Goldberg M A, Antin J H, Guinan E C, Rappeport J M
Blood. 1986 Nov;68(5):1114-8.
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.
接受骨髓移植的患者通常会使用环磷酰胺（CYA）进行免疫抑制，其剂量通常根据患者体重计算。在这些高剂量的CYA治疗下，可能会发生严重的心脏毒性，但尚未明确描述发生这种心脏毒性的危险因素。由于化疗药物的毒性通常与每体表面积的剂量相关，我们回顾性计算了在我们机构接受移植患者的CYA剂量，以确定CYA心脏毒性的发生率是否与每体表面积的剂量相关。80例准备接受CYA 50mg/kg/d共4天作为骨髓移植预处理的患者，因再生障碍性贫血、威斯科特-奥尔德里奇综合征或严重联合免疫缺陷综合征共接受了84次移植。84例患者中有14例（17%）在接受1至4剂CYA后的10天内出现了与CYA心脏毒性一致的症状和体征。14例患者中有6例死于充血性心力衰竭。计算了所有患者每体表面积的CYA剂量，并根据每日CYA剂量将患者分为两组：第1组，CYA小于或等于1.55g/m²/d；第2组，CYA大于1.55g/m²/d。第1组32例患者中有1例（3%）发生了被认为与CYA相关的心脏毒性，第2组52例患者中有13例（25%）发生了相关心脏毒性（P<0.025）。第1组32例患者中因充血性心力衰竭导致或促成死亡的为0例，而第2组52例患者中有6例（12%）（P<0.25）。两组中可评估患者的植入率没有差异（P>0.5）。我们得出结论，CYA心脏毒性与按体表面积计算的CYA剂量相关，再生障碍性贫血和免疫缺陷患者可以在CYA剂量为1.55g/m²/d共4天的情况下有效地进行骨髓移植预处理，其心脏毒性发生率低于根据体重计算CYA剂量的患者。本研究重申了药物毒性与每体表面积剂量相关的原则。
