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肾衰竭的骨髓瘤患者适合进行自体干细胞移植吗?

Are myeloma patients with renal failure candidates for autologous stem cell transplantation?

作者信息

San Miguel J F, Lahuerta J J, García-Sanz R, Alegre A, Bladé J, Martinez R, García-Laraña J, De La Rubia J, Sureda A, Vidal M J, Escudero A, Pérez-Esquiza E, Conde E, García-Ruiz J C, Cabrera R, Caballero D, Moraleda J M, Leon A, Besalduch J, Hernandez M T, Rifon J, Hernandez F, Solano C, Palomera L, Parody R, Gonzalez J D, Mataix R, Maldonado J, Constela J, Carrera D, Bello J L, De Pablos J M, Pérez-Simón J A, Torres J P, Olanguren J, Prieto E, Acebede G, Peñarrubia M J, Torres P, Díez-Martín J L, Rivas A, Sánchez J M, Díaz-Mediavilla J

机构信息

Spanish Registry for Transplant in Multiple Myeloma, Grupo Español de Trasplante Hematopoyético (GETH), Spain.

出版信息

Hematol J. 2000;1(1):28-36. doi: 10.1038/sj.thj.6200003.

Abstract

INTRODUCTION

Renal function is one of the most important prognostic factors in multiple myeloma (MM). Patients with renal failure are generally excluded from high dose therapy even though they display a poor prognosis with conventional chemotherapy schemes. The aim of this study was to analyze the outcome of MM patients with renal insufficiency undergoing autologous stem cell transplantation (ASCT), including the evaluation of the quality of PB stem cell collections, kinetics of engraftment, transplant-related mortality, response to high dose chemotherapy and survival.

MATERIALS AND METHODS

From a total of 566 valuable patients included in the MM Spanish ASCT registry, three groups of patients were defined: group BA, patients with abnormal renal function at diagnosis but normal at transplant (73 cases); group BB, patients with abnormal function both at diagnosis and at transplant (14 cases); and group AA (control group, 479 cases), patients who constantly had normal renal function.

RESULTS AND CONCLUSION

Patients from groups BA and BB presented with a significantly higher number of adverse prognostic factors, reflecting that we were dealing with high tumor MM cases, as compared with patients from group AA. The number of mononuclear cells, CD34+ cells and CFU-GM cells collected in patients with non-reversible renal insufficiency was similar to those harvested in MM patients with normal renal function. Moreover, neutrophil and platelet engraftments were identical in patients with and without renal failure (days +11 and +12, respectively). By contrast, transplant-related mortality (TRM) was significantly higher in group BB patients (29%) than in groups BA (4.1%) and AA (3.3%). In multivariate analysis only three variables showed independent influence on TRM: poor performance status (ECOG 3), hemoglobin <9.5 g/dl and serum creatinine > or =5 mg/dl. The response to high dose therapy was independent of renal function. Interestingly, 43% of patients from group BB showed an improvement in renal function (creatinine < 2 mg/dl) after transplant. The three-year overall survival from transplantation was 56, 49 and 61% for the BB, BA and AA groups, respectively, with a statistically significant difference favoring group AA (P<0.01). PFS did not differ significantly between the three groups of patients. In multivariate analysis the only unfavorable independent prognostic factors for overall survival were poor performance status either at diagnosis or at transplant, high beta(2)-microglobulin levels, and no response to transplant. According to these results, ASCT is an attractive alternative for MM patients with renal insufficiency, and it should not constitute a criterion for exclusion from transplant unless patients display poor performance status and very high creatinine levels (>5 mg/dl).

摘要

引言

肾功能是多发性骨髓瘤(MM)最重要的预后因素之一。尽管肾衰竭患者采用传统化疗方案预后较差,但通常被排除在高剂量治疗之外。本研究的目的是分析接受自体干细胞移植(ASCT)的肾功能不全MM患者的预后,包括评估外周血干细胞采集质量、植入动力学、移植相关死亡率、对高剂量化疗的反应和生存率。

材料与方法

在西班牙MM自体干细胞移植登记处纳入的566例有价值的患者中,定义了三组患者:BA组,诊断时肾功能异常但移植时正常的患者(73例);BB组,诊断和移植时功能均异常的患者(14例);AA组(对照组,479例),肾功能一直正常的患者。

结果与结论

与AA组患者相比,BA组和BB组患者的不良预后因素明显更多,这表明我们处理的是高肿瘤负荷的MM病例。不可逆肾功能不全患者采集的单个核细胞、CD34+细胞和CFU-GM细胞数量与肾功能正常的MM患者采集的相似。此外,有和没有肾衰竭的患者中性粒细胞和血小板植入情况相同(分别为第+11天和第+12天)。相比之下,BB组患者的移植相关死亡率(TRM)显著高于BA组(4.1%)和AA组(3.3%)。多变量分析中,只有三个变量对TRM有独立影响:体能状态差(ECOG 3)、血红蛋白<9.5 g/dl和血清肌酐>或=5 mg/dl。对高剂量治疗的反应与肾功能无关。有趣的是,BB组43%的患者移植后肾功能有所改善(肌酐<2 mg/dl)。移植后三年的总生存率,BB组、BA组和AA组分别为56%、49%和61%,AA组有统计学显著差异(P<0.01)。三组患者的无进展生存期(PFS)无显著差异。多变量分析中,总生存唯一不利的独立预后因素是诊断或移植时体能状态差、β2-微球蛋白水平高以及对移植无反应。根据这些结果,ASCT是肾功能不全MM患者的一个有吸引力的选择,除非患者体能状态差且肌酐水平非常高(>5 mg/dl),否则不应构成排除移植的标准。

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