
Copyright © 1986 by The American Society of Hematology
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