体重及美法仑相对剂量与POEMS综合征ASCT预处理不良反应的相关性分析

Analysis of the association of adverse reactions with relative dose of melphalan and body weight in POEMS syndrome patients undergoing melphalan-based ASCT

目的分析POEMS综合征患者接受自体外周血造血干细胞移植(ASCT)预处理中美法仑根据单位实际体重(ABW)计算的相对剂量与不良反应的关系,为临床药物剂量调整提供参考。方法回顾性分析首都医科大学宣武医院血液科收治的5例接受以大剂量美法仑为预处理方案ASCT的POEMS综合征患者的临床资料,总结治疗相关不良反应,分析与美法仑相对剂量的关系。结果1例患者为低体重,按照ABW计算的体表面积(BSA)计算美法仑剂量进行预处理,美法仑相对剂量为5.45 mg·kg^(-1),该患者移植过程中肾功能正常,出现了1级口腔黏膜炎及3级药物性肠病。中性粒细胞植入时间为+10 d,血小板植入时间为+11 d。3例患者为正常体重,按照ABW计算的BSA计算美法仑剂量进行预处理,美法仑相对剂量为4.44~5.41 mg·kg^(-1),移植过程中肾功能正常,分别出现了0级(2例)、2级(1例)口腔黏膜炎,1级(1例)、2级(1例)、3级(1例)药物性肠病。中性粒细胞植入时间为+11~+13 d,血小板植入时间为+11~+13 d。1例患者为超体重,ABW为理想体重(IBW)130%,按照IBW计算的BSA计算美法仑剂量进行预处理,剂量调整后的美法仑相对剂量为4.22 mg·kg^(-1),因回输干细胞中较多红细胞溶解出现肾功能不全,移植过程中出现3级口腔黏膜炎和2级药物性肠病。中性粒细胞植入时间为+11 d,血小板植入时间为+12 d。结论POEMS综合征患者接受ASCT预处理过程中,美法仑相对剂量升高或者存在肾功能不全时,口腔黏膜炎及药物性肠病的严重程度呈增加趋势,但似乎并不影响干细胞植入。在充分预防口腔黏膜炎及药物性肠病的情况下,肥胖患者是否可以不根据体重进行美法仑剂量调整还需要大量的临床数据进一步明确。

Objective To analyze the association of adverse reactions and the dose per actual body weight(ABW)of melphalan hydrochloride for injection in POEMS patients undergoing melphalan-based autologous stem cell transplantation(ASCT)and provide reference for clinical drug dose adjustment.Methods The clinical data of five patients with POEMS syndrome undergoing melphalan-based ASCT in the Department of Hematology of Xuanwu Hospital was analyzed retrospectively,to summary the adverse reactions and explore the association of those with relative dose of melphalan.Results One low-body-weight patient was given melphalan calculated based on BSA,with relative melphalan dose of 5.45 mg·kg^(-1),had normal renal function,grade one oral mucositis(OM)and grade three drug-induced intestinal disaese(DID).Neutrophil engraftment occured on day+10,platelet on day+11.Three normal-body-weight patients were given melphalan calculated based on ABW,with relative melphalan dose of 4.44~5.41 mg·kg^(-1),had normal renal function,no(two patients)and grade two(one patient)OM,grade one,two and three DID,respectively.Neutrophil engraftment occured on day+11~+13,platelets on day+11~+13.One overweight patient with ABW of 130% ideal body weight(IBW),was given melphalan calculated based on IBW,with relative melphalan dose of 4.22 mg·kg^(-1),had renal insufficiency because of stem cell mixed with much lysed erythrocyte,grade three OM and grade two DID.Neutrophil engraftment occured on day+11,platelet on day+12.Conclusion In POEMS patients undergoing melphalan-based ASCT,high relative dose of melphalan and renal insufficiency may increase the grade of OM and DID,and may not affect neutrophil and platelet engraftment.Whether body weight based dose adjustment of melphalan is necessary with adequate precautions in overweight patients still need more clinical data to be verified.