Alegre A, Díaz-Mediavilla J, San-Miguel J, Martínez R, García Laraña J, Sureda A, Lahuerta J J, Morales D, Bladé J, Caballero D, De la Rubia J, Escudero A, Díez-Martín J L, Hernández-Navarro F, Rifón J, Odriozola J, Brunet S, De la Serna J, Besalduch J, Vidal M J, Solano C, Leon A, Sánchez J J, Martínez-Chamorro C, Fernández-Rañada J M
Hospital Universitario de la Princesa, Madrid, Spain.
Bone Marrow Transplant. 1998 Jan;21(2):133-40. doi: 10.1038/sj.bmt.1701062.
Between January 1989 and November 1995, 259 patients with multiple myeloma (MM), 22 stage I, 57 stage II and 180 stage III at diagnosis were treated with myeloablative high-dose therapy followed by autologous peripheral blood stem cell (PBSC) transplantation. The median time from diagnosis to transplantation was 17 months (6-112). At the time of transplant, 56 patients were in CR, 153 in PR, 25 were nonresponders and 25 had progressive disease. Mobilization of stem cells was performed with G-CSF alone in 141 cases, chemotherapy plus G-CSF in 65, chemotherapy plus GM-CSF in 36 and chemotherapy alone in 17 patients. The conditioning regimen consisted of high-dose melphalan alone in 96 patients, melphalan plus TBI in 73, busulfan plus melphalan in 56, busulfan plus cyclophosphamide in 27 and cyclophosphamide plus TBI in seven. The median durations of neutropenia (>0.5 x 10(9)/l) and thrombocytopenia (>20 x 10(9)/l) were 12 (5-118) and 13 days (5-360), respectively. Transplant-related mortality occurred in 11 patients (4%). Once a stable graft was achieved, 114 patients (44%) received maintenance treatment with recombinant alpha interferon (IFN-alpha). Among the 248 patients evaluable for response 125 (51%) had a CR and 100 had a PR (40%). The median duration of progression-free survival (PFS) and overall survival (OS) after transplantation was 23 and 35 months, respectively. Univariate analysis showed that response status pretransplant, only one line of primary induction treatment and IFN-alpha maintenance treatment post-transplant significantly influenced OS. Female sex, pretransplant responsive disease, and treatment with IFN-alpha post-transplant were the factors significantly influencing PFS. The conditioning regimen and method of stem cell mobilization had no significant impact on OS and PFS. On multivariate analysis the only independent factors associated with a longer survival were the number of chemotherapy courses prior to autologous PBSC transplantation and the pretransplant response status. The present analysis from the Spanish Registry confirms the feasibility of autologous PBSC transplantation in myeloma patients with a very low toxicity (4% toxic deaths). The high complete response rate after transplantation is encouraging. The best results are obtained when the procedure is performed early after the first line of induction therapy and in patients with chemosensitive disease. Whether early high-dose therapy followed by autotransplantation in responding patients is superior to conventional chemotherapy is currently being investigated in prospective randomized studies.
1989年1月至1995年11月期间，259例多发性骨髓瘤（MM）患者在诊断时处于I期的有22例，II期57例，III期180例，接受了清髓性大剂量治疗，随后进行自体外周血干细胞（PBSC）移植。从诊断到移植的中位时间为17个月（6 - 112个月）。移植时，56例患者处于完全缓解（CR），153例部分缓解（PR），25例无反应，25例病情进展。141例患者仅用粒细胞集落刺激因子（G - CSF）动员干细胞，65例用化疗加G - CSF，36例用化疗加粒细胞-巨噬细胞集落刺激因子（GM - CSF），17例仅用化疗。预处理方案包括96例患者仅用大剂量美法仑，73例用美法仑加全身照射（TBI），56例用白消安加美法仑，27例用白消安加环磷酰胺，7例用环磷酰胺加TBI。中性粒细胞减少（>0.5×10⁹/L）和血小板减少（>20×10⁹/L）的中位持续时间分别为12天（5 - 118天）和13天（5 - 360天）。11例患者（4%）发生移植相关死亡。一旦获得稳定的移植物，114例患者（44%）接受重组α干扰素（IFN - α）维持治疗。在可评估反应的248例患者中，125例（51%）达到CR，100例（40%）达到PR。移植后无进展生存期（PFS）和总生存期（OS）的中位持续时间分别为23个月和35个月。单因素分析显示，移植前的反应状态、仅一线初次诱导治疗以及移植后IFN - α维持治疗对OS有显著影响。女性、移植前反应性疾病以及移植后用IFN - α治疗是显著影响PFS的因素。预处理方案和干细胞动员方法对OS和PFS无显著影响。多因素分析显示，与较长生存期相关的唯一独立因素是自体PBSC移植前的化疗疗程数和移植前的反应状态。来自西班牙登记处的本分析证实了自体PBSC移植在骨髓瘤患者中的可行性，毒性非常低（4%毒性死亡）。移植后高完全缓解率令人鼓舞。当在一线诱导治疗后早期进行该手术且用于化疗敏感疾病患者时可获得最佳结果。目前正在前瞻性随机研究中调查反应性患者早期大剂量治疗后自体移植是否优于传统化疗。
