Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor.
Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor.
复制标题
DOI：
10.1182/blood.v68.5.1114.1114
复制
发表时间：
1986-11
期刊：
影响因子：
20.3
通讯作者：
M. Goldberg;J. Antin;E. Guinan;J. Rappeport
中科院分区：
文献类型：
--
作者：
M. Goldberg;J. Antin;E. Guinan;J. Rappeport
接受骨髓移植的患者通常使用环磷酰胺（CYA）进行免疫抑制，该剂量通常基于患者的体重计算。在这些高剂量的CYA下，可能发生严重的心脏毒性，但尚未描述发生此类心脏毒性的明确风险因素。由于化疗药物毒性通常与单位体表面积剂量相关，我们回顾性计算了在我们机构移植的患者中CYA的剂量，以确定CYA心脏毒性的发生率是否与单位体表面积剂量相关。80名接受CYA 50 mg/kg/d治疗4天作为骨髓移植准备的患者因再生障碍性贫血、Wiskott-Aldrich综合征或重度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 - 4剂CYA后10天内出现与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。计算所有患者的CYA/体表面积剂量，并根据CYA每日剂量将患者分为两组：第1组，CYA ≤ 1.55 g/m2/d;第2组，CYA> 1.55 g/m2/d。第1组中1/32（3%）例患者和第2组中13/52（25%）例患者发生了被认为与CYA相关的药物毒性（P <0.025）。充血性心力衰竭导致或促成第1组0/32例患者死亡，第2组6/52例患者死亡（12%）（P <0.25）。两组可评价患者的植活率无差异（P> 0.5）。我们得出结论，CYA心脏毒性与CYA剂量计算的体表面积，并与再生障碍性贫血和免疫缺陷的患者可以有效地准备骨髓移植在CYA剂量为1.55 g/m2/d的4天，心脏毒性的发生率低于CYA剂量计算的基础上体重的患者。这项研究重申了药物毒性与单位体表面积剂量相关的原则。
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.