Tosi P, Zamagni E, Ronconi S, Benni M, Motta M R, Rizzi S, Tura S, Cavo M
Institute of Hematology and Medical Oncology, Seràgnoli University of Bologna, Italy.
Leukemia. 2000 Jul;14(7):1310-3. doi: 10.1038/sj.leu.2401819.
Patients with multiple myeloma (MM) and chronic renal failure have generally been excluded from myeloablative therapy programs followed by hematopoietic stem cell support because of the potential increase in transplant-related morbidity and mortality. We here report our experience treating six MM patients with moderate to severe renal insufficiency, with autologous stem cell transplantation. One of these patients required chronic hemodialysis since the diagnosis of MM was made. Peripheral blood stem cell collection was performed with either cyclophosphamide 5.5-7 g/m2 + G-CSF, 5 microg/kg/day (patients 1-3, 5 and 6) or G-CSF, 15 microg/kg/day alone (patient No. 4). Four patients (Nos 1-4) received autotransplant as front-line therapy, while the last two patients were treated in relapse, which occurred following prior autologous stem cell transplantation in support of melphalan, 200 mg/m2 (No. 5) or maintainance therapy with alpha-interferon (No. 6). High-dose chemotherapy administered as preparation to transplant included busulfan 12 mg/kg + melphalan 80 mg/m2 (patients 1-3 and 6) or melphalan 80 mg/m2 alone (patients 4 and 5) in order to reduce mucosal damage. Following transplant, prompt and sustained recovery of hematopoiesis was documented in all the patients; 500 PMN/microI and 20000 platelets/microI were reached after a median of 13 and 14 days, respectively. None of the patients suffered from WHO grade 3-4 infectious complications. Transplant-related toxicity included grade 3-4 oral mucositis (patients 1, 4 and 5) and veno-occlusive disease (patient No. 3). Renal function either improved or remained stable throughout the transplant period. All the patients but one responded to therapy, three of them are progression free after 2, 15 and 26 months; two relapsed after 16 and 4 months and one died from cholangiocarcinoma 7 months after transplant, while still in remission. Although our experience is limited so far, these results appear promising and support the investigational use of myeloablative therapy in MM patients with chronic renal failure.
由于与移植相关的发病率和死亡率可能增加，多发性骨髓瘤（MM）和慢性肾衰竭患者通常被排除在清髓性治疗方案及后续造血干细胞支持治疗之外。我们在此报告对6例中度至重度肾功能不全的MM患者进行自体干细胞移植的经验。其中1例患者自确诊MM起就需要长期血液透析。外周血干细胞采集采用环磷酰胺5.5 - 7 g/m² + 粒细胞集落刺激因子（G-CSF）5 μg/kg/天（患者1 - 3、5和6）或单独使用G-CSF 15 μg/kg/天（患者4）。4例患者（1 - 4号）接受自体移植作为一线治疗，最后2例患者在复发时接受治疗，其中1例在先前支持美法仑200 mg/m²的自体干细胞移植后复发（5号），另1例在α干扰素维持治疗后复发（6号）。作为移植预处理的大剂量化疗包括白消安12 mg/kg + 美法仑80 mg/m²（患者1 - 3和6）或单独使用美法仑80 mg/m²（患者4和5），以减少黏膜损伤。移植后，所有患者均出现迅速且持续的造血恢复；中性粒细胞绝对值中位数为13天达到500/μl，血小板中位数为14天达到20000/μl。无一例患者发生世界卫生组织3 - 4级感染并发症。与移植相关的毒性包括3 - 4级口腔黏膜炎（患者1、4和5）和静脉闭塞性疾病（3号患者）。在整个移植期间，肾功能要么改善要么保持稳定。除1例患者外，所有患者对治疗均有反应，其中3例分别在2、15和26个月后无疾病进展；2例分别在16和4个月后复发，1例在移植后7个月死于胆管癌，当时仍处于缓解期。尽管目前我们的经验有限，但这些结果似乎很有前景，支持在慢性肾衰竭的MM患者中进行清髓性治疗的研究应用。
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