Reece D E, Brockington D A, Phillips G L, Barnett M J, Klingemann H G, Nantel S H, Sutherland H J, Shepherd J D
University of Kentucky Blood and Marrow Transplant Program, Lexington 40536-0093, USA.
Bone Marrow Transplant. 2000 Sep;26(6):621-6. doi: 10.1038/sj.bmt.1702574.
Despite numerous strategies, the cure of multiple myeloma remains a difficult challenge. Recent approaches have involved dose-intensive therapy followed by stem cell transplantation, most often with autologous stem cells (ASCT). Although ASCT is of benefit, it is not considered curative. Between 1988 and 1995, we utilized an aggressive three-drug conditioning regimen followed by ABMT using marrow purged with either 4-hydroperoxycyclophosphamide (4-HC) or mafosphamide (MAF). Twenty-nine of 42 patients who had first received VAD (14 patients) or VAD followed by cyclophosphamide (7 g/m2 i.v.) + dexamethasone (40 mg/day p.o. x4) + GM-CSF (15 patients) met the eligibility criteria needed to undergo bone marrow harvest and ABMT, ie < or =10% marrow plasma cells and > or =50% decrease in paraprotein level. Alpha-interferon maintenance therapy was given post ABMT. Median follow-up is 7.5 years (range 5.0-11.25). Six early and two late non-relapse deaths occurred; 15 patients have relapsed. Seven patients remain in continuous CR (five) or PR (two), including three with stage IIIB disease at diagnosis. One patient developed a soft tissue sarcoma 8 years post ASCT. Although this protocol produced excessive toxicity compared with current approaches, the results demonstrate that dose-intensive therapy and ASCT can produce durable remission in this disease. Further development of dose-intensive strategies is warranted.
尽管有多种治疗策略，但多发性骨髓瘤的治愈仍然是一项艰巨的挑战。最近的治疗方法包括剂量密集化疗后进行干细胞移植，多数情况下使用自体干细胞（ASCT）。虽然ASCT有益，但它并不被认为是治愈性的。在1988年至1995年间，我们采用了一种激进的三联药物预处理方案，随后进行ABMT，所用骨髓用4-氢过氧环磷酰胺（4-HC）或马磷酰胺（MAF）进行净化处理。42例患者中，29例首先接受了VAD方案（14例患者），或VAD方案后接受环磷酰胺（7 g/m²静脉注射）+地塞米松（40 mg/天口服×4）+粒细胞巨噬细胞集落刺激因子（15例患者），这些患者符合进行骨髓采集和ABMT所需的入选标准，即骨髓浆细胞≤10%且副蛋白水平下降≥50%。ABMT后给予α-干扰素维持治疗。中位随访时间为7.5年（范围5.0 - 11.25年）。发生了6例早期和2例晚期非复发死亡；15例患者复发。7例患者仍处于持续完全缓解（5例）或部分缓解（2例）状态，其中包括3例诊断时为IIIB期疾病的患者。1例患者在ASCT后8年发生了软组织肉瘤。尽管该方案与目前的治疗方法相比产生了过度的毒性，但结果表明剂量密集化疗和ASCT可以使这种疾病产生持久的缓解。剂量密集策略的进一步发展是有必要的。
