Berz D, Colvin G A, McCormack E M, Winer E S, Karwan P, Colvin L, Rathore R, Lum L G, Elfenbein G J, Quesenberry P J
Brown University, Providence, Rhode Island, USA.
Transplant Proc. 2009 Nov;41(9):3863-7. doi: 10.1016/j.transproceed.2009.06.196.
Tandem high-dose melphalan therapy with autologous peripheral stem cell support has emerged as the standard of care for patients without prohibitive comorbidities. Mucositis and gastrointestinal side effects are the most common extrahematologic side effects. Two previously published studies presented a triple transplant with a conditioning regimen of melphalan 100 mg/m(2) (MEL100) with peripheral stem cell support every 2 to 5 months for patients with prohibitive comorbidities for high-dose tandem transplantation. We present a novel approach that investigates the triple melphalan 100/m(2) approach on a dose-dense, every-3-weeks schedule in a patient population without significant comorbidities.
Thirteen standard or high-risk patients with stage III multiple myeloma were prospectively treated. This population contained eight patients with immunoglobin G clonality, three immunoglobin A, one nonsecretory, and one light chain isotype. The induction regimens of the 13 patients were heterogenous and included five VAD, three DCIE, two Thal/Dex, two CIE, and one pulse decadron. Patients underwent peripheral blood leukopheresis, and these cells were divided into three equal sets and frozen. The patients were scheduled to receive melphalan at 100 mg/m(2) on days 1, 20, and 41, and then the autologous infusions occurred at days 0, 21, and 42.
All patients were able to receive all three cycles of the MEL100 regimen. Seven patients (54%) received the treatments on the every-3-weeks schedule; three treatments (23%) during the second cycle and six treatments (46%) of the third cycle had to be delayed a median of 6 and 4 days, respectively. Three patients were managed completely in the outpatient setting, and the average total hospital stay for the three transplants was 18 days. Median progression-free survival was 854 days (range 73 to 1571), and the overall survival of this cohort has yet to be reached. No patient had worse than grade II mucositis, and no serious adverse events were recorded.
Our regimen of three consecutive autologous peripheral stem cell transplants with a reduced dose of melphalan at 100 mg/m(2) given every 3 weeks was very well tolerated. The progression-free survival and overall survival are similar and can be compared favorably with the standard tandem myeloma regimens. Our data is intriguing, and further studies with larger numbers need to be performed to confirm these results.
对于没有严重合并症的患者，采用自体外周干细胞支持的串联大剂量美法仑疗法已成为标准治疗方案。粘膜炎和胃肠道副作用是最常见的血液学外副作用。两项先前发表的研究提出了一种三联移植方案，对于高剂量串联移植存在严重合并症的患者，采用每2至5个月一次的美法仑100 mg/m²（MEL100）预处理方案并给予外周干细胞支持。我们提出了一种新方法，在没有明显合并症的患者群体中，以每3周一次的密集剂量方案研究三联美法仑100/m²方法。
前瞻性地治疗了13例III期多发性骨髓瘤的标准或高危患者。该群体包括8例免疫球蛋白G克隆型患者、3例免疫球蛋白A患者、1例非分泌型患者和1例轻链同种型患者。13例患者的诱导方案各不相同，包括5例采用VAD方案、3例采用DCIE方案、2例采用Thal/Dex方案、2例采用CIE方案以及1例采用脉冲地塞米松方案。患者接受外周血白细胞分离术，采集的细胞被分成三等份并冷冻保存。患者计划在第1天、第20天和第41天接受100 mg/m²的美法仑治疗，然后在第0天、第21天和第42天进行自体输注。
所有患者均能够接受MEL100方案的全部三个周期治疗。7例患者（54%）按照每3周一次的方案接受治疗；第二个周期的三次治疗（23%）和第三个周期的六次治疗（46%）分别不得不中位延迟6天和4天。3例患者在门诊完成治疗，三次移植的平均总住院天数为18天。中位无进展生存期为854天（范围73至1571天），该队列的总生存期尚未达到。没有患者的粘膜炎超过II级，也没有记录到严重不良事件。
我们每3周给予100 mg/m²降低剂量美法仑的连续三次自体外周干细胞移植方案耐受性良好。无进展生存期和总生存期相似，与标准的串联骨髓瘤方案相比具有优势。我们的数据很有趣，需要进行更多患者的进一步研究来证实这些结果。
